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.
Overall, few patients have a compelling contraindication to testosterone treatment. The majority of men with late onset hypogonadism can be safely treated with testosterone but all will require monitoring of prostate parameters HDL cholesterol, hematocrit and psychological state. It is also wise to monitor symptoms of sleep apnea. Other specific concerns may be raised by the mode of delivery such as local side effects from transdermal testosterone. 

Diabetes. Erectile Dysfunction is common in people with diabetes. An estimated 10.9 million adult men in the U.S. have diabetes, and 35 to 50 percent of these men are impotent. The process involves premature and unusually severe hardening of the arteries. Peripheral neuropathy, with involvement of the nerves controlling erections, is commonly seen in people with diabetes.
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.

Richard J. Wassersug, PhD, an adjunct professor of urology at the University of British Columbia, described his personal experience with androgen deprivation therapy (ADT). "If you are on ADT," he said, "and you see those Low T ads, what are you supposed to make of it? This produces a cognitive dissonance." He called the ads "hurtful" for suggesting that low testosterone makes a man less of a man.

show that total testosterone levels increase after exercising, especially after resistance training. Low testosterone levels can affect your sex drive and your mood. The good news is that exercise improves mood and stimulates brain chemicals to help you feel happier and more confident. Exercise also boosts energy and endurance, and helps you to sleep better. Fitness experts recommend 30 minutes of exercise every day.
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.
Two of the immediate metabolites of testosterone, 5α-DHT and estradiol, are biologically important and can be formed both in the liver and in extrahepatic tissues.[147] Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by aromatase.[2][147][153][154] 5α-Reductase is highly expressed in the male reproductive organs (including the prostate gland, seminal vesicles, and epididymides),[155] skin, hair follicles, and brain[156] and aromatase is highly expressed in adipose tissue, bone, and the brain.[157][158] As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression,[148] and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone,[159] it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.[160]
In summary, low testosterone levels are linked to the presence of numerous cardiovascular risk factors. Testosterone treatment acts to improve some of these factors, but effects may vary according to pre- and post-treatment testosterone levels, as well as other factors. There is little data from trials specific to aging males. Appropriately-powered randomized controlled trials, with cardiovascular disease primary endpoints, are needed to clarify the situation, but in the meantime the balance of evidence is that testosterone has either neutral or beneficial effects on the risk of cardiovascular disease in men. It is particularly important to define the effect of testosterone treatment on cardiovascular disease in view of its potential use as an anti-anginal agent.

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.
Organic ED involves abnormalities the penile arteries, veins, or both and is the most common cause of ED, especially in older men. When the problem is arterial, it is usually caused by arteriosclerosis, or hardening of the arteries, although trauma to the arteries may be the cause. The controllable risk factors for arteriosclerosis--being overweight, lack of exercise, high cholesterol, high blood pressure, and cigarette smoking--can cause erectile failure often before progressing to affect the heart. 
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).
ED can also occur among younger men. A 2013 study found that one in four men seeking their first treatment for ED were under the age of 40. The researchers found a stronger correlation between smoking and illicit drug use and ED in men under 40 than among older men. That suggests that lifestyle choices may be a main contributing factor for ED in younger men.

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).


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
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.
When stimulated by the nerves, the spongy tissue arranges itself in such a way that more blood can be stored in the penis. The veins running through the outer sheath of the penis then compress which stops the blood from leaving the penis. As the blood is stopped from flowing out, the penis fills with blood and stretches within the outer casing, giving an erection.
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.
Some men report being helped by an oral medication called yohimbine, which comes from the bark of a tree that grows in India and Africa. This drug, which needs to be taken every day, has been reported to help about 20 to 25 percent of the men taking it. A relatively new but widely used oral medication called Viagra requires a careful medical evaluation by your doctor.
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.
The participants were seen every 4 weeks. Blood was taken to measure hormone levels, and questionnaires were given to assess physical function, health status, vitality, and sexual function. Body fat and muscle measurements were also taken at the beginning and end of the 16 weeks. The study was funded in part by NIH’s National Institute on Aging (NIA) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results appeared in the September 12, 2013, issue of the New England Journal of Medicine.
The hypogonadal-obesity-adipocytokine cycle hypothesis. Adipose tissue contains the enzyme aromatase which metabolises testosterone to oestrogen. This results in reduced testosterone levels, which increase the action of lipoprotein lipase and increase fat mass, thus increasing aromatisation of testosterone and completing the cycle. Visceral fat also promotes lower testosterone levels by reducing pituitary LH pulse amplitude via leptin and/or other factors. In vitro studies have shown that leptin also inhibits testosterone production directly at the testes. Visceral adiposity could also provide the link between testosterone and insulin resistance (Jones 2007).
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.
Examples of common neurologic conditions that can lead to ED include cerebral vascular accident, multiple sclerosis, Parkinson’s disease, and spinal cord injury. Microvascular disease associated with diabetes is thought to compound the endothelial and neural injuries associated with this disease. Pelvic surgery may disrupt both neural and vascular pathways, resulting in ED.
When I first started TRT, my physician prescribed a cream that you rub into your skin. The cream version of TRT is not too convenient, because if someone touches you while you have the cream on, the testosterone can rub off on him/her. This can be really bad around kids or pregnant women. If you’re sleeping next to someone, the cream can get on the sheets and transfer over that way, too. The cream can be annoying, but it works. There’s also a gel version called AndroGel; I skipped it because it doesn’t absorb as well as the cream does. 
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