June 2024 | George M. Pikler, M.D., Ph.D., FACP, Lead Oncology Advocate N1X10

Influence of Menopausal Hormone Therapy on Breast and Gynecologic Cancer Incidence and Mortality

Use of menopausal hormone therapy (MHT) fell precipitously after 2002, after the federally funded Women’s Health Initiative (WHI), the largest randomized, placebo-controlled clinical trial evaluating the effects of the combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) in healthy menopausal women demonstrated increased the risk of breast cancer, cardiovascular disease (CVD), and no improvement in quality of life.

Although the study demonstrated increased risk of CVD events with MHT in the overall cohort, subsequent secondary analyses showed that these risks were influenced by the woman’s age and time since menopause: absolute risks of CVD are low when MHT is started close to menopause in healthy women and hazard ratios tend to be lower for younger than older women. For women in early menopause and without contraindications to treatment, the benefits of MHT are likely to outweigh the risks when used for managing the vasomotor symptoms of menopause.

Results from a 20-year follow-up of this clinical trial, are now available. The trial found CEE alone significantly increased ovarian cancer incidence and mortality in women who had a prior hysterectomy. In contrast, in women with an intact uterus, combination CEE plus MPA did not increase ovarian cancer incidence or mortality and actually reduced endometrial cancer incidence.

Associations of CEE-alone and CEE plus MPA with breast cancer incidence and related mortality were reviewed from observational studies (The Collaborative Group on Hormonal Factors in Breast Cancer and The Million Women Study, 2019) and the WHI (2020) two randomized trials evaluating CEE-alone, for women with prior hysterectomy or with MPA. Based on the randomized clinical trials, CEE therapy, for women with prior hysterectomy decreases breast cancer incidence and mortality. In contrast, the combination of CEE and MPA increases breast cancer incidence, which persists through two decades.

Women considering estrogen plus progestin use for vasomotor symptoms should understand the breast cancer risk.

Menopause. 2023. 30 (4): 454-461
Cancer J. 2022. 28 (3): 169-175

Erica Cross, PA


Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.