Strength, Muscle and Extended Living Through Chemistry? Part 2Part 1 was all about growth hormone, what it does and the pros and cons of hormone-replacement therapy. This installment covers testosterone.
Does Testosterone Prolong Life?
A recent longitudinal study, however, found that having low testosterone increased the risk of death in men over age 50. For 18 years, beginning in the 1970s, researchers tracked the causes of death in 800 men aged 50 to 91 living in Rancho Bernardo, California. In the early 1980s a third of the men had low testosterone. Over the term of the study that group had a 33 percent greater death rate than the men who had higher testosterone levels. The difference in death rate wasn’t explained by negative habits, such as smoking, drinking, lack of exercise or even such diseases as diabetes and heart disease.
The men with low T had more cytokines, which are markers of body inflammation. They also had larger waistlines, a marker of the visceral abdominal fat that is linked to insulin insensitivity, diabetes and cardiovascular disease. Indeed, the amount of visceral fat is proportional to testosterone levels and inflammation—more fat equals less testosterone and more inflammation. Men with low T are three times as likely to have the metabolic syndrome, characterized by insufficient high-density lipoprotein (the good cholesterol), high blood fat, hypertension and elevated blood glucose.
When men age, T tends to decline and bodyfat to increase. That leads to an increase of estrogen levels because of the presence in peripheral fat stores of aromatase, the enzyme that converts androgens such as testosterone into estrogen. An imbalance between T and estrogen can lead to insulin insensitivity, which boosts abdominal fat and its attendant health problems.
Testosterone-deficient men experience a reduced quality of life and such symptoms as heart disease, high blood pressure, lower bone density, fatigue, depression, insomnia, erectile dysfunction and diabetes. Recent studies directly link low T levels to insulin insensitivity and diabetes in men. Some studies link lack of testosterone with the onset of Alzheimer’s disease.
Bodybuilders are particularly affected by testosterone levels. One study found that having low testosterone resulted in a decrease in strength and muscle endurance of 90 to 100 percent.21
Testosterone maintains the function of beta-adrenergic receptors in fat cells, without which fat oxidation is severely blunted. That explains the frequent emergence of potbellies in men over 40—along with bad eating and not getting enough exercise. Conversely, testosterone reverses that process, enabling a man to reduce both dangerous, deep-lying visceral fat and superficial, subcutaneous fat. Dropping subcutaneous fat may even return abdominal muscle definition when combined with judicious exercise and a good diet. Testosterone inhibits a fat cell enzyme called lipoprotein lipase, which advances the cellular uptake and production of fat. It also keeps fat-cell precursors from morphing into full-grown fat cells.22
T-Therapy Concerns
Some scientists suggest that the increased bodyfat produced by men low in testosterone leads to their producing more estrogen, which may promote prostate cancer. That makes sense when you realize that, unlike testosterone, estrogen is a known carcinogen.
The goal of testosterone-replacement therapy is not to produce the results that anabolic-steroid-using athletes are after. Rather, therapy aims at boosting depressed T levels to a mid-normal range, thus preventing the side effects linked to T therapy, such as gynecomastia and water retention. In fact, injecting testosterone to treat low T has gone out of fashion. It causes a temporary surge that’s frequently above the normal range—great for bodybuilding but priming the pump for side effects. Supplemental forms of T such as creams and gels, which get users only to the normal range, are preferred.
Considering that having low T leads to the production of cytokines and considering the significant beneficial effects of T on body composition, you have to conclude that testosterone likely does prolong life when provided in the right dosage. Conversely, T-deficient men face a shorter life span because of the risks of of cardiovascular disease, too much bodyfat and possibly accelerated degenerative brain disease.24
A recent study showed that testosterone may even help activate GH release.25 Thirty-four men aged 65 to 88 who had low-normal T and IGF-1 counts were injected with 100 milligrams of T every two weeks for 26 weeks. That brought about a 33 percent increase in total T levels. Estrogen rose by 31 percent, while sex-hormone-binding globulin, which transports T in the blood, dropped by 17 percent, thus raising free, or active, T levels. The supplementation increased release of GH by 60 percent at night and a whopping 79 percent during the day, while IGF-1 rose by 22 percent.
You might grimace at the 31-percent elevation of estrogen, but keep in mind that conversion of testosterone into estrogen is what pushes the GH release.26 Having abundant testosterone also blunts the ability of IGF-1 to shut down GH release.
Future Developments
Aromatase is particularly active in obese men. Their high-level estrogen signals the hypothalmus to stop secreting gonadatropin-releasing hormone and shut down testosterone synthesis in the Leydig cells. The effect is so potent that obese men don’t respond to replacement therapy.27 On the other hand, studies show that obese men have normalized testosterone levels when they take aromatase-inhibiting drugs.28
Aromatase inhibitors were developed mainly to treat estrogen-sensitive breast cancer in older women. The drugs have gone through several generations, and current versions are remarkably potent estrogen blockers. Since testosterone and other anabolic drugs can convert into estrogen and result in gynecomastia and water retention, bodybuilders who use steroids usually also add an aromatase inhibitor, such as Arimidex, to their anabolic stack.
About 8 percent of a man’s testosterone normally converts into estrogen, so some researchers have suggested that aromatase inhibitors may boost testosterone. A major advantage of that approach is that it forestalls the potential side effects of T therapy. One study investigated whether Arimidex could do the trick. For 12 weeks 37 testosterone-deficient older men received one of three treatments:
- One milligram of Arimidex daily
- One milligram of Arimidex twice a week
- A daily placebo tablet
Nevertheless, doctors still resist prescribing the relatively benign aromatase inhibitors to men with low testosterone. Their position is that there’s not enough research to justify using aromatase inhibitors as a form of T therapy and that the drugs should be used only to treat older women with breast cancer. Another fear is adverse cardiovascular symptoms, since estrogen helps maintain benefical HDL cholesterol in men. Fortunately, over-the-counter aromatase inhibitors are available that seem to work well as testosterone boosters, according to several recent studies.
A further refinement in T therapy will likely ensue with the release of selective androgen receptor modulators. SARMs, as they’re called, are experimental drugs that are taken orally. They target specific androgen receptors in various tissues, including muscle, and are designed to avoid interacting with androgen receptors in the prostate gland, thus bypassing the major health threats linked to T therapy.
As Ronald Klatz, M.D., president of the Academy of Anti-Aging Medicine, notes,“Replacing the hormones that decline with age, such as estrogen, testosterone, DHEA, melatonin and GH, is as important as replacing normal levels of insulin to a diabetic.”
References
21 Kohn, F. (2006). Testosterone and body functions. Aging Male. 9:183-88.
22 Dieudonne, M.N., et al. (2000). Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes: Evidence for sex and site-related specificities and possible involvement of IGF-1 receptor and peroxisome proliferator-activated receptor gamma-2. Endocrinol. 141:649-56.
23 Wiren, S., et al. (2007). Androgens and prostate cancer risk: A prospective study. Prostate. 67:1230-37.
24 Shores, M.M., et al. (2006). Low serum testosterone and mortality in male veterans. Arch Intern Med. 166:1660-1665.
25 Muntiyappa, R., et al. (2007). Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men. Am J Physiol Endocrinl Metab. In press.
26 Meinhardt, M., et al. (2006). Modulation of growth hormone action by sex steroids. Clin Endocrinol. 65:413-22.
27 Cohen, P. (1999). The hypogonadal-obesity cycle: Role of aromatase in modulating the testosterone-estradiol shunt—a major factor in the genesis of morbid obesity.Med Hypotheses. 52:49-51.
28 Boer, H., et al. (2005). Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism. Diabetes Obes Metabol. 7:211-215.
©,2015 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited
