ANDROPAUSE- (Testosterone Decline w/Specific Symptoms)This information is under copyright by Harvey S. Bartnof, M.D. and California Longevity and Vitality Medical Institute®. It may be copied only for individual, personal use and is not for distribution or publication of any type without the explicit written permission of Dr. Bartnof. Copyright 2004-2011-All rights reserved. Disclaimer: This section about Andropause is meant for educational and informational purposes only and is not intended to diagnose or treat any medical condition, including Andropause. The diagnosis and appropriate treatment of Andropause should be performed only by a competent, experienced physician.TAKE-HOME SUMMARY:
Dr. Bartnof's Published Letter-To-The-Editor at the San Francisco Chronicle about Testosterone Decline in Men SHORTER LIFESPAN What is the link between Andropause and Alzheimer’s Disease? ANDROPAUSE (MALE MENOPAUSE) REFERENCES Dr. Bartnof's Published Letter-To-The-Editor At The San Francisco Chronicle About Testosterone Decline In MenSan Francisco Chronicle Letters to Datebook Carolyn Zinko’s article in the San Francisco Chronicle was titled, “Could a man's midlife crisis be more than a state of mind, but be linked to his endocrine system instead?”
What is Andropause? (Testosterone Decline w/ Specific Symptoms)Andropause is a diagnosis reflecting a decline in male hormones, called androgens, with symptoms, changes in blood and physical changes. (“Andro” mean ‘male’ and “gen” refers to ‘generate’ or ‘generating maleness.’ The main androgen in men is testosterone. Andropause may also have other hormone imbalances, including increased estrogen (the main female hormone in women), a decline of DHT (dihydrotestosterone), and other possible hormone imbalances. The term ‘andropause’ is Greek, with ‘andro‘ meaning male or man and ‘pause’ meaning cessation or stopping (cessation of maleness). In Europe, the European Menopause and Andropause Society (EMAS) is composed of physicians and researchers with an interest in those topics (menopause is a decline in female hormones in women). What is a Hormone?A hormone is a natural substance produced in a gland in the body and travels through the blood to target normal cell functioning throughout the body. There are many different hormones in the human body and they are essential for optimal health. When certain hormones are lacking, that would be lethal (e.g.; thyroid hormone). Hormone declines (“pauses”) and hormone imbalances are associated with declining health and risk for many diseases. Medical textbooks describe many disease “syndromes” with hormone levels that are either too low or that are too high. Hormone levels need to be normal or optimal. The specialty of hormone study is called Endocrinology Does Andropause have other names?Andropause has other terms, including: Male Menopause (menopause is decline in female hormones in women); Male Climacteric (climax or ending of maleness); ADAM or Androgen Deficiency in the Aging Male (androgen refers to male-like hormones); PADAM or Partial Androgen Deficiency in the Aging Male; Viropause (decline in virility or masculinity); and Late Onset Hypogonadism (low production of testosterone from the testicles in later or older life). Are Andropause and hypogonadism in men the same?Hypogonadism in men generally means low testosterone with symptoms that occurs anytime during adult life, including teenage years (puberty) or older. Andropause generally refers to a decline in testosterone with symptoms, after an earlier time when a man normal testosterone and no andropause symptoms. A common term for Andropause is ‘Late-Onset Hypogonadism.’ Men with either diagnosis may have decreased fertility or even be sterile, although this occurs when testosterone levels are very low. What are Andropause symptoms?Note that not all men will have all symptoms listed here. The individual patient may have only 1 or 2 or many of these symptoms. These may include: fatigue or lower energy; softer erections, ‘erectile dysfunction’ or loss of morning erections; lower libido or (lower sex drive); difficulty achieving orgasm (climax); complaints of breast discomfort or gynecomastia (enlargement of breasts possibly with a more female appearance); hot flushes or night sweats; loss of vitality, motivation, or self-confidence; feeling sad, depressed or anxious; poor concentration; declining memory; sleep disturbance; increased need for napping; symptoms of decreased physical strength or capability either for labor work or for sports; increased muscle recovery time after labor work or sports; possible increased urinary frequency; and other symptoms associated with individual organ diseases that are associated with Andropause, including chronic liver, lung, kidney, or heart disease. Is Andropause common?Andropause affects approximately 30% or more of men from the ages of 40-79 years. Levels of this vital hormone in men, testosterone, begin to decrease at age 30 years, due to aging itself. The Leydig cells in the testicles start to produce less and less testosterone as men become older. According to the New England Journal of Medicine in 2004, approximately 10% men in their 40s have low testosterone; 25% of men in their 50s; 45% of men in their 60s; 70% of men in their 70s; and further increases in older men. What are Andropause changes on the body?Note that not all men with Andropause will have all changes listed here. The individual patient may have only 1 or 2 or many of these physical changes. These may include: decrease in muscle mass and strength and eventual “frailty” (difficulty with standing up, walking, climbing stairs); increased body weight, especially increased body fat, often around the mid-section or waistline and inside the abdomen; gynecomastia (enlargement of breasts possibly with a more female appearance); less armpit hair (occurs slowly that patients often do not notice); less pubic hair (occurs slowly that patients often do not notice); other changes in body hair (several patterns); loss of height; lower bone strength (measured by a scan) and risk of osteoporosis (severe loss of bone density and strength), osteopenia (mild loss of bone density) and risk bone fracture; increased skin wrinkling (with very low levels of testosterone, note there are many co-factors for wrinkling); thinner skin (note there are many co-factors for skin thinning); blood pressure may also be high, (note there are many co-factors for high blood pressure); and others. What are Andropause changes in blood?There are several Andropause changes that may be occur in the blood. Note that not all men will have all changes. The main change is a low or low-end level of testosterone, the main male hormone. Measuring total testosterone is insufficient, since most of the testosterone is bound to protein, making it relatively inactive. Other possible changes may include: estrogen changes (female hormone, although men do need some estrogen); DHT (dihydrotestosterone) changes (another male hormone); insulin changes (helps to regular blood glucose or sugar); other hormone abnormalities; increased glucose (sugar) related to diabetes or pre-diabetes; anemia (low red cell count); liver and kidney tests; abnormal lipids (cholesterol, triglycerides, others, although there are many co-factors for abnormal lipids); increased markers of inflammation; and others. Does Andropause cause other abnormal tests?Other diseases may be associated with Andropause. Many types of cardiac disease are associated with Andropause, so several heart tests could be abnormal, including electrocardiogram, treadmill, and heart calcium CT or MRI scans; abnormal carotid artery (neck) ultrasound or other imaging tests; other artery tests (abdomen, pelvis, legs) showing partial or complete blockages (atherosclerosis) or calcium deposits; abnormal breathing tests, lung x-ray or other imaging tests that occur with chronic lung disease (emphysema, chronic bronchitis, others); low bone density (osteopenia, osteoporosis, determined by a specific scan called DXA); possible abnormal imaging studies (CT, MRI, x-rays) of the brain; low sperm count; and others. What are the causes of Andropause?Starting at age 30 years, testosterone production in men starts to decline. The source of testosterone in men is the Leydig cells in the testicles. Production can decrease due to many factors, although “aging” itself is a major cause. Research in the last decade has revealed co-factors for aging itself. Men with any of the following conditions are more likely to develop or have Andropause: aging; obesity; diabetes; and pre-diabetes; chronic kidney disease; emphysema (chronic lung scarring) or chronic bronchitis; liver cirrhosis (scarring); alcoholism; sleep apnea (stopped or shallow breathing while sleeping); HIV-AIDS; prior illegal steroid use; other hormone imbalances; iron excess; narcotic (pain) medications (either prescribed or illicit, note other hormone declines may also occur); certain other prescription medications; radiation treatments; traumatic brain injury; possible “xeno-estrogens” (chemicals in the environment that act like estrogen, the main female hormone); and shortened telomeres (as we age, telomeres that protect the tips of chromosomes in cells become shorter). How is Andropause diagnosed?Medical diagnoses are made by a qualified physician who evaluates a patient’s symptoms, blood or other test results, and the physical examination. Andropause is no different. However, many physicians do not have the training or experience to establish the diagnosis. Sometimes another abnormal test may be a clue for possible Andropause. For example, a bone fracture might indicate low bone density that would be measured on a DXA scan. Low bone density is a possible result of Andropause. Why is Andropause important to diagnose?There are several reasons why Andropause is very important to diagnose. There are many studies indicating that men with low testosterone do not live as long as men with normal testosterone. And the earlier deaths are due to the common causes of death, including heart disease, cancer and stroke. Some of these studies are summarized below: 1. Dr. Andre Araujo reported at the Endocrine Society annual meeting in June 2011 about a “meta-analysis” of testosterone levels and mortality in men. (A meta-analysis combines other previously reported studies.) The combination analysis represented 14 studies of 18,492 men. The average (mean) age was 60 years who were followed for an average of 9.5 years. The results showed that the men with the lowest testosterone had a 37% increased risk of death and 26% increased risk of cardiac death. The report appeared in Endocrine Reviews. 2. Professor Kay-Tee Khaw reported in the cardiology journal Circulation the results of 11,606 men who were tracked for up to 10 years starting in 1993. At that time, the men were 40-79 years of age and from the United Kingdom. Men with the highest testosterone levels (still in the normal range) had a significant 25% decreased risk of dying by 2003, when compared to men with the lowest level! Men with mid-range levels also lived longer than those in the lowest level. The most common cause of death was heart disease. All traditional factors for heart disease were considered, and the increased risk still existed. Professor Khaw concluded, "Low testosterone may be a predictive marker for those at high risk of cardiovascular disease." 3. In the Rancho Bernardo Study in California, Dr. Gail Laughlin reported results of 794 men, ages 50-91 who were enrolled in the mid-1980s and were followed for an average 11.8 years (longest 20 years). In 2004, men with the lowest levels of testosterone in the 1980s were 40% significantly more likely to die than those with normal levels. Low testosterone increased heart deaths by 38% and lung deaths by 129%! Traditional risk factors for these diseases were considered in the analysis. Dr. Laughlin concluded, "Testosterone insufficiency in older men is associated with increased risk of death over the following 20 years, independent of multiple risk factors and several preexisting health conditions." The report was published in Journal of Clinical Endocrinology and Metabolism. 4. Asa Tivesten, M.D. reported that low testosterone in 3,014 elderly men from Sweden predicted a 65% increased risk of dying 4.5 years after starting the study. Dr. Tivesten concluded, "Elderly men with low serum testosterone and estradiol have increased risk of mortality." The study was published in Journal of Endocrinology and Metabolism. 5. Molly Shores, M.D. reported that low testosterone in 858 male veterans from Washington State predicted an 88% increased risk of dying sooner compared to those men with normal levels. The men enrolled in the study in the late 1990s and were followed for up to 8 years. Traditional risk factors for diseases were considered, and the risk remained. Dr. Shores concluded, "Low testosterone levels were associated with increased mortality in male veterans." The study was published in Archives of Internal Medicine. 6. Dr. Torkel Vikan found that those men with the lowest free testosterone levels among 1,568 men from Norway had a 24% increased risk of dying sooner, when compared to those men with normal levels. The study was started in 1994, and the men were followed until 2007. Heart disease was a common cause of death; traditional risk factors for disease and dying were considered in the analysis. Dr. Vikan concluded, "Men with free testosterone in the lowest quartile had a 24% increased risk of all-cause mortality." The study was published in European Journal of Endocrinology. 7. Marcello Maggio, M.D. reported that low levels of 3 hormones (including testosterone) in 410 men from Baltimore predicted early death after 6 years. Compared to men with normal levels, those with low levels of testosterone, DHEA (adrenal hormone) and IGF-1 (reflecting levels of growth hormone) had a significant 144% increased risk of dying. Traditional risk factors for death were considered in the analysis; all men were at least 65 years. Dr. Maggio concluded, "Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men." The report was published in Archives of Internal Medicine. 8. Aapo Lehtonen, M.D. found that in a study of 310 men from Finland followed for 10 years, those who were still alive had a significant 14% increased level of testosterone when first enrolled, compared to those who had died. At the beginning of the study, the men were 71-72 years. The report was published in the medical journal Age and Ageing. 9. Dr. Andy Menke reported that low testosterone in 1,114 U.S. men in the NHANES III study was associated with 43% increased risk of mortality after 9 years, when adjusted for other co-factors. The men had no history of cardiovascular disease upon entering into the study. Dr. Menke concluded, “Men with low free and bioavailable testosterone levels may have a higher risk of mortality within 9 years of hormone measurement.” The article was published in American Journal of Epidemiology. 10. Dr. Shiho Fukai from the University of Tokyo reported that low testosterone in 117 elderly men was associated with a 3.2-fold increased risk of death after 2.75 years, independent of other risk factors for death. The average age at baseline was 83 years. The report was published in Geriatrics Gerontology International. 11. Dr. R. Haring reported that among 1,954 men followed for 7.2 years, testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. The report was published in the European Heart Journal, and Dr. Haring is from Ernst Moritz Arndt University Greifswald in Germany. RISK OF COMMON DISEASES AND CONDITIONS Low testosterone is a risk factor for many common diseases of middle-age and elderly men. These include: atherosclerosis (artery blockages with risk of heart attack, stroke and Alzheimer’s disease); diabetes and pre-diabetes; abnormal cholesterol (note there are many co-factors for abnormal cholesterol and other lipids); increased blood pressure (note there are many co-factors for high blood pressure); increased body fat in the mid-section (abdomen and in between abdominal organs [visceral fat] and risk for heart attack) with risk for increased waistline; obesity and overweight; “metabolic syndrome” (combination related to items 2-6 above); low bone density (osteopenia, osteoporosis) and risk for bone fracture and height loss; decline in muscle mass, with eventual risk for frailty (difficulty in walking, standing up, climbing stairs); increased markers of inflammation in blood, with associated increased risk for many diseases; and likely increased risk for Alzheimer’s disease (memory decline, dementia). Men with Andropause generally will have a poorer quality-of-life, due to associated symptoms (note that not all men have all symptoms): lower energy; lower motivation; lower productivity; decline in libido; decline in quality of erections or even no erections; decline in sexual satisfaction; decline in physical capability for sports, athletics and physical work; decline in muscle mass; increase in body fat; possible decline in self-image; and risk for depression, anxiety, memory decline, decreased mental concentration, sleep disruption, and increased urination. What is the link between Andropause and ED (Erectile Dysfunction)?Research in the last 5-10 years indicates that lower testosterone is a co-factor for ED (Erectile Dysfunction). Normal erections require several co-factors, including testosterone, normal nerve function into the pelvis region, normal blood flow into the pelvic region, and many other normal physiologic parameters, including other hormones and psychological factors. There have been many published reports in the medical literature that ED, particularly in middle-age and elderly men, may be an early sign of overall vascular disease (atherosclerosis), with future risk for heart attack and stroke due to vascular disease in those organs (heart, brain). Many men who have been prescribed medications for ED (Viagra, Levitra or Cialis) may have Andropause that was not detected, not treated or not treated effectively. We have many patients who fit this profile and do not need their ED medications after treatment for Andropause. What are the treatments for Andropause?After a diagnosis of Andropause has been determined by a competent physician, the most common treatment is testosterone replacement therapy (there are other possible treatments). The most common testosterone treatment would be a gel or cream applied on the skin, or by injection (shot) in the muscle. There are minor preference differences associated with each form. Patches can be associated with skin rash and may be aesthetically not preferred by some men. There is a gum-cheek form, but this can be associated with irritation there. Pellets require a minor surgery for insertion. Oral forms are not legally available in the US currently and require frequent dosing. Depending upon associated hormone imbalances other than testosterone itself, the treatment might be another hormone or hormone blocker. If a pituitary gland hormone is low, sometimes treatment with a signal hormone may increase testosterone levels. Sometimes a specific cause for Andropause is found—when that cause is treated, the Andropause may resolve. What does testosterone do in men’s bodies?Testosterone is essential for normal function in men. It increases libido (interest in sexual activity), is anabolic (will build body tissues, including muscles and bones), helps maintain normal oil secretion in the skin and hair, and has effects, directly or indirectly on the brain, that are partly responsible for normal cognition (thinking), mental sharpness and concentration, visual-spatial abilities, sense of well-being, sense of stamina, sense of energy and normal mood. Testosterone is necessary co-factor for normal erectile functioning and sperm production and fertility. Testosterone and other androgen hormones lead to typical male sexual characteristics, including facial hair and (in many men) body hair and a deeper voice. Testosterone has beneficial benefits on the heart and arteries—it was used to treat angina (heart pain due to artery blockage) in the 1940s. Several studies have shown that testosterone dilates the heart and other arteries, although the effects may be due to its conversion to estradiol. Several more current studies have shown beneficial effects of testosterone on results of exercise treadmill testing, reducing abnormal changes on electrocardiograms (ST depression improves) and improving angina. Low testosterone levels in men are associated with “atherosclerotic” (blockages) disease in the heart arteries. Testosterone generally will decrease total and LDL (“bad”) cholesterol, but, in some men, will also decrease the HDL (“good”) cholesterol somewhat. This decrease is counterbalanced by increased clearance (decrease in blood level of) of total cholesterol. Low HDL can be treated with lifestyle intervention and/or prescriptive and non-prescriptive medication. Testosterone helps to regulate normal blood glucose (sugar) and insulin, to help offset diabetes and pre-diabetes. Testosterone helps to decrease blood markers of inflammation, which if elevated, increases risk of vascular disease. Testosterone also helps to regulate normal urination. What is the link between Andropause and Alzheimer’s Disease?Several research studies have shown a significant association between low testosterone levels in men and Alzheimer’s disease of the brain. In general, men with Andropause and some memory changes will report better memory with testosterone treatment. However, other hormones and other co-factors may also be involved in memory decline. Also, men who are treated to block their testosterone production generally report memory decline. In the January 27, 2004 issue of the journal Neurology, 574 men were followed for an average of 19 years in the Baltimore Longitudinal Study of Aging. The results showed that higher free (unbound) testosterone levels in men predicted a decreased future risk of developing Alzheimer’s. Put another way, for every 50% increase in free testosterone at baseline, there was a 26% decreased risk of developing the disease. This “dose-response” relationship is something that statistics researchers use to add credence to the results and significantly adds weight to the conclusions. At the end of the study, those men with Alzheimer’s had about half the level of free testosterone as those men who did not have the disease. The same researchers had reported previously that older men with higher levels of free testosterone have better visual memory, better verbal memory and better performance on “spatial” tasks than those men with lower levels. Robert S. Tan, MD, of the University of Texas at Houston, reported in 2003 in the journal Aging Male his results of a pilot study of 10 men with dementia (loss of brain function, a prominent finding in Alzheimer’s) and who had low testosterone blood levels (hypogonadism). After testosterone replacement therapy, quarterly measurements for 1 year revealed significant improvements in thinking abilities (MMSE, Mini-Mental State Examination) and visual-spatial abilities (Clock-Drawing test). This is only a pilot study and additional research is necessary. What is the relationship between Andropause and high cholesterol?Men with Andropause are more likely to develop abnormal cholesterol (and other abnormal blood lipids or fats, including high triglycerides). Treatment with testosterone generally is associated with improvements in cholesterol levels, but there are several other co-factors for abnormal cholesterol. What is the relationship between Andropause and diabetes?Men with Andropause are much more likely to develop diabetes and pre-diabetes. The opposite is also true: men with diabetes and pre-diabetes are more likely to develop Andropause. There are now published studies indicating that men with diabetes who have Andropause and are treated with testosterone live longer than men with both conditions that are not treated with testosterone. Men with both conditions who are treated with testosterone generally have improvements in their diabetes (glucose, insulin, hemoglobin A1C), need less diabetes medication, and tend to lose body fat. They also generally feel better with increased energy, improved libido, and improved erections (depends upon severity of vascular disease). What is the relationship between Andropause and sleep apnea?Men with Sleep Apnea (stopped or shallow breathing while sleeping) are more likely to develop Andropause. However, those men may have other risks for apnea, including being overweight, which also is associated with Andropause. Occasionally, when men with Apnea and Andropause are treated with testosterone, apnea may become worse; although not all studies show this relationship. But generally, testosterone will lead to weight loss, particularly body fat loss, and apnea itself may improve. Men with apnea may require specific treatment with a breathing device to help maintain safe oxygen levels in blood. What is the relationship between Andropause and gynecomastia?Several conditions that can cause gynecomastia (breast enlargement due to fatty tissue) also can cause Andropause. Also, Andropause itself might cause gynecomastia or other conditions that could cause gynecomastia. Patients with Andropause who are treated with testosterone require monitoring to make sure that gynecomastia or precursors to gynecomastia do not develop. Depending upon the severity of the gynecomastia, medical treatments or surgical treatments might be beneficial. Does testosterone treatment have side effects?A competent physician will know what side effects to monitor. Most men with Andropause who are treated with testosterone will not show side effects. Most of the side effects are minor and are manageable. Possible side effects may include: increased red cell count in blood (treatable); acne (treatable); possible oily skin (treatable) although this is often an improvement due to dry skin before treatment); increase in estrogen and nipple symptoms (treatable); increase in DHT and hair thinning (treatable); decrease in testicle size, sperm count and fertility ( all treatable); possible worsening or evoking sleep apnea (stopped breathing during sleep, uncommon and treatable); possible mild increase in PSA count (to a level that would have been present had there been no testosterone decline), increased Prostate Specific Antigen may occur in prostate enlargement, prostate infection and if pre-existing, prostate cancer—see section below about Prostate Cancer); and possible fluid retention (preventable and treatable). Is it possible for my doctor to tell me if I have Andropause?Unfortunately, many doctors are not comfortable making the diagnosis of Andropause in men or in treating Andropause. This is due to the fact that many physicians may not have had specific training in diagnosis and treating the condition. Some doctors only measure the total testosterone level in blood, which is insufficient to establish the diagnosis, per Society guidelines. Many doctors are not familiar with testing hormones related to testosterone that may be imbalanced, either for diagnosing Andropause or for monitoring the treatment. This is why many patients do not receive optimal treatment related to their Andropause. Also, reports in the media of illegal testosterone use by athletes and even celebrities tend to cause some doctors to be very uncomfortable with diagnosing and treating Andropause. I heard that testosterone is illegal - is this true?Hypogonadism in men and Andropause have been defined in medical and endocrine (hormone) textbooks for decades. Drs. G. Myers and C.G. Heller wrote their first medical article about the topic in 1944 called, “The Male Climacteric, its Symptomatology, Diagnosis and Treatment.” It was published in the Journal of the American Medical Association. In the same medical journal in 1946, Dr. A. A. Werner reported his findings among 273 men with ‘male climacteric.’ Medical treatment for Andropause has been described in standard medical and endocrine textbooks along with guidelines established by the Endocrine Society of physicians and other medical societies. Prescribing of testosterone legally is regulated by the US Food and Drug Administration (FDA), Department of Justice and many states in the US. However, testosterone (or bottles with labels claiming to contain testosterone) may be purchased illegally on the Internet and on the “black market.” Self-prescribing and self-dosing is extremely dangerous and illegal. This author has seen patients who tried to self-treat, resulting in severe hormone imbalances, side effects, and many ill symptoms. As a group, many professional body builders and professional wrestlers generally die younger due to illegal usage of testosterone and side effects that are not monitored or detected. What will happen if I have Andropause and don’t get treated?Men with Andropause who are not treated generally will have a poorer quality-of-life, will have a higher risk for many diseases and a shortened lifespan. Why is Andropause important to diagnose? What do medical studies show when men with Andropause are treated with testosterone?Many published studies of men with Andropause who are treated with testosterone therapy show improvements. Most of the studies are up to 1-2 years. (One study has lasted longer than 13 years.) In general, the results show that in most men: fatigue decreases and energy improves; sense of well being generally improves; mood may improve; sense of vitality and productivity may improve; memory may improve (several co-factors may be involved with memory decline); muscle mass and strength increases; physical capability for labor and sports generally improves; body fat decreases; waist size decreases; libido generally improves; erections generally improve (several co-factors may be involved with ED); blood glucose (sugar), insulin and other markers of diabetes and pre-diabetes improve; lifespan increases in men with diabetes and andropause; triglycerides (blood fat) may improve; other disease markers may improve, including markers of inflammation and those related to "metabolic syndrome" What are Andropause changes in blood?; bone density generally increases (several co-factors are involved with bone density decline); anemia improves (if present before starting treatment and was due to Andropause); frequent urination often improves but not always; skin appearance may appear healthier (if baseline skin changes were due to andropause); and studies of heart function generally show improvements. Most of the published medical studies do not last longer than 1-2 years, because men generally know when they have been prescribed testosterone (and not “placebo” inactive drug) since they simply feel better. Men who are given “placebo” (inactive drug) do not feel better, and tend to drop out of the study, making it difficult to complete the study for longer than 1-2 years. There are published studies of men in Europe with Andropause and testosterone therapy for over 13 years, without significant side effects. With professional monitoring, testosterone treatment is safe. Is it dangerous to be treated with testosterone?Testosterone replacement therapy is safe when a man is accurately diagnosed with Andropause and treated by an experienced and competent physician who is able to monitor the patient. Does testosterone treatment cause cancer?There is a myth in the medical profession and in the lay public for many decades that testosterone causes prostate cancer. In a 2008 review of 18 medical studies, the US National Cancer Institute reported that “sex hormones were not associated with risk of prostate cancer.” Dr. Abraham Morgentaler, M.D., urologist at Harvard Medical School has published many medical articles in the last several years describing where this myth originated and why testosterone does not cause prostate cancer. Prostate cancer is a common cancer in men, so all men need regular check-ups for screening after the age of 40 years, including men without Andropause, men with Andropause and men with Andropause who have been prescribed testosterone therapy. I have been diagnosed with prostate cancer; is it safe to be prescribed testosterone?Currently, men with active prostate cancer should not be prescribed testosterone, unless they are part of a research study. Dr. Morgentaler from Harvard Medical School (and other research physicians) has treated some men who had active prostate cancer and Andropause with testosterone. However, currently this is considered experimental. Men who have recovered and been cured of their prostate cancer may possibly have testosterone treatment for Andropause, although close monitoring by an experienced physician would be required. My own testosterone has been blocked with medication, as a treatment for my prostate; is this dangerous?In certain situations, doctors prescribe medications to block testosterone production in the body, usually as a treatment for prostate cancer. For every treatment, there are potential benefits and potential side effects and risks. These are generally reviewed with the patient by the treating physician as a part of Informed Consent. There are published studies indicating that when compared to men without blocked testosterone, men with blocked testosterone are more likely to: develop pre-diabetes and diabetes; develop high blood fats (triglycerides); gain body fat in the mid-section (abdomen and in between the organs in the abdomen); develop “metabolic syndrome” (combination of first 3 and possibly high blood pressure); lose muscle mass; develop bone thinning (osteoporosis and osteopenia); have a life-threatening bone fracture to due bone thinning; develop depression or other mood changes; have lower libido; develop ED (erectile dysfunction); have lower energy; have a heart attack; and die of a heart attack. After asking my doctor, he does not want to test my testosterone; what should I do?There are many physicians who do not have the training or clinical experience to diagnose and treat Andropause. If your doctor does not want to test your testosterone, then it would be reasonable to find a physician who is comfortable and experienced in diagnosing and treating the many facets of Andropause. My blood shows low testosterone and I think I have Andropause, but my doctor does not want to treat me; what should I do?There are many physicians who do not have the training or clinical experience to treat Andropause. If your doctor does not want to treat your Andropause, then it would be reasonable to find a physician who is experienced in diagnosing and treating the many facets of Andropause. Does testosterone treatment for Andropause affect the whole body?Testosterone is a hormone that has effects on the entire body. In the past, physicians believed that testosterone was only important for sperm production (fertility), libido, erections, and maintaining muscle mass. We now understand that testosterone is an important hormone for nearly every organ in the body, and a co-factor for normal lifespan and quality-of-life. Also, testosterone helps to maintain normal blood glucose (sugar), cholesterol, maintain muscle and bone strength, maintain normal artery functioning, and maintain and even improve normal heart functioning. I have been treated by my doctor with testosterone for Andropause, but I really don’t feel any different; why?Testosterone can change into other hormones, and the dosing of testosterone should be monitored for optimal symptom improvement. Some physicians merely prescribe one dose and are not monitoring for: improvements in symptoms; not monitoring for optimal blood levels; and not monitoring other hormones that increase with testosterone treatment. Complete treatment for Andropause is about complete sex hormone balance, including estrogen and DHT (dihydrotestosterone). Also, there are some treatable causes of Andropause that should be determined before starting treatment. If the treatable causes are not addressed, then patients might not be expected to have optimal improvements with testosterone treatment. Lastly, certain prescription medications might interfere with optimal improvements of symptoms. Is Andropause related to other hormone changes?There are several hormones that decline with aging, and testosterone is only one of those hormones. People have better quality-of-life and decreased risk for diseases when all of the hormones are in balance. However, professional diagnosis, treatment and monitoring are necessary. Since I had mumps as an adult; could that be the reason for my Andropause?Mumps virus can affect the testicles when the infection occurs during the teenage years or adulthood. Scarring could result, eventually leading to Andropause or an earlier Andropause. I read that fathers with Andropause who have small children should not be prescribed testosterone; is this true?This is not true. Men with Andropause who are prescribed topical testosterone gel or cream for the skin need to be aware and to take precautions so that there is no direct skin-to-skin contact with others, especially children. This is because the testosterone could rub off onto the other person, especially a child, which could be unsafe. When a father applies cream or gel to a skin area that is covered by clothing, transfer to the other person would not be expected to happen. During sexual contact with a spouse or partner, there could also be skin-to-skin transfer to the sex partner, so specific precautions need to be taken. This problem is easily manageable with education, information and simple precautions. Transfer would not occur from men who are receiving a regular injection (shot) of testosterone. Won’t I get ‘rhoid rage’ if my Andropause is treated with testosterone?‘Rhoid rage’ would not occur when testosterone is prescribed and monitored by an experienced physician to make sure that the levels are in a safe range. Rage and other emotional changes could occur when men use testosterone illegally, leading to levels that are dangerously high. In that situation, mood may become abnormal. Was Andropause the cause for Barry Bond’s treatment at “Balco?”There were news reports that several athletes including Barry Bonds were allegedly treated through Balco for sports “performance enhancement.” This would be dangerous and illegal and would not be due to Andropause. A “designer” testosterone was allegedly used called THG. This type of hormone (TetraHydroGestrinone) is not the same as naturally-occurring testosterone. Any synthetic testosterone that is not the exact same size and shape as naturally-occurring testosterone would be associated with side effects making it unhealthy. Professional wrestler Chris Benoit was treated with testosterone with bad effects; did he have Andropause?The professional wrestler Chris Benoit was allegedly being treated with testosterone according to newspaper reports. However, those news reports indicated that the levels were allegedly 10 times the normal range at the time of his unfortunate death. Sadly, according to news reports, he killed his wife and son and then committed suicide. This underscores why monitoring by a competent and experienced physician is so important and that treating for “performance enhancement” is dangerous. Chris Benoit was not the only pro-wrestler or professional body builder who died young due to complications related to illicit testosterone usage. Please call (415) 986-1300 to learn more. ANDROPAUSE (MALE MENOPAUSE) REFERENCESGENERAL GENERALBartnof, Harvey S. Andropause. http://www.drbartnof.com/andropause-male-menopause-treatments.html Bartnof, Harvey S. See testosterone for all it is - not just a male sex hormone, Letter to the Editor: sfgate.com (San Francisco Chronicle). February 13, 2009. http://www.drbartnof.com/andropause-male-menopause-treatments.html#link_21 Zinko, Carolyne. Could a man's midlife crisis be more than a state of mind, but be linked to his endocrine system instead? San Francisco Chronicle February, 2009, review of Dr. Jed Diamond's book, "Irritable Male Syndrome." Lamberts SW and others. The endocrinology of aging. Science. 1997 Oct 17; 278(5337):419-24. http://www.ncbi.nlm.nih.gov/pubmed/9334293 “Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity.” Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with aging in men. Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2002 Feb; 57(2): M76-99. http://www.ncbi.nlm.nih.gov/pubmed/11818427 Morley JE. Andropause, testosterone therapy, and quality of life in aging men. Cleveland Clinic Journal of Medicine. 2000 Dec; 67(12): 880-2. http://www.ncbi.nlm.nih.gov/pubmed/11127982 “Testosterone therapy can improve quality of life in aging men because aging is accompanied by declining testosterone levels that may contribute to decreases in muscle mass, bone density, libido, stamina, and cognition.” Haren MT, Kim MJ, Tariq SH, Wittert GA, Morley JE. Andropause: a quality-of-life issue in older males. Med Clin North Am. 2006 Sep;90(5):1005-23. http://www.ncbi.nlm.nih.gov/pubmed/16962854 “Testosterone deficiency occurs commonly in men as they grow older. This deficiency often is associated with a decline in sexual activity and a loss of muscle mass. Testosterone replacement can reverse many of these effects.” Morley JE. Andropause: is it time for the geriatrician to treat it? Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2001 May; 56(5): M263-5. http://www.ncbi.nlm.nih.gov/pubmed/11320104 Hafez B, Hafez ES. Andropause: endocrinology, erectile dysfunction, and prostate pathophysiology. Archives of Andrology. 2004 Mar-Apr; 50(2): 45-68. http://www.ncbi.nlm.nih.gov/pubmed/14761837 Tan RS, Culberson JW. An integrative review on current evidence of testosterone replacement therapy for the andropause. Maturitas. 2003 May 30; 45(1): 15-27. http://www.ncbi.nlm.nih.gov/pubmed/12753940 Tan RS, Pu SJ. Is it andropause? Recognizing androgen deficiency in aging men. Postgraduate Medicine 2004 Jan; 115(1): 62-6. http://www.ncbi.nlm.nih.gov/pubmed/14755879 Bain J. Andropause. Testosterone replacement therapy for aging men. Can Fam Physician. 2001 Jan; 47: 91-7. http://www.ncbi.nlm.nih.gov/pubmed/11212438 Tan RS, Philip PS. Perceptions of and risk factors for andropause. Archives of Andrology. 1999 Nov-Dec; 43(3): 227-33. http://www.ncbi.nlm.nih.gov/pubmed/10624507
The majority of men have heard of a male climacteric, but only a minority had consulted a practitioner about their symptoms. More information and knowledge are needed, for the general population to better motivate men to seek medical advice and also for the health care professionals to better deal with the symptoms of LOH [Late Onset Hypogonadism}.”
“The age-related decline in testosterone likely contributes to the concomitant decrease in lean mass [muscle, bone] documented in men.”
“Testosterone deficiency afflicts approximately 30% of men aged 40-79 years, with an increase in prevalence strongly associated with aging and common medical conditions including obesity, diabetes, and hypertension. A strong relationship is noted between testosterone deficiency and metabolic syndrome, although the relationship is not certain to be causal. Repletion [treatment] of testosterone in testosterone-deficient men with these comorbidities [diseases] may indeed reverse or delay their progression. While testosterone repletion has been largely thought of in a sexual realm, we discuss its potential role in general men's health concerns: metabolic, body composition, and all-cause mortality through the use of a single clinical vignette.” Rohrmann S, Platz EA, Selvin E, Shiels MS, Joshu CE, Menke A, Feinleib M, Basaria S, Rifai N, Dobs AS, Kanarek N, Nelson WG. The prevalence of low sex steroid hormone concentrations in men in the Third National Health and Nutrition Examination Survey (NHANES III). Clin Endocrinol (Oxf). 2011 Aug;75(2):232-239. http://www.ncbi.nlm.nih.gov/pubmed/21521312 “We estimated that 8·4 million men 40+ years old may have low total testosterone…a substantial number of US men may have low sex steroid hormone levels, possibly putting them at risk for adverse health consequences and premature death.” Bhasin S, Cunningham GR, Hayes FJ, and others. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J. Clin Endocrinol. Metab. 2010; 95:2536-2559. http://www.ncbi.nlm.nih.gov/pubmed/20525905 “We recommend testosterone therapy for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density.” Wang C, Nieschlag E, Swerdloff R, and others. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. European Urology. 2009; 55:121-130. http://www.ncbi.nlm.nih.gov/pubmed/18762364 Wu FC, others. Identification of late-onset hypogonadism in middle-aged and elderly men. New England Journal of Medicine. 2010 Jul 8;363(2):123-35. http://www.ncbi.nlm.nih.gov/pubmed/20554979 “Symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels.” Haring R, Baumeister SE, Völzke H, Kohlmann T, Marschall P, Flessa S, Nauck M, Wallaschofski H. Prospective association of low serum total testosterone levels with health care utilization and costs in a population-based cohort of men. Int J Androl. 2010 Dec;33(6):800-9. http://www.ncbi.nlm.nih.gov/pubmed/20059581 “Longitudinal models revealed a significant association of low serum testosterone levels with increased number of follow-up outpatient visits (+28.6%) and costs (+38.0%).” HISTORICALBrown-Sequard C.E. M.D. Note on the effects produced on man by subcutaneous injections of a liquid obtained from the testicles of animals. The Lancet 1889 July 20:105-107. http://www.sciencedirect.com/science/article/pii/S0140673600641181 Brown-Sequard C.E., M.D. On a new therapeutic method consisting in the use of organic liquids extracted from glands and other organs. The British Medial Journal 1893. June 10, http://www.bmj.com/content/1/1693/1212.full.pdf Heller CG, M.D., Ph.D. and Myers G, M.D. The male climacteric, its symptomatology, diagnosis and treatment. Journal of the American Medical Association 1944; 126(8):472-477. http://jama.ama-assn.org/content/126/8/472.short Heller CG, Nelson WO. Classification of male hypogonadism and a discussion of the pathologic physiology, diagnosis and treatment. J Clin Endocrinol Metab. 1948 May;8(5):345-66. http://www.ncbi.nlm.nih.gov/pubmed/18863967 McCullagh EP, M.D. Climacteric, male and female. Cleve Clin Q. 1946 Jul;13:166-76. http://www.ncbi.nlm.nih.gov/pubmed/20987362 McCullagh, EP, M.D. Treatment of testicular deficiency with testosterone propionate. Journal of the American Medical Association. 1939; 112(11):1037-1044. http://jama.ama-assn.org/content/112/11/1037.short Werner AA, M.D. The male climacteric. Journal of the American Medical Association 1939: 112(15):1441-1443. http://jama.ama-assn.org/content/112/15/1441.short Werner AA, M.D. The male climacteric: report of 273 cases. Journal of the American Medical Association 1946; 132:188-194. http://jama.ama-assn.org/content/132/4/188.short Werner AA, M.D. The climacteric in women and men. Postgraduate Medicine. 1948 Aug;4(2):102-10. http://www.ncbi.nlm.nih.gov/pubmed/18876114 PAPERBACK BOOKS FOR GENERAL READINGLife, Jeffry S, MD. The Life Plan: How Any Man Can Achieve Lasting Health, Great Sex, and a Stronger, Leaner Body. Atria Books, 2011. Morgentaler, Abraham, MD. Testosterone for Life: Recharge Your Vitality, Sex Drive, Muscle Mass, and Overall Health. McGraw Hill, Publishers, 2008. Rothenberg, Ron, MD and Hart, Kris, FNP, RN-C. Hormone Optimization in Preventive/Regenerative Medicine, 2010. Rouzier, Neal, M.D. Natural Hormone Replacement For Men and Women - How to Achieve Healthy Aging 2nd Edition, 2010. Shippen, Eugene, MD. The Testosterone Syndrome. M. Evans & Co., 1998. Shippen, Eugene, MD and Fryer, William. The Testosterone Syndrome: The Critical Factor for Energy, Health, and Sexuality--Reversing the Male Menopause. M. Evans & Co., 2001. Tan, Robert S., MD. The Andropause Mystery. AMRED Publishing, 2001. SHORTER LIFESPAN, Endogenous testosterone and all-cause and cardiovascular disease mortality in men: a systematic review and meta-analysis. Endocrine Reviews 2011; 32: OR35-3. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/OR35-3?sid=e434ad80-4f99-4d3b-a8ee-fdc842682340 Among 14 studies with 18,492 subjects [men] followed for 9.5 years on average, low versus higher testosterone levels, (generally, lowest (e.g., quartile 1) versus highest (e.g., quartile 4) category), were associated with a 37% increased risk of all-cause mortality and 26% increased risk of cardiovascular mortality. “Low endogenous testosterone levels are associated with increased risk of death in population-based studies of men.” Fukai S and others. Plasma sex hormone levels and mortality in disabled older men and women. Geriatr Gerontol Int. 2011 Apr; 11(2):196-203. http://www.ncbi.nlm.nih.gov/pubmed/21143567 “Low testosterone in men (and low DHEA-S in women) receiving care at facilities are associated with increased mortality risk, independent of other risk factors and pre-existing health conditions.” Khaw, K.-T. and others. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007 Dec 4; 116(23):2694-701. http://www.ncbi.nlm.nih.gov/pubmed/18040028 “In [11,606] men followed for 6-10 years], endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular [heart artery] disease.” Laughlin GA, Barrett-Connor E and others. Low serum testosterone and mortality in older men. Journal of Clinical Endocrinology & Metabolism. 2008 Jan; 93(1):68-75. http://www.ncbi.nlm.nih.gov/pubmed/17911176 “Among 794 older men, “testosterone insufficiency (in older men) is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions.” Lehtonen A and others. Serum testosterone but not leptin predicts mortality in elderly men. Age and Ageing 2008 July; 37(4):461-4. http://ageing.oxfordjournals.org/content/37/4/461.long “We have demonstrated an independent inverse association between endogenous testosterone concentration in serum and mortality in [370] 70-year-old non-diabetic men followed for 10 years.” Maggio M and others. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging study in the Chianti Area study. Archives of Internal Medicine 2007 November; 167(20):2249-54. http://www.ncbi.nlm.nih.gov/pubmed/17998499 “Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons.” Menke A, Guallar E, Rohrmann S, Nelson WG, Rifai N, Kanarek N, Feinleib M, Michos ED, Dobs A, Platz EA. Sex steroid hormone concentrations and risk of death in US men. American Journal of Epidemiology 2010; 171(5): 583-592. ttp://www.ncbi.nlm.nih.gov/pubmed/20083549 “Men with low free and bioavailable testosterone levels may have a higher risk of mortality within 9 years of hormone measurement [1,114 men from NHANES Study].” Shores MM and others. Low serum testosterone and mortality in male veterans. Archives of Internal Medicine. 2006 Aug 14-28; 166(15):1660-5. http://www.ncbi.nlm.nih.gov/pubmed/16908801 “Low testosterone levels were associated with increased mortality in male veterans [858 men followed for 8 years].” Tivesten A and others. Low serum testosterone and estradiol predict mortality in elderly men. Journal of Clinical Endocrinology and Metabolism 2009 July; 94(7):2482-2488. http://www.ncbi.nlm.nih.gov/pubmed/19401373 “[Among 3,014 elderly men followed for 4.5 years, those] with low serum testosterone and estradiol have increased risk of mortality, and subjects with low values of both testosterone and estradiol have the highest risk of mortality.” Vikan T and others. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromso Study. European Journal of Endocrinology 2009 September; 161(3):435-42. http://www.ncbi.nlm.nih.gov/pubmed/19542243 “Men with free testosterone levels in the lowest quartile had a 24% increased risk of all-cause mortality.” Ruige JB and others. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart. 2011 Jun;97(11):870-5. http://www.ncbi.nlm.nih.gov/pubmed/21177660 “In elderly men, testosterone may weakly protect against cardiovascular [heart artery] disease.” Corona G and others. Low testosterone is associated with an increased risk of MACE [Major Adverse Cardiac {heart} Events] lethality in subjects with erectile dysfunction. J Sex Med. 2010 Apr;7(4 Pt 1):1557-64. http://www.ncbi.nlm.nih.gov/pubmed/20102478 “Testosterone levels are associated with a higher mortality of Major Adverse Cardiac Events. The identification of low testosterone levels should alert the clinician thus identifying subjects with an increased cardiovascular [heart artery] risk.” Haring R, Völzke H, Steveling A, Krebs A, Felix SB, Schöfl C, Dörr M, Nauck M, Wallaschofski H. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79. Eur Heart J. 2010 Jun;31(12):1494-501. http://www.ncbi.nlm.nih.gov/pubmed/20164245 “Among 1,954 men followed for 7.2 years, low serum testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. As serum testosterone levels are inversely related to mortality due to CVD and cancer, it may be used as a predictive marker.” Malkin CJ and others. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010 Nov;96(22):1821-5. (Sheffield, UK) http://www.ncbi.nlm.nih.gov/pubmed/20959649 “Among 930 consecutive men with coronary [heart artery] disease referred for diagnostic angiography…and followed up for a mean of 6.9 years, excess mortality was noted in the androgen-deficient group [21%] compared with normal [12%], p=0.002. In patients with coronary disease testosterone deficiency is common and impacts significantly negatively on survival.” ERECTILE DYSFUNCTION and EJACULATIONCorona G, Maggi M. The role of testosterone in erectile dysfunction. Nature Reviews Urology. 2010 Jan;7(1):46-56. http://www.ncbi.nlm.nih.gov/pubmed/19997070 “Testosterone clearly has a relevant role in all three causes of erectile dysfunction.” Blute M, Hakimian P, Kashanian J, Shteynshluyger A, Lee M, Shabsigh R. Erectile dysfunction and testosterone deficiency. Frontiers of Hormone Research. 2009;37:108-22. http://www.ncbi.nlm.nih.gov/pubmed/19011292 “Testosterone deficiency is associated with a decline in erectile function and testosterone levels are inversely correlated with increasing severity of erectile dysfunction. Erectile dysfunction can be caused by multifactorial pathologies. In particular, erectile dysfunction may be the first symptom of cardiovascular disease. Animal studies have demonstrated that castration causes vascular smooth muscle cell atrophy, venous leakage, adipocytes in the subtunical space, loss of elastic fibers and increase in collagen deposition. Testosterone increases the expression of nitric oxide synthase and phosphodiesterase type 5, both principal enzymes involved in the erectile process. Testosterone replacement alone in hypogonadal men can restore erectile function. A significant proportion of men who fail to respond to a PDE5 inhibitor [Viagra, Levitra, Cialis] are testosterone deficient. Testosterone replacement therapy can convert over half of these men into phosphodiesterase type 5 responders. It is now recommended that testosterone levels should be assessed in all patients with erectile dysfunction.” Traish AM & others. The dark side of testosterone deficiency: I. Metabolic syndrome & erectile dysfunction. Journal of Andrology 2009 Jan-Feb; 30(1):10-22. http://www.ncbi.nlm.nih.gov/pubmed/18641413 “In this review we discuss the current literature pertaining to androgen deficiency, Metabolic Syndrome, and Erectile Dysfunction, because the relationship of these factors is of scientific and clinical importance.” Diaz-Arjonilla M and others. Obesity, low testosterone and erectile dysfunction. International Journal of Impotence Research 2009 March-April; 21(2):89-98. http://www.ncbi.nlm.nih.gov/pubmed/18843273 “Obesity is an important risk factor for many common diseases including cardiovascular [heart artery] disease, type 2 diabetes, cancer and erectile dysfunction (ED). Recent studies show that BMI [Body Mass Index] is inversely proportional to free testosterone concentration. The characteristic low serum testosterone concentrations observed in obese men are also present in men with the metabolic syndrome and type 2 diabetes mellitus.” Yassin AA, Akhras F, El-Sakka AI, Saad F. Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency. Andrologia. 2011 Feb;43(1):1-8. http://www.ncbi.nlm.nih.gov/pubmed/21219375 “It is erroneous not to include testosterone measurements in the progress of cardiovascular [heart artery] disease, diabetes mellitus and erectile dysfunction. These conditions correlate strongly with testosterone deficiency.” Traish AM, Feeley RJ, Guay A. Mechanisms of obesity and related pathologies: androgen deficiency and endothelial dysfunction may be the link between obesity and erectile dysfunction. FEBS Journal. 2009 Oct;276(20):5755-67. http://www.ncbi.nlm.nih.gov/pubmed/19754871 “Obesity is associated with a high prevalence of erectile dysfunction. Clinical screening for the risk of erectile dysfunction in obese patients should include the assessment of waist circumference, testosterone levels, body mass index [weight divided by height] and physical inactivity.”
“Penile erection is a vascular [blood vessel, artery] event that requires an intact endothelium [artery inner lining] to occur. It is now well-understood that ED is a symptom of underlying disease rather than a disease itself. Aging in the man is also associated with several changes in arterial structure and function, part of them related to the decline of circulating levels of..testosterone and estradiol.” Aversa A and others. Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users. Int J Impot Res. 2008 Nov-Dec;20(6):566-73. http://www.ncbi.nlm.nih.gov/pubmed/18997809 “We conclude that early endothelial damage may be induced by chronic cannabis [marijuana] use; insulin resistance may be the hallmark of early endothelial dysfunction and may concur to determine vascular ED in the absence of obesity.” , Severity of erectile dysfunction and testosterone deficiency are associated with reduced quality of life in men with type 2 diabetes mellitus. Endocrine Reviews 2011; 32: P1-332. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P1-332?sid=755cf241-e421-42c3-a8de-bdd1015fa100 “This is the first study to report that lower testosterone and severity of ED are both independently associated with reduced Health-related quality-of-life in diabetic men. The results also show that severity of ED is related to testosterone levels in diabetic men.” Elliott JA and others. The endocrine effects of long-term oral opioid [narcotic] therapy: a case report and review of the literature. J Opioid Manag. 2011 Mar-Apr; 7(2):145-54. http://www.ncbi.nlm.nih.gov/pubmed/21561038 “Up to five million men with chronic nonmalignant pain suffer from opioid [narcotic pain medication]-induced androgen deficiency (OPIAD) in the United States. In view of the increasing use of opioids for chronic pain, we must anticipate the potential occurrence of hypogonadism during chronic opioid therapy.” Traish AM and others. Adverse side effects of 5a-reductase inhibitors therapy [Propecia and Avodart]. Persistent diminished libido and erectile dysfunction and depression in a subset of patients. The Journal of Sexual Medicine. 2011 Mar; 8(3):872-84. http://www.ncbi.nlm.nih.gov/pubmed/21176115 Irwig MS and others. Persistent sexual side effects of finasteride [Propecia] for male pattern hair loss. The Journal of Sexual Medicine. 2011 Jun; 8(6):1747-53. http://www.ncbi.nlm.nih.gov/pubmed/21418145 “Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride [Propecia, blocker of dihydrotestosterone], [including] low libido, erectile dysfunction, decreased arousal, and problems with orgasm.” Corona G, Boddi V, Balercia G, Rastrelli G, De Vita G, Sforza A, Forti G, Mannucci E, Maggi M. The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. Journal of Sexual Medicine. 2010 Apr;7(4 Pt 1):1547-56. http://www.ncbi.nlm.nih.gov/pubmed/20141585 “Among 3,484 men, 244 (7%) patients were being treated with a statin drug [for high cholesterol]. “Our data demonstrated that statin therapy might induce an overt primary hypogonadism [low testosterone] and should be considered as a possible confounding factor for the evaluation of testosterone levels in patients with erectile dysfunction.” Bruheim K and others. Radiotherapy [radiation treatment] for rectal cancer is associated with reduced serum testosterone and increased FSH and LH. Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):722-7. http://www.ncbi.nlm.nih.gov/pubmed/18262088 “Subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.” Guay AT and Traish A. Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction [ED]. Urologic Clinics of North America. 2011 May; 38(2):175-83. http://www.ncbi.nlm.nih.gov/pubmed/21621084 “Type 2 diabetes mellitus, hypertension, hyperlipidemia, and obesity underlie the pathophysiology [cause] of metabolic syndrome. Hypogonadism, or testosterone deficiency, is an integral component of the pathology underlying endothelial dysfunction and Metabolic Syndrome with insulin resistance at its core. Testosterone replacement therapy for testosterone deficiency has been shown to ameliorate [improve] some of the components of the metabolic syndrome, improve insulin resistance, and may serve as treatment for decreasing cardiovascular and ED risk. Corona G, Jannini EA, Lotti F, Boddi V, De Vita G, Forti G, Lenzi A, Mannucci E, Maggi M. Premature and delayed ejaculation: two ends of a single continuum influenced by hormonal milieu. International Journal of Andrology. 2011 Feb;34(1):41-8. http://www.ncbi.nlm.nih.gov/pubmed/20345874 “This study indicates endocrine system is involved in the control of ejaculatory function and that...testosterone play[s] an independent role.” Budweiser S and others. Sleep apnea [nighttime stopped breathing] is an independent correlate of erectile and sexual dysfunction. J Sex Med. 2009 Nov;6(11):3147-57. http://www.ncbi.nlm.nih.gov/pubmed/19570042 “Mean nocturnal SaO(2) [nighttime oxygen level] as well as age were independently associated with erectile dysfunction. ED and overall sexual dysfunction were highly prevalent in patients with suspected Obstructive Sleep Apnea.” Margel D, Cohen M, Livne PM, Pillar G. Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction. Urology. 2004 Mar;63(3):545-9. http://www.ncbi.nlm.nih.gov/pubmed/15028455 Soukhova-O'Hare GK and others. Erectile dysfunction in a murine model of sleep apnea. Am J Respir Crit Care Med. 2008 Sep 15;178(6):644-50. http://www.ncbi.nlm.nih.gov/pubmed/18535258 http://www.ncbi.nlm.nih.gov/pubmed/18519168 ALZHEIMER'S DISEASE, MEMORY, DEPRESSION, ANXIETYPike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol. 2009 Jul; 30(2):239-58. http://www.ncbi.nlm.nih.gov/pubmed/19427328 “Like estrogen, testosterone has been established as an endogenous neuroprotective factor that not only increases neuronal resilience against AD [Alzheimer’s Disease]-related insults, but also reduces beta-amyloid accumulation [brain-related change in Alzheimer’s Disease].” Rosario ER and Pike CJ. Androgen regulation of beta-amyloid protein and the risk of Alzheimer’s Disease [AD]. Brain Research Reviews 2008 March; 57(2):444-453. http://www.ncbi.nlm.nih.gov/pubmed/17658612 “Testosterone depletion leads to functional impairments and increased risk of disease in androgen-responsive tissues throughout the body, including brain. In this review we discuss the relationship between age-related testosterone depletion and the development of Alzheimer’s Disease. Specifically, we focus on androgen regulation of beta-amyloid protein (Abeta), the accumulation of which is a key initiating factor in AD pathogenesis. Emerging data suggest that the regulatory actions of androgens on both Abeta and the development of AD support consideration of androgen therapy for the prevention and treatment of Alzheimer’s Disease. Chu LW, Tam S, Wong RL, Yik PY, Song Y, Cheung BM, Morley JE, Lam KS. Bioavailable testosterone predicts a lower risk of Alzheimer's disease in older men. Journal of Alzheimer’s Disease. 2010;21(4):1335-45. http://www.ncbi.nlm.nih.gov/pubmed/21504130 “Bioavailable testosterone in late life predicts a lower risk of future Alzheimer’s Disease development in older men.” Fuller SJ, Tan RS, Martins RN. Androgens in the etiology [cause] of Alzheimer's disease in aging men and possible therapeutic interventions. Journal of Alzheimer’s Disease. 2007 Sep;12(2):129-42. http://www.ncbi.nlm.nih.gov/pubmed/17917157 “Lower than normal testosterone levels have also been detected in patients prior to the onset of Alzheimer’s Disease, as well as in younger late-onset male Alzheimer’s Disease patients, when compared to appropriate controls. The results of some small clinical trials suggest that testosterone can improve cognitive [thinking, memory] function in andropause.” Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM. Free testosterone and risk for Alzheimer disease in older men. Neurology. 2004 January. http://www.ncbi.nlm.nih.gov/pubmed/14745052 (National Institute of Aging) “Calculated free testosterone concentrations were lower in men who developed Alzheimer disease, and this difference occurred before diagnosis. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive [thinking] status in elderly men. Journal of Clinical Endocrinology and Metabolism. 2002 Nov; 87(11): 5001-7. http://www.ncbi.nlm.nih.gov/pubmed/12414864 “Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory…These results suggest a possible beneficial relationship between circulating free testosterone concentrations and specific domains of cognitive performance in older men.” Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab. 1999 October;84(10):3681-5. http://www.ncbi.nlm.nih.gov/pubmed/10523014 “In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive [thinking, memory] function…suggesting that an optimal level of sex hormones may exist for some cognitive functions.” Alexander GM, Swerdloff RS, Wang C, Davidson T, McDonald V, Steiner B, Hines M. Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities. Horm Behav. 1998 Apr; 33(2):85-94. http://www.ncbi.nlm.nih.gov/pubmed/9647934 “Hypogonadal men were impaired in their verbal fluency and showed improved verbal fluency following treatment with testosterone. These data suggest that testosterone may enhance verbal fluency in hypogonadal men and support the general hypothesis that current levels of testosterone may influence some aspects of cognitive [thinking, memory] function.” Fukai S, Akishita M, Yamada S, Toba K, Ouchi Y. Effects of testosterone in older men with mild-to-moderate cognitive impairment. Am Geriatr Soc. 2010 Jul;58(7):1419-21. http://www.ncbi.nlm.nih.gov/pubmed/20672465 Yeap BB, Almeida OP, Hyde Z, Chubb SA, Hankey GJ, Jamrozik K, Flicker L. Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study. Clin Endocrinol (Oxf). 2008 Mar; 68(3):404-12. http://www.ncbi.nlm.nih.gov/pubmed/17888021 “Serum free testosterone greater than or equal to 210 pmol/l is associated with better cognitive [thinking, memory] performance.” Nguyen TV, Jayaraman A, Quaglino A, Pike CJ. Androgens selectively protect against apoptosis [cell death] in hippocampal [memory part of brain] neurones. J Neuroendocrinol. 2010 Sep;22(9):1013-22. http://www.ncbi.nlm.nih.gov/pubmed/20561156 “These data suggest that androgens directly activate a neuroprotective mechanism specific to inhibition of cell death involving apoptosis [programmed cell death].” Cherrier MM, Anawalt BD, Herbst KL, Amory JK, Craft S, Matsumoto AM, Bremner WJ. Cognitive effects of short-term manipulation of serum sex steroids in healthy young men. J Clin Endocrinol Metab. 2002 Jul;87(7):3090-6. http://www.ncbi.nlm.nih.gov/pubmed/12107206 “Decreased serum testosterone levels induced by LNG [progestin] or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men.” Shores MM, Moceri VM, Sloan KL, Matsumoto AM, Kivlahan DR. Low testosterone levels predict incident depressive illness in older men: effects on age and medical morbidity. Journal of Clinical Psychiatry 2005 January; 66(1):7-14. http://www.ncbi.nlm.nih.gov/pubmed/15669883 “Low testosterone levels are associated with an earlier onset and greater incidence of depressive illness.” Shores MM, Sloan KL, Matsumoto AM, Moceri VM, Felker B, Kivlahan DR. Increased incidence of diagnosed depressive illness in hypogonadal older men. Archives of General Psychiatry 2004 February; 61(2):162-7. http://www.ncbi.nlm.nih.gov/pubmed/14757592 “Hypogonadal men showed an increased incidence of depressive illness and a shorter time to diagnosis of depression.” Wainwright SR, Lieblich SE, Galea LA. Hypogonadism predisposes males to the development of behavioural and neuroplastic depressive phenotypes. Psychoneuroendocrinology. 2011 Apr 9. http://www.ncbi.nlm.nih.gov/pubmed/21481538 “These findings indicate that testicular hormones confer resiliency to chronic stress in males therefore reducing the likelihood of developing putative physiological, behavioural or neurological depressive-like phenotypes.” Almeida OP, Yeap BB, Hankey GJ, Jamrozik K, Flicker L. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch Gen Psychiatry. 2008 Mar; 65(3):283-9. http://www.ncbi.nlm.nih.gov/pubmed/18316674 “A free testosterone concentration in the lowest quintile [lowest fifth] is associated with a higher prevalence of depression, and this association cannot be adequately explained by physical comorbidity [other diseases].” Berglund LH, Prytz HS, Perski A, Svartberg J. Testosterone levels and psychological health status in men from a general population: the Tromsø study. Aging Male. 2011 Mar;14(1):37-41. http://www.ncbi.nlm.nih.gov/pubmed/20923289 “Men presumed being testosterone deficient had a higher symptom score, in particularly regarding anxiety, but they did not have pathological symptoms.” HEART, STROKE, BLOOD PRESSURE, ARTERIES, LUNGSCorona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, Forti G, Mannucci E, Maggi M. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol. 2011 Aug 18. http://www.ncbi.nlm.nih.gov/pubmed/21852391 Among 70 studies, “low testosterone and higher estradiol correlate with increased risk of cardiovascular [heart artery] disease and cardiovascular mortality. Testosterone replacement therapy in hypogonadism moderates metabolic components associated with cardiovascular risk... Longitudinal studies showed that baseline testosterone was significantly lower among patients with incident overall- and cardiovascular-related mortality, in comparison to controls.” Guder G, Frantz S, Bauersachs J, Allolio B, Ertl G, Angermann CE, Störk S. Low circulating androgens and mortality risk in heart failure. Heart 2010 Apr ;96(7):504-9. http://www.ncbi.nlm.nih.gov/pubmed/19875366 “In male heart failure patients, low serum levels of androgens are associated with adverse prognosis [poorer future], but this relation is confounded by indicators of a poor health state.” English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000 Jun; 21(11):890-4. http://www.ncbi.nlm.nih.gov/pubmed/10806012 “Men with coronary artery disease have significantly lower levels of androgens than normal controls, challenging the preconception that physiologically high levels of androgens in men account for their increased relative risk for coronary artery disease.” Maggio M, Basaria S. Welcoming low testosterone as a cardiovascular risk factor. International Journal of Impotence Research 2009; Jul-Aug;21(4):261-4. http://www.ncbi.nlm.nih.gov/pubmed/19536127 “Low serum testosterone levels are a risk factor for diabetes, metabolic syndrome, inflammation and dyslipidemia [high cholesterol, triglycerides]. Recent studies have shown low serum testosterone levels to be an independent risk factor of cardiovascular [heart artery] and all-cause mortality. It is time to welcome low serum testosterone levels as a cardiovascular risk factor.” Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, Mercuro G, Volterrani M, Aversa A, Fini M. Low testosterone levels are associated with coronary artery disease in male patients with angina. International Journal of Impotence Research 2007; 19:176-182. http://www.ncbi.nlm.nih.gov/pubmed/16943795 “Patients with Coronary [heart] Artery Disease have lower testosterone and estradiol levels than healthy controls. These changes are inversely correlated to the degree of Coronary Artery Disease, suggesting that low plasma testosterone may be involved with the increased risk of Coronary Artery Disease in men.” Muller M, van der Schouw YT, Thijssen JH, Grobbee DE. Endogenous sex hormones and cardiovascular disease in men. J Clin Endocrinol Metab 2003 Nov;88(11):5076-86. http://www.ncbi.nlm.nih.gov/pubmed/14602729 “Endogenous sex hormones and estrogens have a neutral or beneficial effect on cardiovascular disease in men.” Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y. Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. Atherosclerosis 2010 May; 2010(1):232-6. http://www.ncbi.nlm.nih.gov/pubmed/19963216 “A low plasma testosterone level is associated with cardiovascular [heart artery] events in middle-aged Japanese men, independent of coronary risk factors and endothelial function. This is the first report to show the relationship between endogenous testosterone and cardiovascular events in Asian population.” Traish AM and others. The dark side of testosterone deficiency: III Cardiovascular disease. Journal of Andrology 2009 September-October; 30(5):477-94. http://www.ncbi.nlm.nih.gov/pubmed/19342698 “A considerable body of evidence exists suggesting that androgen deficiency contributes to the onset, progression, or both of cardiovascular disease [heart artery disease]. Low testosterone, whether attributed to hypogonadism or androgen deprivation therapy, in men with prostate carcinoma, produces adverse effects on cardiovascular health. Androgen deficiency is associated with increased levels of total cholesterol, low-density [‘bad’] lipoprotein [cholesterol], increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction [all unfavorable markers for artery functioning].” Kaushik M, Sontineni SP, Hunter C. Cardiovascular disease and androgens: a review. Int J Cardiol. 2010 Jun 25;142(1):8-14. http://www.ncbi.nlm.nih.gov/pubmed/19923015 “Lower androgen levels predict poor cardiovascular risk profile.” Yeap BB and others. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. Journal of Clinical Endocrinology and Metabolism 2009 July; 94(7):2353-9. http://www.ncbi.nlm.nih.gov/pubmed/19351733 “In older men, lower total testosterone levels predict increased incidence of stroke or TIA [transient ischemic attack, precursor to stroke] after adjusting for conventional risk factors for cardiovascular [heart artery] disease. Men with low-normal testosterone levels had increased risk.”
“…lower levels of testosterone in men are associated with higher blood pressure, left ventricular [heart chamber] mass and left ventricular hypertrophy [heart chamber enlargement].” Khaw, K-T and Barrett-Connor, E. Blood pressure and endogenous testosterone in men: inverse relationship. Journal of Hypertension 1988 April; 6(4):329-332. http://www.ncbi.nlm.nih.gov/pubmed/3379300 “Systolic and diastolic blood pressure inversely correlated with testosterone levels in the whole cohort. This association was present over the whole range of blood pressures and sex hormone levels with a stepwise decrease in mean Systolic Blood Pressure and Diastolic Blood Pressure per increasing quartile of testosterone.” Torkler S, Wallaschofski H, Baumeister SE, Völzke H, Dörr M, Felix S, Rettig R, Nauck M, Haring R. Inverse association between total testosterone concentrations, incident hypertension and blood pressure. Aging Male. 2010 Nov 19. http://www.ncbi.nlm.nih.gov/pubmed/21087174 “Men with baseline total testosterone concentrations in the lowest quartile had an increased risk of incident hypertension compared to men with higher total testosterone concentrations. These results show that low male total testosterone concentrations are predictive of hypertension, suggesting total testosterone as a potential biomarker of increased cardiovascular risk.” Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. Journal of Clinical Endocrinology and Metabolism 2002 August; 87(8):3632-9. http://www.ncbi.nlm.nih.gov/pubmed/12161487 “We found an independent inverse association between levels of testosterone and aortic atherosclerosis in men.” Hougaku H, Fleg JL, Najjar SS, Lakatta EG, Harman SM, Blackman MR, Metter EJ. Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements. Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E234 - E242. (National Institute on Aging) http://www.ncbi.nlm.nih.gov/pubmed/16159908 “Testosterone was the only hormone that predicted the stiffness index [note higher artery stiffness associated with higher blood pressure and abnormal artery function] after adjustment for age, pulse pressure, fasting plasma glucose, body mass index [weight divided by height], and total cholesterol. Testosterone values 5-10 years before the carotid study also predicted the stiffness index. Thus the adverse influence of low testosterone on the cardiovascular system in men may be mediated in part via the effects of testosterone on vascular [blood vessel] structure and function.” Mäkinen J, Järvisalo MJ, Pöllänen P, Perheentupa A, Irjala K, Koskenvuo M, Mäkinen J, Huhtaniemi I, Raitakari OT. Increased carotid atherosclerosis in andropausal middle-aged men. J Am Coll Cardiol. 2005 May 17; 45(10):1603-8. http://www.ncbi.nlm.nih.gov/pubmed/15893174 “Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT[intimal medial thickness, early marker of atherosclerosis, artery disease]. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.” Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation, May 4, 2004; 109(17): 2074 - 2079. http://www.ncbi.nlm.nih.gov/pubmed/15096452 “Low free testosterone levels were related to intimal medial thickness [first sign of atherosclerosis in artery] of the common carotid artery in elderly men independently of cardiovascular risk factors.” Svartberg J, von Mühlen D, Mathiesen E, Joakimsen O, Bønaa KH, Stensland-Bugge E. Low testosterone levels are associated with carotid atherosclerosis in men. Journal of Internal Medicine 2006 June; 259(6):576-82. http://www.ncbi.nlm.nih.gov/pubmed/16704558 “We found an inverse association between total testosterone levels and IMT [intimal medial thickness, marker of arterial atherosclerosis] of the carotid artery in men that was present also after excluding men with CVD [cardiovascular disease], but was not independent of BMI [body mass index or weight divided by height].” Tivesten A, Mellström D, Jutberger H, Fagerberg B, Lernfelt B, Orwoll E, Karlsson MK, Ljunggren O, Ohlsson C. Low serum testosterone and high serum estradiol associate with lower extremity peripheral arterial disease in elderly men: The MrOS Study in Sweden. J. Am. Coll. Cardiol., September 11, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17825717 “Low serum testosterone and high serum estradiol levels associate with lower extremity [leg] peripheral artery disease in elderly men.” Kupelian V, Chiu GR, Araujo AB, Williams RE, Clark RV, McKinlay JB. Association of sex hormones and C-reactive protein levels in men. Clin Endocrinol (Oxf). 2010 Apr;72(4):527-33. http://www.ncbi.nlm.nih.gov/pubmed/19769617 “A robust, inverse dose-response correlation between testosterone and SHBG [sex hormone binding globulin] levels with CRP [C-reactive protein] levels provides further evidence of a potential role of androgens in inflammatory processes [lower testosterone correlates with higher CRP, a marker of inflammation that increases risk of vascular disease].” Svartberg J, Schirmer H, Medbø A, Melbye H, Aasebø U. Reduced pulmonary [lung] function is associated with lower levels of endogenous total and free testosterone. The Tromsø study. Eur J Epidemiol. 2007;22(2):107-12. http://www.ncbi.nlm.nih.gov/pubmed/17260104 “Men with chronic obstructive pulmonary disease [emphysema, chronic bronchitis] have reduced endogenous testosterone levels. A reduction in pulmonary function was associated with lower levels of total and free testosterone.” DIABETES, CHOLESTEROL, METABOLIC SYNDROME, OBESITY, BODY COMPOSITION (FAT, MUSCLE)Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. Journal of the American Medical Association. 2006 Mar 15;295(11):1288-99. http://www.ncbi.nlm.nih.gov/pubmed/16537739 In a meta-analysis [combination of 43 published studies including 6,427 men] from Harvard Medical School, men with higher testosterone levels had a 42% lower risk of developing type 2 diabetes, in prospective studies. “High testosterone levels are associated with...lower risk [of type 2 diabetes] in men.” Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. Journal of Andrology 2009 Jan-Feb; 30(1):23-32. http://www.ncbi.nlm.nih.gov/pubmed/18772488 “Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Androgen [testosterone] therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and HbA1c levels.” Ponikowska B, Jankowska EA, Maj J, Wegrzynowska-Teodorczyk K, Biel B, Reczuch K, Borodulin-Nadzieja L, Banasiak W, Ponikowski P. Gonadal and adrenal androgen deficiencies as independent predictors of increased cardiovascular mortality in men with type II diabetes mellitus and stable coronary artery disease. Int. J. Cardiology 2010 Sep 3;143(3):343-8. http://www.ncbi.nlm.nih.gov/pubmed/19395096 “In diabetic men with stable coronary artery disease, testosterone and DHEA-S [adrenal hormone] deficiencies are common and related to high cardiovascular [heart artery] mortality.” Wang C, Jackson G, Jones TH, Matsumoto AM, Nehra A, Perelman MA, Swerdloff RS, Traish A, Zitzmann M, Cunningham G. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care. 2011 Jul;34(7):1669-75. http://www.ncbi.nlm.nih.gov/pubmed/21709300 Oh JY, Barrett-Connor E, Wedick NM, Wingard DL; Rancho Bernardo Study. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002 Jan;25(1):55-60. http://www.ncbi.nlm.nih.gov/pubmed/11772901 “After 8 years, low testosterone levels in [294] men predict insulin resistance and incident type 2 diabetes in older adults.” Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000 Apr;23(4):490-4. http://www.ncbi.nlm.nih.gov/pubmed/10857940 “[Among 1,156 men followed for 7-10 years], our prospective findings are consistent with previous, mainly cross-sectional reports, suggesting that low levels of testosterone and SHBG [sex hormone binding globulin] play some role in the development of insulin resistance and subsequent type 2 diabetes.” Yeap BB and others. Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study. European Journal of Endocrinology. 2009 Oct;161(4):591-8. http://www.ncbi.nlm.nih.gov/pubmed/19661128 “In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range.” Brand JS, van der Tweel I, Grobbee DE, Emmelot-Vonk MH, van der Schouw YT. Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. International Journal of Epidemiology. 2011 Feb;40(1):189-207. http://www.ncbi.nlm.nih.gov/pubmed/20870782 “[Among 52 studies of 22,043 men] total testosterone and free testosterone levels are lower in men with Metabolic Syndrome” [constellation of abnormalities relating to high blood pressure, increased waist size, abnormal cholesterol, diabetes/ pre-diabetes]. Haring R, Völzke H, Felix SB, Schipf S, Dörr M, Rosskopf D, Nauck M, Schöfl C, Wallaschofski H. Prediction of metabolic syndrome by low serum testosterone levels in men. Diabetes 2009 September 58(9):2027-31. http://www.ncbi.nlm.nih.gov/pubmed/19581420 “Low testosterone but not DHEAS [adrenal hormone] predicts development of Metabolic Syndrome in a population-based cohort of 1,004 men aged 20-79 years [followed for 5.0 years]. Especially in young men aged 20-39 years, results suggest low testosterone as a strong predictor for incident Metabolic Syndrome.”
“Longitudinal population studies have found that low testosterone status in men is a risk factor for the later development of metabolic syndrome. Men with metabolic syndrome and type 2 diabetes mellitus have a higher incidence of hypotestosteronaemia [low testosterone in blood]. Furthermore, in men, testosterone levels are inversely associated with the degree of carotid [neck artery] and aortic [large artery in chest & abdomen] atherosclerosis [artery blockages]. Early interventional, short-term studies have shown that testosterone replacement therapy has a beneficial effect on visceral obesity [body fat in between the abdominal organs], insulin sensitivity, glycaemic [blood sugar] control and lipid profiles in men with diagnosed hypogonadism with and without diabetes. Testosterone is an arterial vasodilator and has been shown to improve myocardial [heart] ischaemia [blood insufficiency] in men with coronary [heart] artery disease.” Corona G, Rastrelli G, Morelli A, Vignozzi L, Mannucci E, Maggi M. Hypogonadism and metabolic syndrome. J Endocrinol Invest. 2011 Jun 27. http://www.ncbi.nlm.nih.gov/pubmed/21720206 Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab. 2011 Apr; 25(2):337-53. http://www.ncbi.nlm.nih.gov/pubmed/21397202 “Low, rather than high, testosterone is associated with increased male morbidity [disease] and mortality [death]. Low testosterone is associated with increased risk of cardiovascular death in community-dwelling men, and in men with Erectile Dysfunction...A meta-analysis on the effect of testosterone replacement therapy in Metabolic-Syndrome-associated hypogonadism [low testosterone with symptoms] demonstrated positive effects of testosterone on some of the components of Metabolic Syndrome.” Haring R, Baumeister SE, Völzke H, Dörr M, Felix SB, Kroemer HK, Nauck M, Wallaschofski H. Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia [cholesterol, triglycerides]. Eur J Cardiovasc Prev Rehabil. 2011 Feb;18 (1):86-96. http://www.ncbi.nlm.nih.gov/pubmed/20562628 “Low total testosterone concentrations are prospectively associated with an adverse lipid profile and increased risk of incident dyslipidemia [abnormal cholesterol and triglycerides in blood]. These findings are particularly interesting and may contribute to an explanation for the higher cardiovascular disease risk in men with lower total testosterone concentrations.” Tan RS, Pu SJ. Impact of obesity on hypogonadism in the andropause. International Journal of Andrology 2002 Aug; 25(4): 195-201. http://www.ncbi.nlm.nih.gov/pubmed/12121568 “Testosterone replacement in ageing men can alter body composition whereby fat is exchanged for muscle.” Svartberg J, von Mühlen D, Sundsfjord J, Jorde R. Waist circumference and testosterone levels in community dwelling men. The Tromsø study. Eur J Epidemiol. 2004;19(7):657-63. http://www.ncbi.nlm.nih.gov/pubmed/15461197 “The lowest levels of total and free testosterone were observed in men with relatively high waist circumference despite relatively low overall obesity (BMI, Body Mass Index), suggesting that waist circumference should be the preferred anthropometric [body composition] measurement in predicting endogenous testosterone levels.” BONE, URINE, KIDNEYLeBlanc ES, Nielson CM, Marshall LM, Lapidus JA, Barrett-Connor E, Ensrud KE, Hoffman AR, Laughlin G, Ohlsson C, Orwoll ES; Osteoporotic Fractures in Men Study Group. The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. Journal of Clinical Endocrinology and Metabolism 2009 September; 94(9):3337-46. http://www.ncbi.nlm.nih.gov/pubmed/19584177 “A significant interaction between SHBG [Sex Hormone Binding Globulin] and bio-available testosterone resulted in men with low bio-available testosterone and high SHBG having higher fracture risk. Men with low bio-available estradiol, low bio-available, and high SHBG were at highest risk.” Ward KA, Pye SR, Adams JE, Boonen S, Vanderschueren D, Borghs H, Gaytant J, Gielen E, Bartfai G, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Wu FC, O'Neill TW; EMAS study group. Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men. Osteoporos Int. 2011 May;22(5):1513-23. http://www.ncbi.nlm.nih.gov/pubmed/21052641 “There is age-related change in bone density and geometry at the midshaft radius [forearm bone] in middle-aged and elderly European men... Bio-available testosterone may influence bone health through associations with muscle mass and bone area.” Gacci M, Corona G, Apolone G, Lanciotti M, Tosi N, Giancane S, Masieri L, Serni S, Maggi M, Carini M. Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2010 Jun; 13(2):168-72. http://www.ncbi.nlm.nih.gov/pubmed/20212520 “We found a significant correlation between sexual function scores and testosterone in patients with normal testosterone [levels]. Sexual function was significantly higher in patients with normal testosterone compared with those with low testosterone. Furthermore, Urinary Function and Urinary Bother were significantly correlated with sexual function. The correlation between basal testosterone and preoperative erectile function and urinary continence [not losing urine] underlines the importance of assessing testosterone before radial prostatectomy [removal of prostate gland by surgery].” , High prevalence of hypogonadism in male patients with chronic renal failure. Endocrine Reviews 2011: 32: P3-215. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P3-215?sid=632a007a-eabb-4d79-830e-969c81637020 “One-third of male patients with Chronic Renal Failure have testosterone deficiency. Decreasing renal function is associated with decreasing total and free testosterone levels.” FRAILTYFlicker L, Almeida OP, Hankey GJ, McCaul KA, Chubb SA, Yeap BB Lower free testosterone was independently associated with frailty at baseline and follow-up.” O'Connell MD, Mitnitski AB, O'Neill TW, Searle SD, Huhtaniemi IT, Finn JD, Bartfai G, Boonen S, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Rockwood K, Wu FC; European Male Aging Study Group.
Nguyen A-H, Handelsman, DJChanges in reproductive hormone concentrations predict the prevalence and progression of the frailty syndrome in older men: The Concord Health and Aging in Men Project. Endocrine Reviews 2011; 32: P1-329. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P1-329?sid=4698ff63-c87c-4bb7-bb92-f0d7cee125a4 “Age-related decreases in blood androgens and estrogens may accelerate the development of frailty in men.”
Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, Stefanick ML, Cummings SR, Orwoll ES; Osteoporotic Fractures in Men (MrOS) Research Group “Low levels of bio-available testosterone were independently associated with worse baseline frailty status.” Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy D, Yialamas M, Groop L, Elahi D, Hayes FJ
SLEEPCortés-Gallegos V and others. Sleep deprivation reduces circulating androgens in healthy men. Archives Andrology. 1983 Mar; 10(1):33-7. http://www.ncbi.nlm.nih.gov/pubmed/6405703
Budweiser S and others. Sleep apnea [nighttime stopped breathing] is an independent correlate of erectile and sexual dysfunction. J Sex Med. 2009 Nov;6(11):3147-57. http://www.ncbi.nlm.nih.gov/pubmed/19570042 “Mean nocturnal SaO(2) [nighttime oxygen level] as well as age were independently associated with erectile dysfunction. ED and overall sexual dysfunction were highly prevalent in patients with suspected Obstructive Sleep Apnea.” Margel D, Cohen M, Livne PM, Pillar G. Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction. Urology. 2004 Mar;63(3):545-9. http://www.ncbi.nlm.nih.gov/pubmed/15028455 Soukhova-O'Hare GK and others. Erectile dysfunction in a murine model of sleep apnea. Am J Respir Crit Care Med. 2008 Sep 15;178(6):644-50. http://www.ncbi.nlm.nih.gov/pubmed/18535258
http://www.ncbi.nlm.nih.gov/pubmed/18519168 TESTOSTERONE TREATMENT FOR ANDROPAUSE, INCLUDING SAFETYSmith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment is associated with reduced mortality in men with low serum testosterone levels. Endocrine Reviews 2011; 32: P1-772. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P1-772?sid=995aa523-95f1-468c-98a8-ff164f809f8f “Our data suggest that testosterone-treatment in men with low testosterone levels is associated with decreased mortality, particularly in men ages 40-65 years old and in diabetic men [1,031 men followed for 13.1 months].” , Marsh H, Dip PS, Channer KS, Jones HLong-Term testosterone replacement improves survival in men with type 2 diabetes and hypogonadism. Endocrine Reviews 2011; 32: OR35-2. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/OR35-2?sid=23f7fe03-7983-4a6e-9f29-964a5d4eba3c “Men with type 2 diabetes and low testosterone have a significantly increased mortality [compared to diabetic men with with normal testosterone]. This study provides evidence which indicates that long-term testosterone replacement therapy in hypogonadal [low testosterone with symptoms] men with type 2 diabetes improves survival [585 men followed for 5.8 years].” Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A, Lenzi A. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol (Oxf). 2005 Oct;63(4):381-94. http://www.ncbi.nlm.nih.gov/pubmed/16181230 “...in men with an average testosterone level at baseline [that was low], treatment moderately improved the number of nocturnal [night time] erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas testosterone had no effect on erectile function in eugonadal [normal testosterone] men compared to placebo.” Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A. Androgens improve cavernous vasodilation and response to sildenafil [Viagra] in patients with erectile dysfunction. Clin Endocrinol (Oxf). 2003 May;58(5):632-8. http://www.ncbi.nlm.nih.gov/pubmed/12699447 “In patients with arteriogenic erectile dysfunction and low-normal androgen levels, short-term testosterone administration increases testosterone and free testosterone levels and improves the erectile response to sildenafil [Viagra] likely by increasing arterial inflow to the penis during sexual stimulation.” Amiaz R Pope HG, Mahne T, Kelly JF, Brennan BP, Kanayama G, Weiser M, Hudson JI, Seidman SN. Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial. J Sex Marital Ther. 2011 Jul-Sep; 37(4):243-54. http://www.ncbi.nlm.nih.gov/pubmed/21707327 “In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants [SSRI inhibitor drugs, including Prozac, Paxil, Celexa, others], treatment with exogenous testosterone was associated with a significant improvement in sexual function, particularly including ejaculatory ability.” Zitzmann, MD, PhD and Saad, F, PhD. Intramuscular testosterone undecanoate for substitution in male hypogonadism -- the experience of 13.5 years elucidates beneficial effects on the newly defined metabolic syndrome and reveals a high degree of safety. Endocrine Reviews 2011; 32: P1-348. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P1-348?sid=bc8bbd6d-8b01-469f-807e-935f8d35c8d7 “Injections of testosterone represent a feasible, safe and well tolerated modality of androgen substitution in hypogonadal men of a wide age-range, substantiated by more than one decade of experience, facilitating a decrement of metabolic/cardiovascular risk factors [281 patients, up to 13.5 years, ‘1,069 treatment-years’].” Zitzmann Hanisch JU, Mattern A, Maggi MTestosterone replacement therapy in male hypogonadism: final results from the largest international substitution trial involving 1,493 patients. Endocrine Reviews 2011; 32: P1-347. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P1-347?sid=bc8bbd6d-8b01-469f-807e-935f8d35c8d7 “These results from the largest worldwide sample of hypogonadal men receiving substitution therapy by injectable testosterone document that this form of therapy is well tolerated in daily clinical practice, extending previous findings especially in regard to psychological and metabolic efficacy as well as safety [‘1,103 patient years’].” Zitzmann M and others. Intramuscular testosterone undecanoate for substitution in male hypogonadism-an experience of 11 years elucidating beneficial effects on cardiovascular risk factors and simultaneously providing marked degree of safety. Abstract and poster P3-307 at Endo 09, annual meeting of the Endocrine Society; Washington D.C.; June 12, 2009. Saad F, Kamischke A, Yassin A, Zitzmann M, Schubert M, Jockenhel F, Behre HM, Gooren L, Nieschlag E. More than eight years hands-on experience with the novel long-acting parenteral testosterone undecanoate. Asian Journal of Andrology 2007; 9(3):291-297. http://www.ncbi.nlm.nih.gov/pubmed/17486268 “It reverses the effects of hypogonadism [low testosterone with symptoms] on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma testosterone levels. No polycythemia [high red cell counts] has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. Testosterone [undecanoate] is a valuable treatment option of androgen deficiency.” Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clinical Endocrinology (Oxford) 2005 September; 63(3):280-93. http://www.ncbi.nlm.nih.gov/pubmed/16117815 “1,083 subjects were evaluated. Mean age was 64.5 years (range 49.9-77.6). Testosterone treatment produced: (i) a reduction of 1.6 kg (3.5 pounds) of total body fat, corresponding to 6.2% [reduction], (ii) an increase in fat free mass [muscle, bone] of 1.6 kg (3.5 pounds), and (iii) no change in body weight. The effects of testosterone on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm. Testosterone improved bone mineral density at the lumbar spine by +3.7%, but not at the femoral [hip] neck. Testosterone also reduced total cholesterol by 9 mg/dl, with no change in LDL-cholesterol.” Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R; North American AA2500 T Gel Study Group. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab. 2003 Jun; 88(6):2673-81. http://www.ncbi.nlm.nih.gov/pubmed/12788872 “Treatment improved lean body mass [muscle] by 1.7 kg [3.7 pounds] and [decreased] percentage of body fat by 1.2% to a significantly greater degree than either control treatment. Significant improvements in spontaneous erections, sexual desire, and sexual motivation were also evidenced with the 100 mg [per day dose of] AA2500 dose in comparison with placebo.” Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone therapy prevents gain in visceral adipose [fat] tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab. 2008 Jan;93(1):139-46. http://www.ncbi.nlm.nih.gov/pubmed/17940111 “Testosterone therapy, relative to placebo [inactive drug], selectively lessened visceral [between the organs in the abdomen] fat accumulation...and increased total body and thigh skeletal muscle mass.” Atkinson RA, Srinivas-Shankar U, Roberts SA, Connolly MJ, Adams JE, Oldham JA, Wu FC, Seynnes OR, Stewart CE, Maganaris CN, Narici MV. Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men. J Gerontol A Biol Sci Med Sci. 2010 Nov;65(11):1215-9. http://www.ncbi.nlm.nih.gov/pubmed/20601412 “Testosterone replacement in men is associated with preservation of muscle thickness. The results suggest that testosterone mitigates sarcopenia [muscle wasting or loss] by improving muscle tissue to maintain a state of normality in aging men.” Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J. 2006 Jan;27(1):57-64. http://www.ncbi.nlm.nih.gov/pubmed/16093267 “Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure.” Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M, Rosano GM. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 2009 Sep 1; 54(10):919-27. http://www.ncbi.nlm.nih.gov/pubmed/19712802 “Testosterone therapy improves exercise capacity, muscle strength, glucose metabolism, and BRS [baroreceptor sensitivity] in men with moderately severe CHF [congestive heart failure]. Testosterone benefits seem to be mediated by metabolic and peripheral effects.” Caminiti G, Marazzi G, Vitale C, Patrizi R, Volterrani M, Miceli M, Fini M, Spera G, Rosano G. “Testosterone has beneficial effect on serum cholesterol and triglyceride levels in [diabetic male] patients with CAD [coronary or heart artery disease] and reduces the number of anginal attacks [chest pain due to insufficient blood flow], and ischemic [low blood flow] episodes.” Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycemic [blood sugar] control, visceral adiposity [fat in abdomen] and hypercholesterolemia in hypogonadal men with type 2 diabetes. European Journal of Endocrinology. 2006 Jun; 154(6):899-906. http://www.ncbi.nlm.nih.gov/pubmed/16728551 “Testosterone replacement therapy reduces insulin resistance and improves glycaemic [blood sugar] control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity [fat between organs in abdomen] together represent an overall reduction in cardiovascular [heart artery] risk.” LHojlund K, Hougaard DM, Mosbech TH, Larsen R, Flyvbjerg A, Frystyk J, Brixen K, Andersen M. Testosterone therapy decreased adiponectin and subcutaneous fat in aging men. Endocrine Reviews 2011; 32: P3-470. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P3-470?sid=2008cade-b4ff-4fc3-8e70-f57f39138b8f “In aging men with low normal bioavailable testosterone levels, six months of testosterone treatment reduced serum adiponectin and subcutaneous [under the skin] adipose [fat] tissues on abdomen and thigh, whereas no significant changes in visceral [in between organs in abdomen] adipose tissue were observed.” Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, Morales AM, Volterrani M, Yellowlees A, Howell JD, Channer KS; TIMES2 Investigators. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011 Apr; 34(4):828-37. http://www.ncbi.nlm.nih.gov/pubmed/21386088 “Over a 6-month period, transdermal [applied to skin] testosterone replacement therapy was associated with beneficial effects on insulin resistance, total and LDL [“bad”]-cholesterol, Lipoprotein-a [unfavorable cholesterol marker], and sexual health in hypogonadal [low testosterone with symptoms] men with type 2 diabetes and/or Metabolic Syndrome [constellation of large waist, abnormal cholesterol, diabetes, blood pressure].” Monami M, Rastrelli G, Aversa A, Tishova Y, Saad F, Lenzi A, Forti G, Mannucci E, Maggi M
Saad F, Gooren LJ. The role of testosterone in the etiology [cause] and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. Journal of Obesity. 2011; 2011. http://www.ncbi.nlm.nih.gov/pubmed/20847893 “Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis.” Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic [glucose] control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. Journal of Andrology. 2009 Nov-Dec;30(6):726-33. http://www.ncbi.nlm.nih.gov/pubmed/19578132 “Addition of testosterone [to diet and exercise] significantly further improved these measures [of metabolic syndrome: hemoglobin-A1c, fasting glucose, HDL {“good”}-cholesterol, triglycerides, and waist circumference]. [After 1 year,] 81% of the patients randomized to testosterone/diet/exercise no longer matched the criteria of the “metabolic syndrome,” [compared to] 31% of the diet and exercise [no testosterone] patients. Additionally, testosterone treatment improved insulin sensitivity, and high-sensitivity C-reactive protein [CRP].” Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M
Zemlyanoy A, Gooren LJ “Beneficial effects of administration of testosterone to hypogonadal with a diabetic foot [heals foot ulcers] may be due to improved vascularization [blood supply] and to anti-inflammatory action.” J, , , , , , , , FREffects of Testosterone and rhGH on metabolic syndrome components in older men: The HORMA Study. Endocrine Reviews 2011: 32: P3-208. http://edrv.endojournals.org/cgi/content/meeting_abstract/32/03_MeetingAbstracts/P3-208?sid=8553a319-6499-45f4-aa5e-5e07bddcb42b “In older men, testosterone supplementation with or without rhGH [recombinant human Growth Hormone] affects some components of the Metabolic Syndrome beneficially and others adversely but together improve Metabolic Syndrome composite scores. Change in Body Mass Index [weight divided by height] is the best predictor of change in Metabolic Syndrome elements and is jointly affected by both total fat [decrease] and lean body mass [muscle increase].” Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf). 2010 Nov;73(5):602-12. http://www.ncbi.nlm.nih.gov/pubmed/20718771 “Thirty weeks of testosterone administration...in hypogonadal men with the Metabolic Syndrome improved some components of the [Syndrome] and a number of inflammatory markers,”[with] “significant decreases in weight, BMI [body mass index and waist circumference...insulin also decreased..Of the inflammatory markers, IL-1ß, TNF-a and CRP decreased.” Aversa A Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study. Journal of Sexual Medicine. 2010 Oct;7(10):3495-503. http://www.ncbi.nlm.nih.gov/pubmed/20646185 “[After 24 months of treatment,] testosterone reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with Metabolic Syndrome. Resumption and maintenance of testosterone levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in Metabolic Syndrome without significant hematological [blood] and prostate adverse events.” La Vignera, S Calogero AE, D'Agata R, Di Mauro M, Tumino S, Condorelli R, Lanzafame F, Finocchiaro C, Giammusso B, Vicari E. Testosterone therapy improves the clinical response to conventional treatment for male patients with metabolic syndrome associated to late onset hypogonadism. Minerva Endocrinol. 2008 Sep;33(3):159-67. http://www.ncbi.nlm.nih.gov/pubmed/18846023 “The group of patients treated with testosterone showed a profile of clinical response better than the group of controls.” Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004 Jul;89(7):3313-8. http://www.ncbi.nlm.nih.gov/pubmed/15240608 “Testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol. Testosterone induced reductions in TNF-alpha and IL-1beta [both pro-inflammatory] and an increase in IL-10 [anti-inflammatory].” Nguyen CT, Aaronson A, Morrissey RP, Agarwal M, Willix RD, Schwarz ER. Myths and truths of growth hormone and testosterone therapy in heart failure. Expert Review of Cardiovascular Therapy. 2011 Jun;9(6):711-20. http://www.ncbi.nlm.nih.gov/pubmed/21714602 “Testosterone has been shown to improve hemodynamic parameters [in heart failure] via reduction in peripheral vascular resistance and increased coronary [heart] blood flow through vasodilation, thereby improving functional and symptomatic status.” Naghi JJ, Philip KJ, DiLibero D, Willix R, Schwarz ER. Testosterone therapy: treatment of metabolic disturbances in heart failure. Journal of Cardiovascular Pharmacology and Therapeutics. 2011 Mar;16(1):14-23. http://www.ncbi.nlm.nih.gov/pubmed/21097668 “Recent clinical studies have confirmed that functional, biochemical, and cardiopulmonary status in patients with HF [heart failure] have significant improvements when treated with testosterone supplementation.” Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, Aleman A, Lock TM, Bosch JL, Grobbee DE, van der Schouw YT. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. Journal of the American Medical Association. January 2, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18167405 “Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects.” Svartberg J, Agledahl I, Figenschau Y, Sildnes T, Waterloo K, Jorde R. Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD [bone mineral density] in the hip. Int J Impot Res. 2008 Jul-Aug;20(4):378-87. http://www.ncbi.nlm.nih.gov/pubmed/18480825 “Testosterone treatment had a large impact on body composition with reduced fat mass and abdominal adipose [fat] tissue and increased fat-free mass [muscle, bone], but it did not affect weight and glucose and lipid metabolism. Bone mineral density in the hip was significantly higher after the testosterone treatment.” Snyder PJ Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab. 1999 Aug; 84(8):2647-53. http://www.ncbi.nlm.nih.gov/pubmed/10443654 “We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass, principally in the arms and legs, and increased lean [muscle] mass, principally in the trunk, but did not increase the strength of knee extension and flexion, as measured by dynamometer.” Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May; 89(5):2085-98. http://www.ncbi.nlm.nih.gov/pubmed/15126525 “Sexual function and mood parameters improved rapidly and were maintained throughout testosterone treatment. Lean body mass [muscle] increased and fat mass decreased, and these changes were maintained with treatment… gradual and progressive increases in bone mineral density more in the spine than the hip.” Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MD, Adams JE, Oldham JA, Wu FC. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010 Feb; 95(2):639-50. http://www.ncbi.nlm.nih.gov/pubmed/20061435 “Testosterone treatment in intermediate-frail and frail elderly men with low to borderline-low T for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition, quality of life, and physical function.” English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low-dose transdermal testosterone therapy improves [heart] angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation. 2000 Oct17; 102(16). http://www.ncbi.nlm.nih.gov/pubmed/11034937 “Low-dose supplemental testosterone treatment in men with chronic stable angina [chest pain due to inadequate blood supply] reduces exercise-induced myocardial [heart muscle] ischemia [low blood flow].” Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, Channer KS. Testosterone replacement in hypogonadal men with angina improves [heart] ischemic threshold and quality of life. Heart, August 1, 2004; 90(8): 871 - 876. http://www.ncbi.nlm.nih.gov/pubmed/15253956 “Testosterone replacement therapy in hypogonadal men delays time to ischaemia [low blood flow], improves mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor alpha.” English KM, Jones RD, Jones TH, Morice AH, Channer KS. Testosterone acts as a coronary [heart artery] vasodilator by a calcium antagonistic action. J Endocrinol Invest. 2002 May; 25(5):455-8. http://www.ncbi.nlm.nih.gov/pubmed/12035943 Güder G, Allolio B, Angermann CE, Störk S. Androgen deficiency in heart failure. Current Heart Failure Reports. 2011 Jun;8(2):131-9. http://www.ncbi.nlm.nih.gov/pubmed/21387202 “Fatigue or muscle weakness, may be particularly aggravated in heart failure, and disease severity may be indirectly affected by low levels of androgen. Recently, androgen replacement therapy has been suggested as a new treatment option of heart failure symptoms, and placebo-controlled pilot trials showed a modest improvement of physical performance.” Tan RS, Pu SJ. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Aging Male. 2003 Mar; 6(1):13-7. http://www.ncbi.nlm.nih.gov/pubmed/12809076 “The placebo-treated group deteriorated gradually. This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer's disease.” Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol. 2009 Jul; 30(2):239-58. http://www.ncbi.nlm.nih.gov/pubmed/19427328 “Like estrogen, testosterone has been established as an endogenous neuroprotective factor that not only increases neuronal resilience against AD [Alzheimer’s Disease]-related insults, but also reduces beta-amyloid accumulation [brain-related change in Alzheimer’s Disease].” Merza Z, Blumsohn A, Mah PM, Meads DM, McKenna SP, Wylie K, Eastell R, Wu F, Ross RJ. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Int J Androl. 2006. http://www.ncbi.nlm.nih.gov/pubmed/16390499 “There was a significant decrease in total body fat mass, as well as a…difference in quality of life according to the Male Erectile Dysfunction Quality of Life questionnaire… When the active treatment period was combined for placebo and testosterone groups, the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption and to increase lean body mass.” Bhasin S, Calof OM, Storer TW, Lee ML, Mazer NA, Jasuja R, Montori VM, Gao W, Dalton JT. Drug insight: Testosterone & selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab. 2006 Mar; 2(3):146-59. http://www.ncbi.nlm.nih.gov/pubmed/16932274 “[There is] unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic [muscle generating] lineage and inhibit their adipogenic [fat generating] differentiation...Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid [prednisone types]-treated men, and older men with low or low-normal testosterone levels.” Sugimoto K, Konaka H, Iijima M, Fukushima M, Maeda Y, Mizokami A, Koh E, Origasa H, Iwamoto T, Namiki M “Androgen [testosterone] replacement therapy improved lower urinary tract symptoms [more frequent urination, smaller urine volumes, other] in hypogonadal [low testosterone with symptoms] men with mild Benign Prostatic Hypertrophy (mild prostate enlargement.” Yassin AA, El-Sakka AI, Saad F, Gooren LJ. Lower urinary-tract symptoms and testosterone in elderly men. World Journal of Urology 2008 August; 26(4):359-64. http://www.ncbi.nlm.nih.gov/pubmed/18594831 “Some studies investigating the effects of normalizing testosterone levels in elderly men have found a positive effect on variables of the metabolic syndrome and, simultaneously, on scores of the International Prostate Symptoms Score (IPSS).” Kalinchenko S, Vishnevskiy EL, Koval AN, Mskhalaya GJ, Saad F. Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: a pilot study. Aging Male. 2008 Jun;11(2):57-61. http://www.ncbi.nlm.nih.gov/pubmed/18570056 “Testosterone administration improved symptoms of LUTS [lower urinary tract symptoms, including more frequent urination] in men with late-onset hypogonadism.” Haider A, Gooren LJ, Padungtod P, Saad F. Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalization of plasma testosterone levels in hypogonadal elderly men. Andrologia. 2009 Feb;41(1):7-13. http://www.ncbi.nlm.nih.gov/pubmed/19143723 “Along with the improvement of the metabolic syndrome upon testosterone administration, there was also an improvement of the IPSS [International Prostate Symptom Score {urinary frequency, others}] and of RBV [residual {urinary} bladder volume of urine {due to incomplete emptying} and CRP [C-reactive protein {inflammation marker}].” Giltay EJ and others. Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. J Sex Med. 2010 Jul;7(7):2572-82. http://www.ncbi.nlm.nih.gov/pubmed/20524974 “Testosterone administration may improve depressive symptoms, aging male symptoms and sexual dysfunction in hypogonadal men with the Metabolic Syndrome. The beneficial effects of testosterone were most evident in men with the lowest baseline total testosterone levels.” Shores MM, Kivlahan DR, Sadak TI, Li EJ, Matsumoto AM. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). J Clin Psychiatry. 2009 Jul;70(7):1009-16. http://www.ncbi.nlm.nih.gov/pubmed/19653976 “These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism.” Orengo CA, Fullerton G, Tan R. Male depression: a review of gender concerns and testosterone therapy. Geriatrics. 2004 Oct; 59(10):24-30. http://www.ncbi.nlm.nih.gov/pubmed/15508552 “Research involving depressed hypogonadal and eugonadal men suggests that depressed men may benefit from testosterone augmentation.” Rhoden E.L. and Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. New England Journal of Medicine 2004 Jan; 350:482-492. http://www.ncbi.nlm.nih.gov/pubmed/14749457 Fernández-Balsells MM and others. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010 Jun;95(6):2560-75. http://www.ncbi.nlm.nih.gov/pubmed/20525906 The reviewers included 51 different studies and found, “There was no significant effect on mortality, prostate, or cardiovascular outcomes. The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol.” Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22. http://www.ncbi.nlm.nih.gov/pubmed/20592293 207 elderly men with baseline limitations in mobility: mean [average] age 74 years; 85% hypertension [high blood pressure] and taking medication for same; 63% hyperlipidemia [high cholesterol] and taking medication for same; 45% obese [mean body mass index 29.7]; and 24% had diabetes. Before enrolling in the study, “participants were required to have evidence of limitations in mobility, defined as having difficulty walking two blocks on a level surface or climbing 10 steps and having a score between 4 and 9 on the Short Physical Performance Battery (which measures performance on a scale of 0 to 12, with higher scores indicating better performance).” “The testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load…in this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.” The patients were not assessed for baseline sleep apnea, adherence to prescribed medications or increase in estradiol, which can increase risk of vascular incidents. Tan RS, Salazar JA. Risks of testosterone replacement therapy in ageing men. Expert Opin Drug Saf. 2004 Nov; 3(6):599-606. http://www.ncbi.nlm.nih.gov/pubmed/15500418 “Treatment relating to hypogonadism has relieved symptoms and improved the quality of life of many individuals. Epidemiological studies point toward an association with increased morbidity [disease] and mortality, with low testosterone states in ageing males. For example, there is a higher prevalence of depression, coronary heart disease, osteoporosis, fracture rates, frailty and even dementia with low testosterone states.” Corona G, Rastrelli G, Forti G, Maggi M. Update in testosterone therapy for men. J Sex Med. 2011 Mar; 8(3):639-54. http://www.ncbi.nlm.nih.gov/pubmed/21711483 “Testosterone deficiency is highly prevalent in the aging male and represents a sign of physical and sexual frailty.” Hobbs CJ, Plymate SR, Rosen CJ, Adler RA. Testosterone administration increases insulin-like growth factor-I levels in normal men. J Clin Endocrinol Metab. 1993 Sep;77(3):776-9. http://www.ncbi.nlm.nih.gov/pubmed/7690364 Muniyappa R, Sorkin JD, Veldhuis JD, Harman SM, Münzer T, Bhasin S, Blackman MR. Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men. Am J Physiol Endocrinol Metab. 2007 Sep;293(3):E769-75. http://www.ncbi.nlm.nih.gov/pubmed/17550998 Svartberg J and others. Testosterone treatment improves body composition and sexual function in men with COPD [chronic obstructive pulmonary disease, emphysema/chronic bronchitis], in a 6-month randomized controlled trial. Respir Med. 2004 Sep;98(9):906-13. http://www.ncbi.nlm.nih.gov/pubmed/15338805 “Administration of a low-dose testosterone to men with COPD for 26 weeks was associated with improvement of body composition, better erectile function and sexual quality of life. Furthermore, there were no clinical or biochemical side effects.” Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren LJ. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol. 2011 Jul 13. http://www.ncbi.nlm.nih.gov/pubmed/21753068 “The time-course of the spectrum of effects of testosterone [treatment] shows considerable variation.” EFFECTS OF BLOCKED TESTOSTERONEGrunfeld EA, Halliday A, Martin P, Drudge-Coates L. Andropause syndrome in men treated for metastatic prostate cancer: A Qualitative Study of the Impact of Symptoms. Cancer Nurs. 2011 May 9. http://www.ncbi.nlm.nih.gov/pubmed/21558849 “The most frequently mentioned adverse effects were hot flashes and night sweats, gynecomastia [breast enlargement], cognitive [memory, thinking] decline, and changes in sexual function. Hot flashes did impact on everyday functioning, and night sweats regularly disturbed sleep patterns and led to participants feeling tired and irritable. Participants reported a lack of control over their hot flashes and night sweats.” Jones TH. Cardiovascular risk during androgen deprivation therapy for prostate cancer. British Medical Journal. 2011 May 24;342:d3105. http://www.ncbi.nlm.nih.gov/pubmed/21610041 “Accumulating evidence suggests that androgen [testosterone] deprivation therapy for prostate cancer is associated with adverse effects on cardiovascular [heart artery] risk factors such as diabetes, the incidence of cardiovascular events, and, in some studies, death from cardiovascular disease. Although not all studies concur, a science advisory statement from the American Heart Association, American Cancer Society, and the American Urological Association has recommended that all patients receiving such treatment should have periodic follow-ups for assessment of cardiovascular risk factors and those with coexisting cardiovascular disease should have their treatment for secondary prevention optimized. A large follow-up study of 73,196 men (older than 65 years) with locoregional [not metastasized or spread elsewhere] prostate cancer in which about a third were given androgen deprivation therapy reported a higher incidence of cardiovascular disease, diabetes, myocardial infarction, and sudden death from cardiac disease or life threatening ventricular arrhythmia [abnormal heart rhythm].” Corona G, Baldi E, Maggi M. Androgen regulation of prostate cancer: where are we now? J Endocrinol Invest. 2011 Mar;34(3):232-43. http://www.ncbi.nlm.nih.gov/pubmed/21297383 “Because androgens are essential for the regulation of fat distribution, insulin sensitivity, and lipid and bone metabolism, recent publications have highlighted the concept that Androgen [Testosterone] Deprivation Therapy may also be involved with an increase in overall, as well as cardiovascular, morbidity and mortality. While Androgen Deprivation Therapy still represents a cornerstone for the palliative therapy of a small fraction of aggressive prostate cancer, a ‘misuse and/or abuse’ of Androgen Deprivation Therapy should be avoided.” Galvão DA, Taaffe DR, Spry N, Joseph D, Turner D, Newton RU. Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer and Prostatic Diseases 2009(12):198-203. http://www.ncbi.nlm.nih.gov/pubmed/18852703 Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. New England Journal of Medicine 2005 Jan 13; 352(2):154-64. http://www.ncbi.nlm.nih.gov/pubmed/15647578 “Androgen [testosterone]-deprivation therapy for prostate cancer increases the risk of fracture.” Shahinian VB. Prostate cancer: Reducing fracture risk in men on androgen deprivation therapy. Nat Rev Urol. 2011 Jan;8(1):9-10. http://www.ncbi.nlm.nih.gov/pubmed/21135877 “Androgen [testosterone] Deprivation Therapy is associated with potentially serious adverse effects—it is now well established as a cause of osteoporosis and increased risk of fracture.” Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS; And the Urologic Diseases in America Project. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007 Oct 1; 110(7):1493-500. http://www.ncbi.nlm.nih.gov/pubmed/17657815 “Androgen [testosterone] Deprivation Therapy is associated with significantly increased cardiovascular [heart artery] morbidity [disease] in men with prostate cancer and may lower overall survival in men with low-risk disease.” D'Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS, Joseph D, Tai KH, Malone S, Ludgate C, Steigler A, Kantoff PW. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions [heart attacks]. Journal of Clinical Oncology 2007 June 10; 25(17):2420-5. http://www.ncbi.nlm.nih.gov/pubmed/17557956 “The use of Androgen [testosterone] Suppression Therapy is associated with earlier onset of fatal MIs [myocardial infarctions, heart attacks] in men age 65 years or older who are treated for 6 months compared with men who are not treated with Androgen Suppression Therapy.” Tsai HK, D'Amico AV, Sadetsky N, Chen MH, Carroll PR. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. Journal of the National Cancer Institute 2007 October 17; 99(20):1516-24. http://www.ncbi.nlm.nih.gov/pubmed/17925537 “The use of Androgen [testosterone] Deprivation Therapy appears to be associated with an increased risk of death from cardiovascular [heart artery] causes in patients undergoing radical prostatectomy for localized prostate cancer.” Basaria S. Androgen [testosterone] deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth. Journal of Andrology 2008 September-October; 29(5):534-9. http://www.ncbi.nlm.nih.gov/pubmed/18567642 Shahani S, Braga-Basaria M, Basaria S. Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis. Journal of Clinical Endocrinology and Metabolism 2008 June; 93(6):2042-9. http://www.ncbi.nlm.nih.gov/pubmed/18349064 “Prospective studies evaluating early (3-6 months) metabolic changes of Androgen [testosterone] Deprivation Therapy show development of hyperinsulinemia [high insulin, marker of type 2 diabetes or pre-diabetes]; however, glucose levels remain normal. Cross-sectional studies of men undergoing long-term (greater than or equal to 12 months) Androgen Deprivation Therapy reveal higher prevalence of diabetes and metabolic syndrome compared with controls. Furthermore, men undergoing Androgen Deprivation Therapy also experience higher cardiovascular [heart artery] mortality.” Smith JC, Bennett S, Evans LM, Kynaston HG, Parmar M, Mason MD, Cockcroft JR, Scanlon MF, Davies JS. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. Journal of Clinical Endocrinology and Metabolism 2001 September; 86(9):4261-7. http://www.ncbi.nlm.nih.gov/pubmed/11549659 “These data indicate that induced hypogonadism [blocked testosterone] in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.” Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Hyperglycemia [high blood sugar] and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer 2006 February 1; 106(3):581-8. http://www.ncbi.nlm.nih.gov/pubmed/16388523 “The current data suggested that men with Prostate Cancer who are receiving long-term Androgen [testosterone] Deprivation Therapy are at risk for developing insulin resistance and hyperglycemia, [high blood sugar, pre-diabetes or diabetes] thus leading to their increased risk of cardiovascular [heart artery] disease. This adverse metabolic profile developed independent of age and Body Mass Index [weight normalized for height] and appeared to be a direct result of androgen deprivation.” Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Relation between duration of androgen deprivation therapy and degree of insulin resistance in men with prostate cancer. Archives of Internal Medicine 2007 March 26; 167(6):612-13. http://www.ncbi.nlm.nih.gov/pubmed/17389294 Braga-Basaria M, Muller DC, Carducci MA, Dobs AS, Basaria S. Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy. International Journal of Impotence Research 2006; 18:494-498. http://www.ncbi.nlm.nih.gov/pubmed/16617314 “These data show that men undergoing long-term Androgen [testosterone] Deprivation Therapy have higher total and LDL [low density lipoprotein “bad”] cholesterol than age-matched controls.” Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J, Basaria S. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol 2006 Aug 20;24(24):3979-83. http://www.ncbi.nlm.nih.gov/pubmed/16921050 “These data suggest that metabolic syndrome [constellation of abnormal cholesterol-lipids, diabetes, high blood pressure, increased waist] was present in more than 50% of the men undergoing long-term ADT [Androgen Deprivation Therapy], predisposing them to higher cardiovascular [heart artery] risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence.” Saylor PG, Smith MR. Metabolic complications of androgen deprivation therapy for prostate cancer. Journal of Urology 2009 May; 181(5):1998-2006. http://www.ncbi.nlm.nih.gov/pubmed/19286225 “Androgen [testosterone] deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms.” Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer 2009 June 1; 115(11):2388-99. http://www.ncbi.nlm.nih.gov/pubmed/19399748 “Androgen [testosterone] Deprivation Therapy was associated with an increased risk of skeletal fracture, incident diabetes, and cardiovascular [heart artery]-related mortality.” Kintzel PE, Chase SL, Schultz LM, O'Rourke TJ. Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy 2008 December; 28(12):1511-22. http://www.ncbi.nlm.nih.gov/pubmed/19025432 “Body composition changes [increased abdomen fat], hyperlipidemia [high cholesterol, triglycerides], insulin resistance [pre-diabetes, diabetes], metabolic syndrome, and acute coronary syndrome [heart artery pain] are all reported adverse effects of Androgen [testosterone] Deprivation Therapy], which are consequences of reduced levels of circulating testosterone. Metabolic and body composition changes associated with Androgen Deprivation Therapy arise within months of beginning medical Androgen Deprivation Therapy and persist after discontinuation of therapy...We found that the increased risk for serious cardiovascular [heart artery] disease becomes evident within months of beginning Androgen Deprivation Therapy.” Hakimian P, Blute M Jr, Kashanian J, Chan S, Silver D, Shabsigh R. Metabolic and cardiovascular effects of androgen deprivation therapy. BJU International 2008 December; 102(11):1509-14. http://www.ncbi.nlm.nih.gov/pubmed/18727614 “Men with prostate cancer who undergo long-term Androgen [testosterone] Deprivation Therapy are at greater risk of developing dyslipidemia [high cholesterol, triglycerides], insulin resistance [pre-diabetes], hyperglycemia [high blood sugar] and metabolic syndrome [constellation of previous 3 items, plus high blood pressure, increased waist size]. These metabolic and physiological changes are a direct result of the induced severe hypogonadism and might predispose patients to a greater risk of cardiovascular [heart artery] morbidity [disease] and mortality [death].” PROSTATE AND TESTOSTERONEMarks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, Veltri RW, Makarov DV, Partin AW, Bostwick DG, Macairan ML, Nelson PS. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Journal of the American Medical Association. 2006 Nov 15; 296(19):2351-61. http://www.ncbi.nlm.nih.gov/pubmed/17105798 “These preliminary data suggest that in aging men with late-onset hypogonadism [low testosterone with symptoms, 6 months of Testosterone Replacement Therapy normalizes serum androgen [testosterone] levels but appears to have little effect on prostate tissue androgen [testosterone, DHT or dihydrotestosterone] levels and cellular functions.” Morgentaler A, Lipshultz LI, Bennett R, Sweeney M, Avila D Jr, Khera M. Testosterone therapy in men with untreated prostate cancer. The Journal of Urology. 2011 Apr; 185(4):1256-60. http://www.ncbi.nlm.nih.gov/pubmed/21334649 “Testosterone therapy in men with untreated prostate cancer was not associated with prostate cancer progression in the short to medium term [median 2.5 years, range 1.0-8.1 years]. These results are consistent with the saturation model, i.e., maximal prostate cancer growth is achieved at low androgen concentrations. The longstanding prohibition against testosterone therapy in men with untreated or low risk prostate cancer or treated prostate cancer without evidence of metastatic or recurrent disease merits reevaluation.” Isbarn H, Pinthus JH, Marks LS, Montorsi F, Morales A, Morgentaler A, Schulman C. Testosterone and prostate cancer: revisiting old paradigms. Eur Urol. 2009 Jul;56(1):48-56. http://www.ncbi.nlm.nih.gov/pubmed/19375844 “The notion that pathologic prostate growth, benign or malignant, can be stimulated by androgens is a commonly held belief without scientific basis. Therefore, the current prostatic guidelines for testosterone therapy appear to be overly restrictive and should be reexamined…The available literature strongly suggests that testosterone therapy neither increases the risk of prostate cancer diagnosis in normal men nor causes cancer recurrence in men who were successfully treated for prostate cancer.” Morgentaler A. Testosterone and prostate cancer: What are the risks for middle-aged men? Urol Clin North Am. 2011 May;38(2):119-24. http://www.ncbi.nlm.nih.gov/pubmed/21621078 “With increased recognition of the benefits of testosterone therapy for middle-aged men, there has been a concomitant reexamination of the historical fear that raising testosterone will result in more prostate cancer. Studies have failed to show increased risk of prostate cancer in men with higher serum testosterone, and supraphysiologic [higher than the laboratory reference range] testosterone fails to increase prostate volume or prostate-specific antigen in healthy men. This apparent paradox is explained by the Saturation Model, which posits a finite capacity of androgen to stimulate prostate growth. Modern studies indicate no increased risk of Prostate Cancer among men with serum testosterone in the therapeutic range.” Agarwal P.K., Oefelein M.G. Testosterone replacement therapy after primary treatment for prostate cancer. Journal of Urology 2005; 173:533-536. http://www.ncbi.nlm.nih.gov/pubmed/15643240 “At a median [average] of 19 months of Testosterone Replacement Therapy, hypogonadal [low testosterone] patients with a history of prostate cancer had no PSA recurrence and had statistically significant improvements in Total Testosterone and hypogonadal [low testosterone] symptoms.” Rhoden EL, Averbeck MA, Teloken PE. Androgen replacement in men undergoing treatment for prostate cancer. J Sex Med. 2008 Sep; 5(9):2202-8. http://www.ncbi.nlm.nih.gov/pubmed/18638000 “Although further studies are necessary before definitive conclusions can be drawn, the available evidence suggests that Testosterone Replacement Therapy can be cautiously considered in selected hypogonadal [low testosterone] men treated with curative intent for Prostate Cancer and without evidence of active disease.” Coward RM, Simhan J, Carson CC 3rd. Prostate-specific antigen changes and prostate cancer in hypogonadal men treated with testosterone replacement therapy. BJU Int. 2009 May; 103(9):1179-83. http://www.ncbi.nlm.nih.gov/pubmed/19154450 “Late Onset [older age] Hypogonadism [testosterone decline with symptoms] is an increasingly prevalent disease characterized by a symptomatically low testosterone level, and Testosterone Replacement Therapy is effective in normalizing serum testosterone levels, providing a beneficial cardiovascular [heart artery] effect, and improving sexual function and overall quality of life. PSA levels remain stable after normalization of testosterone for greater than or equal to 5 years, prostate cancer can be effectively diagnosed and treated in men taking Testosterone Replacement Therapy, and the incidence of prostate cancer among men with Late Onset Hypogonadism on Testosterone Replacement Therapy is no greater than that in the general population.” Khera M. Androgen replacement therapy after prostate cancer treatment. Curr Urol Rep. 2010 Nov; 11(6):393-9. http://www.ncbi.nlm.nih.gov/pubmed/20838944 “Finally, because patients with hypogonadism [low testosterone with symptoms] already may be at a significant disadvantage in recovering their erectile function after prostatectomy [prostate gland removal by surgery], they perhaps should receive special consideration as candidates for androgen [testosterone] replacement therapy.” Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer. 2007 Feb 1; 109(3):536-41. http://www.ncbi.nlm.nih.gov/pubmed/17183557 “For patients with low serum testosterone levels and symptoms of hypogonadism, Testosterone Replacement Therapy may be used with caution and close follow-up after prostate brachytherapy [radioactive seed implants into prostate gland].” Morgentaler A. Testosterone deficiency and prostate cancer: emerging recognition of an important and troubling relationship. Eur Urol. 2007 Sep; 52(3):623-5. http://www.ncbi.nlm.nih.gov/pubmed/17433531 “However, the accelerating accumulation of new studies demonstrating a worrisome association between LOW testosterone and Prostate Cancer can no longer be ignored...I believe we are on the verge of a major shift in attitudes regarding the relationship of testosterone and prostate cancer.” Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol. 2006 Nov; 50(5):935-9. http://www.ncbi.nlm.nih.gov/pubmed/16875775 “This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that testosterone causes Prostate Cancer to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of testosterone and Prostate Cancer that may be clinically and scientifically rewarding.” Endogenous Hormones, Prostate Cancer Collaborative Group, Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. Journal National Cancer Institute 2008 Feb 6; 100(3):170-83. (No association) http://www.ncbi.nlm.nih.gov/pubmed/18230794 “In this collaborative analysis of the worldwide data on endogenous hormones and prostate cancer risk, serum concentrations of sex hormones were not associated with the risk of prostate cancer.” Carpenter WR, Robinson WR, Godley PA. Getting over testosterone: postulating a fresh start for etiologic [causes] studies of prostate cancer. Journal National Cancer Institute 2008 Feb 6;100(3):158-9. http://www.ncbi.nlm.nih.gov/pubmed/18230791 Morgentaler A. Testosterone replacement therapy and prostate risks: where's the beef? Can J Urol. 2006 Feb; 13 Suppl 1:40-3. http://www.ncbi.nlm.nih.gov/pubmed/16526980 “It has been part of the conventional medical wisdom for six decades that higher testosterone in some way increases the risk of prostate cancer. This belief is derived largely from the well-documented regression of prostate cancer in the face of surgical or pharmacological castration. However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer. Specifically, no increased risk of prostate cancer was noted in 1) clinical trials of testosterone supplementation, 2) longitudinal population-based studies, or 3) in a high-risk population of hypogonadal [low testosterone with symptoms] men receiving testosterone treatment. Moreover, hypogonadal men have a substantial rate of biopsy-detectable prostate cancer, suggesting that low testosterone has no protective effect against development of prostate cancer. These results argue against an increased risk of prostate cancer with testosterone replacement therapy.” Questions? Please enter confidential registration at our website: Confidential Registration Form or send an email to This e-mail address is being protected from spambots. You need JavaScript enabled to view it . |
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