Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism

Morbid obesity is associated with increased estradiol production as a result of aromatase-dependent conversion of testosterone to estradiol. The elevated serum estradiol levels may inhibit pituitary LH secretion to such extent that hypogonadotropic hypogonadism can result. Normalization of the disturbed estradiol-testosterone balance may be beneficial to reverse the adverse effects of hypogonadism.

To examine whether aromatase inhibition with Letrozole can normalize serum testosterone levels in severely obese men with hypogonadotropic hypogonadism.

Ten severely obese men, mean age 48.2 +/- 2.3 (s.e.) years and body mass index 42.1 +/- 2.6 kg/m(2), were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week.

Six weeks of treatment decreased serum estradiol from 120 +/- 20 to 70 +/- 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 +/- 0.8 to 14.8 +/- 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 +/- 1.0 to 23.8 +/- 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone-binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response.

Short-term Letrozole treatment normalized serum testosterone levels in all obese men. The clinical significance of this intervention remains to be established in controlled, long-term studies.