Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial.
BACKGROUND
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.


METHODS
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).


METHODS
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).


METHODS
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.
D000368:Aged; D001706:Biopsy; D004311:Double-Blind Method; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000453:epidemiology; D004717:Endometrium / Q000473:pathology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D005833:Genital Neoplasms, Female / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology; D017698:Postmenopause; D016016:Proportional Hazards Models; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000453:epidemiology; D014626:Vaginal Smears
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate