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

Abstract

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.

• Authors: E Barrett-Connor, S Slone, G Greendale, D Kritz-Silverstein, M Espeland, S R Johnson, M Waclawiw, S E Fineberg
• Journal: Maturitas (Maturitas) Vol. 27 Issue 3 Pg. 261-74 (Jul 1997) ISSN: 0378-5122 [Print] Ireland
• PMID: 9288699 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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, adverse effects)
• Fibrinogen (metabolism)
• Glucose Tolerance Test
• Humans
• Insulin (blood)
• Medroxyprogesterone Acetate (administration & dosage, adverse effects)
• Middle Aged
• Progesterone (administration & dosage, adverse effects)
• Progestins (administration & dosage, adverse effects)
• Treatment Outcome
• Triglycerides