OBJECTIVE: To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. DESIGN: Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. SETTING:University hospital PMS medical 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; treatment data are available for 170. There were no medical withdrawals for adverse events. INTERVENTION: A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through 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 alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. MAIN OUTCOME MEASURES: Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. RESULTS:Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms 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 response 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 phase. Oral micronized progesterone is ineffective for PMS.
RCT Entities:
OBJECTIVE: To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. DESIGN: Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. SETTING: University hospital PMS medical 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; treatment data are available for 170. There were no medical withdrawals for adverse events. INTERVENTION: A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through 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 alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. MAIN OUTCOME MEASURES: Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. RESULTS:Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms 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 response 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 phase. Oral micronized progesterone is ineffective for PMS.