Obese men have lower testosterone levels. Because fat mass produces aromatase [the enzyme that converts testosterone into estradiol] obese men are more likely to have problems with reduced libido and depression, in addition to physical problems. Endocrinologists at the Rijnstate Hospital in Arnhem, the Netherlands, discovered that they could change this with surprisingly low doses of letrozole.
The researchers gave twelve obese men with low testosterone levels a weekly pill containing 2.5 mg letrozole. Letrozole is an aromatase inhibitor, and a very good one at that. One of the reasons that letrozole works so well is that it breaks down relatively slowly. In fact underground handbooks contain warnings about letrozole. It’s not a substance for recreational athletes, they say.
The figure below shows the effect of letrozole on the male test subjects. The effect on testosterone level is maintained for six months; the inhibitory effect on the estradiol level starts to decline after six weeks.
The figures below show the result of six weeks’ of letrozole administration on the free testosterone> and free estradiol levels. The figures underestimate the effect on estradiol in some men: in some subjects the estradiol level dropped below the level that the researchers were able to measure.
The researchers suspect that even better results would be achieved if the 2.5 mg dose were spread out over several days. They suggest that obese men could be given a pill containing 1 mg letrozole twice a week.
This study may be of interest to chemical athletes. Chemical athletes often use anti-oestrogens after taking a course of steroids to normalise their hormone balance. Since designer supplements have been available, chemical athletes often mess about with weak androgens, which also happen to sabotage the aromatase enzyme. Tamoxifen or clomiphene are expensive and sometimes have side effects. A low-dose letrozole preparation may provide an alternative.
Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism
Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E2) production and E2-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.
Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0?kg/m2) with obesity-related IHH and free testosterone levels <225?pmol/l, treated with 2.5?mg letrozole once a week for 6 months.
Six weeks of treatment reduced total E2 from 123±11 to 58±7?pmol/l (P<0.001, mean±S.E.M.), and increased serum LH from 4.4±0.6 to 11.1±1.5?U/l (P<0.001). Total testosterone rose from 5.9±0.5 to 19.6±1.4?nmol/l (P<0.001), and free testosterone from 163±13 to 604±50?pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E2 levels were stable throughout the week and during the 6-month treatment period.
Letrozole 2.5mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5?mg once a week is recommended.