Hormonal Management of Menopausal Symptoms in Women With a History of Gynecologic Malignancy

Benjamin S. Harris, MD, MPH; Katherine C. Bishop, MD; Jeffrey A. Kuller, MD; Anne C. Ford, MD; Lisa C. Muasher, MD, MPH; Sarah E. Cantrell, MLIS; Thomas M. Price, MD


Menopause. 2020;27(2):243-248. 

In This Article

Endometrial Cancer

The association between unopposed estrogen and endometrial hyperplasia among postmenopausal women receiving HT has been evaluated extensively in the literature. According to a 2012 Cochrane Database Systematic Review evaluating HT in postmenopausal women and risk of endometrial hyperplasia, unopposed estrogen was associated with an increased risk of endometrial hyperplasia at all doses and even with short duration of administration of 1 to 3 years.[43] For women with an intact uterus, the risk of endometrial hyperplasia with HT with low-dose estrogen combined with norethindrone acetate (1 mg) or MPA (1.5 mg) was not significantly different from placebo (1 mg norethindrone acetate: odds ratio [OR] 0.04 (0–2.8); 1.5 mg MPA: no hyperplasia events).[43]

Among endometrial cancer survivors who underwent hysterectomy, ET has no effect on recurrence and overall survival after endometrial cancer treatment. In a 2014 systematic review and meta-analysis of 896 endometrial cancer survivors who received HT (estrogen alone vs combined estrogen-progestin) and 1,079 non-HT users, the study authors found no significant increase in the risk of recurrence in endometrial cancer survivors relative to the control group (OR 0.53; 95% CI 0.30–0.96).[44] This pattern was consistent in subgroup analysis controlling for stage and type of HT.[44] Similarly, current data suggest similar recurrence and death rates for women who have been treated surgically for early stage, low-risk (eg, grade 1 or 2, endometrioid subtype, estrogen/progesterone negative) endometrial cancers.[44,45]

In contrast, there is no evidence to support safe administration of HT to women with a history of advanced (eg, high grade, late stage) endometrial cancer. Among patients with advanced endometrial cancers, there is a theoretical risk of stimulating residual tumor cells after suboptimal surgical treatment if HT is used. Furthermore, aggressive tumor types, such as endometrial stromal sarcoma, have high baseline recurrence rates and commonly are hormone sensitive. Thus, the risk of recurrence appears to outweigh the benefits of HT administration.[46–48]

According to the North American Menopause Society 2017 position statement, HT in endometrial cancer survivors may be considered for management of menopausal symptoms following surgical treatment of early stage, low-risk endometrial cancer if nonhormone options are not effective.[17]