Progesterone for premenstrual syndrome
Abstract
Background
Premenstrual Syndrome (PMS) is the term for severe symptoms experienced by about 5% of menstruating women up to two weeks before their menstrual periods, but not at other times. Treatment with progesterone may restore a deficiency, or balance the level of progesterone with other menstrual hormones. Progesterone therapy may reduce the effects of falling progesterone levels on the brain or on electrolytes in the blood.
Objectives
The objectives were to determine if progesterone has been found to be an effective treatment for all or some premenstrual symptoms, and if adverse events associated with this treatment have been reported.
Search methods
We last searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to 2005) and EMBASE (1980 to 2005) in March 2005, and PsycINFO (1806 to 2006) in April 2006. We contacted pharmaceutical companies for information about unpublished trials.
Selection criteria
We included randomised double‐blind, placebo‐controlled trials of progesterone on women with PMS diagnosed by at least two prospective cycles, without current psychiatric disorder.
Data collection and analysis
Two reviewers (BM and OF) extracted data independently, and decided on the trials to be included. OF wrote to the trial investigators to ask for missing data.
Main results
We considered 17 studies . We included two trials totalilng 280 participants aged from 18 to 45 years. Of these 115 yielded analysable results. Both studies measured outcomes using subjective scales of symptom severity but made calculations as if they were interval data. The two studies differed in design, participants, dose of progesterone, how and when the dose was administered and in outcome measures. It was impossible to combine data in a meta‐analysis.
Adverse events which may or may not have been the side effects of the treatment, were generally described as mild.
Both trials intended to exclude women whose symptoms continued after their periods; unfortunately the larger multicentre study had some ineligible participants. Overall, participants benefited more from progesterone than placebo. This was statistically significant in per protocol analysis but not in the intention‐to‐treat analysis, except for the first cycle. The smaller, crossover study found no statistically significant difference between oral progesterone, vaginally absorbed progesterone and placebo.
Authors' conclusions
We could not say that progesterone helped women with PMS, nor that it was ineffective. Neither trial distinguished a subgroup of women who benefited.
PICOs
Plain language summary
There is only a little good evidence for treating premenstrual syndrome with progesterone
Five per cent or more of women experience symptoms, severe enough to damage work and relationships, only in the days leading to their menstrual periods. Blood progesterone levels usually rise after ovulation and fall again before menstruation. It has been suggested that premenstrual syndrome (PMS) might have been caused by too little progesterone or falling levels.
This review found some evidence for relief with progesterone, but trials differed in route of administration, dose, duration of treatment and selection of participants. Not unexpectedly, outcomes also differed. The studies all had flaws in method and handling outcome data.
Adverse effects which may or may not have been the result of the treatment were generally mild.
Claims in the literature based on observational evidence, for the effectiveness of very high doses of progesterone, have not been refuted nor borne out as yet. Further research with higher doses would be needed. Selection of participants and assessment of outcomes using each woman's own symptoms would be more sensitive than checklists of largely irrelevant symptoms. Knowing the number of women who had fewer days with symptoms, fewer or milder symptoms, or the converse, would be more valuable than calculations based on subjective data for groups of women.
