Written by Jose Antonio, PhD
09 October 2006

Where No T Has Gone Before

 

Inhaled Testosterone

Looking for a convenient way to deliver testosterone? Why not inhale it?  A study from the Journal of Clinical Pharmacology examined just such a delivery system. It looked at the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system. The study subjects consisted of postmenopausal women. Why do I think MD readers would have been happy to volunteer for this clinical trial?

Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose of testosterone (0.1, 0.2, or 0.3 milligrams) by inhalation. Plasma concentrations of sex steroids were measured between one and 360 minutes. These are rather small doses, mind you. Nevertheless, inhaled testosterone produced a dose-dependent increase in plasma total and free testosterone. At the highest dose (0.3 milligrams), total and free testosterone increased from baseline (0.6 nmol/L, 2.5 pmol/L) to maximum levels of 62.6 nmol/L (total) and 168.2 pmol/L(free), occurring one to two minutes after dosing. Wow! That's a huge change. In fact, that's a 6,628 percent increase!

The researchers also found that DHT, or dihydrotestosterone, levels were higher than baseline at 60 minutes. Estradiol did not vary, but sex hormone binding globulin and albumin fell. There were no adverse events related to the treatment. Therefore, according to the study authors, "administration of inhaled testosterone is safe and achieves a supraphysiologic "pulse" kinetic profile of total and free testosterone with a rapid return to pretreatment levels."1 All I can say is pass the inhalerJ!

 

            It's Free T and Albumin-Bound T, Dammit

            Lesson for the day: Not only is free testosterone important, but keep in mind that albumin-bound testosterone is also bioavailable. Memorize and regurgitate that fact. Moving on: A recent study looked at measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone and their associations with markers of insulin resistance and body fat measures in 221 middle-aged non-diabetic men. Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG and albumin, and they were not significantly correlated with SHBG. In contrast, total testosterone correlated significantly with SHBG.

We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]), as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). After examining the data, they basically found an inverse association between testosterone and insulin resistance, independent of SHBG, that was mediated through body fat.2 In plain English, ‘tis good to have high T levels, as well as low body fat levels, if you want normal insulin metabolism.

 

            Arginine: Permissive Effect on Testosterone?

            OK, follow me now. If you feed mice an arginine-deficient diet, it will decrease plasma concentrations of arginine, citrulline and ornithine in the females and arginine in the males. This abolishes the sexual dimorphic (i.e., male vs. female) pattern of these amino acids found in mice fed the standard diet. In addition, the restriction of dietary arginine produces a drop in body and renal weights, as well as in the activity of renal ornithine decarboxylase (a kidney enzyme), decreases that were sex-dependent since they were observed exclusively in males.

The fact that these changes were not associated with the decrease in the circulating levels of testosterone and that the dietary arginine restriction prevented the bodyweight gain induced by testosterone treatment of female mice fed the standard diet, indicates that dietary arginine is required for the anabolic action of androgens. Thus, dietary arginine may be relevant to the anabolic action of testosterone, suggesting this effect may be mediated by changes in the insulin-like growth factor system.3 

 

            Skinny Chicks Need Some T

            Anorexia nervosa (AN) is complicated by "severe bone loss, cognitive function deficits and a high prevalence of major depression." In other words, it messes with you big time! In this study of 33 women with AN and relative testosterone deficiency, the scientists treated the subjects to transdermal testosterone (Intrinsa, Procter & Gamble Pharmaceuticals, Cincinnati, OH), 150 micrograms, 300 micrograms or placebo, for three weeks. Depressed patients receiving testosterone improved from severely depressed to moderately depressed; the placebo group was unchanged. Spatial cognition improved in the testosterone group compared with placebo. Therefore, short-term, low-dose testosterone may improve depressive symptoms and spatial cognition in women with AN. Let's face it: Testosterone is clearly a medically viable treatment for many things. Who woulda thought anorexia would be one of them?4 

 

            Stay Away from Licorice

            Licorice- both the plant and the candy made from it- is sweet. This sweetness can be traced to glycyrrhizic acid, which resides naturally in the root of the licorice plant, Glycyrrhiza glabra. Now, licorice has been considered a medicinal plant for thousands of years. But did you know it can affect testosterone levels? Yes, indeed, Sherlock Holmes, read on. A recent study looked at the effect of licorice on androgen metabolism in nine healthy women (22-26 years old) in the luteal phase of the menstrual cycle. They were given 3.5 grams of a commercial preparation of licorice (containing 7.6 percent W.W. of glycyrrhizic acid) daily for two cycles. They were not on any other treatment.

  Total serum testosterone decreased from 27.8 to 19.0 in the first month and to 17.5 ng/dL in the second month of therapy. That, my friends, is a 59 percent drop. It returned to pre-treatment levels after discontinuation. Androstenedione, 17OH-progesterone and LH levels did not change significantly during treatment. The mechanism for this decrease in serum testosterone is probably due to the block of 17-hydroxysteroid dehydrogenase and 17-20 lyase.5   

 

References

1.         Davison, S., et al., Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women. J Clin Pharmacol, 2005. 45(2): p. 177-84.

2.         Tsai, E.C., et al., Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat. Diabetes Care, 2004. 27(4): p. 861-8.

3.         Cremades, A., et al., Influence of dietary arginine on the anabolic effects of androgens. J Endocrinol, 2004. 183(2): p. 343-51.

4.         Miller, K., K. Grieco, and A. Klibanski, Testosterone Administration in Women with Anorexia Nervosa. J Clin Endocrinol Metab, 2004.

5.         Armanini, D., et al., Licorice reduces serum testosterone in healthy women. Steroids, 2004. 69(11-12): p. 763-6.