Metformin & PCOS Treatment

Occasionally, my patients express some confusion over the drug Metformin (brand name: Glucophage). They've heard it is a fertility drug but are thrown off by the fact that it is an FDA-approved drug for type 2 diabetes. Indeed, metformin is used as a fertility medication as it is a promising treatment in the portfolio of ovulation induction medications for women with polycystic ovary syndrome (PCOS).

Many women with PCOS suffer from insulin resistance (high blood insulin levels), a problem that is thought to possibly impede ovulation and elevate male hormone levels.

By way of background, PCOS is experienced by as many as 10 percent of women of reproductive age. An inability to ovulate normally and problems associated with an overproduction of male type hormone are typical findings in women diagnosed with PCOS. The “polycystic” aspect can be seen in the ovaries via ultrasound, which reveals a large multitude of tiny follicular cysts instead of a smaller group of well-defined emerging follicles preparing for ovulation.

Many women with PCOS respond well to clomiphene citrate (brand name: Clomid), which stimulates increased blood levels of FSH (follicle stimulating hormone) and LH (luteinizing hormone) to induce the growth of a follicle and eventual ovulation. Approximately 70% of patients treated with clomiphene citrate will ovulate and 40% will conceive, the majority within three to six ovulatory cycles.

A small fraction of patients who see no improvement from clomiphene treatment alone are good candidates for metformin, or a combination of clomiphene and metformin. Offering metformin provides such women with an alternative oral medication before being directed to the injectable stimulation medications. As an insulin-sensitizing medication, metformin decreases insulin levels, which is thought to help restore the normal ovarian hormone profile (reduces male hormone), thus allowing for spontaneous growth of a follicle and ovulation to occur. Alternatively, metformin enables the patient to become more sensitive to clomiphene. It is important to note that of those patients who do not ovulate on clomiphene alone, most benefit by the combination of metformin with clomiphene.

Metformin and other insulin-sensitizing medications may offer other benefits for women with PCOS, who are reported to be three times more prone to early pregnancy loss compared to ovulatory women. In several reports involving as yet small populations of PCOS patients, the use of these drugs appears to significantly reduce the rate of early miscarriage. One must approach this news with caution, however, until prospective controlled trials on this topic are conducted.