INVESTIGATION OF THE EFFICACY OF PROGESTERONE PESSARIES IN THE RELIEFOF SYMPTOMS OF PREMENSTRUAL-SYNDROME

Background A variety of definitions have been applied to premenstrual syndrome. The severity of the syndrome is also variable. Aim. A study was undertaken to compare progesterone pessaries with placebo in the r elief of symptoms of premenstrual syndrome. In this study the conditio n was characterized by a wide range of symptoms recurring in the late luteal phase but absent in the follicular phase (that is, the specific definition published by Dalton in 1953). Method. A multicentre, prosp ective, double-blind, randomized, parallel group study was undertaken by 45 general practitioners. Patients were deemed eligible after two p rospective menstrual cycles of observation (selection phase) in which a precise definition of symptoms was applied. Patients were randomized to use either progesterone pessaries (400 mg twice a day) or matching placebo, by vaginal or rectal administration, from 14 days before the expected onset of menstruation until the onset of vaginal bleeding, f or four consecutive cycles. Baseline data for the outcome variables we re determined in the selection phase. The main outcome variables were changes in the severity (categorized as none, mild, moderate or severe ) of each patient's most severe symptom, and in the average score of a ll the patient's symptoms characteristic of premenstrual syndrome. Spo ntaneous reports of adverse events were recorded. Results. A total of 281 patients were screened for premenstrual syndrome; of these, 141 pa tients were randomized to treatment or placebo groups. Efficacy was ev aluated in 93 patients. Reductions in the scores of the highest scorin g, most severe, symptoms and in the average symptom score, were consis tently observed in patients receiving progesterone pessaries and in th ose receiving placebo. The response to progesterone was greater than t o placebo during each cycle; the differences were clinically and stati stically significant. Adverse events were reported by 51% of patients in the progesterone treatment group and by 43% in the placebo group. I rregularity of menstruation, vaginal pruritus and headache were report ed more frequently by patients taking active therapy. Conclusion. In t his study, progesterone, given as pessaries by vaginal or rectal admin istration, was more effective than placebo in the relief of symptoms o f premenstrual syndrome in a population of patients selected by strict entry criteria.