T Nation

Study: Letrozole Normalizes Serum Test

DOI: 10.1530/EJE-07-0663
European Journal of Endocrinology, Vol 158, Issue 5, 741-747
Copyright © 2008 by Society of the European Journal of Endocrinology

CLINICAL STUDIES
Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism
Sandra Loves1, Janneke Ruinemans-Koerts2 and Hans de Boer1

Departments of1 , Internal Medicine2 Clinical Chemistry, Ziekenhuis Rijnstate, Wagnerlaan 55, 6800 TA Arnhem, The Netherlands

(Correspondence should be addressed to H de Boer; Email: hdeboer@alysis.nl)

Objective: 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.

Design: 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.

Results: 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.

Conclusion: Letrozole 2.5 mg 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.

I’ve read of at least one study where Letrozole went too far: “In one male test subject Letrozole was able to reduce estrogen levels to undetectable levels”

So this would be a real concern. Estrogen is essential for health and “undetectable levels” is not good. Anyone taking letrozole needs to be monitoring their E2 levels very carefully with frequent blood tests.

Treating obesity-related hypogonadism with letrozole is, in my opinion, a poor choice of therapy.

Fat produces estrogen and aromatase. Clearly, the best way to treat obesity-related hypogonadism is by eliminating the obesity.

The message to take away from this study is that you need to keep your fat levels in check, not that you should be on letrozole.

The study does not list lab ranges and does not address the long term effects as a therapy. It is a dose-response study, but oddly, it also suggests a medical dose.

This technique does not work when there is a problem with the release of LHRH or a pituitary that does not work. Ditto for testicles that do not respond properly to LH. Odd that they did not report the age of the fat guys. They may have been younger and their HPTA may not have been aged.

Many will run with this as a simple answer to their problems. A little knowledge is dangerous.