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Women under 40 who use estrogen to manage menopausal symptoms after having their ovaries removed do not have an increased risk of breast cancer, but their older counterparts might, according to the results of a study published in Obstetrics and Gynecology.

Women who carry an inherited mutation in one of two genes—BRCA1 and BRCA2—have a substantially increased lifetime risk of developing breast and ovarian cancer. These women may opt to undergo preventive surgery in order to reduce their risk of developing cancer. Oophorectomy refers to the removal of the ovaries. Removing the ovaries reduces the circulating levels of estrogen in the body; estrogen is a female hormone that can stimulate the growth of breast and ovarian cancers. Salpingo-oophorectomy refers to the removal of the ovaries and fallopian tubes and total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) refers to the removal of the uterus, ovaries, and fallopian tubes.

When performed during the mid-30s to early 40s, oophorectomy can substantially reduce the risk of both ovarian and breast cancer. However, this risk reduction comes with a cost in younger women—because removal of the ovaries causes abrupt early menopause and can result in severe menopausal symptoms, such as hot flashes, sleep disturbances, and vaginal dryness. One way to manage these menopausal symptoms is with hormone replacement therapy (HRT) and researchers continue to evaluate whether HRT is safe for women with BRCA1/BRCA2 mutations, as some research has indicated that HRT may increase the risk of breast cancer. Removing the ovaries—and consequently, the estrogen produced by them—is intended to reduce cancer risk, so the question remains: will taking estrogen as part of HRT only serve to negate the benefits of the surgery?

Researchers conducted a study to determine whether the protective benefit of premenopausal TAHSBO was mitigated by subsequent estrogen therapy. They collected data from over 22,000 women aged 50-79; 10,449 had postmenopausal invasive breast cancer and 11,787 age-matched controls did not have cancer. They found that the effects of estrogen therapy after TAHBSO varied depending on age.

Overall, women who underwent TAHBSO and continued to take estrogen had a 14 percent increase in breast cancer compared with women who did not have the surgery and experienced natural menopause and never used HRT. However, women who underwent TAHBSO prior to age 40 had a reduced risk of developing breast cancer, regardless of estrogen use. Among women who used the estrogen therapy, the risk of developing breast cancer was 24 percent lower than among women who did not have surgery and did not use estrogen. Women who underwent TAHBSO before age 40 but never used HRT had an even bigger reduction in the risk of breast cancer—30 percent.

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The researchers concluded that the protective benefit of the surgery is only slightly diminished by subsequent estrogen use in younger women; however, the reverse is true for women who undergo TAHBSO at an older age—in fact, they found that women who underwent the surgery after age 50 experienced a 26 percent increase in breast cancer risk when taking estrogen.

The final word—estrogen therapy in women who undergo TAHBSO under age 40 is probably safe, but initiating estrogen therapy after TAHBSO at ages 45 and older can increase breast cancer risk.


Nichols HB, Trentham-Dietz A, Newcomb, PA, et al. Postoophorectomy estrogen use and breast cancer risk. Obstetrics & Gynecology. 2012; 120: 27-36.

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