PMS: A Response to Normal Hormonal Changes
ABSTRACT & COMMENTARY
Synopsis: The symptoms of the premenstrual syndrome represent an abnormal response to normal hormonal changes.
Source: Schmidt PJ, et al. N Engl J Med 1998;338:209-216.
Schmidt and colleagues from the national Institute of Mental Health designed a study to examine the role of estrogen and progesterone in the premenstrual syndrome. In many women with established PMS, the effects of ovarian suppression with the GnRH agonist were compared to placebo, following which 10 women in a double-blind, crossover study were given estradiol or progesterone and, finally, the two together each for four weeks. Estradiol was administered as the 100 g patch, providing an average blood level of 110 pg/mL, and progesterone was administered as vaginal suppositories, 200 mg bid, providing an average blood level of 11.8 ng/mL. Ten women with PMS receiving leuprolide experienced an improvement in the rating of common symptoms of PMS. In 15 normal women, there was no change. In the women who improved receiving leuprolide, the administration of either estradiol or progesterone increased their symptoms, in contrast to the normal women who once again had no change. Schmidt et al conclude that the symptoms of PMS represent an abnormal response to normal hormonal changes.
COMMENT BY LEON SPEROFF, MD
This study confirms previous reports that suppression of ovarian function with a GnRH agonist can eliminate PMS symptoms. However, it should be pointed out that this is not a universal response. In this study, 10 of 18 women with PMS improved. In general, this treatment can achieve success in 60-70% of women with PMS.
The surprising finding in this study was the worsening of symptoms with both estradiol and progesterone. It triggered a series of speculations such as the possibility that estradiol fluctuations early in the menstrual cycle may create a central nervous system response that leads to the symptom reaction in women who are susceptible. The problem presumably lies within the central nervous system with a mechanism that determines susceptibility. The important point is that women with PMS do not have abnormalities in their reproductive hormones.
It is now well demonstrated by appropriately designed studies that the most effective treatment for PMS is either elimination of the menstrual cycle or serotonin reuptake inhibitors. Long before these studies were available, it had been my practice to treat patients with PMS by eliminating the menstrual cycle with relatively inexpensive methods such as the daily administration of an oral contraceptive or Depo-Provera. From a cost-effective point-of-view, this still makes sense, and many patients have a gratifying response. The next choice of therapy would be one of the serotonin reuptake inhibitors, and an empirical approach is warranted. It is not necessary to treat many of these patients every day, but a period of treatment from seven to 10 days during the luteal phase can be effective. Because of the expense, which includes the necessity of hormonal add-back therapy, I would reserve treatment with a GnRH agonist and certainly bilateral oophorectomy for extremely difficult patients who are unresponsive to initial therapy.
We have certainly made progress in our understanding and treatment of PMS. No longer is there a place for progesterone therapy, as it accomplishes no more than a placebo response.1 (Dr. Speroff is Professor of Obstetrics and Gynecology, Oregon Health Sciences University, Portland.)
Reference
1. Freeman E, et al. JAMA 1990;264:349-353.
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