by Aaron Tallent
Key Points:
- Hormone replacement therapy (HRT) can reduce bothersome symptoms of menopause, but there is concern it may increase the incidence of certain cancers.
- An analysis from the Women’s Health Initiative shows that estrogen-only HRT may increase the risk of developing and dying from ovarian cancer, but combined HRT does not increase that risk and may reduce the risk of developing uterine cancer.
- The findings will most likely be integrated in guidelines that cover the risk and benefit for menopausal hormone therapy use.
An analysis of clinical trials data shows that estrogen-only HRT may increase the risk of developing and dying from ovarian cancer, but combined HRT does not increase that risk and may actually reduce the risk of developing uterine cancer (Abstract 10506). The findings, presented at the 2024 ASCO Annual Meeting, provide insights for individuals who have received or are considering taking menopausal HRT.
“Our study provides the only long-term information from a randomized clinical trial on 2 common cancers in postmenopausal women for 2 of the most commonly used medications,” said Rowan Chlebowski, MD, PhD, FASCO, lead author of the study with The Lundquist Institute.
Endometrial and ovarian cancer are 2 major causes of cancer death for U.S. women, with 13,030 and 13,270 deaths in 2023, respectively.1 Although hormone therapy has been available for decades, its impact on endometrial and ovarian cancer incidence and mortality is still a subject of debate; the majority of data available are from observational studies.
Researchers assessed the influence of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) and CEEs alone on ovarian and endometrial cancer events in the Women’s Health Initiative randomized clinical trials. The Women’s Health Initiative was a series of studies launched in 1991 by the U.S. National Institutes of Health to evaluate the effects of HRT on women who had been through menopause.
“The Women’s Health Initiative has been a really rich source of information over the past few years because we are concerned about the potential for hormone therapy to increase the risk of cancer,” said Discussant Onyinye Balogun, MD, MSc, of NewYork-Presbyterian/Weill Cornell Medicine. “At the same time, women are going through menopausal symptoms where decreased estrogen levels are causing symptoms such as hot flashes, night sweats, and vaginal dryness that can be addressed with hormone therapy.”
Study Methods and Results
For this study, researchers performed a long-term follow-up of 2 randomized clinical trials that ran from 1993 to 1998. They evaluated data from 27,347 women between the ages of 50 to 79 from 40 different centers in the United States who had been through menopause and who had not had breast cancer or another type of cancer within the past decade. Dr. Chlebowski noted that enrollment included racial and ethnic minority groups totaling 18.5% of the cohort, proportional to the U.S. population of women aged 50 to 79 years, which was 18.2% in the 1990 U.S. Census.
Of the participants, 16,608 still had a uterus and 10,739 had undergone a hysterectomy to remove their uterus. Both groups of women were randomly assigned to receive either HRT or a placebo. Based on the standards of care, patients who still had a uterus were given CEE plus MPA, and those who had a hysterectomy were only given CEE.
At a 20-year follow-up, the researchers found that patients who received only CEE were twice as likely to develop ovarian cancer and nearly 3 times more likely to die from ovarian cancer than those who received the placebo (Figure 1). This increased risk began at 12 years of follow-up and did not diminish over time.
“This long-term follow-up of the Women’s Health Initiative study shows that while postmenopausal women taking conjugated equine estrogen alone had a higher incidence of ovarian cancer and mortality compared to women taking placebo, the absolute risk of ovarian cancer was extremely low in both groups,” said Eleonora Teplinsky, MD, with Valley Mount Sinai Comprehensive Cancer Care, who provided analysis on the study. “While this new information is an important part of patient counseling and education, given the low numbers, it should not necessarily impact a woman’s decision to take menopausal hormone therapy for symptomatic relief of menopausal symptoms.”
Patients who received CEE plus MPA did not have an increased risk of developing or dying from ovarian cancer compared to those who received the placebo. In addition, they also were 28% less likely to develop endometrial cancer than those who received the placebo (Figure 2).
“Currently, CEE is a less commonly used estrogen preparation, and this makes it hard to extrapolate these study results to modern-day estrogen preparations, although the historical context is helpful,” Dr. Teplinsky said.
Outstanding Questions and Next Steps
Dr. Balogun said she finds these data interesting because “there’s been a historical bad rap for hormonal therapy when it comes to the world of oncology, but there could be a way to harness its power for actually decreasing the risk of endometrial cancer.”
“There’s been a historical bad rap for hormonal therapy when it comes to the world of oncology, but there could be a way to harness its power for actually decreasing the risk of endometrial cancer.” – Dr. Onyinye Balogun
She said outstanding questions include if there is a role for HRT in reducing the risk of endometrial cancer in younger women or if it should primarily still be administered for women in their 50s, since the disease is more common in older women. Also, she would like to see the exact percentages of Black women evaluated in the study, as their incidence and death from endometrial cancer is disproportionately high.
“If you look at [the] 5-year survival rate for White women, it is 80%. For Black women, it falls to about 60%,” Dr. Balogun said.
Dr. Chlebowski said that the findings will most likely be integrated in guidelines that cover the risk and benefit for menopausal hormone therapy use. He added that future research will also include biomarkers in assessing risk.
“As molecular markers are in more common clinical use, we plan to test women with ovarian cancer for BRCA1/2 and potential other markers for ovarian cancer risk. The goal is to determine if women entering menopause with prior hysterectomy should have such testing to inform risk–benefit of CEE-alone use,” Dr. Chlebowski said.
This article was published by: ASCO Daily News