A DOUBLE-BLIND TRIAL OF ORAL PROGESTERONE, ALPRAZOLAM, AND PLACEBO INTREATMENT OF SEVERE PREMENSTRUAL-SYNDROME

Objective.-To determine the effectiveness of oral micronized progester one, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. Design.-Ran domized, double-blind, placebo-controlled 3-month parallel treatment a rms with flexible dosage and with the length of clinical contact rando mized within each treatment group. Setting.-University hospital PMS me dical treatment outpatient program in obstetrics/gynecology department . Subjects.-Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatm ent data are available for 170. There were no medical withdrawals for adverse events. Intervention.-A double-blinded protocol in which 300 m g of oral micronized progesterone, 0.25 mg of alprazolam, or placebo w as administered four times a day from day 18 of the menstrual cycle th rough day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazol am. Subjects were randomized to brief (<20 minutes) or extended (50 mi nutes) visits. Main Outcome Measures.-Daily symptom report (DSR) scare d for total DSR symptoms, four DSR factors. Results.-Alprazolam was si gnificantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-s even percent of the alprazolam group experienced a 50% reduction in to tal DSR scores. There were no clinically significant withdrawal sympto ms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment resp onse was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. Conclusions.-Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phas e. Oral micronized progesterone is ineffective for PMS.