Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice

Br J Clin Pharmacol. 2002 May;53(5):469-73. doi: 10.1046/j.1365-2125.2002.01575.x.


Aims: To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome (PCOS) in an infertility clinic.

Methods: This was a randomized placebo controlled double-blind crossover study of 3 months metformin (1500 mg day-1)/placebo, followed by 3 months metformin/placebo together with clomiphene (50-100 mg for 5 days) for three cycles in clomiphene resistant women with PCOS. The primary outcomes were restoration of spontaneous menses, ovulation induction (spontaneous or clomiphene induced) and pregnancy. Secondary endpoints were changes in biochemical parameters related to androgens and insulin.

Results: Twelve women completed the metformin arm and 14 the placebo arm. Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women, P=0.63. No women given metformin spontaneously ovulated, although one patient given placebo did, P=0.30. There was no difference in the efficacy of clomiphene between the two groups with ovulation being induced in five (out of 12) metformin treated women and four (out of 14) placebo treated women, P=0.63. Pregnancy occurred in three (out of 12) women given metformin and two (out of 14) women given placebo, P=0.59.

Conclusions: Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Clomiphene / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Resistance
  • Female
  • Fertility Agents, Female / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Infertility, Female / drug therapy
  • Infertility, Female / etiology
  • Metformin / therapeutic use*
  • Ovulation Induction*
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Rate
  • Treatment Failure


  • Fertility Agents, Female
  • Hypoglycemic Agents
  • Clomiphene
  • Metformin