A 46-year-old woman of Euroasian descent had been treated for 2 years with 500 mg metformin twice daily for polycystic ovarian disease (PCO). While menarche occurred at age 12 years, she had no more than two to three menstrual periods per year except on two occasions in her 20s when, following a 9- to 10-kg weight loss, she achieved regular menstrual periods, became pregnant, and delivered two healthy infants with no complications.
While being treated with metformin, the woman was diagnosed as having diabetes based on two fasting serum glucoses tests >7 mmol/l. She was switched to a combination tablet containing 2-mg rosiglitazone and 500 mg metformin twice daily. Following this change, her serum total testosterone dropped from 2.5 to 1.12 nmol/l and her menstrual periods became regular for 4 months, after which she became amenorrheic. Because of her age and history of PCO, this did not cause concern, even though she had no menopausal symptoms. Six months later, after presenting with abdominal pain, it was discovered by ultrasonography that she was 30 weeks’ pregnant. Metformin and rosiglitazone were discontinued, and she was started on insulin therapy. At 36 weeks’ gestation she became hypertensive and at 37 weeks delivered a healthy 3.4-kg baby girl without neonatal complications.
Spontaneous pregnancy in this age range is unusual and has been estimated to be near 0% (1). The average age of last conception in a stable North American population (Hutterites) not practicing contraception was 40.9 years (1). This age-related decrease in fertility is attributed to loss of oocytes through years of ovulation. However, it has recently been noted that there is an increase in primary follicles in polycystic ovaries, a phenomenon described as “stockpiling,” possibly due to anovulation or stasis (2). We suggest that in PCO patients, even in the age range where the rate of spontaneous pregnancy is low, utilization of thiazolidinediones should be accompanied by concurrent contraceptive use. These patients may achieve a more favorable hormonal milieu for ovulation in the setting of “stockpiled” ovarian follicles.
This case is also unique in that the patient was older and the length of rosiglitazone exposure longer than in the previous two reports of rosiglitazone exposure during pregnancy. Despite the known presence of rosiglitazone in fetal tissue, three reports have now documented normal fetal outcomes (3–5).
