Effects of Estrogen-Only Treatment in Women With Prior Hysterectomy

Senior woman taking pill with water at home
For women aged 50 to 59 years with a history of bilateral oophorectomy, estrogen therapy may have beneficial effects in the long-term.

If initiated before age 60 years, estrogen-only menopausal therapy is safe and may be effective for women who have a history of bilateral oophorectomy, according to study results published in the Annals of Internal Medicine. However, the beneficial effects of estrogen treatment may not occur in women with intact ovaries and may be harmful in older women.

As limited information is available regarding the safety and efficacy of estrogen treatment in young women who underwent bilateral oophorectomy, the goal of this study was to assess the effect of oral conjugated equine estrogens in women enrolled in the Women’s Health Initiative Estrogen-Alone Trial. Effects of estrogen therapy were assessed according to both bilateral oophorectomy status and age at treatment initiation.

The study cohort included 9939 women aged 50 to 79 years with a history of hysterectomy, of whom 4049 women also had bilateral oophorectomy. The patients were assigned to receive estrogen therapy or placebo. The treatment was given for a median of 7.2 years, and follow-up for coronary heart disease, invasive breast cancer, and all-cause mortality continued for a median of 18 years. In addition, the researchers assessed the health effects of estrogen, using a global score that combined these conditions with incidence of stroke, pulmonary embolism, colorectal cancer, and hip fracture during follow-up.

During the course of estrogen therapy, the global score for health effects was worse in women with a history of bilateral oophorectomy aged ≥70 years at the start of the study, but not in women aged <70 years (P =.016 for trend by age). Treatment-related hazard ratios for the global health effects score were 0.85, 0.94, and 1.42 for women aged 50 to 59, 60 to 69, and 70 to 79 years, respectively.

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Across the cumulative follow-up period, estrogen therapy was associated with a lower mortality risk in women aged 50 to 59 years (hazard ratio, 0.68), but not in older women (P =.034 for trend by age).

Estrogen therapy had no clear health-related benefits or harms in women without prior bilateral oophorectomy, regardless of age.

The researchers acknowledged several study limitations, including variation in the timing of the bilateral oophorectomy and subsequent estrogen treatment. In addition, only a single formulation and dose of estrogen therapy was investigated, limiting generalizability to other preparations or routes of delivery.

The researchers concluded that for women aged 50 to 59 years with a history of bilateral oophorectomy, estrogen therapy may have beneficial effects in the long-term. However, this effect is not expected in older women or in those with intact ovaries.

Disclosure: Several study authors disclosed affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Manson JE, Aragaki AK, Bassuk SS, et al. Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy [published online September 10, 2019]. Ann Intern Med. doi:10.7326/M19-0274