Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome

N Engl J Med. 1998 Jan 22;338(4):209-16. doi: 10.1056/NEJM199801223380401.


Background: The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome.

Methods: We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales.

Results: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration.

Conclusions: In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Emotions / drug effects*
  • Estradiol / pharmacology*
  • Estradiol / physiology
  • Female
  • Gonadotropin-Releasing Hormone / agonists*
  • Hot Flashes / chemically induced
  • Humans
  • Leuprolide / adverse effects
  • Leuprolide / pharmacology*
  • Leuprolide / therapeutic use
  • Middle Aged
  • Premenstrual Syndrome / drug therapy
  • Premenstrual Syndrome / physiopathology*
  • Premenstrual Syndrome / psychology
  • Progesterone / pharmacology*
  • Progesterone / physiology


  • Gonadotropin-Releasing Hormone
  • Progesterone
  • Estradiol
  • Leuprolide