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


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


METHODS
Nineteen study centers across the United States.


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


METHODS
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.


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


RESULTS
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.


CONCLUSIONS
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.
Pickar
James H
JH
Wyeth Research, Philadelphia, Pennsylvania 19101-2528, USA. pickarj@wyeth.com
Yeh
I Tien
IT
Wheeler
James E
JE
Cunnane
Mary F
MF
Speroff
Leon
L
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000453:epidemiology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D010919:Placebos
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D010919:Placebos; D017258:Medroxyprogesterone Acetate