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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.
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Accepted: April 4, 1997
Received in revised form: April 3, 1997
Received: January 20, 1997
☆See Appendix A for key PEPI personnel list.
© 1997 Published by Elsevier Inc.