No Evidence to Support the Use of Progesterone in the Management of Premenstrual Syndrome (PMS)

Researchers from the United Kingdom reported in the October 6, 2001 issue of the British Medical Journal that published medical evidence does not support the use of progesterone in the treatment of premenstrual syndrome (PMS) and that it is unlikely that progestogens are effective in this disorder.

Progesterone is a naturally occurring hormone produced in women’s bodies and progestogens are synthetic variations of progesterone. The progestogens medroxy-progesterone (PROVERA) and norethisterone known in the U.S. as norethindrone (AYGESTIN), both marketed in this country, and dydrogesterone, an agent not available in the U.S., were included in the research.

There are several Food and Drug Administration regulated progesterone products on the market. Examples are PROMETRIUM capsules and CRINONE, a vaginal gel preparation. None of the progesterone or progestogen products are approved for the treatment of PMS. When these drugs are prescribed for PMS it is being done without proof that they are effective or safe for this use. Prescribing drugs in this manner is referred to as “off-label” prescribing. No laws or regulations exist that prevent physicians from prescribing drugs for off-label uses and there is no requirement that patients be informed that they are receiving a drug for what amounts to an experimental use.

The U.K. study is a meta-analysis, which is a statistical summary of clinical trials. The researchers identified clinical trials involving the use of progesterone or progestogens in the management of PMS. Those clinical trials that met a predefined quality standard were included in the meta-analysis. There were 10 trials of progesterone treatment in 531 women and four trials of progestogen use in 378 women with PMS that were deemed of sufficient quality to be included in the study.

The main outcome measure the researchers evaluated was the proportion of women whose PMS symptoms showed improvement with progesterone or progestogen preparations. For progesterone preparations, either oral or suppositories, no clinically important difference was found between this drug and placebo. In the progestogen trials there was a statistically positive finding, but not a clinically significant improvement in symptoms for women using a progestogen.

In the absence of large randomized controlled clinical trials, the scientific “gold standard,” meta-analyses offer the best evidence of the therapeutic value of a treatment. One disadvantage of meta-analyses based only on published studies is that published clinical trials tend to be those with a positive result, in this case a positive effect for progesterone or progestogen. This is known as publication bias which can lead to an overestimation of the benefit of a treatment.

The authors of the study included a very interesting discussion of the rationale for use of progesterone or progestogens in PMS. The use of these drugs is based on the unsubstantiated premise that progesterone deficiency is the cause of PMS. The authors point out that initial studies suggested there were abnormal concentrations of the breakdown products of progesterone; however there is no consistent evidence that low concentrations of this hormone are found in women with PMS.

The off-label use of progesterone and progestogens in PMS illustrates a frequent error on the part of those who view the human body as a simple machine. The ability of biochemists and other scientists to identify chemical reactions and measure levels of naturally occurring chemicals in the body has led to the belief that manipulation of these chemicals is all that is needed for good health. Add a little estrogen to protect the heart after menopause, fine tune serotonin levels to lose weight, or top up with progesterone for PMS are presented as solutions. When the aforementioned practices are carefully studied, it becomes apparent that billions of dollars have been spent on worthless remedies and there is a realization that a lot of people needlessly suffered adverse drug reactions from these treatments.

Progesterone and progestogens are significantly associated with serious drug reactions. These include blood-clotting disorders that can lead to clots in the legs, stroke, and blindness. Also, there is an increased risk of minor birth defects in children whose mothers take these drugs during the first four months of pregnancy. Several reports suggest an association between mothers who take these drugs in the first trimester of pregnancy and genital abnormalities in male and female babies.

What You Can Do

You should avoid the use of progesterone and progestogens to manage the symptoms of PMS. The best evidence does not support their use in PMS.