Ovarian cancer and hormone replacement therapy (HRT)
There is evidence from observational studies that there is a small increased risk of ovarian cancer in hysterectomised women with long-term use of oestrogen-only hormone replacement therapy (HRT) (1,2). The risks of ovarian cancer with combined HRT are unknown (2).
When considering the cumulative risk of ovarian cancer over 15 or 20 years (2).
ovarian cancer | age of woman 50-69 years old | expected cases 9 cases per 1000 non-HRT users | 5 years HRT use resulted in 1 (+/-1) (oestrogen-only) extra cases of ovarian cancer | 10 years HRT use resulted in 3 (+/-2) (oestrogen-only) extra cases of ovarian cancer |
The MHRA has summarised the risks of HRT with respect to breast, endometrial and ovarian cancer (3):
Summary of HRT risks and benefits* during current use and current use plus post-treatment from age of menopause up to age 69 years, per 1000 women with 5 years or 10 years use of HRT (3)

Long-Term Follow-Up of the Women's Health Initiative Randomized Trials
- 20-year follow-up, compared to placebo, conjugated equine estrogen (CEE) alone increased ovarian cancer incidence (35 cases [0.041%] v 17 [0.020%]; HR, 2.04;95% CI,1.14 to 3.65; p=0.014) & ovarian cancer mortality (p=0.006), while CEE +medroxyprogesterone acetate did not (4)
- in contrast, CEE plus medroxyprogesterone acetate (MPA) significantly reduced endometrial cancer incidence. (106 cases [0.073%] v 140 [0.10%]; HR, 0.72; 95% CI, 0.56 to 0.92, p=0.01)
Reference:
- Current Problems in Pharmacovigilance (2002), 28, 11-12.
- Current Problems in Pharmacovigilance (2003), 29, 1-3.
- MHRA (August 2019). Hormone replacement therapy and risk of breast cancer
- Chlebowski JT et al. Menopausal Hormone Therapy and Ovarian and Endometrial Cancers: Long-Term Follow-Up of the Women's Health Initiative Randomized Trials. JCO August 22nd 2024.
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