Context The effects of continuous combined hormone therapy on gynecologic cancers
have not been investigated previously in a randomized trial setting.
Objective To determine the possible associations of estrogen plus progestin on
gynecologic cancers and related diagnostic procedures.
Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal
women, who had not had a hysterectomy at baseline and who had been recruited
from 40 US clinical centers between September 1993 and October 1998 (average
follow-up, 5.6 years).
Intervention One tablet per day containing 0.625 mg of conjugated equine estrogens
plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).
Main Outcome Measure Incident invasive cancer of the ovary and endometrium.
Results In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer,
58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13
cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard
ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus
progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24).
The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable
differences were found in the distributions of tumor histology, stage, or
grade for either cancer site. The incidence of other gynecologic cancers was
low and did not differ by randomization assignment. More women taking estrogen
plus progestin required endometrial biopsies (33% vs 6%; P<.001).
Conclusions This randomized trial suggests that continuous combined estrogen plus
progestin therapy may increase the risk of ovarian cancer while producing
endometrial cancer rates similar to placebo. The increased burden of endometrial
biopsies required to assess vaginal bleeding further limits the acceptability
of this regimen. These data provide additional support for caution in the
use of continuous combined hormones.