Changes in the length of the menstrual cycle are not typically monitored or identified as adverse effects during trials of medications, although shortening and lengthening of the menstrual cycle have been noted occasionally during studies of fluoxetine. Steiner and colleagues studied the effect of fluoxetine on menstrual patterns in women who previously reported having stable cycle lengths.

Women 20 to 45 years of age were recruited from seven Canadian university clinics. All participants had mood-change symptoms associated with premenstrual syndrome (PMS) that failed to respond to lifestyle, dietary and exercise interventions. Women were excluded if they were pregnant or lactating, taking psychoactive or contraceptive medications, had ever taken fluoxetine, had seizure disorders or other medical conditions, or reported having irregular menstrual cycles. After extensive clinical and laboratory testing, all patients received a placebo for two cycles. Those who did not respond to the placebo were randomly assigned to receive fluoxetine, in a dosage of 20 or 60 mg daily, or placebo. All treatment began on the first day of the menstrual cycle. Compliance was verified by pill counts, reports by the participants and, in 15 percent of the group, by measurement of serum fluoxetine levels. Patients kept records of menstrual flow as part of the data gathered on PMS symptoms.

A total of 313 women entered the treatment phase of the study, and 193 of these were randomized into one of three groups. Sixty-one women were given placebo, 70 were given 20 mg of fluoxetine daily and 62 were given 60 mg of fluoxetine daily. The mean age of the participants was 36 years. All of the women were high school graduates, approximately one half were married, and 70 percent had at least one child. At the end of the first treatment cycle, 11 (18 percent) of those receiving the 60-mg dosage and seven (10 percent) of those receiving the 20-mg dosage reported cycle lengthening or shortening of at least four days compared with baseline. Only one woman in the placebo group reported such a change. Over the three cycles studied, nine women (15 percent) taking the 60-mg dosage and four women (6 percent) taking the 20-mg dosage reported changes in cycle length, compared with two women (3 percent) taking placebo. Fluoxetine lengthened the cycles of eight women and shortened the cycles of 10 women by at least four days. The differences were statistically significant, showing a dose-dependent effect on menstrual cycle length. This effect disappeared within one to two cycles when the medication was discontinued.

The authors conclude that fluoxetine can cause changes in menstrual patterns, and they propose several explanations for the fluctuations. Since this drug is widely used in women of reproductive age, further research into its effects on menstruation, fertility and sexual behavior is indicated.