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- Title
Progesterone Suppression of Luteinizing Hormone Pulse Frequency in Adolescent Girls With Hyperandrogenism: Effects of Metformin.
- Authors
Lundgren, Jessica A; Kim, Su Hee; Burt Solorzano, Christine M; McCartney, Christopher R; Marshall, John C
- Abstract
<bold>Context: </bold>Polycystic ovary syndrome (PCOS) and adolescent hyperandrogenism (HA) are characterized by rapid luteinizing hormone (LH) pulse frequency. This partly reflects impaired gonadotropin-releasing hormone pulse generator (hypothalamic) sensitivity to progesterone (P4) negative feedback. We assessed whether metformin may improve P4 sensitivity in adolescent HA, for which it is prescribed widely.<bold>Objective: </bold>To test the hypothesis that metformin improves hypothalamic P4 sensitivity in adolescent HA.<bold>Design: </bold>Nonrandomized, interventional trial.<bold>Setting: </bold>Academic clinical research unit.<bold>Participants: </bold>Ten adolescent girls with HA.<bold>Intervention: </bold>The girls underwent LH sampling every 10 minutes for 11 hours, at study baseline and after 7 days of oral P4 and estradiol (E2). Participants then took metformin (1 g twice daily) for 9.4 to 13.7 weeks, after which participants 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-hour oral glucose tolerance tests were performed.<bold>Main Outcome Measure: </bold>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].<bold>Results: </bold>Free T levels decreased by 29% with metformin (P = 0.0137). Measures of hyperinsulinemia and P4 sensitivity index did not significantly change with metformin use.<bold>Conclusion: </bold>Short-term metformin use improved biochemical hyperandrogenemia, but did not improve hypothalamic sensitivity to P4 suppression, in adolescent girls.
- Subjects
PROGESTERONE antagonists; HYPOGLYCEMIC agents; METFORMIN; CLINICAL trials; GLUCOSE tolerance tests; INSULIN resistance; LONGITUDINAL method; LUTEINIZING hormone; PHYSICS; PROGNOSIS; PSYCHOTHERAPY; RESEARCH funding; HYPERANDROGENISM
- Publication
Journal of Clinical Endocrinology & Metabolism, 2017, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2017-02068