Conflicting results have been obtained concerning the importance of testosterone in maintaining cardiovascular health. Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters that are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.
The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study, designed to determine whether an individual man’s sexual outcomes after most common treatments for early-stage prostate cancer could be accurately predicted on the basis of baseline characteristics and treatment plans, found that 2 years after treatment, 177 (35%) of 511 men who underwent prostatectomy reported the ability to attain functional erections suitable for intercourse. 
In men with hypogonadism, a low level of testosterone is produced due to a problem in the testicles or the pituitary gland. According to Harvard Medical School, determining exactly what constitutes a low testosterone level is a controversial matter. Levels of this hormone fluctuate wildly and even vary according to the time of day. However, generally physicians only decide to treat a patient for hypogonadism if the blood testosterone level is below 300 ng/dL and the following symptoms outlined by The National Institutes of Health are present.
Testosterone is the primary sex hormone in men, and it is responsible for the development of many of the physical characteristics that are considered typically male. Women also produce the hormone in much smaller amounts. Testosterone, part of a hormone class known as androgens, is produced by the testicles after stimulation by the pituitary gland, which is located near the base of the brain, and it sends signals to a male's testicles (or to a woman's ovaries) that spark feelings of sexual desire. (1)
The largest amounts of testosterone (>95%) are produced by the testes in men, while the adrenal glands account for most of the remainder. Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, thecal cells of the ovaries, and, during pregnancy, by the placenta. In the testes, testosterone is produced by the Leydig cells. The male generative glands also contain Sertoli cells, which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone-binding globulin (SHBG).
There is a polymorphic CAG repeat sequence in the androgen receptor gene, which codes for a variable number of glutamine amino acids in the part of the receptor affecting gene transcription. A receptor with a short CAG sequence produces greater activity when androgens attach, and men with shorter CAG polymorphisms exhibit androgenic traits, such as preserved bone density (Zitzmann et al 2001) and prostate growth during testosterone treatment (Zitzmann et al 2003). Indirect evidence of the importance of androgens in the development of prostate cancer is provided by case control study findings of a shorter, more active CAG repeat sequence in the androgen receptor gene of patients with prostate cancer compared with controls (Hsing et al 2000, 2002).
Trials of testosterone treatment in men with type 2 diabetes have also taken place. A recent randomized controlled crossover trial assessed the effects of intramuscular testosterone replacement to achieve levels within the physiological range, compared with placebo injections in 24 men with diabetes, hypogonadism and a mean age of 64 years (Kapoor et al 2006). Ten of these men were insulin treated. Testosterone treatment led to a significant reduction in glycated hemoglobin (HbA1C) and fasting glucose compared to placebo. Testosterone also produced a significant reduction in insulin resistance, measured by the homeostatic model assessment (HOMA), in the fourteen non-insulin treated patients. It is not possible to measure insulin resistance in patients treated with insulin but five out of ten of these patients had a reduction of insulin dose during the study. Other significant changes during testosterone treatment in this trial were reduced total cholesterol, waist circumference and waist-hip ratio. Similarly, a placebo-controlled but non-blinded trial in 24 men with visceral obesity, diabetes, hypogonadism and mean age 57 years found that three months of oral testosterone treatment led to significant reductions in HbA1C, fasting glucose, post-prandial glucose, weight, fat mass and waist-hip ratio (Boyanov et al 2003). In contrast, an uncontrolled study of 150 mg intramuscular testosterone given to 10 patients, average age 64 years, with diabetes and hypogonadism found no significant change in diabetes control, fasting glucose or insulin levels (Corrales et al 2004). Another uncontrolled study showed no beneficial effect of testosterone treatment on insulin resistance, measured by HOMA and ‘minimal model’ of area under acute insulin response curves, in 11 patients with type 2 diabetes aged between 33 and 73 years (Lee et al 2005). Body mass index was within the normal range in this population and there was no change in waist-hip ratio or weight during testosterone treatment. Baseline testosterone levels were in the low-normal range and patients received a relatively small dose of 100 mg intramuscular testosterone every three weeks. A good increase in testosterone levels during the trial is described but it is not stated at which time during the three week cycle the testosterone levels were tested, so the lack of response could reflect an insufficient overall testosterone dose in the trial period.
Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.
Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.
The first period occurs between 4 and 6 weeks of the gestation. Examples include genital virilisation such as midline fusion, phallic urethra, scrotal thinning and rugation, and phallic enlargement; although the role of testosterone is far smaller than that of dihydrotestosterone. There is also development of the prostate gland and seminal vesicles.
Testosterone is most commonly associated with sex drive in men. It also affects mental health, bone and muscle mass, fat storage, and red blood cell production. Abnormally low or high levels can affect a man’s mental and physical health. Your doctor can check your testosterone levels with a simple blood test. Testosterone therapy is available to treat men with low levels of testosterone. If you have low T, ask your doctor if this type of therapy might benefit you.
Replacement therapy may produce desired results, such as greater muscle mass and a stronger sex drive. However, the treatment does carry some side effects. Oily skin and fluid retention are common. The testicles may also shrink, and sperm production could decrease significantly. Some studies have found no greater risk of prostate cancer with testosterone replacement therapy, but it continues to be a topic of ongoing research.
Dr. Wyne told me that although she has seen an increase in male patients asking about low testosterone, she hasn't seen an actual increase in the condition itself. "I do see an increase in guys who are fatter," she said. "The question is whether, if you lose 15 or 20 pounds, your testosterone would revert [to normal]. We know that even 15 pounds makes a huge difference to their level. Most of these guys actually have 50 pounds to lose."
“Although having sex at 70 is not the same as having sex at 20, erectile dysfunction is not a normal part of aging,” according to Michael Feloney, MD, urologic surgeon and expert on sexual dysfunction issues at the Nebraska Medical Center in Omaha. “You should still be able to have a satisfying sex life as you age." If you are experiencing erectile dysfunction, these 10 dos and don'ts may help.
In addition to its role as a natural hormone, testosterone is used as a medication, for instance in the treatment of low testosterone levels in men and breast cancer in women. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to enhance physique and performance, for instance in athletes.
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In a recent study of male workers, men with low testosterone levels had an increased chance of severe erectile dysfunction (Kratzik et al 2005), although such a link had not been found previously (Rhoden et al 2002). Certainly erectile dysfunction is considered part of the clinical syndrome of hypogonadism, and questions regarding erectile dysfunction form part of the clinical assessment of patients with hypogonadism (Morley et al 2000; Moore et al 2004).
Erectile dysfunction, also known as ED or impotence, is the inability to attain or maintain an erection of the penis adequate for the sexual satisfaction of both partners. It can be devastating to the self-esteem of a man and of his partner. As many as 30 million American men are afflicted on a continuing basis, and transient episodes affect nearly all adult males. But nearly all men who seek treatment find some measure of relief.
Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Urological Association, Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, Western Section of the American Urological Association, Association of Clinical Research Professionals, American Society of Clinical Oncology, International Society of Urology, International Society of Urological Pathology
It is normal for a man to have five to six erections during sleep, especially during rapid eye movement (REM). Their absence may indicate a problem with nerve function or blood supply in the penis. There are two methods for measuring changes in penile rigidity and circumference during nocturnal erection: snap gauge and strain gauge. A significant proportion of men who have no sexual dysfunction nonetheless do not have regular nocturnal erections.
In a prospective study from the Prostate Cancer Prevention Trial database, Thompson et al reported that men presenting with ED had a significantly higher chance of developing a cardiovascular event over a 7-year follow-up period.  The hazard ratio was 1.45, which is in the range of risk associated with current smoking or a family history of MI.
This post can absolutely change your life, and probably help you avoid some pitfalls. Like shrunken balls. (I am not an expert in the synthetic anabolic testosterone drugs used by bodybuilders — they carry lots of risks but pack a big punch if you want to get swole. Bulletproof is all about having massive clean energy, looking good, and living a very long time…so anabolic steroids aren’t on my roadmap.)
The FDA recommends that men follow general precautions before taking a medication for ED. Men who are taking medications that contain nitrates, such as nitroglycerin, should NOT use these medications. Taking nitrates with one of these medications can lower blood pressure too much. In addition, men who take tadalafil or vardenfil should use alpha blockers with care and only as instructed by their physician, as they could result in hypotension (abnormally low blood pressure). Experts recommend that men have a complete medical history and physical examination to determine the cause of ED. Men should tell their doctor about all the medications they are taking, including over-the-counter medications.
The link between chronic disease and ED is most striking for diabetes. Men who have diabetes are two to three times more likely to have erectile dysfunction than men who do not have diabetes. Among men with erectile dysfunction, those with diabetes may experience the problem as much as 10 to 15 years earlier than men without diabetes. Yet evidence shows that good blood sugar control can minimize this risk. Other conditions that may cause ED include cardiovascular disease, atherosclerosis (hardening of the arteries), kidney disease, and multiple sclerosis. These illnesses can impair blood flow or nerve impulses throughout the body.
A related issue is the potential use of testosterone as a coronary vasodilator and anti-anginal agent. Testosterone has been shown to act as a vasodilator of coronary arteries at physiological concentrations during angiography (Webb, McNeill et al 1999). Furthermore men given a testosterone injection prior to exercise testing showed improved performance, as assessed by ST changes compared to placebo (Rosano et al 1999; Webb, Adamson et al 1999). Administration of one to three months of testosterone treatment has also been shown to improve symptoms of angina and exercise test performance (Wu and Weng 1993; English et al 2000; Malkin, Pugh, Morris et al 2004). Longer term studies are underway. It is thought that testosterone improves angina due its vasodilatory action, which occurs independently of the androgen receptor, via blockade of L-type calcium channels at the cell membrane of the vascular smooth muscle in an action similar to the dihydropyridine calcium-channel blockers such as nifedipine (Hall et al 2006).
The chemical synthesis of testosterone from cholesterol was achieved in August that year by Butenandt and Hanisch. Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, published their synthesis of testosterone. These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry. Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C19H28O2), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation.
"Stress and anxiety can adversely affect sexual performance and are common causes of erectile dysfunction,” warns Feloney. “Feelings of stress and anxiety can also lead to depression and a loss of interest in sex." It's important to get these feelings out in the open where you can deal with them. Issues that can lead to erectile dysfunction include fear from previous bad experiences with sex, family or work related stress, poor communication with your partner, and unrealistic goals and expectations.
Intramuscular testosterone injections were first used around fifty years ago. Commercially available preparations contain testosterone esters in an oily vehicle. Esterification is designed to retard the release of testosterone from the depot site into the blood because the half life of unmodified testosterone would be very short. For many years intramuscular preparations were the most commonly used testosterone therapy and this is still the case in some centers. Pain can occur at injection sites, but the injections are generally well tolerated and free of major side effects. Until recently, the available intramuscular injections were designed for use at a frequency of between weekly and once every four weeks. These preparations are the cheapest mode of testosterone treatment available, but often cause supraphysiological testosterone levels in the days immediately following injection and/or low trough levels prior to the next injection during which time the symptoms of hypogonadism may return (Nieschlag et al 1976). More recently, a commercial preparation of testosterone undecanoate for intramuscular injection has become available. This has a much longer half life and produces testosterone levels in the physiological range throughout each treatment cycle (Schubert et al 2004). The usual dose frequency is once every three months. This is much more convenient for patients but does not allow prompt cessation of treatment if a contraindication to testosterone develops. The most common example of this would be prostate cancer and it has therefore been suggested that shorter acting testosterone preparations should preferably used for treating older patients (Nieschlag et al 2005). Similar considerations apply to the use of subcutaneous implants which take the form of cylindrical pellets injected under the skin of the abdominal wall and steadily release testosterone to provide physiological testosterone levels for up to six months. Problems also include pellet extrusion and infection (Handelsman et al 1997).
But when a premenopausal woman’s testosterone levels are too high, it can lead to polycystic ovary syndrome (PCOS), a condition that increases the risk of irregular or absent menstrual cycles, infertility, excess hair growth, skin problems, and miscarriage. High levels of testosterone in women, whether caused by PCOS or by another condition, can cause serious health conditions such as insulin resistance, diabetes, high cholesterol, high blood pressure, and heart disease. (12)
The effect excess testosterone has on the body depends on both age and sex. It is unlikely that adult men will develop a disorder in which they produce too much testosterone and it is often difficult to spot that an adult male has too much testosterone. More obviously, young children with too much testosterone may enter a false growth spurt and show signs of early puberty and young girls may experience abnormal changes to their genitalia. In both males and females, too much testosterone can lead to precocious puberty and result in infertility.
The other interesting thing about the study: men’s testosterone levels were lowest in March (at the end of winter) and highest in August (at the end of summer). Sunlight affects your vitamin D production, so you have seasonal dips and peaks. Get a blood test to check your levels, and if you’re low, take a high-quality vitamin D3 supplement. If you’re going to take D3, take vitamin K2 and vitamin A with it. The three work in sync, so you want them all to be balanced. Here are my dosage recommendations.
Epidemiological studies suggest that many significant clinical findings and important disease states are linked to low testosterone levels. These include osteoporosis (Campion and Maricic 2003), Alzheimer’s disease (Moffat et al 2004), frailty, obesity (Svartberg, von Muhlen, Sundsfjord et al 2004), diabetes (Barrett-Connor 1992), hypercholesterolemia (Haffner et al 1993; Van Pottelbergh et al 2003), hypertension (Phillips et al 1993), cardiac failure (Tappler and Katz 1979; Kontoleon et al 2003) and ischemic heart disease (Barrett-Connor and Khaw 1988). The extent to which testosterone deficiency is involved in the pathogenesis of these conditions, or to which testosterone supplementation could be useful in their treatment is an area of great interest with many unanswered questions.
Erectile dysfunction is known to be associated with general health status, thus, lifestyle modification improves erectile function and decreases the rate of decline of function with aging. One year after discontinuation of smoking, patients were found to have a 25% improvement in erectile quality.16 In addition, multivariate analysis found obesity is associated with erectile dysfunction with an approximately 50% increase in ED in obese men as compared with normal weight men.17
Testosterone is used as a medication for the treatment of males with too little or no natural testosterone production, certain forms of breast cancer, and gender dysphoria in transgender men. This is known as hormone replacement therapy (HRT) or testosterone replacement therapy (TRT), which maintains serum testosterone levels in the normal range. Decline of testosterone production with age has led to interest in androgen replacement therapy. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful.
Alprostadil (also known as prostaglandin E1 [PGE1]) is the prominent known smooth-muscle dilator of the corpus cavernosum. Its mechanism of action is believed to be the promotion of intracellular accumulation of cyclic adenosine monophosphate, thereby causing decreased intracellular accumulation of calcium and resulting smooth muscle relaxation. Alprostadil can be delivered to the erectile tissue either via an intraurethral suppository that is massaged and then absorbed across the corpus spongiosum of the urethra to the corpora cavernosa, or directly injected into the corpora cavernosa. When administered urethrally, doses are substantially higher than when directly injected (typical dosing is 500 mcg to 1 mg intraurethral compared with 2.5 mcg to 20 mcg intracavernosal).
As blood levels of testosterone increase, this feeds back to suppress the production of gonadotrophin-releasing hormone from the hypothalamus which, in turn, suppresses production of luteinising hormone by the pituitary gland. Levels of testosterone begin to fall as a result, so negative feedback decreases and the hypothalamus resumes secretion of gonadotrophin-releasing hormone.
The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
When Solvay Pharmaceuticals, maker of market-dominating Androgel, launched its "Low T" campaign, in 2008, it claimed that 13 million American men over age 45 suffered from low testosterone, 90 percent of them undiagnosed. Its website, IsItLowT.com, showed dumpy, depressed men and their unhappy spouses remembering how it "used to be." Why settle for dumpiness and depression, the website and related TV ads suggested, when a little dab'll do you?
Erectile dysfunction (ED) is commonly called impotence. It’s a condition in which a man can’t achieve or maintain an erection during sexual performance. Symptoms may also include reduced sexual desire or libido. Your doctor is likely to diagnose you with ED if the condition lasts for more than a few weeks or months. ED affects as many as 30 million men in the United States.
Over a 2-year period, a third of the men randomized to a weight loss program demonstrated resolution of erectile dysfunction.10 A Mediterranean diet and nutritional counseling reported increased erectile quality.18 Little evidence supports that increased physical activity alone improves erectile quality; however, the strong association between physical activity and lower BMI is well described, and therefore recommended for men with erectile dysfunction and without a contraindication to physical activity.
A large number of side-effects have been attributed to testosterone. In our clinical experience, the incidence of significant adverse effects with treatment producing physiological testosterone levels is low, and many side effects attributed to testosterone are mainly relevant to supraphysiological replacement. Some adverse effects are specific to a given mode of delivery and have already been described. Potential adverse effects concerning the prostate have also been discussed and require appropriate monitoring of symptoms, PSA and digital rectal examination. Other tumors which may be androgen responsive include cancer of the breast and primary liver tumors, and these are both contraindications to testosterone treatment
^ Jump up to: a b Sapienza P, Zingales L, Maestripieri D (September 2009). "Gender differences in financial risk aversion and career choices are affected by testosterone". Proceedings of the National Academy of Sciences of the United States of America. 106 (36): 15268–73. Bibcode:2009PNAS..10615268S. doi:10.1073/pnas.0907352106. PMC 2741240. PMID 19706398.
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
Other side effects include increased risk of heart problems in older men with poor mobility, according to a 2009 study at Boston Medical Center. A 2017 study published in JAMA found that treatments increase coronary artery plaque volume. Additionally, the Food and Drug Administration (FDA) requires manufactures to include a notice on the labeling that states taking testosterone treatments can lead to possible increased risk of heart attacks and strokes. The FDA recommends that patients using testosterone should seek medical attention right away if they have these symptoms:
More can be learned from a large, randomized, placebo-controlled trial of finasteride treatment in 18,800 men aged 55 or more. Finasteride is a 5α-reductase inhibitor which acts to prevent the metabolism of testosterone to dihydrotestosterone (DHT) – the most active androgen in the prostate. The trial showed a greater overall incidence of prostate cancer in the control group, but men treated with finasteride were more likely to have high grade tumors (Thompson et al 2003), suggesting that reduced androgen exposure of the prostate may delay the presentation of prostate cancer and/or promote advanced disease in some other way.
In one study, 9.6% reported ‘occasional’ erectile dysfunction, 8.9% reported erectile dysfunction occurring ‘often’, and 18.6% reported erectile dysfunction occurring ‘all the time’. Of these, only 11.6% had received treatment.In another study, only 14.1% of men reported that they had received treatment, despite experiencing erectile dysfunction for longer than 12 months.
There is a dirty little secret about testosterone cream that almost no one knows, and I’m going to share it here. Please don’t abuse it. If you take a vanishingly small dose of testosterone cream and apply it to your labia and the vulva (or your partner’s), you will witness a form of vasodilation rarely seen no matter how good you are in bed. It has a profound local effect and will produce a night you won’t forget for years.
Think of erectile dysfunction as your body’s “check engine light.” The blood vessels in the penis are smaller than other parts of the body, so underlying conditions like blocked arteries, heart disease, or high blood pressure usually show up as ED before something more serious like a heart attack or stroke. ED is your body’s way of saying, “Something is wrong.” And the list of things that cause erectile dysfunction can include: