Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism.
Level 4 - case-series / case-control
Uncontrolled single-arm prospective interventional pilot study without a control group.
PubMed 18426834 · doi:10.1530/EJE-07-0663
What was done
In an open, uncontrolled 6-month pilot study, 12 severely obese men (body mass index >35.0 kg/m²) with obesity-related isolated hypogonadotropic hypogonadism and free testosterone <225 pmol/l received 2.5 mg of letrozole once weekly for 6 months. Serum estradiol, LH, total testosterone, and free testosterone were measured at baseline, 6 weeks, and throughout the 6-month period.
What was found
At 6 weeks, letrozole reduced mean total estradiol from 123 ± 11 to 58 ± 7 pmol/l (P < 0.001) and increased mean LH from 4.4 ± 0.6 to 11.1 ± 1.5 U/l (P < 0.001). Mean total testosterone increased from 5.9 ± 0.5 to 19.6 ± 1.4 nmol/l (P < 0.001) and free testosterone increased from 163 ± 13 to 604 ± 50 pmol/l (P < 0.001). Total testosterone normalized in all 12 subjects, while free testosterone reached supraphysiological levels in 7 out of 12 men. Hormone levels remained stable across the week and over the 6-month period.
Why it matters
This study demonstrates that once-weekly aromatase inhibition can restore endogenous testosterone production in obesity-associated hypogonadotropic hypogonadism, though a starting dose lower than 2.5 mg weekly may be necessary to avoid supraphysiological free testosterone levels.
Limits
The study was very small (n = 12), uncontrolled, and open-label. Clinical symptoms, metabolic outcomes, bone density, body composition changes, and adverse events were not reported in the abstract.
Cited by
- supports Obesity elevates the aromatization of testosterone to estrogen in adipose tissue, which causes heightened negative feedback on the hypothalamic-pituitary-gonadal axis and suppresses testosterone production.