Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate.
OBJECTIVE
To determine the endometrial safety of lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA).


METHODS
Randomized, double-blind, placebo-controlled study (the Women's Health, Osteoporosis, Progestin, Estrogen study).


METHODS
Study centers across the United States.


METHODS
Healthy, postmenopausal women (n = 2,673) with an intact uterus.


METHODS
Patients received CEE 0.625 mg/day, CEE 0.625/MPA 2.5 mg/day, CEE 0.45 mg/day, CEE 0.45/MPA 2.5 mg/day, CEE 0.45/MPA 1.5 mg/day, CEE 0.3 mg/day, CEE 0.3/MPA 1.5 mg/day, or placebo for 1 year. Endometrial biopsies were evaluated at baseline, cycle 6, and year 1 using a centralized protocol.


METHODS
Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed CEE.


RESULTS
Endometrial hyperplasia rates ranged from 0 to 0.37% for all CEE/MPA doses. Twenty-nine of the 32 cases of endometrial hyperplasia developed in women who were administered CEE 0.625 mg or CEE 0.45 mg. The incidence of endometrial hyperplasia increased with age for patients administered CEE alone. As expected, there were some inconsistencies among pathologists' ratings in the numbers of hyperplasias and incidence rates for the CEE-alone regimens. There were too few cases of hyperplasia in the combination groups to evaluate consistency among pathologists.


CONCLUSIONS
One year of treatment with lower doses of CEE/MPA provides endometrial protection comparable to commonly prescribed doses. These regimens may be used by clinicians to individualize hormone replacement therapy in postmenopausal women.
Pickar
J H
JH
Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, Pennsylvania, USA. pickarj@war.wyeth.com
Yeh
I
I
Wheeler
J E
JE
Cunnane
M F
MF
Speroff
L
L
D000328:Adult; D000375:Aging / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000453:epidemiology; D004717:Endometrium / Q000187:drug effects*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006736:Horses; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate