Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate: two-year substudy results.

Abstract

OBJECTIVE:

To determine the endometrial safety of 2 years of treatment with lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA).

DESIGN:

Randomized, double-blind, placebo-controlled, multicenter metabolic and osteoporosis substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study.

SETTING:

Nineteen study centers across the United States.

PATIENT(S):

Healthy, postmenopausal women (n = 822) with an intact uterus were recruited.

INTERVENTION(S):

Patients received CEE 0.625, CEE 0.625/MPA 2.5, CEE 0.45, CEE 0.45/MPA 2.5, CEE 0.45/MPA 1.5, CEE 0.3, CEE 0.3/MPA 1.5 (all doses mg/day), or placebo for 2 years. Endometrial biopsies were evaluated at baseline and years 0.5, 1, 1.5, and 2 using a centralized protocol.

MAIN OUTCOME MEASURE(S):

Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed estrogen (E).

RESULT(S):

No cases of endometrial hyperplasia were seen in the four CEE/MPA groups. For the CEE-alone groups, a dose-related increase in incidence rates from 3.17% (CEE 0.3 mg) to 27.27% (CEE 0.625 mg) was seen at 2 years. The number of cases increased from year 1 to year 2. For the CEE-alone groups, the incidence rates and types of hyperplasia diagnosed varied among the pathologists.

CONCLUSION(S):

Two years of treatment with lower doses of CEE/MPA provided endometrial protection comparable to that seen with commonly prescribed doses. These regimens should be considered for postmenopausal women who are candidates for hormone therapy.

• Authors: James H Pickar, I Tien Yeh, James E Wheeler, Mary F Cunnane, Leon Speroff
• Journal: Fertility and sterility (Fertil Steril) Vol. 80 Issue 5 Pg. 1234-40 (Nov 2003) ISSN: 0015-0282 [Print] United States
• PMID: 14607581 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Estrogens, Conjugated (USP)
• Placebos
• Medroxyprogesterone Acetate

Topics

• Adult
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Endometrial Hyperplasia (epidemiology)
• Estrogen Replacement Therapy
• Estrogens (administration & dosage)
• Estrogens, Conjugated (USP) (administration & dosage)
• Female
• Humans
• Incidence
• Medroxyprogesterone Acetate (administration & dosage)
• Middle Aged
• Placebos