This Article Full Text Full Text (PDF) All Versions of this Article: 91/3/946    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eisenhardt, S. Articles by Strowitzki, T. Search for Related Content PubMed PubMed Citation Articles by Eisenhardt, S. Articles by Strowitzki, T. Related Collections Female Endocrinology Metabolism

Early Effects of Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomized, Double-Blind, Placebo-Controlled Trial

Departments of Gynecological Endocrinology and Reproductive Medicine (S.E., N.S., A.G., M.v.W., T.S.), Obstetrics and Gynecology (S.E.), and Internal Medicine (A.H.), Division of Endocrinology and Metabolism, and Biostatistics (V.H.), University of Heidelberg, 69115 Heidelberg, Germany

Address all correspondence and requests for reprints to: S. Eisenhardt, M.D., Women’s University Hospital, Department of Gynecological Endocrinology and Reproductive Medicine and Department of Obstetrics and Gynecology, Vossstr. 9, 69115 Heidelberg, Germany. E-mail: stefan.eisenhardt{at}med.uni-heidelberg.de.

Context: Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome (PCOS). No data of the exact point and the impact of insulin resistance (IR) on metformin’s efficacy exist.

Objective: The objective of the study was to evaluate the early potential effects of metformin treatment, their time of onset, and the role of IR on metformin’s efficacy.

Design: This was a prospective randomized, double-blind, placebo-controlled trial.

Setting: The study was conducted at the University of Heidelberg, Heidelberg, Germany.

Patients: The patient population was 45 oligo-/anovulatory PCOS women with typical ovaries.

Interventions: Women were stratified for IR (32 of 13) and then randomly allocated to receive either metformin (n = 22) or placebo (n = 23) and were assessed before and every 4 wk within a treatment period of 12 wk.

Main Outcome Measures: Menstrual disturbance and markers of insulin metabolism were measured.

Results: The main outcome criterion menstrual disturbance was successfully improved in the metformin-treated group, depending on IR (12 of 15 vs. three of 17), whereas women without IR (four of seven vs. four of six) had no significant amelioration of their menstrual irregularities (P < 0.05). Estradiol levels increased continuously only in the treatment group (P < 0.005), indicating an improvement of ovulatory function. Sixty-seven percent of metformin-treated women had at least one ovulation, compared with only 45% in the placebo group, shown by biphasic body temperature curves. Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005).

Conclusions: IR is a baseline predictor of clinical efficacy in metformin treatment in PCOS women measured by improved menstrual cyclicity and ovulatory function.

This article has been cited by other articles:

				A. A. Creanga, H. M. Bradley, C. McCormick, and C. T. Witkop Use of Metformin in Polycystic Ovary Syndrome: A Meta-Analysis Obstet. Gynecol., April 1, 2008; 111(4): 959 - 968. [Abstract] [Full Text] [PDF]

				R. S. Legro, H. X. Barnhart, W. D. Schlaff, B. R. Carr, M. P. Diamond, S. A. Carson, M. P. Steinkampf, C. Coutifaris, P. G. McGovern, N. A. Cataldo, et al. Ovulatory Response to Treatment of Polycystic Ovary Syndrome Is Associated with a Polymorphism in the STK11 Gene J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 792 - 800. [Abstract] [Full Text] [PDF]

				E. Moll, F. van der Veen, and M. van Wely The role of metformin in polycystic ovary syndrome: a systematic review Hum. Reprod. Update, November 1, 2007; 13(6): 527 - 537. [Abstract] [Full Text] [PDF]

				L. Tian, H. Shen, Q. Lu, R. J. Norman, and J. Wang Insulin Resistance Increases the Risk of Spontaneous Abortion after Assisted Reproduction Technology Treatment J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1430 - 1433. [Abstract] [Full Text] [PDF]

				R. L. Rosenfield Identifying Children at Risk for Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 787 - 796. [Abstract] [Full Text] [PDF]