How does menopausal hormone replacement therapy (HRT) affect ovarian cancer risk?

Updated: Sep 13, 2021
  • Author: Nicole K Banks, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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In various studies, effects of postmenopausal hormones on ovarian cancer risk have been inconsistent. Some researchers reported an increased risk with estrogen use, whereas others reported either no effect or a protective one. This confounding of results has been attributed to the fact that ovarian cancer is a rare disease and that numbers of patients were insufficient in the studies that have tried to elucidate the relationship.

A large prospective study showed that postmenopausal estrogen use for 10 years or longer was associated with increased risk of ovarian cancer mortality. [18] Swedish investigators reported that estrogen use alone and estrogen-progestogen used sequentially (progestogen used on average 10 d/mo) may be associated with an increased risk for ovarian cancer. [19] In contrast, continuous estrogen-progestogen (progestogen used on a mean of 28 d/mo) seemed to confer no increased risk of ovarian cancer. The WHI study demonstrated that continuous combined HT may slightly increase the risk of ovarian cancer.

In the NCI Study of Hormone Therapy and Ovarian Cancer, researchers examined data from a large study that included 23,722 women who had hysterectomies and 73,483 women with intact uteri. [20] Their objective was to learn whether menopausal hormone use affected the risk of ovarian cancer. The risk of ovarian cancer was higher in women who received menopausal hormone therapy than in women who never used such therapy. However, the increased risks differed by hormone therapy formulation and regimen and varied according to the women's hysterectomy status.

In women who have undergone a hysterectomy, the use of estrogen alone for more than 10 years was linked to an increased risk of ovarian cancer. This increase in risk was not observed in women who took HT for less than 10 years.

In women with intact uteri, 5 or more years of sequential, but not continuous, estrogen plus progestogen was positively associated with ovarian cancer. This increased risk was also demonstrated in the Million Women Study.

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