Low-dose combination of flutamide, metformin and an oral contraceptive for non-obese, young women with polycystic ovary syndrome

Hum Reprod. 2003 Jan;18(1):57-60. doi: 10.1093/humrep/deg056.

Abstract

Background: The endocrine-metabolic status of non-obese, young women with polycystic ovary syndrome (PCOS) is normalized more effectively by combined treatment with flutamide and metformin than by either of these drugs in monotherapy. In this follow-up study, we assess whether the endocrine-metabolic benefits of combined flutamide-metformin treatment are maintained in the presence of a low-dose oral contraceptive (OC).

Methods: To a population of non-obese, young PCOS women already receiving flutamide-metformin (125 mg/day and 1275 mg/day), a low-dose OC (ethinyl estradiol 20 microg + gestodene 75 microg) was administered to reduce the risk of pregnancy. A total of 12 women elected to receive the OC and this subgroup (OC+) was matched to a subgroup continuing on flutamide-metformin alone (OC-), for a total study population of 24 women (mean age +/- SEM 18.7 +/- 0.3 years; body mass index, 21.8 +/- 0.5 kg/m(2)). Endocrine-metabolic indices were assessed before any treatment (0 months), on flutamide-metformin (12 months), and again after a further 6 months with or without additional OC (18 months).

Results: In OC- and OC+ women, the beneficial effects of flutamide-metformin on hyperandrogenaemia, hyperinsulinaemia and dyslipidaemia were maintained. In OC+ women, there was an additional increase in sex hormone-binding globulin (SHBG), and thus a further drop in the free androgen index.

Conclusion: When a low-dose OC is administered with a low-dose flutamide-metformin combination in women with PCOS, the beneficial effects are maintained on hyperinsulinaemia-dyslipidaemia, which are key determinants of long-term complications. Hence, in daily practice, such a low-dose quatuor may become a therapeutic option of first choice for young women with PCOS.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgen Antagonists / administration & dosage*
  • Cohort Studies
  • Contraceptives, Oral / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Flutamide / administration & dosage*
  • Humans
  • Hyperandrogenism / drug therapy
  • Hyperandrogenism / etiology
  • Hyperinsulinism / drug therapy
  • Hyperinsulinism / etiology
  • Hyperlipidemias / drug therapy
  • Hyperlipidemias / etiology
  • Metformin / administration & dosage*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / drug therapy*
  • Sex Hormone-Binding Globulin / analysis

Substances

  • Androgen Antagonists
  • Contraceptives, Oral
  • Sex Hormone-Binding Globulin
  • Flutamide
  • Metformin