Sometimes I wish tryptophan supplements were back on the shelves.  The best over-the-counter sleep aid— or at least it was. As the next best thing, many of you have been using melatonin. Perhaps it helps you adjust to jet lag.  Or maybe it gives you that little bit of drowsiness you need on those nights when you’re “Tivo-ing” through reruns of “Charmed,” hoping to get a glimpse of Alyssa Milano’s tattoos. 

Well, melatonin does more to you than give your brain a knockout punch; it also hits you below the belt. What on the third planet from the sun am I talking about? Researchers at Hamek Medical Center in Israel performed a six-month, double-blind, crossover study of a daily treatment dose of three milligrams of melatonin (vs. placebo) in eight men. The men consumed the melatonin or placebo orally at 6 p.m.  Semen quality (concentration, motility and morphology), serum and seminal plasma 17-beta-estradiol (E(2)), testosterone, melatonin and serum gonadotropin levels were determined after three months and at the end of the study. In six men, there was no change in semen quality or in serum and seminal plasma hormone levels.

On the other hand, during the melatonin treatment period, two men experienced a significant drop in sperm concentration and motility (32 and 30 percent, respectively). These coincided with a decline in seminal plasma and serum E(2) levels and with an increase in testosterone: E(2) ratios. Six months after the cessation of melatonin, sperm concentration and motility were normal in one man, but remained abnormal in the other one with a still elevated testosterone: E(2) ratio. Serum gonadotropin levels were unchanged during the study in all eight men.

According to the authors, “Our preliminary observations suggest that long-term melatonin administration is associated with decreased semen quality in a number of healthy men, probably through the inhibition of aromatase at the testicular level.” So, from my count, two out of every eight men may experience an elevation in serum testosterone via aromatase inhibition.  Mmmm… makes ya wonder. What if you stacked melatonin with one of the various OTC prohormones? Would the anti-aromatase activity of the melatonin offset the estrogen elevations seen with most of the oral prohormone products?

Viatrel: Time-Released Testosterone
Men with hypogonadism (suboptimal testicular function) require testosterone replacement for optimal health. In the United States, testosterone is currently administered by daily transdermal patches, topical gels or intramuscular injections every one to three weeks. 

Biodegradable polylactide-co-glycolide microcapsules are now used for long-term drug delivery in humans. Such microcapsules that contain testosterone might provide a better means of long-term testosterone therapy.  Isn’t technology great?

In a very fine study, 14 men who had been treated previously with testosterone were enrolled in an open-label, prospective study of testosterone microcapsule administration. Subjects were injected with a single dose of either 267 milligrams or 534 milligrams of (Viatrel) testosterone microcapsule. Serum total testosterone, DHT, estradiol, sex-hormone binding globulin, LH, and FSH levels were determined at days -14, -7, and 0 before the injection; at days 1, 2, and 7 after the injection; and then weekly thereafter for eight to 12 weeks. Mean serum total testosterone levels peaked immediately following injection on day one and declined gradually and fell to low levels by 42 days after injection in the 267-milligram group, and 70 days after injection in the 534- milligram group. Estradiol and dihydrotestosterone levels followed a similar pattern. 

No significant adverse reactions were seen, although two subjects complained of transient tenderness and fullness at their injection sites.   According to the study authors, “We conclude that a single injection of 534 milligrams of testosterone microcapsules to men with hypogonadism normalizes serum hormone levels for up to 10-11 weeks, albeit with a pronounced early peak and a relatively long period of low-normal serum total testosterone. Subcutaneously administered testosterone microcapsules may provide a safe and convenient method for the long-term treatment of male hypogonadism or testosterone replacement in male contraceptive regimens.” 

This is a perfect example of utilizing technology to get around the issue of testosterone’s ephemeral half-life. One shot keeps you going for two to three months. Of course, the extreme of that would be to do multiple shots in one day and then let the androgen do their magic over the next two to three months. 

Exemestane – Potent Aromatase Inhibitor
Exemestane (Aromasin) is a potent and selective irreversible aromatase inhibitor.  To characterize its suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy eugonadal subjects (14-26 years of age) were studied in a cross-over study. Twelve were randomly assigned to 25 and 50 milligrams exemestane daily, orally, for 10 days with a 14-day washout period. Blood was withdrawn before and 24 hours after the last dose of each treatment period. A PK study was performed (n = 10) using a 25-milligram dose. Exemestane suppressed plasma estradiol by 38 percent at the 25-milligram dose and by 32 percent at the 50-milligram dose. And of course, there was an increase in testosterone concentrations at the 25-milligram (60 percent) and 50-milligram doses (56 percent).

There were no changes in plasma lipids and IGF-I concentrations. The PK properties of the 25-milligram dose showed the highest exemestane concentrations one hour after administration, thus indicating rapid absorption. The terminal half-life was 8.9 hours. Maximal estradiol suppression of 62 +/- 14 percent was observed at 12 hours. The drug was well tolerated. Again, we have an alternative method of manipulating blood levels of testosterone. The question is whether this could have effects on skeletal muscle if the treatment were administered for several weeks!

 Big T Good for the Ticker
    You’ve heard that taking testosterone contributes to greater coronary disease risk, correct? Well, as with any drug, there must be a dose-response relationship. Clearly, taking 100 milligrams per week of T isn’t the same as stacking various androgen preparations at a weekly dose of 10,000 milligrams.  Also, supra-physiological doses of testosterone, such as those used by athletes and recreational bodybuilders, decrease plasma high-density lipoprotein (HDL) cholesterol concentrations. Replacement doses of testosterone have had only a modest or no effect on plasma HDL in placebo-controlled trials.  In fact, according to a review by the preeminent androgen physiologist Shalendar Bhasin, MD, “In epidemiological studies, serum total and free testosterone concentrations have been inversely correlated with intra-abdominal fat mass, risk of coronary artery disease and type 2 diabetes mellitus. Testosterone administration to middle-aged men is associated with decreased visceral fat and glucose concentrations and increased insulin sensitivity. Testosterone infusion increases coronary blood flow. Similarly, testosterone replacement retards atherogenesis in experimental models of atherosclerosis.” 

Clearly, testosterone isn’t the bad guy it’s made out to be in the mainstream press. I can see ahead five to 10 years from now, when testosterone administration in middle-aged to older men becomes as commonplace and accepted as botox injections, liposuction and other “accepted” forms of physical enhancement.