Abstract
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.
premenstrual syndrome estrogen progesterone abnormal response, Schmidt Rubinow PMS leuprolide GnRH agonist suppression, ovarian suppression premenstrual syndrome symptom relief, estradiol progesterone add-back PMS symptom recurrence, GnRH agonist double-blind crossover premenstrual syndrome, gonadal steroids behavioral effects premenstrual syndrome, premenstrual syndrome normal hormonal changes abnormal response, leuprolide treatment PMS estrogen progesterone challenge, ovarian function suppression mood symptoms premenstrual women, neuroendocrine sensitivity progesterone estrogen PMS pathophysiology
PMID 9435325 9435325 DOI 10.1056/NEJM199801223380401 10.1056/NEJM199801223380401
Keywords
Adult, Cross-Over Studies, Double-Blind Method, Emotions/drug Effects, Estradiol/pharmacology/physiology, Female, Gonadotropin-Releasing Hormone/agonists, Hot Flashes/chemically Induced, Humans, Leuprolide/adverse Effects/pharmacology/therapeutic Use, Middle Aged, Premenstrual Syndrome/drug Therapy/physiopathology/psychology, Progesterone/pharmacology/physiology, Gonadotropin-Releasing Hormone, Progesterone, Estradiol, Leuprolide