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Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism
H de Boer1, L Verschoor, J Ruinemans-Koerts
1Department of Internal Medicine, Ziekenhuis Rijnstate, Wagnerlaan 55, 6800 TA Arnhem, The Netherlands. hdeboer@alysis.nl
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/m(2), 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.