Does Estrogen Replacement Therapy Increase Ovarian Cancer Risk?

Peter Kovacs, MD, PhD


July 20, 2016

Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk

Lee AW, Ness RB, Roman LD, et al, on behalf of the Ovarian Cancer Association Consortium
Obstet Gynecol. 2016;127:828-836


As the ovarian follicle pool is depleted, women reach menopause. The transition and the menopausal years are characterized by specific endocrine and clinical changes. The most obvious of them is the onset of vasomotor symptoms. Estrogen replacement therapy (ERT) and estrogen-progestin combined hormone replacement therapy (HRT) have been reported to be the most effective treatments for improving vaginal atrophy, sexual function, and urinary incontinence, and for reducing the risk for osteoporosis and improving overall quality of life.[1,2]

Hormone use in menopause is not without risks, however. HRT is associated with an increased risk for venous thromboembolism and cardiovascular and ischemic stroke when initiated at an older age and when taken for more than 10 years. There is also controversy regarding the risk for ovarian cancer with use of ERT/HRT.[1,3] Limited data are available on the association with duration of use and specific histologic types. This case-control study evaluated the association between ERT and specific subtypes of ovarian cancer in menopausal women.

The Study

This was a pooled analysis based on 10 case-control studies in which women over the age of 50 who had undergone a simple hysterectomy (ovaries retained) were considered. The cases (n = 906) included women with diagnosis of primary ovarian cancer. Five histologic subtypes were evaluated: serous, mucinous, endometrioid, clear cell, and other. Controls (n = 1220) were women without a diagnosis of cancer. Data for primary outcome and for confounding variables were collected through questionnaires or interviews. The association between ERT use, duration of use, and ovarian cancer was studied. Almost half of the women reported having used estrogen beyond the age of 50.

The researchers reported:

  • ERT use after 50 years of age was associated with an increased risk for ovarian cancer (OR, 1.3; 95% CI, 1.06-1.59).

  • The risk was increased for serous and endometrioid tumors but not for other types.

  • The risk increased with duration of use. When 5-year age categories were analyzed separately, the risk was only increased with more than 10 years of use for all cancers combined.

The authors concluded that the risk for ovarian cancer is increased with ERT use in women over the age of 50, especially if the duration of use is long.


Hormone use should be evaluated carefully among women who are more than 10 years beyond menopause. Estrogen seems to have a stimulating effect on cancer either directly (increased proliferation) or indirectly. In the case of the endometrioid subtype, the response to estrogen can be explained; while in the case of the serous subtype, it may have a proliferative effect on the tube from which most such cancers originate.

Because the risk is associated with duration of use, ERT use beyond 5-10 years should be re-evaluated. Individual risk factors need to be taken into consideration and the patient must be informed about this potential adverse effect.



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