Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified. The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells. In the corpora cavernosa, NO activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.

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.


There are treatments available to help you to get and maintain an erection. In addition, making healthy changes to your lifestyle could help with impotence. Switching to a healthier balanced diet, taking more exercise and cutting down on or giving up alcohol and cigarettes could help you to see an improvement in sexual function. If you think that the problem may be related to stress or anxiety, counselling can also help.

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The normal development of the prostate gland is dependent on the action of testosterone via the androgen receptor, and abnormal biosynthesis of the hormone or inactivating mutations of the androgen receptor are associated with a rudimentary prostate gland. Testosterone also requires conversion to dihydrotestosterone in the prostate gland for full activity. In view of this link between testosterone and prostate development, it is important to consider the impact that testosterone replacement may have on the prevalence and morbidity associated with benign prostatic hypertrophy (BPH) and prostate cancer, which are the common conditions related to pathological growth of the prostate gland.
Saw palmetto: Uses, dosage, and side effects Saw palmetto is an extract from the berries of a type of palm tree. The berries have traditionally been used to ease urinary and reproductive problems. The extract is now used in herbal remedies to stabilize testosterone. Learn about its use, its effectiveness, the science behind the claims, and any side effects. Read now
Most men may not openly talk about their erection problems, but erectile dysfunction — when a man cannot achieve or maintain an erection well enough or long enough to have satisfying sex — is very common. According to the National Institutes of Health, 5 percent of 40-year-olds and 15 to 25 percent of 65-years old have ED. But while ED is more likely to occur as a man gets older, it doesn’t come automatically with age.
Transdermal preparations of testosterone utilize the fact that the skin readily absorbs steroid hormones. Initial transdermal preparations took the form of scrotal patches with testosterone loaded on to a membranous patch. Absorption from the scrotal skin was particularly good and physiological levels of testosterone with diurnal variation were reliably attained. The scrotal patches are now rarely used because they require regular shaving or clipping of scrotal hair and because they produce rather high levels of dihydrotestosterone compared to testosterone (Behre et al 1999). Subsequently, non-scrotal patches were developed but the absorptive capacity of non-scrotal skin is much lower, so these patches contain additional chemicals which enhance absorption. The non-scrotal skin patches produce physiological testosterone levels without supraphysiological dihydrotestosterone levels. Unfortunately, the patches produce a high rate of local skin reactions often leading to discontinuation (Parker and Armitage 1999). In the last few years, transdermal testosterone gel preparations have become available. These require daily application by patients and produce steady state physiological testosterone levels within a few days in most patients (Swerdloff et al 2000; Steidle et al 2003). The advantages compared with testosterone patches include invisibility, reduced skin irritation and the ability to adjust dosage, but concerns about transfer to women and children on close skin contact necessitate showering after application or coverage with clothes.
Unlike women, who experience a rapid drop in hormone levels at menopause, men experience a more gradual decrease of testosterone levels over time. The older the man, the more likely he is to experience below-normal testosterone levels. Men with testosterone levels below 300 ng/dL may experience some degree of low T symptoms. Your doctor can conduct a blood test and recommend treatment if needed. They can discuss the potential benefits and risks of testosterone medication, as well.
The prevalence of biochemical testosterone deficiency increases with age. This is partly due to decreasing testosterone levels associated with illness or debility but there is also convincing epidemiological data to show that serum free and total testosterone levels also fall with normal aging (Harman et al 2001; Feldman et al 2002). The symptoms of aging include tiredness, lack of energy, reduced strength, frailty, loss of libido, decreased sexual performance depression and mood change. Men with hypogonadism experience similar symptoms. This raises the question of whether some symptoms of aging could be due to relative androgen deficiency. On the other hand, similarities between normal aging and the symptoms of mild androgen deficiency make the clinical diagnosis of hypogonadism in aging men more challenging.

Following a detailed discussion about the history of erectile dysfunction and its risk factors, your doctor will examine the testicles and penis to help determine the cause of erectile dysfunction. Your doctor will check reflexes and pulses in the area to see if problems with blood vessels or nerves are contributing to the erectile dysfunction. If necessary, your doctor will order tests to help diagnose erectile dysfunction.

ICI therapy often produces a reliable erection, which comes down after 20-30 minutes or with climax. Since the ICI erection is not regulated by your penile nerves, you should not be surprised if the erection lasts after orgasm. The most common side effect of ICI therapy is a prolonged erection. Prolonged erections (>1 hour) can be reversed by a second injection (antidote) in the office.

The second theory is similar and is known as "evolutionary neuroandrogenic (ENA) theory of male aggression".[78][79] Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible.[78] The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. Higher pre-natal testosterone indicated by a low digit ratio as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game.[80] Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males.[81][82][83][84][85]
Does drinking water improve erectile dysfunction? Erectile dysfunction or ED is a common concern for men. Everyday factors, such as hydration levels, may affect a person's ability to get or maintain an erection. Drinking water may, therefore, help some men with ED. In this article, learn about the link between hydration and ED, and other factors that can cause ED. Read now
Erectile dysfunction (ED) affects 50% of men older than 40 years, [4] exerting substantial effects on quality of life. [5] This common problem is complex and involves multiple pathways. Penile erections are produced by an integration of physiologic processes involving the central nervous, peripheral nervous, hormonal, and vascular systems. Any abnormality in these systems, whether from medication or disease, has a significant impact on the ability to develop and sustain an erection, ejaculate, and experience orgasm.
Although not proven, it is likely that erectile dysfunction can be prevented by good general health, paying particular attention to body weight, exercise, and cigarette smoking. For example, heart disease and diabetes are problems that can cause erectile dysfunction, and both are preventable through lifestyle changes such as sensible eating and regular exercise. Furthermore, early diagnosis and treatment of associated conditions like diabetes, hypertension and high cholesterol may prevent or delay erectile dysfunction, or stop the erectile dysfunction from getting more serious.
Another effect that can limit treatment is polycythemia, which occurs due to various stimulatory effects of testosterone on erythropoiesis (Zitzmann and Nieschlag 2004). Polycythemia is known to produce increased rates of cerebral ischemia and there have been reports of stroke during testosterone induced polycythaemia (Krauss et al 1991). It is necessary to monitor hematocrit during testosterone treatment, and hematocrit greater than 50% should prompt either a reduction of dose if testosterone levels are high or high-normal, or cessation of treatment if levels are low-normal. On the other hand, late onset hypogonadism frequently results in anemia which will then normalize during physiological testosterone replacement.
One study examined the role of testosterone supplementation in hypogonadal men with ED. These men were considered nonresponders to sildenafil, and their erections were monitored by assessing nocturnal penile tumescence (NPT). After these men were given testosterone transdermally for 6 months, the number of NPTs increased, as did the maximum rigidity with sildenafil. [18] This study suggests that a certain level of testosterone may be necessary for PDE5 inhibitors to function properly.
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.
A physical exam checks your total health. Examination focusing on your genitals (penis and testicles) is often done to check for ED. Based on your age and risk factors, the exam may also focus on your heart and blood system: heart, peripheral pulses and blood pressure. Based on your age and family history your doctor may do a rectal exam to check the prostate. These tests are not painful. Most patients do not need a lot of testing before starting treatment.
Dr. Fugh-Berman said these campaigns encourage men to "ask your doctor" whether their weight gain, falling asleep after dinner, reduced energy, and diminished sex drive are due to "Low T." At the same time, the companies are working other angles to influence doctors' prescribing practices through industry-sponsored continuing medical education (CME) courses and sponsored medical journal articles. They have even created a respectable-sounding journal called The Aging Male. Fugh-Berman said all these channels "are being used to persuade doctors they should be treating this."
Testosterone does a lot more than you’d think, whether we’re talking about male or female biology. It’s the hormone that helps you burn fat, build muscle [1], and increase your sex drive [2], and its power doesn’t stop there. Keeping your testosterone levels in a normal range can make you happier, too [3], and testosterone can even improve your cardiovascular health and decrease your risk of mortality (from all causes!), according to a study of 83,000 older men who underwent testosterone replacement therapy [4].

Even before the study yields its findings, Dr. Swerdloff said a few important points should be emphasized. "I want to make it clear that this is not a made-up disease," he said. "It is well known in younger men that if you have a failure to produce normal testosterone, there are certain signs and symptoms that create a kind of syndrome. Treatment for low testosterone has been documented to be beneficial."


They also don't make clear how risky exposure to testosterone gel is for others—female partners, children, even pets. The gel is actually notorious for transferring to others. It can cause excess hair to grow on women's faces and arms, deepen their voices, interrupt menstruation, and make them anxious and irritable. In children, exposure to testosterone gels and creams can cause premature puberty and aggression. And in pets, it can cause aggressive behavior and enlargement of the genitalia.
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

Before assessing the evidence of testosterone’s action in the aging male it is important to note certain methodological considerations which are common to the interpretation of any clinical trial of testosterone replacement. Many interventional trials of the effects of testosterone on human health and disease have been conducted. There is considerable heterogenicity in terms of study design and these differences have a potential to significantly affect the results seen in various studies. Gonadal status at baseline and the testosterone level produced by testosterone treatment in the study are of particular importance because the effects of altering testosterone from subphysiological to physiological levels may be different from those of altering physiological levels to supraphysiological. Another important factor is the length of treatment. Randomised controlled trials of testosterone have ranged from one to thirty-six months in duration (Isidori et al 2005) although some uncontrolled studies have lasted up to 42 months. Many effects of testosterone are thought to fully develop in the first few months of treatment but effects on bone, for example, have been shown to continue over two years or more (Snyder et al 2000; Wang, Cunningham et al 2004).

Even before the study yields its findings, Dr. Swerdloff said a few important points should be emphasized. "I want to make it clear that this is not a made-up disease," he said. "It is well known in younger men that if you have a failure to produce normal testosterone, there are certain signs and symptoms that create a kind of syndrome. Treatment for low testosterone has been documented to be beneficial."

These "disease-awareness" campaigns—ostensibly a public service intended to educate those potentially at risk about a condition they may not even have heard of but "could" have—are subtle, even insidious. They may not mention a specific product, but a bit of sleuthing reveals that their sponsors are usually pharmaceutical companies that "just happen" to manufacture products used to treat the real (or at least alleged) condition.
Treatment involves addressing the underlying causes, lifestyle modifications, and addressing psychosocial issues.[1] In many cases, a trial of pharmacological therapy with a PDE5 inhibitor, such as sildenafil, can be attempted. In some cases, treatment can involve inserting prostaglandin pellets into the urethra, injecting smooth muscle relaxants and vasodilators into the penis, a penile prosthesis, a penis pump, or vascular reconstructive surgery.[1][2] It is the most common sexual problem in men.[3]
Most studies support a link between adult criminality and testosterone, although the relationship is modest if examined separately for each sex. Nearly all studies of juvenile delinquency and testosterone are not significant. Most studies have also found testosterone to be associated with behaviors or personality traits linked with criminality such as antisocial behavior and alcoholism. Many studies have also been done on the relationship between more general aggressive behavior/feelings and testosterone. About half the studies have found a relationship and about half no relationship.[66]
The largest amounts of testosterone (>95%) are produced by the testes in men,[2] 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.[122] In the testes, testosterone is produced by the Leydig cells.[123] 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).

Several treatments were promoted in the pre-PGE1, pre-prostaglandin era, including yohimbine, trazodone, testosterone, and various herbal remedies. None of these is currently recommended under the updated American Urological Association Guidelines for the Treatment of Erectile Dysfunction.15 Testosterone supplementation is only recommended for men with low testosterone levels.

Research has even found possible links to frequent ejaculation and a lower risk of prostate cancer. In one study of 32,000 men published in 2016 in the journal European Urology, for example, men who ejaculated at least 21 times per month while in their 20s were less likely to be diagnosed with prostate cancer than those who ejaculated four to seven times per month. And men who ejaculated more often in their 40s were 22 percent less likely to get a prostate cancer diagnosis.
Erectile dysfunction - (ED) or impotence is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual activity. A penile erection is the hydraulic effect of blood entering and being retained in sponge-like bodies within the penis. The process is most often initiated as a result of sexual arousal, when signals are transmitted from the brain to nerves in the penis.
Androgens may modulate the physiology of vaginal tissue and contribute to female genital sexual arousal.[48] Women's level of testosterone is higher when measured pre-intercourse vs pre-cuddling, as well as post-intercourse vs post-cuddling.[49] There is a time lag effect when testosterone is administered, on genital arousal in women. In addition, a continuous increase in vaginal sexual arousal may result in higher genital sensations and sexual appetitive behaviors.[50]
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.
There are risks to prosthetic surgery and patients are counselled before the procedure. If there is a post-operative infection, the implant will likely be removed. The devices are reliable, but in the case of mechanical malfunction, the device or a part of the device will need to be replaced surgically. If a penile prosthesis is removed, other non-surgical treatments may no longer work.
The partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone's effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon's group[183] was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. The period of the early 1930s to the 1950s has been called "The Golden Age of Steroid Chemistry",[184] and work during this period progressed quickly. Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and well-being.[185]
Psychological Causes of ED – Between 10% and 20% of ED cases have a psychological cause. Because arousal starts in the brain, psychological issues can be a significant contributing factor to erectile dysfunction. Mental health conditions like depression or anxiety can negatively impact your libido, making it more difficult for you to become aroused.
Currently available testosterone preparations in common use include intramuscular injections, subcutaneous pellets, buccal tablets, transdermal gels and patches (see Table 2). Oral testosterone is not widely used. Unmodified testosterone taken orally is largely subject to first-pass metabolism by the liver. Oral doses 100 fold greater than physiological testosterone production can be given to achieve adequate serum levels. Methyl testosterone esters have been associated with hepatotoxicity. There has been some use of testosterone undecanoate, which is an esterified derivative of testosterone that is absorbed via the lymphatic system and bypasses the liver. Unfortunately, it produces unpredictable testosterone levels and increases testosterone levels for only a short period after each oral dose (Schurmeyer et al 1983).
Dr Kenny du Toit is a urologist practicing in Rondebosch, Cape Town. He is also consultant at Tygerberg hospital, where he is a senior lecturer at Stellenbosch University. He is a member of the South African Urological Association, Colleges of Medicine South Africa and Société Internationale d’Urologie. Board registered with both the HPCSA (Health professions council of South Africa) and GMC (General medical council UK). He has a keen interest in oncology, kidney stones and erectile dysfunction.http://www.dutoiturology.co.za
If you’re experiencing psychological ED, you may benefit from talk therapy. Therapy can help you manage your mental health. You’ll likely work with your therapist over several sessions, and your therapist will address things like major stress or anxiety factors, feelings around sex, or subconscious conflicts that could be affecting your sexual well-being.

In order to establish whether normal erections are occurring overnight (nocturnal erections), the doctor may organise nocturnal penile tumescence (NPT) testing. This involves wearing a monitor overnight in your own home. The data from this monitor is then assessed to analyse how often erections occurred, how long they lasted, and how rigid and large the penis was during the erections. If NPT testing is normal, the cause of erectile dysfunction is usually psychological. If not, further testing of the blood flow in the genital area may be required to see if there is blockage or leakage. The doctor may also organise a blood test of levels of hormones such as testosterone, prolactin and thyroid stimulating hormone to see if these are contributing to the erectile dysfunction.
Overall there is evidence that testosterone treatment increases lean body mass and reduces obesity, particularly visceral obesity, in a variety of populations including aging men. With regard to muscle changes, some studies demonstrate improvements in maximal strength but the results are inconsistent and it has not been demonstrated that these changes lead to clinically important improvements in mobility, endurance or quality of life. Studies are needed to clarify this. Changes in abdominal obesity are particularly important as visceral fat is now recognised as predisposing the metabolic syndrome, diabetes and cardiovascular disease.
Late onset hypogonadism reflects a particular pathophysiology and it may not be appropriate to extrapolate results from studies concerning the effects of testosterone in treating hypogonadism of other etiology to aging males. For this reason, the age of men treated in clinical trials is certainly relevant. Other important factors include patient comorbidities and the preparation and route of testosterone replacement used in the study, which can affect the production of estrogen and dihydrotestosterone, testosterone’s active metabolites
Mood disturbance and dysthymia are part of the clinical syndrome of hypogonadism. Epidemiological studies have found a positive association between testosterone levels and mood, and depressed aging males have lower testosterone levels than controls (Barrett-Connor, Von Muhlen et al 1999). Furthermore, induction of a hypogonadal state during treatment of men for prostate cancer leads to an increase in depression scores (Almeida et al 2004). Trials of testosterone treatment effects on mood have varied in outcome. Data on the effects on men with depression are conflicting (Seidman et al 2001; Pope et al 2003) but there is evidence that testosterone treatment of older hypogonadal men does result in improvements in mood (Wang et al 1996) and that this may occur through changes in regional brain perfusion (Azad et al 2003).
Research has even found possible links to frequent ejaculation and a lower risk of prostate cancer. In one study of 32,000 men published in 2016 in the journal European Urology, for example, men who ejaculated at least 21 times per month while in their 20s were less likely to be diagnosed with prostate cancer than those who ejaculated four to seven times per month. And men who ejaculated more often in their 40s were 22 percent less likely to get a prostate cancer diagnosis.

The medications are extremely effective, which is very good. And the medications are, for the most part, extremely well-tolerated. But there are, like with any medications, a potential downside. The one absolute downside to the use of any of these erection what we call PDE5 medications is if a patient is using a nitroglycerin medication. And nitroglycerins are used for heart disease and for angina, for the most part, although there are some recreational uses of nitrites. And that’s important because your blood vessels will dilate and your blood pressure will drop. And that is an absolute contraindication.
Epidemiological studies have also assessed links between serum testosterone and non-coronary atherosclerosis. A study of over 1000 people aged 55 years and over found an inverse correlation between serum total and bioavailable testosterone and the amount of aortic atherosclerosis in men, as assessed by radiological methods (Hak et al 2002). Increased intima-media thickness (IMT) is an early sign of atherosclerosis and has also been shown to predict cardiovascular mortality (Murakami et al 2005). Cross-sectional studies have found that testosterone levels are negatively correlated with carotid IMT in independently living men aged 74–93 years (van den Beld et al 2003), diabetic men (Fukui et al 2003) and young obese men (De Pergola et al 2003). A 4-year follow up study of the latter population showed that free testosterone was also inversely correlated with the rate of increase of IMT (Muller et al 2004).
Some anti-aging physicians also use sublingual ( taken under the tongue) forms of non-bioidentical testosterone like oxandrolone. I took oxandrolone with a physician’s guidance for about two weeks, and I got pimples and hair loss. I quit and was bummed that it didn’t generate enough impact to write a blog post about it. I have continued to recommend bioidentical testosterone since.
Testosterone is a steroid from the androstane class containing a keto and hydroxyl groups at the three and seventeen positions respectively. It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites.[5] It exerts its action through binding to and activation of the androgen receptor.[5] In humans and most other vertebrates, testosterone is secreted primarily by the testicles of males and, to a lesser extent, the ovaries of females. On average, in adult males, levels of testosterone are about 7 to 8 times as great as in adult females.[6] As the metabolism of testosterone in males is greater, the daily production is about 20 times greater in men.[7][8] Females are also more sensitive to the hormone.[9]
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