SAT376 Luteinizing Hormone Secretion in Hyperandrogenic Girls Taking Spironolactone or Metformin

Abstract

Abstract Disclosure: C.M. Burt Solorzano: None. M. Gilrain: None. S.H. Kim: None. C.R. McCartney: None. Peri-pubertal hyperandrogenism (HA) typically relates to excess adrenal and/or ovarian androgen production in response to adrenocorticotropin (ACTH) and/or luteinizing hormone (LH), respectively. Spironolactone and metformin are commonly used medications to treat adolescent androgen excess. We examined how end-organ responsiveness and LH pulse patterns are affected by these medications in adolescents with HA. We studied free testosterone (T) levels (including baseline and peaks after ACTH and recombinant human chorionic gonadotropin [r-hCG] stimulation), oral glucose tolerance testing (OGTT), and 12-hr overnight LH secretion (sampled q 10 min) in post-menarcheal girls with HA before and after 3-months of either spironolactone (100 mg BID) or metformin (500 mg BID). Free T was calculated using total T (LC-MS/MS) and sex hormone binding globulin (SHBG).To date, 3 girls (aged 12-18) have been studied using spironolactone and 4 girls (aged 14-17) using metformin. (1 girl was studied twice, once with each medication.) After spironolactone treatment, free T changed by -19% (-58 to +37) (median [range]) unstimulated, by -53% (-62 to -15) after ACTH, and by -54% (-66 to +12) after r-hCG. Peak insulin level during OGTT changed by +28% (+16 to +98). Overnight LH pulse frequency changed by -64% (-89 to -10) and LH mean by -74% (-89 to -17). Two subjects in the spironolactone group demonstrated luteal LH patterns despite serum progesterone concentrations < 0.7 ng/mL. In the metformin group, free T changed by +35% (-32 to +125) unstimulated, by 36% (-54 to +66) after ACTH, and by 21% (-41 to +105) after r-hCG. Peak insulin level during OGTT changed by -47% (-74 to +102). LH pulse frequency changed by +10% (-29 to +22) and LH mean by +1% (-2 to +74). To summarize findings to date, mean LH and LH pulse frequency decreased in all three subjects taking spironolactone, including marked reductions in two subjects who demonstrated luteal LH patterns. While free T levels decreased in some of these girls, this seems unlikely to account for such marked changes in LH secretion. And despite similar decreases in T and also decreases in peak insulin in some girls taking metformin, LH pulse frequency did not change markedly. LH pulse patterns in two girls taking spironolactone suggest a progesterone-like effect on LH pulsatility. Spironolactone can cause irregular uterine bleeding, and canrenone (the major metabolite of spironolactone) binds to uterine progesterone receptors competitively (Fernandez MD, Br J Clin Pharm 1983). However, to our knowledge, this is the first report of LH pulse changes in HA girls using spironolactone. Further studies are needed to confirm this finding. Presentation Date: Saturday, June 17, 2023