Hormone replacement therapy and the risk of endometrial cancer: A systematic review.
Level 2 - randomized trial
Systematic review primarily of observational cohort and case-control studies
PubMed 27451318 · doi:10.1016/j.maturitas.2016.05.013
What was done
This systematic literature review searched PubMed, EMBASE, and the Cochrane Library (identifying 527 publications) to evaluate the safety of hormone replacement therapy and endometrial cancer risk. It analyzed 28 included studies involving postmenopausal women with intact uteri treated for at least one year with estrogen only, estrogen plus progestin (considering regimen and progestin type), or tibolone, compared to placebo or never-users.
What was found
No numerical estimates, relative risks, hazard ratios, or confidence intervals are reported in the abstract. Qualitatively, observational literature demonstrated: - Estrogen alone was associated with increased endometrial cancer risk. - Continuous combined therapy showed lower risk than sequential combined therapy. - Micronized progesterone notably increased risk, even when given continuously. - Tibolone was associated with increased risk in most included studies.
Why it matters
It emphasizes that endometrial cancer risk varies substantially by progestin regimen and formulation, cautioning against assuming all combined regimens—particularly those with micronized progesterone—confer equal endometrial protection.
Limits
The abstract provides no effect sizes, confidence intervals, or numerical data. The underlying evidence base is largely observational and subject to confounding, and specific dosages, treatment durations beyond one year, and individual synthetic progestin comparisons are not detailed.
Cited by
- supports Administering unopposed estrogen without progesterone in women with an intact uterus increases the risk of endometrial hyperplasia and endometrial cancer.