Male hypogonadism becomes more common with increasing age and is currently an under-treated condition. The diagnosis of hypogonadism in the aging male requires a combination of symptoms and low serum testosterone levels. The currently available testosterone preparations can produce consistent physiological testosterone levels and provide for patient preference.
This evidence, together with the beneficial effects of testosterone replacement on central obesity and diabetes, raises the question whether testosterone treatment could be beneficial in preventing or treating atherosclerosis. No trial of sufficient size or duration has investigated the effect of testosterone replacement in primary or secondary prevention cardiovascular disease. The absence of such data leads us to examine the relationship of testosterone to other cardiovascular risk factors, such as adverse lipid parameters, blood pressure, endothelial dysfunction, coagulation factors, inflammatory markers and cytokines. This analysis can supply evidence of the likely effects of testosterone on overall cardiovascular risk. This has limitations, however, including the potential for diverging effects of testosterone on the various factors involved and the resultant impossibility of accurately predicting the relative impact of such changes.
Studies of the effects on cognition of testosterone treatment in non-cognitively impaired eugonadal and hypogonadal ageing males have shown varying results, with some showing beneficial effects on spatial cognition (Janowsky et al 1994; Cherrier et al 2001), verbal memory (Cherrier et al 2001) and working memory (Janowsky et al 2000), and others showing no effects (Sih et al 1997; Kenny et al 2002). Other trials have examined the effects of testosterone treatment in older men with Alzheimer’s disease or cognitive decline. Results have been promising, with two studies showing beneficial effects of testosterone treatment on spatial and verbal memory (Cherrier et al 2005b) and cognitive assessments including visual-spatial memory (Tan and Pu 2003), and a recent randomized controlled trial comparing placebo versus testosterone versus testosterone and an aromatase inhibitor suggesting that testosterone treatment improves spatial memory directly and verbal memory after conversion to estrogen (Cherrier et al 2005a). Not all studies have shown positive results (Kenny et al 2004; Lu et al 2005), and variations could be due to the different measures of cognitive abilities that were used and the cognitive state of men at baseline. The data from clinical trials offers evidence that testosterone may be beneficial for certain elements of cognitive function in the aging male with or without cognitive decline. Larger studies are needed to confirm and clarify these effects.
If a young man's low testosterone is a problem for a couple trying to get pregnant, gonadotropin injections may be an option in some cases. These are hormones that signal the body to produce more testosterone. This may increase the sperm count. Hedges also describes implantable testosterone pellets, a relatively new form of treatment in which several pellets are placed under the skin of the buttocks, where they release testosterone over the course of about three to four months. Injections and nasal gels may be other options for some men.

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).
Epidemiological data has associated low testosterone levels with atherogenic lipid parameters, including lower HDL cholesterol (Lichtenstein et al 1987; Haffner et al 1993; Van Pottelbergh et al 2003) and higher total cholesterol (Haffner et al 1993; Van Pottelbergh et al 2003), LDL cholesterol (Haffner et al 1993) and triglyceride levels (Lichtenstein et al 1987; Haffner et al 1993). Furthermore, these relationships are independent of other factors such as age, obesity and glucose levels (Haffner et al 1993; Van Pottelbergh et al 2003). Interventional trails of testosterone replacement have shown that treatment causes a decrease in total cholesterol. A recent meta-analysis of 17 randomized controlled trials confirmed this and found that the magnitude of changes was larger in trials of patients with lower baseline testosterone levels (Isidori et al 2005). The same meta-analysis found no significant overall change in LDL or HDL cholesterol levels but in trials with baseline testosterone levels greater than 10 nmol/l, there was a small reduction in HDL cholesterol with testosterone treatment.
These are not currently approved by the FDA for ED management, but they may be offered through research studies (clinical trials). Patients who are interested should discuss the risks and benefits (informed consent) of each, as well as costs before starting any clinical trials. Most therapies not approved by the FDA are not covered by government or private insurance benefits.
"Some say it's just a part of aging, but that's a misconception," says Jason Hedges, MD, PhD, a urologist at Oregon Health and Science University in Portland. A gradual decline in testosterone can't explain a near-total lack of interest in sex, for example. And for Hedges' patients who are in their 20s, 30s, and early 40s and having erectile problems, other health problems may be a bigger issue than aging.
Low testosterone levels can cause mood disturbances, increased body fat, loss of muscle tone, inadequate erections and poor sexual performance, osteoporosis, difficulty with concentration, memory loss and sleep difficulties. Current research suggests that this effect occurs in only a minority (about 2%) of ageing men. However, there is a lot of research currently in progress to find out more about the effects of testosterone in older men and also whether the use of testosterone replacement therapy would have any benefits.
Patients receiving penile prostheses should be instructed in the operation of the prosthesis before surgery and again in the postoperative period. The prosthesis usually is not activated until approximately 6 weeks after surgery, so as to allow the edema and pain to subside. The prosthesis is checked in the office before the patient begins to use it.

Cross-sectional studies conducted at the time of diagnosis of BPH have failed to show consistent differences in testosterone levels between patients and controls. A prospective study also failed to demonstrate a correlation between testosterone and the development of BPH (Gann et al 1995). Clinical trials have shown that testosterone treatment of hypogonadal men does cause growth of the prostate, but only to the size seen in normal men, and also causes a small increase in prostate specific antigen (PSA) within the normal range (Rhoden and Morgentaler 2005). Despite growth of the prostate a number of studies have failed to detect any adverse effects on symptoms of urinary obstruction or physiological measurements such as flow rates and residual volumes (Snyder et al 1999; Kenny et al 2000, 2001). Despite the lack of evidence linking symptoms of BPH to testosterone treatment, it remains important to monitor for any new or deteriorating problems when commencing patients on testosterone treatment, as the small growth of prostate tissue may adversely affect a certain subset of individuals.


^ Jump up to: a b Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S (April 2017). "Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe". The Journal of Clinical Endocrinology and Metabolism. 102 (4): 1161–1173. doi:10.1210/jc.2016-2935. PMC 5460736. PMID 28324103.
While testosterone stimulates a man’s sex drive, it also aids in achieving and maintaining an erection. Testosterone alone doesn’t cause an erection, but it stimulates receptors in the brain to produce nitric oxide. Nitric oxide is a molecule that helps trigger a series of chemical reactions necessary for an erection to occur. When testosterone levels are too low, a man may have difficulty achieving an erection prior to sex or having spontaneous erections (for example, during sleep).
Hypogonadism (as well as age-related low testosterone) is diagnosed with blood tests that measure the level of testosterone in the body. The Endocrine Society recommends testing for suspected low T with a total testosterone test. It may be performed in the morning when testosterone levels tend to be highest in young men, although this isn't necessarily the case in older men. The test may be repeated on another day if the results show a low T level. (5)
Cross-sectional studies have not shown raised testosterone levels at the time of diagnosis of prostate cancer, and in fact, low testosterone at the time of diagnosis has been linked with more locally aggressive and malignant tumors (Massengill et al 2003; Imamoto et al 2005; Isom-Batz et al 2005). This may reflect loss of hormone related control of the tumor or the effect of a more aggressive tumor in decreasing testosterone levels. One study found that 14% of hypogonadal men, with normal digital rectal examination and PSA levels, had histological prostate cancer on biopsy. It is possible that low androgen levels masked the usual evidence of prostate cancer in this population (Morgentaler et al 1996). Most longitudinal studies have not shown a correlation between testosterone levels and the future development of prostate cancer (Carter et al 1995; Heikkila et al 1999; Stattin et al 2004) but a recent study did find a positive association (Parsons et al 2005). Interpretation of such data requires care, as the presentation of prostate cancer could be altered or delayed in patients with lower testosterone levels.
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.
Dr. Adriane Fugh-Berman, associate professor of pharmacology and director of the industry watchdog group PharmedOut.org at Georgetown University School of Medicine, calls this kind of direct-to-consumer pharmaceutical advertising "evil." She likened the efforts to sell TRT to earlier campaigns to push hormone replacement therapy for post-menopausal women. "They stole the playbook," she said. "This hormone is being thrown around like sugar water." 

In rare cases, the drug Viagra ® can cause blue-green shading to vision that lasts for a short time. In rare cases, the drug Cialis® can cause or increase back pain or aching muscles in the back. In most cases, the side effects are linked to PDE5 inhibitor effects on other tissues in the body, meaning they are working to increase blood flow to your penis and at the same time impacting other vascular tissues in your body. These are not ‘allergic reactions'.
Patients receiving penile prostheses should be instructed in the operation of the prosthesis before surgery and again in the postoperative period. The prosthesis usually is not activated until approximately 6 weeks after surgery, so as to allow the edema and pain to subside. The prosthesis is checked in the office before the patient begins to use it. 

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.
The group's 2010 clinical practice guidelines make it clear that "the threshold testosterone level below which symptoms of androgen deficiency and adverse health outcomes occur and testosterone administration improves outcomes in the general population is not known." They also clearly advise against screening men in the general population to avoid "labeling and medicalization of otherwise healthy men for whom testing, treatment, and monitoring would represent a burden with unclear benefit."
The symptoms of erectile dysfunction include difficulty achieving an erection, trouble maintaining an erection, and a reduced interest in sex. Because male sexual arousal is a fairly complex process, it can sometimes be difficult to identify a specific cause. Arousal starts in the brain but it also involves the nerves, muscles, and blood vessels and can be impacted by hormones and emotions. If a problem develops with any of these things, erectile dysfunction could be the consequence.
Findings that improvements in serum glucose, serum insulin, insulin resistance or glycemic control, in men treated with testosterone are accompanied by reduced measures of central obesity, are in line with other studies showing a specific effect of testosterone in reducing central or visceral obesity (Rebuffe-Scrive et al 1991; Marin, Holmang et al 1992). Furthermore, studies that have shown neutral effects of testosterone on glucose metabolism have not measured (Corrales et al 2004), or shown neutral effects (Lee et al 2005) (Tripathy et al 1998; Bhasin et al 2005) on central obesity. Given the known association of visceral obesity with insulin resistance, it is possible that testosterone treatment of hypogonadal men acts to improve insulin resistance and diabetes through an effect in reducing central obesity. This effect can be explained by the action of testosterone in inhibiting lipoprotein lipase and thereby reducing triglyceride uptake into adipocytes (Sorva et al 1988), an action which seems to occur preferentially in visceral fat (Marin et al 1995; Marin et al 1996). Visceral fat is thought to be more responsive to hormonal changes due to a greater concentration of androgen receptors and increased vascularity compared with subcutaneous fat (Bjorntorp 1996). Further explanation of the links between hypogonadism and obesity is offered by the hypogonadal-obesity-adipocytokine cycle hypothesis (see Figure 1). In this model, increases in body fat lead to increases in aromatase levels, in addition to insulin resistance, adverse lipid profiles and increased leptin levels. Increased action of aromatase in metabolizing testosterone to estrogen, reduces testosterone levels which induces further accumulation of visceral fat. Higher leptin levels and possibly other factors, act at the pituitary to suppress gonadotrophin release and exacerbate hypogonadism (Cohen 1999; Kapoor et al 2005). Leptin has also been shown to reduce testosterone secretion from rodent testes in vitro (Tena-Sempere et al 1999). A full review of the relationship between testosterone, insulin resistance and diabetes can be found elsewhere (Kapoor et al 2005; Jones 2007).
Conditions that may be associated with ED include diabetes, [25, 26, 27] hypertension, [28] , and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [29] , sleep apnea [30] , COPD, [31] and depression (see Table 1 below). [32, 33, 34, 35] In fact, almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient’s psychological mood and behavior.
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.

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.


Dr. Wyne, in Houston, said, "When I hear a catchy little phrase, or someone is trying to get us to use a drug that is not based on clinical data, the cynical part of me asks where did it come from." She added, "There is a very important role for testosterone replacement therapy. It's wonderful that we have all these options, but we need to be using them appropriately, in a safe and efficacious manner."
The aim of treatment for hypogonadism is to normalize serum testosterone levels and abolish symptoms or pathological states that are due to low testosterone levels. The exact target testosterone level is a matter of debate, but current recommendations advocate levels in the mid-lower normal adult range (Nieschlag et al 2005). Truly physiological testosterone replacement would require replication of the diurnal rhythm of serum testosterone levels, but there is no current evidence that this is beneficial (Nieschlag et al 2005).
In the U.S., where millions watch the Super Bowl simply to see the clever and costly commercials, and where pharmaceuticals with potentially deadly side effects are pushed on the public at every turn, it's probably not surprising that ads for "Low T" are now splayed across billboards in Florida, with its huge number of older residents, or that a chain of "Low T Centers" has sprung up in Texas and around the heartland.
The Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)".[177] They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The structure was worked out by Schering's Adolf Butenandt, at the Chemisches Institut of Technical University in Gdańsk.[178][179]

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.
The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina; it is now mostly replaced by more precise terms, such as erectile dysfunction (ED). The study of ED within medicine is covered by andrology, a sub-field within urology. Research indicates that ED is common, and it is suggested that approximately 40% of males experience symptoms compatible with ED, at least occasionally.[38] The condition is also on occasion called phallic impotence.[39] Its antonym, or opposite condition, is priapism.[40][41]
Medications for erectile dysfunction don't work for everyone and may cause side effects that make a particular drug hard to take. "Work with your doctor to find the right treatment. There are still options for people who fail at medical treatment," advises Feloney. Alternatives to erectile dysfunction drugs include vacuum pump devices, medications injected into the penis, testosterone replacement if needed, and a surgical penile implant.
I’m telling you all of this because no matter who you are, keeping your testosterone levels balanced is more important now than ever before. Modern living has not been kind to our hormones. In American men, serum testosterone levels have declined by about 1% each year for the past 30 years [5], and you can make a few educated guesses about why. Hormone-disrupting chemicals are more prevalent than ever before, physical activity is less and less common, veganism is popular (I was a raw vegan for a while), and many doctors insist on pushing a low-fat, low-cholesterol diet for health (by the way, the concept of a low-fat diet began in the mid-70s, shortly before the nationwide testosterone decline. It could be a coincidence, but I doubt it).

For some men who are aging, the idea of testosterone replacement therapy seems like an enticing option. Effects such as increased vigour, increased muscle strength, enhanced memory, sharpened concentration, a boost in libido and increased energy levels can make this drug seem like the miracle anti-aging therapy. However, it is unclear whether or not this therapy can offer any health benefits to men who simply have a normal age-related decline in testosterone. Few large studies have examined the effects of this therapy in men who have a healthy testosterone level and the few smaller studies that have been conducted reveal conflicting results.
Studies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. When testosterone-deprived rats were given medium levels of testosterone, their sexual behaviors (copulation, partner preference, etc.) resumed, but not when given low amounts of the same hormone. Therefore, these mammals may provide a model for studying clinical populations among humans suffering from sexual arousal deficits such as hypoactive sexual desire disorder.[37]

Cavernosography measurement of the vascular pressure in the corpus cavernosum. Saline is infused under pressure into the corpus cavernosum with a butterfly needle, and the flow rate needed to maintain an erection indicates the degree of venous leakage. The leaking veins responsible may be visualized by infusing a mixture of saline and x-ray contrast medium and performing a cavernosogram.[21] In Digital Subtraction Angiography (DSA), the images are acquired digitally.


Cross-sectional studies have not shown raised testosterone levels at the time of diagnosis of prostate cancer, and in fact, low testosterone at the time of diagnosis has been linked with more locally aggressive and malignant tumors (Massengill et al 2003; Imamoto et al 2005; Isom-Batz et al 2005). This may reflect loss of hormone related control of the tumor or the effect of a more aggressive tumor in decreasing testosterone levels. One study found that 14% of hypogonadal men, with normal digital rectal examination and PSA levels, had histological prostate cancer on biopsy. It is possible that low androgen levels masked the usual evidence of prostate cancer in this population (Morgentaler et al 1996). Most longitudinal studies have not shown a correlation between testosterone levels and the future development of prostate cancer (Carter et al 1995; Heikkila et al 1999; Stattin et al 2004) but a recent study did find a positive association (Parsons et al 2005). Interpretation of such data requires care, as the presentation of prostate cancer could be altered or delayed in patients with lower testosterone levels.

early 15c., "physical weakness," also "poverty," from Middle French impotence "weakness," from Latin impotentia "lack of control or power," from impotentem (nominative impotens); see impotent. In reference to a want of (male) sexual potency, from c.1500. The figurative senses of the word in Latin were "violence, fury, unbridled passion." Related: Impotency.
Low-intensity extracorporeal shock wave therapy has been proposed as a new non-invasive treatment for erectile dysfunction caused by problems with blood vessels. Shock wave therapy machines are now available in some medical practices in Australia. Although there is some evidence that it may help a proportion of men with erectile dysfunction, more research is needed before clear recommendations on its use can be made.
Patients with both ED and cardiovascular disease who receive treatment with an oral PDE5 inhibitor require education regarding what to do if anginal episodes develop while the drug is in their system. Such education includes stressing the importance of alerting emergency care providers to the presence of the drug so that nitrate treatment is avoided.

While testosterone stimulates a man’s sex drive, it also aids in achieving and maintaining an erection. Testosterone alone doesn’t cause an erection, but it stimulates receptors in the brain to produce nitric oxide. Nitric oxide is a molecule that helps trigger a series of chemical reactions necessary for an erection to occur. When testosterone levels are too low, a man may have difficulty achieving an erection prior to sex or having spontaneous erections (for example, during sleep).
Longitudinal studies in male aging studies have shown that serum testosterone levels decline with age (Harman et al 2001; Feldman et al 2002). Total testosterone levels fall at an average of 1.6% per year whilst free and bioavailable levels fall by 2%–3% per year. The reduction in free and bioavailable testosterone levels is larger because aging is also associated with increases in SHBG levels (Feldman et al 2002). Cross-sectional data supports these trends but has usually shown smaller reductions in testosterone levels with aging (Feldman et al 2002). This is likely to reflect strict entry criteria to cross-sectional studies so that young healthy men are compared to older healthy men. During the course of longitudinal studies some men may develop pathologies which accentuate decreases in testosterone levels.

In rare cases, the drug Viagra ® can cause blue-green shading to vision that lasts for a short time. In rare cases, the drug Cialis® can cause or increase back pain or aching muscles in the back. In most cases, the side effects are linked to PDE5 inhibitor effects on other tissues in the body, meaning they are working to increase blood flow to your penis and at the same time impacting other vascular tissues in your body. These are not ‘allergic reactions'.


Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which promote differentiation of spermatogonia. It regulates acute HPA (hypothalamic–pituitary–adrenal axis) response under dominance challenge.[22] Androgen including testosterone enhances muscle growth. Testosterone also regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans.[23][24]


It appears that testosterone has NOS-independent pathways as well. In one study, castrated rats were implanted with testosterone pellets and then divided into a group that received an NOS inhibitor (L-nitro-L-arginine methyl ester [L-NAME]) and a control group that received no enzyme. [24] The castrated rats that were given testosterone pellets and L-NAME still had partial erections, a result suggesting the presence of a pathway independent of NOS activity.
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