Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial

Obstet Gynecol. 1998 Dec;92(6):982-8. doi: 10.1016/s0029-7844(98)00305-6.


Objective: To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms.

Methods: This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45-64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups.

Results: In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17-0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92-2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61-0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62-0.68).

Conclusion: These results confirm the usefulness of post-menopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Double-Blind Method
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Feeding and Eating Disorders / chemically induced
  • Female
  • Headache / chemically induced
  • Humans
  • Medroxyprogesterone Acetate / therapeutic use*
  • Memory / drug effects
  • Middle Aged
  • Mood Disorders / chemically induced
  • Neurobehavioral Manifestations / drug effects
  • Vasomotor System / drug effects
  • Vasomotor System / physiopathology
  • Weight Gain / drug effects


  • Estrogens, Conjugated (USP)
  • Medroxyprogesterone Acetate