In a long-term follow-up of Women’s Health Initiative (WHI) randomized trials reported in the Journal of Clinical Oncology, Rowan T. Chlebowski, MD, PhD, and colleagues identified risks of ovarian and endometrial cancers associated with the use of menopausal hormone therapy.
Rowan T. Chlebowski, MD, PhD
Study Details
The analysis involved two WHI trials in postmenopausal women aged 50 to 79 years. Among 16,608 women with a uterus, 8,506 participants were randomly assigned to receive once-daily conjugated equine estrogen (CEE) at 0.625 mg plus once-daily medroxyprogesterone acetate (MPA) at 2.5 mg and 8,102 participants were randomly assigned to receive placebo. Among 10,739 women with prior hysterectomy, 5,310 received once-daily CEE alone at 0.625 mg and 5,429 received placebo.
Key Findings
After 20-year follow-up, compared with placebo, CEE alone was associated with a significantly increased incidence of ovarian cancer (35 cases [0.041%] vs 17 cases [0.020%]; hazard ratio [HR] =2.04, 95% confidence interval [CI] = 1.14–3.65, P = .014) and ovarian cancer mortality (25 cases [0.024%] vs 9 cases [0.008%]; HR = 2.79, 95% CI = 1.30–5.99, P = .006).
Compared with placebo, CEE plus MPA did not significantly increase ovarian cancer incidence (75 cases [0.051%] vs 63 cases [0.045%]; HR = 1.14, 95% CI = 0.82–1.59, P = .44) or ovarian cancer mortality (65 cases [0.037%] vs 52 cases [0.031%]; HR = 1.21, 95% CI = 0.84–1.74, P = .31), but was associated with a significantly lower incidence of endometrial cancer (106 cases [0.073%] vs 140 cases [0.10%]; HR = 0.72, 95% CI = 0.56–0.92, P = .01). Risk of endometrial cancer mortality was not significantly reduced (13 cases [0.007%] vs 21 cases [0.013%]; HR = 0.58, 95% CI = 0.29–1.16, P = .12).
The investigators concluded, “In randomized clinical trials, CEE alone increased ovarian cancer incidence and ovarian cancer mortality, while CEE plus MPA did not. By contrast, CEE plus MPA significantly reduced endometrial cancer incidence.”
Dr. Chlebowski, of The Lundquist Institute, Torrance, CA, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The WHI program is supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; the U.S. Department of Health and Human Services; and the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
