Type of menopausal hormone therapy may influence cancer risk
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CHICAGO — Cancer risk among women varied based on the type of menopausal hormone therapy they used, according to randomized study results scheduled for presentation at ASCO Annual Meeting.
Women who used estrogen-only hormone therapy exhibited increased risk for ovarian cancer incidence and mortality, findings presented during a pre-ASCO press conference showed.
In contrast, women with a uterus who received an estrogen-progestin combination exhibited no increased risk for ovarian cancer incidence or mortality, and they exhibited a reduced risk for endometrial cancer.
“These findings inform decisions regarding hormone therapy use and suggest reconsideration of guideline recommendations regarding estrogen-alone use [by] ovarian cancer survivors,” Rowan T. Chlebowski, MD, PhD, chief of the division of medical oncology and hematology at Harbor-UCLA Medical Center and investigator at The Lundquist Institute, said during the press conference.
Background and methods
Ovarian cancer and endometrial cancer are among the most common causes of cancer mortality among women in the United States, causing more than 26,200 deaths combined in 2023, according to study background.
“After [a] half-century, hormone therapy influence on endometrial and ovarian cancer incidence and mortality remain unsettled,” Chlebowski said.
Results of prior observational studies demonstrated “generally consistent” findings about the effect of estrogen alone on ovarian cancer or endometrial cancer incidence, and results related to use of estrogen plus progestin have been inconsistent, he said.
In addition, no randomized study had examined the effect of estrogen alone on ovarian cancer mortality.
Chlebowski and colleagues performed long-term follow-up analyses of two randomized clinical trials conducted as part of the Women’s Health Initiative, a series of studies intended to assess the health of women who had gone through menopause.
The analysis included data on 27,347 postmenopausal women aged 50 to 79 years who had not had any cancer within the prior decade. Approximately 20% of the cohort were part of racial or ethnic minority groups, a percentage comparable to the U.S. population at the time the study took place.
More than half (60.7%) still had a uterus, whereas 39.3% had undergone hysterectomy.
The research took place at 40 U.S. clinical centers, which enrolled postmenopausal women from 1993 to 1998.
One study included 10,739 women who had undergone prior hysterectomy. Researchers randomly assigned them to conjugated equine estrogen alone (n = 5,310) or placebo (n = 5,429).
Another study included 16,608 women with an intact uterus. Per standard care at the time of enrollment, investigators assigned these women to conjugated equine estrogen plus medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102).
Ovarian cancer and endometrial cancer served as secondary study outcomes. Researchers verified cancer incidence by central medical record and pathology report view, and they verified deaths by central death certificate and medical record review, along with 14 serial National Death Index queries.
Results
After follow-up of 20 years, women who received conjugated equine estrogen alone exhibited twice the risk for ovarian cancer (35 cases vs. 17 cases; HR = 2.04; 95% CI, 1.14-3.65), nearly three times the risk for ovarian cancer mortality (HR = 2.79; 95% CI, 1.3-5.99) and more than double the risk for death due to any cause after ovarian cancer diagnosis (HR = 2.47; 95% CI, 1.26-4.84) as women who received placebo. The additional risk for ovarian cancer incidence emerged at 12 years of follow-up and remained consistent over time.
Women who received conjugated equine estrogen plus medroxyprogesterone acetate exhibited no elevated risk for developing ovarian cancer (75 cases vs. 63 cases; HR = 1.14; 95% CI, 0.82-1.59), death due to ovarian cancer (HR = 1.21; 95% CI, 0.84-1.74) or death due to any cause after ovarian cancer diagnosis (HR = 1.37; 95% CI, 0.95-1.98) compared with women who received placebo.
Women assigned conjugated equine estrogen plus medroxyprogesterone acetate also exhibited a 28% reduced risk for endometrial cancer (HR = 0.72; 95% CI, 0.56-0.92) and a reduced risk for death due to any cause after endometrial cancer diagnosis (HR = 0.68; 95% CI, 0.47-0.97) compared with those assigned placebo; however, researchers observed no difference in endometrial cancer mortality between the treatment and placebo groups (HR = 0.58; 95% CI, 0.29-1.16).
“Our study provides the only long-term information from a randomized clinical trial on two common cancers in postmenopausal women for two of the most commonly used medications,” Chlebowski said.
Perspective
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Eleonora Teplinsky, MD
This long-term follow-up of the Women’s Health Initiative tells us postmenopausal women taking conjugate equine estrogen alone seem to have a higher incidence of ovarian cancer, as well as higher risk for ovarian cancer mortality, than women taking placebo. But to put this into context, the absolute risk for ovarian cancer incidence and mortality was extremely low in both groups.
This new information is a really important part of patient counseling and education, but it should not necessarily detract or take away from a woman’s decision to take menopausal hormone therapy for relief of menopausal symptoms.
Currently, conjugated equine estrogen is a less commonly used estrogen preparation, so we must take that into context as we extrapolate to modern-day estrogen formulations.
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Chlebowski RT, et al. Abstract 10506. Presented at: ASCO Annual Meeting; May 31-June 4, 2024.
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