Maddocks, S., Hahn, P., Moller, F., & Reid, R. L. (1986). A double-blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome. American Journal of Obstetrics and Gynecology, 154(3), 573-581. https://doi.org/10.1016/0002-9378(86)90604-6
Maddocks S, Hahn P, Moller F, Reid RL. A double-blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome. Am J Obstet Gynecol. 1986;154(3):573-581. doi:10.1016/0002-9378(86)90604-6
Maddocks, Sarah, et al. "A double-blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome." American Journal of Obstetrics and Gynecology, vol. 154, no. 3, 1986, pp. 573-581.
Vaginal progesterone did not significantly beat placebo in severe PMS
Women with severe premenstrual syndrome improved about as much on vaginal progesterone as on placebo in a double-blind crossover trial. The analysis covered 20 women who kept symptom diaries for eight months. Symptoms eased a little during both treatments. In the final month, with no treatment, symptoms moved back toward pretreatment levels.
Study at a glance, randomized, double-blind crossover trial of 20 women: Vaginal progesterone did not significantly beat placebo in PMS. Source: Maddocks S et al., 1986, PMID 3513587.
Key Findings
Of 79 women referred, 48 consented. Records from 20 who completed all eight months were analyzed: 11 received progesterone first and 9 received placebo first.
Analysis of variance for repeated measures found no significant differences between progesterone and placebo on any of five symptom rating scales in any treatment cycle, including the third.
Premenstrual Beck Depression Inventory scores were 10.6 ± 1.2 on progesterone and 10.9 ± 1.1 on placebo. Moos Menstrual Distress Questionnaire scores were 94.3 ± 4.5 and 94.4 ± 4.4.
Scores were higher in the first no-treatment month than in some progesterone and placebo months. Symptoms moved back toward pretreatment severity in the final no-treatment month.
Plasma lipoprotein patterns in 17 women showed no significant differences between no-treatment, progesterone and placebo cycles.
Interpretation
This was a randomized, double-blind crossover trial. Each woman used vaginal progesterone and placebo for three months each, in random order. Women had to meet strict criteria for severe premenstrual syndrome, confirmed by daily symptom diaries. The authors note the placebo and progesterone suppositories did not look or feel exactly alike. The findings support larger studies of vaginal progesterone for severe PMS.
RRM Context
Restorative reproductive medicine charts the cycle first and looks for the cause of PMS symptoms. Progesterone is the body's own hormone made after ovulation. This trial tested one form of it in severe PMS.
Our editorial summary of this paper, not the article's abstract.
Abstract
Rigorous criteria were used to select women with severe premenstrual syndrome for inclusion in an 8-month double-blind placebo-controlled clinical trial of progesterone vaginal suppositories. Following a control month without treatment, progesterone (200 mg in polyethylene glycol base) or placebo was self administered twice daily by vaginal suppository for a minimum of 12 days before the onset of menstruation for 3 months. Crossover to the opposite medication for a further 3 months was followed by a final control cycle without treatment in month 8. Physician contact was minimized throughout the study to avoid any possible positive effects of psychological support which may have confounded past investigations. Detailed self-report questionnaires were completed every 3 days for the duration of the study. Although the attrition rate was high, 20 women completed the trial and their records are analyzed here. The results of this trial indicate that the response to vaginal progesterone in these dosages is, at best, marginal and not significantly different from response with placebo use.
