This paper will aim to review the current evidence of clinical effects of testosterone treatment within an aging male population. As with any other clinical intervention a decision to treat patients with testosterone requires a balance of risk versus benefit. We shall try to facilitate this by examining the effects of testosterone on the various symptoms and organs involved.
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.
Begot, I., Peixoto, T. C. A., Gonzaga, L. R. A., Bolzan, D. W., Papa, V., Carvalho, A. C. C., ... & Guizilini, S. (2015, March 1). A Home-Based Walking Program Improves Erectile Dysfunction in Men With an Acute Myocardial Infarction. The American Journal of Cardiology, 115(5), 5741-575. Retrieved from http://www.ajconline.org/article/S0002-9149(14)02270-X/abstract
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.
So what is this Big T, anyway? Derived from cholesterol, testosterone is a steroid hormone—called an androgen—that causes the development and maintenance of masculine characteristics. It's mainly secreted by the testicles in males, although the adrenal cortex and ovaries in females also secrete testosterone—though only about one-tenth the amount as in healthy males.
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).
Rest and recovery is just as important as exercise, if not more so. Every time you do an intense workout, give yourself a minimum of 2 days to recuperate afterward, if not more. And don’t mix exercise with sleep hacking. If you’re exercising, get at least 8 hours of sleep every night. Your body uses it to rebuild, and you can throw your hormones out of whack if you don’t rest up properly. Here’s a more in-depth guide to Bulletproof weight training, complete with sample workouts.
Commercials do mention other potential side-effects for the male user, calling them "rare," including swollen and painful breasts, blood clots in the legs, increased risk for prostate cancer, problems breathing during sleep (sleep apnea), change in the size and shape of the testicles, and a low sperm count. But you're not supposed to focus on the details. Instead, just think of the energy you'll have. The great sex you'll have. And the muscles. It will be a veritable second adolescence as your aging body bursts into new bloom.
The sex hormone testosterone is far more than just the stuff of the alpha male's swagger. Though it plays a more significant role in the life of the biological male, it is actually present in both sexes to some degree. Despite popular perceptions that testosterone primarily controls aggression and sex drive—although it does play a role in both of those things—research has shown that individual levels of testosterone are also correlated with our language skills and cognitive abilities. Testosterone occurs in the body naturally, but can be administered as a medication, too: its most common uses are in the treatment of hypogonadism and breast cancer, as well as in hormone therapy for transgender men.
But if a man with sleep apnea is diagnosed with low testosterone alone, taking the supplemental hormone can worsen sleep apnea. That's why it's crucial for men with low testosterone to get a thorough workup by an endocrinologist so underlying conditions that can cause low testosterone, such as sleep apnea or pituitary-gland tumors, don't go undiagnosed, Dr. Goodman says.

Many clinical studies have looked at the effect of testosterone treatment on body composition in hypogonadal men or men with borderline low testosterone levels. Some of these studies specifically examine these changes in older men (Tenover 1992; Morley et al 1993; Urban et al 1995; Sih et al 1997; Snyder et al 1999; Kenny et al 2001; Ferrando et al 2002; Steidle et al 2003; Page et al 2005). The data from studies, on patients from all age groups, are consistent in showing an increase in fat free mass and decrease in fat mass or visceral adiposity with testosterone treatment. A recent meta-analysis of 16 randomized controlled trials of testosterone treatment effects on body composition confirms this pattern (Isidori et al 2005). There have been less consistent results with regard to the effects of testosterone treatment of muscle strength. Some studies have shown an increase in muscle strength (Ferrando et al 2002; Page et al 2005) with testosterone whilst others have not (Snyder et al 1999). Within the same trial some muscle group strengths may improve whilst others do not (Ly et al 2001). It is likely that the differences are partly due to the methodological variations in assessing strength, but it also possible that testosterone has different effects on the various muscle groups. The meta-analysis found trends toward significant improvements in dominant knee and hand grip strength only (Isidori et al 2005).


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.    
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.
The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.

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).


Erectile dysfunction can cause strain on a couple. Many times, men will avoid sexual situations due to the emotional pain associated with ED, causing their partner to feel rejected or inadequate. It is important to communicate openly with your partner. Some couples consider seeking treatment for ED together, while other men prefer to seek treatment without their partner's knowledge. A lack of communication is the primary barrier for seeking treatment and can prolong the suffering. The loss of erectile capacity can have a profound effect on a man. The good news is that ED can usually be treated safely and effectively.


Supplements are popular and often cheaper than prescription drugs for ED. However, supplements have not been tested to see how well they work or if they are a safe treatment for ED. Patients should know that many over-the-counter drugs have been found on drug testing to have ‘bootlegged' PDE 5 Inhibitors as their main ingredient. The amounts of Viagra, Cialis, Levitra or Stendra that may be in these supplements is not under quality control and may differ from pill to pill. The FDA has issued consumer warnings and alerts.
Exercise and lifestyle modifications may improve erectile function. Weight loss may help by decreasing inflammation, increasing testosterone, and improving self-esteem. Patients should be educated to increase activity, reduce weight, and stop smoking, as these efforts can improve or restore erectile function in men without comorbidities. Precise glycemic control in diabetic patients and pharmacologic treatment of hypertension may be important in preventing or reducing sexual dysfunction. [49]

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).

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."


Given the high risk of priapism during escalation of therapy for intracorporeal injection, it is recommended that the drugs be administered in a supervised office visit initially and that the patient be given a well-articulated plan for treatment of priapism if it occurs. Escalation guidelines for alprostadil alone vary, but a general guideline is to start at 2.5 mcg and increase by 2.5 mcg to a dose of 5 mcg and then in increments of 5 mcg to 10 mcg until an erection sufficient for penetration, not lasting more than 1 hour, is achieved. If there is no response to the initial 2.5-mcg dose, escalation dosing can be slightly more liberal.34 A European prospective trial of PGE1 alone found 91% of the 54 patients completing the 4 years of the study reported good or better tolerability and satisfaction with therapy.35

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."


Implantation of penile prosthesis remains an important option for men with ED if medical treatment fails or is inappropriate. Prostheses are available as a saline-filled silicone device or a malleable device. The benefit of the former is a more natural appearance in the deflated state, closely approximating the appearance of a flaccid penis. The trade-off is a higher mechanical failure rate and higher cost. Satisfaction rates for patients who underwent penile prosthesis surgery have been reported to be near 90%.36 However, in the majority of patients who receive this treatment, less invasive alternatives have failed and therefore satisfaction with this treatment would be expected to be higher in this subset of patients. Risks of these devices include surgical and anesthetic risk, device infection, and device malfunction. Mechanical failure rates depend on the specific device being investigated. Overall, the percentage of devices that are free from mechanical failure at 5 years ranges from 84% to 94%.19 Infection rates in the era of coated devices and improved techniques are reported to be less than 1%.37

Side effects include lightheadedness, fainting, priapism, urethral bleeding (intraurethral), dyspareunia in the partner (intraurethral), hematoma (intracavernosal) or penile curvature secondary to scar (intracavernosal). Efficacy of intraurethral alprostadil has been demonstrated to be around 50% ("able to have intercourse") in randomized controlled trials.31,32 For intracorporeal injection, typically alprostadil is tried alone, or compounded with papaverine (nonspecific phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate and cGMP) and/or phentolamine (competitive, non-selective alpha1- and alpha2-adrenoreceptor blocker). Pinsky et al33 reported an extensive review of the benefits and drawbacks of the combinations of these drugs.

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.


If PDE-5 inhibitors are not suitable or don’t work, other therapies include injections into the base of the penis, which cause flow of blood into the penis and a fairly immediate erection that lasts around an hour. The drugs injected are alprostadil (Caverject and Erectile dysfunctionex) and Invicorp (VIP and phentolamine). Alprostadil may also be inserted as a gel into the opening of the penis. This is not suitable if your partner is pregnant.
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