Progesterone Suppression of LH Pulse Frequency in Adolescent Girls with Hyperandrogenism: Effects of Metformin.

Progesterone Suppression of LH Pulse Frequency in Adolescent Girls with Hyperandrogenism: Effects of Metformin.

J Clin Endocrinol Metab. 2017 Oct 31;:

Authors: Lundgren JA, Kim SH, Burt Solorzano CM, McCartney CR, Marshall JC

Abstract
Context: Polycystic ovary syndrome (PCOS) and adolescent hyperandrogenism (HA) are characterized by rapid LH (GnRH) pulse frequency. This partly reflects impaired GnRH pulse generator (hypothalamic) sensitivity to progesterone (P4) negative feedback. We aimed to assess whether metformin may improve P4 sensitivity in adolescent HA, for which it is prescribed widely.
Objective: To test the hypothesis that metformin improves hypothalamic P4 sensitivity in adolescent HA.
Design: Non-randomized interventional trial.
Setting: Academic clinical research unit.
Participants: Ten adolescent girls with HA.
Intervention: Girls underwent LH sampling every 10 minutes for 11 hours, both at baseline and after 7 days of oral P4 and estradiol (E2). Subjects then took metformin (1 g twice daily) for 9.4-13.7 weeks, after which subjects again underwent frequent LH sampling before and after 7 days of oral P4 and E2 (while continuing metformin). Total and free testosterone (T) and fasting insulin were assessed at each admission. At admissions 1 and 3, 2 h oral glucose tolerance tests (OGTT) were performed.
Main Outcome Measure: Metformin-related change in hypothalamic P4 sensitivity index (percent change in LH pulse frequency [before vs. after P4 and E2] divided by day 7 P4 level).
Results: Free testosterone levels decreased by 29% with metformin (p = 0.0137). However, measures of hyperinsulinemia and P4 sensitivity index did not significantly change with metformin use.
Conclusions: Short-term metformin use improves biochemical hyperandrogenemia, but does not improve hypothalamic sensitivity to P4 suppression, in adolescent girls.

PMID: 29095983 [PubMed - as supplied by publisher]

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