Recent study revealed that postmenopausal women with prior hysterectomy who took estrogen-only hormone replacement therapy (HRT) experienced a significant increase in ovarian cancer incidence and mortality. However, combined estrogen and progesterone therapy did not elevate ovarian cancer risk and substantially lowered endometrial cancer risk. Rowan T. Chlebowski, MD, PhD, from The Lundquist Institute, presented these findings at the American Society of Clinical Oncology’s annual meeting in Chicago.
Dr. Chlebowski and colleagues analyzed data from two randomized, placebo-controlled trials involving nearly 28,000 postmenopausal women aged 50-79 without prior cancer. Conducted from 1993 to 1998 across 40 U.S. centers, one trial assigned 17,000 women with a uterus to combined equine estrogen plus medroxyprogesterone acetate or placebo. The other trial involved around 11,000 women with prior hysterectomy, randomized to daily estrogen alone or placebo. Both trials were halted early due to increased stroke risk (estrogen-only trial) and elevated breast cancer and cardiovascular risks (combined therapy trial).
At 20 years’ follow-up, the analysis showed a doubling of ovarian cancer incidence among those on estrogen alone (HR 2.04; 95% CI, 1.14-3.65; P = .01) and a significant increase in ovarian cancer mortality (HR 2.79; 95% CI, 1.30-5.99; P = .006). Despite the statistical significance, the absolute numbers were small, with 35 ovarian cancer cases in the estrogen group versus 17 in the placebo group. In contrast, combined therapy resulted in no increased ovarian cancer risk and a significantly reduced endometrial cancer incidence (106 cases vs. 140; HR 0.72; 95% CI, 0.56-0.92; P = .01).
As reported by Medscape, Dr. Chlebowski noted that despite the long history of conjugated equine estrogen in U.S. clinical practice since 1943, questions about hormone therapy’s effects on endometrial and ovarian cancer remain unresolved. He emphasized the need for practice and guideline changes regarding estrogen-alone use in ovarian cancer survivors.