The Postmenopausal Estrogen/Progestin Interventions Study: primary outcomes in adherent women

Maturitas. 1997 Jul;27(3):261-74. doi: 10.1016/s0378-5122(97)00041-8.


Objective: To assess the efficacy of unopposed estrogen, and three estrogen/progestin regimens on selected heart disease risk factors among adherent women and to contrast those results with efficacy among all women in the PEPI study.

Design: A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial.

Participants: A total of 847 healthy postmenopausal women aged 45 to 64 years of age with no known contraindication to hormone therapy, who attended their 36 month clinical visit.

Intervention: Participants were randomized in equal numbers to one of the following treatments: (1) placebo; (2) conjugated equine estrogen (CEE) 0.625 mg daily; (3) CEE 0.625 daily plus medroxyprogesterone acetate (MPA) 10 mg, days 1-12; (4) CEE 0.625 daily plus MPA 2.5 mg daily; or (5) CEE 0.625 daily plus micronized progesterone (MP) 200 mg, days 1-12.

Analysis: Analyses are based on adherent women, where adherence is defined as taking at least 80% of pills at each 6-month visit.

Results: Adherence rates were high in all groups except women with a uterus assigned to unopposed CEE. The difference in HDL-C levels resulting from the CEE vs. CEE+MP was approximately three times larger than in the intent-to-treat analyses, reaching statistical significance (P < 0.05). In each active treatment, LDL-C decreased 10-15%. Triglycerides increased 15-20% in each opposed CEE arm and over 25% in the CEE only arm; this difference was not statistically significant. Fibrinogen increased by 7% among placebo adherers, but decreased or remained fairly stable among the active arm adherers. Systolic blood pressure increased 3-5% in all treatment arms. Women adherent to the CEE+MPA arms had twice the increase of 2 h glucose levels as women adherent to CEE only, or CEE+MP (8-9% vs. 3-4%). Two-hour insulin levels decreased 3-12% for all arms. The patterns of change for fibrinogen, SBP, 2 h glucose and insulin were similar to those from the intent-to-treat analyses.

Conclusions: In analyses limited to adherent women, all active treatments, compared to placebo, continued to have similar and favorable effects on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or insulin levels. Given the overall high adherence rates in PEPI, the results are similar to the intent-to-treat analyses, as expected. Only the trend of HDL-C to have a larger increase in the CEE only arm (in the intent-to-treat analyses) gained statistical significance in analyses restricted to adherers.

Publication types

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

MeSH terms

  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Climacteric / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy* / adverse effects
  • Estrogens, Conjugated (USP) / administration & dosage
  • Estrogens, Conjugated (USP) / adverse effects
  • Fibrinogen / metabolism
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Medroxyprogesterone Acetate / administration & dosage
  • Medroxyprogesterone Acetate / adverse effects
  • Middle Aged
  • Progesterone / administration & dosage
  • Progesterone / adverse effects
  • Progestins / administration & dosage*
  • Progestins / adverse effects
  • Treatment Outcome
  • Triglycerides


  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Estrogens, Conjugated (USP)
  • Insulin
  • Progestins
  • Triglycerides
  • Progesterone
  • Fibrinogen
  • Medroxyprogesterone Acetate