Progesterone receptor variants and hormone therapy use in postmenopausal endometrial polyps: a case-control study

To investigate whether Progesterone Receptor (PGR) variants +331G/A (rs10895068) and V660L (rs1042838, a PROGINS proxy) are associated with Endometrial Polyps (EP) in postmenopausal women undergoing hysteroscopy.

This exploratory case-control study included 236 histopathologically confirmed EP cases and 73 hysteroscopy-negative controls from the same institution and period, unmatched. All eligible hysteroscopy-negative women during the study period were included, with no declinations. Genotyping of +331G/A and V660L was performed by PCR-HRM. Genetic comparisons used two-sided tests and multivariable logistic regression, with minimum detectable odds ratios estimated for 80% power at α = 0.05. Hormone Therapy (HT) and tamoxifen use were recorded as binary variables reflecting current use at hysteroscopy.

Genotype distributions did not differ between groups for +331G/A (p = 0.245) or V660L (p = 0.435); call rates were 100% for both variants. Neither +331G/A nor V660L carrier status was significantly associated with EP after adjustment (aOR = 0.43, 95% CI 0.17-1.09, p = 0.074; and aOR = 0.59, 95% CI 0.31-1.11, p = 0.100, respectively). Current HT use was inversely associated with EP (aOR = 0.15, 95% CI 0.06-0.40; p < 0.001), though regimen data were unavailable. Genetic associations remained non-significant in the model excluding HT.

Neither PGR variant was significantly associated with EP. The sample could detect only relatively large effects, so smaller genetic associations cannot be excluded. The inverse association with binary HT exposure is hypothesis-generating rather than causal, given incomplete exposure characterization and the possibility of selection or residual confounding.