The 2017 Hormone Therapy Position Statement of The North American Menopause Society

The North American Menopause Society 2017 Hormone Therapy Position Statement Advisory Panel

Disclosures

The North American Menopause Society (NAMS). 2018;24(7):728-753. 

In This Article

Ovarian Cancer

There are no convincing data that estrogen initiates or promotes the development of epithelial ovarian cancer. In the WHI, CEE + MPA after a mean of 5.6 years was not associated with an increased risk of ovarian cancer (HR, 1.41; 95% CI, 0.75–2.66), with an absolute risk of 4 cases with CEE alone versus 3 cases with placebo per 10,000 person-years, which remained nonsignificant after a median 13 years' cumulative follow-up (HR, 1.24; 95% CI, 0.83–1.87).[14] Observational data has suggested a possible increased risk of ovarian cancer with long-term HT use in some, but not all, studies, with inconsistent risk across studies.[245–249]

In the UK Million Women Study, attributable risk was calculated at 0.8 additional ovarian cancer cases per 10,000 women per year of HT and 0.6 additional ovarian cancer deaths per 10,000 women per year of HT (defined as very rare risks).[250]

In a 26-year follow-up of the Nurses' Health Study, a significantly increased risk of ovarian cancer was seen with more than 5 years' estrogen use, regardless of current or past use status (RR, 1.41; 95% CI, 1.07–1.86, and RR, 1.52; 95% CI, 1.01–2.27, respectively).[251] Similarly, increased risks were seen in the NIH-AARP Diet and Health Study, with long duration (> 10 y) with unopposed estrogen (RR, 2.15; 95% CI, 1.30–3.57) and with combined estrogen plus progestin (RR, 1.68; 95% CI, 1.13–2.49).[252] Neither RCT (WHI) nor observational data show consistent findings of risk with duration of use.

Limited observational data have not found an increased risk of ovarian cancer in women with a family history or a BRCA mutation who use EPT.[219]

After Ovarian Cancer

A meta-analysis (largely cohort studies) found no increased risk of recurrence or death in women receiving HT after treatment for ovarian cancer.[253] Concern has been raised regarding HT in tumors that are likely to contain ERs, such as low-grade serous carcinomas, and sex cord stromal malignancies, such as ovarian granulosa cell and Sertoli-Leydig ovarian tumors, but data are very limited.

Key Points

  • If an association between HT and ovarian cancer exists, the absolute risk is likely to be rare (< 1/1,000) or very rare (< 0.01/1,000) and more likely with longer durations of use.

  • Limited observational data have not found an increased risk of ovarian cancer in women with a family history or a BRCA mutation who use EPT.

  • Concern has been raised regarding HT in tumors that are likely to contain ERs, but data are limited.

  • In the WHI, the only randomized trial to date to study ovarian cancer, CEE + MPA had no significant effect on the incidence of ovarian cancer relative to placebo after 5.6 years' active therapy and 13 years' follow-up.

  • Observational data are inconsistent, with some but not all studies showing an increased risk after 5 or 10 years.

Comments

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