Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 11397860 · doi:10.1210/jcem.86.6.7520
What was done
Forty-seven healthy young men were randomly assigned to one of five 5-day double-blind parallel interventions: 1) placebo; 2) high-dose ketoconazole (400 mg 4 times daily) to block steroidogenesis; 3) ketoconazole plus transdermal testosterone (7.5 mg daily); 4) ketoconazole plus transdermal estradiol (0.05 mg daily); or 5) ketoconazole, testosterone, and anastrozole (5 mg twice daily). Blood was sampled every 10 minutes for 27 hours on day 5 to measure 24-hour mean spontaneous and 3-hour post-GnRH-stimulated (100 ng/kg IV) LH and FSH secretion.
What was found
Ketoconazole reduced serum total testosterone from 423 ± 57 ng/dL (placebo) to 58 ± 8.6 ng/dL (P < 0.001), resulting in a 3-fold increase in LH (P < 0.001) and a 2.5-fold increase in FSH (P = 0.015). Transdermal testosterone or estradiol addback suppressed both LH and FSH back to baseline. Coadministration of anastrozole completely abolished testosterone's suppression of both 24-hour spontaneous and GnRH-stimulated LH and FSH release.
Why it matters
This study establishes that testosterone's short-term negative feedback inhibition of LH and FSH release in healthy men is contingent on its aromatization to estrogen.
Limits
The sample size is relatively small (47 split across 5 groups), evaluates only short-term (5-day) pharmacologic suppression and replacement, and included only healthy young men.
Cited by
- supports Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis by inhibiting GnRH release from the hypothalamus and gonadotropins (LH and FSH) from the pituitary.