Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism

Background:  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. Aim:  To examine whether aromatase inhibition with Letrozole can normalize serum testosterone levels in severely obese men with hypogonadotropic hypogonadism. Patients and Methods:  Ten severely obese men, mean age 48.2 ± 2.3 (s.e.) years and body mass index 42.1 ± 2.6 kg/m2, were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week. Results:  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. Conclusion:  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.