Richard Fleming, Ph.D.,a Lyndal Harborne, B.Med.,a David T. MacLaughlin, Ph.D.,b
Daniel Ling,b Jane Norman, M.D.,a Naveed Sattar, M.R.C.Path.,a and David B. Seifer, M.D.c
a University Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow, United Kingdom; b Paediatric Research
Laboratory, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts; and c Department
of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, University
of Medicine and Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswick, New Jersey
Objective: Assessment of ovarian responses to metformin treatment in obese women with polycystic ovary
syndrome (PCOS).
Design: Prospective treatment with randomization to two doses of metformin.
Setting: University teaching hospital.
Patient(s): Obese women (n
82) with PCOS.
Intervention(s): Markers of ovarian function were assessed after 4 and 8 months.
Main Outcome Measure(s): Hormone (androgens and müllerian-inhibiting substance [MIS]) changes over time.
Result(s): There was no difference in the reproductive hormone changes between the doses of metformin, and
data were combined for further analyses. Significant responses to treatment were recorded for menstrual
frequency and androstenedione (A) (reduction) within the first 4 months of treatment. However, suppression of
the elevated circulating MIS concentrations required protracted treatment, because no change was observed in the
first 4 months—only in the second 4-month assessment period.
Conclusion(s): Metformin treatment of PCOS leads to rapid suppression of A and improved menstrual frequency.
Suppression of MIS is a delayed response that may be secondary to the development of a cohort of follicles that
underwent initial recruitment in an environment of reduced insulin stimulation. (Fertil Steril
2005;83:130–6. ©
2005 by American Society for Reproductive Medicine.)
Key Words: Müllerian-inhibiting substance, PCOS, metformin, ovarian follicles