In a long-term follow-up of the Women's Health Initiative (WHI), researchers found that conjugated equine estrogen (CEE) taken alone may increase the risk of developing and dying from ovarian cancer in postmenopausal women. In contrast, conjugated equine estrogen combined with medroxyprogesterone acetate (MPA) does not appear to increase this risk and may even reduce the risk of developing endometrial cancer.
The findings, which will be presented at the 2024 American Society of Clinical Oncology Annual Meeting, provided valuable insights into the long-term effects of menopausal hormone therapy on 2 common cancers in postmenopausal women.
The study analyzed data from 2 randomized clinical trials that were part of the WHI. The trials, which ran from 1993-1998, enrolled 27,347 postmenopausal women aged 50-79 years from 40 U.S. centers. Participants had no prior history of breast cancer or invasive cancer within the past 10 years.
Women who had undergone a hysterectomy were randomized to receive either CEE alone or a placebo, while those with an intact uterus received either CEE plus MPA or a placebo. The intervention was stopped prematurely after 5.6 years in the CEE plus MPA group due to increased breast cancer risk and after 7.2 years in the CEE-alone group due to increased stroke risk.
After a 20-year follow-up, the researchers found that women who received CEE alone had a significantly higher risk of developing ovarian cancer (35 cases [0.041% annualized rate] vs 17 [0.020%]; HR 2.04; 95% CI 1.14-3.65) and a nearly 3-fold increased risk of dying from ovarian cancer (HR 2.79; 95% CI 1.30-5.99; P = 0.006) compared to those who received a placebo. The increased risk of ovarian cancer emerged after 12 years of follow-up and persisted over time.
In the CEE plus MPA group, there was no increased risk of developing (75 cases [0.051%] vs 63 [0.045%]; HR, 1.14; 95% CI, 0.82-1.59; P = 0.44) or dying from ovarian cancer compared to the placebo group. However, women who received CEE plus MPA had a 28% lower risk of developing endometrial cancer (106 cases [0.073%] vs 140 [0.10%]; HR, 0.72; 95% CI, 0.56-0.92; P = 0.01), although this did not translate to a statistically significant reduction in endometrial cancer mortality.
"Before these randomized, placebo-controlled clinical trials, observational studies examining the influence of estrogen plus progestin on ovarian and endometrial cancers gave mixed results. Also, there were no randomized findings regarding the effects of estrogen alone on ovarian cancer mortality. 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," noted study author Dr. Rowan T. Chlebowski.
The researchers plan to integrate these findings into current prescribing guidelines for menopausal hormone therapy, taking into account both the potential harms and benefits identified in the WHI trials.
The WHI trials were funded by serial contracts from the National Institutes of Health continuously from 1993.
