The Pharmaceutical Journal
Vol 278 No 7438 p158
10 February 2007

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Clomifene better than metformin for PCOS infertility

Clomifene is more useful than metformin for helping women with polycystic ovary syndrome (PCOS) achieve pregnancy, report US researchers (New England Journal of Medicine 2007;356:551).

They explain that women with PCOS frequently experience insulin resistance and that previous studies have shown that insulin sensitisers such as metformin can increase ovulation. Several smaller studies have also suggested that metformin, either taken alone or with clomifene, can result in greater fertility rates for PCOS patients than clomifene taken alone.

The researchers randomly assigned 626 infertile women with PCOS to one of three treatments: clomifene plus placebo, metformin plus placebo, or metformin plus clomifene. After six months follow up, fewer women in the metformin-only group had given birth compared with either of the clomifene groups (7.2 per cent compared with 22.5 per cent for clomifene only and 26.8 per cent for the group taking both metformin and clomifene).

Compared with other women, obese women were less likely to conceive during the course of the study and were less likely to ovulate in response to metformin. The researchers note that women in the combination therapy group ovulated more frequently than women in either the clomifene-alone or the metformin-alone groups. However, the tendency to ovulate more frequently did not translate into a significantly greater number of pregnancies for the combination group.

“Our results show that you can’t use ovulation as a surrogate for pregnancy,” lead investigator Richard Legro, Pennsylvania State University College of Medicine, said. “An ovulation on clomifene treatment is twice as likely to result in pregnancy as an ovulation on metformin.”

The researchers also report that women who became pregnant in the clomifene groups had more occurrences of multiple pregnancy: 6.0 per cent for the clomifene-only group, 3.1 per cent for the combination group and 0 per cent for the metformin group.

They also note that although metformin alone did not improve the chances for pregnancy, it was useful for lowering the high blood testosterone levels that occur with PCOS.