Intended for healthcare professionals

Rapid response to:


HRT and breast cancer risk

BMJ 2019; 367 doi: (Published 11 October 2019) Cite this as: BMJ 2019;367:l5928

Rapid Response:

HRT and breast cancer risk - progesterone vs. progestins

Evidence suggests that there are important differences in breast cancer risks with different progestogens used in combined [oestrogen + progestogen] hormone replacement therapy (HRT) regimens; micronised natural/bio-identical progesterone appears to be a far safer choice than synthetic progestins.

A large French study which assessed and compared the association between different HRTs and breast cancer risk, followed up 80,377 women for an average of 8.1 post-menopausal years, and found that compared with HRT never-use, there was no increased risk of breast cancer for oestrogen-progesterone (relative risk 1.00), whereas those using oestrogen plus progestins had a relative risk of 1.16-1.69 (depending on the progestin used). (1)

Another French study also found that breast cancer risk differed by type of progestogen among current users of oestrogen-progestogen therapies. No increased risk was apparent among users of oestrogen + micronised natural progesterone for any duration (odds ratio 0.80), whereas among users of combined HRT containing a synthetic progestin, the odds ratio was 1.57-3.35 (depending on the progestin used). (2)

A meta-analysis of studies of postmenopausal women using progesterone vs. synthetic progestins in combination with oestrogen found that progesterone-oestrogen was associated with a lower risk of breast cancer compared with synthetic progestins (relative risk 0.67). (3)

Although not mentioned in the main body of the paper, the Lancet meta-analysis found that the relative risk for <5 years use of oestrogen + micronised natural progesterone was 0.91, i.e. 9% lower than for never-users of HRT. (4) [See appendix]

1. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat, 2008;107(1):103-11
2. Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS ONE, 2013; 8(11): e78016. doi:10.1371/journal.pone.0078016
3. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Systematic Reviews, 2016; 5:121; DOI 10.1186/s13643-016-0294-5
4. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019. (appendix Figure S15, p. 45)

Competing interests: No competing interests

14 October 2019
Peter J Lewis
General Practitioner with Special Interest in Integrative Medicine
15 South Steyne, Manly, NSW 2095, Australia