Histological signatures of hormone replacement therapy in the endometrium

Hormone replacement therapy (HRT) is widely prescribed for managing menopausal symptoms, yet its effects on the endometrium remain clinically important. While large-scale studies have established that estrogen-only HRT increases endometrial cancer risk and continuous combined regimens reduce this risk, real-world data on endometrial histology remain valuable for understanding contemporary practice patterns.

We conducted a retrospective analysis of women who underwent hysteroscopy with endometrial sampling at Princess Royal University Hospital. Of the 62 patients, we included 24 (38.7%) with explicitly documented HRT status, excluding 38 (61.3%) whose HRT status was unknown or inadequately documented. We characterized HRT regimens by type, route, schedule, and duration when available. Histological findings were compared between HRT users (n = 13) and non-users (n = 11) using Fisher's exact test and Mann-Whitney U tests. Post-hoc power calculations quantified the study's ability to detect clinically meaningful differences.

Among 24 patients (mean age 57.3 ± 6.8 years), 13 (54.2%) received HRT, and 11 (45.8%) did not. HRT regimens included combined estrogen-progestogen therapy (n = 9, 69.2%), estrogen-only therapy (n = 2, 15.4%), and unspecified formulations (n = 2, 15.4%). Routes included transdermal (n = 5, 38.5%), oral (n = 4, 30.8%), and unspecified or mixed (n = 4, 30.8%). Among combined users, continuous combined regimens were most common (n = 5, 55.6%). No endometrial hyperplasia or carcinoma was identified in either group. Normal endometrium was most common in both HRT users (7/13, 53.8%) and non-users (8/11, 72.7%). No significant differences were observed in histological findings (p = 0.74), age (p = 0.23), or endometrial thickness (p = 0.88). Power analysis revealed only 14% power to detect a 10% absolute difference in abnormal histology rates, and achieving 80% power would require 788 patients (394 per group).

In this retrospective case series, no endometrial hyperplasia or cancer was identified among 24 women with documented HRT status. However, the study was severely underpowered to detect rare but clinically significant pathologies. The absence of abnormal findings likely reflects the small sample size and low baseline incidence, rather than a protective effect. The high rate of missing HRT documentation (61.3%) represents a significant quality gap. These findings underscore the limitations of small retrospective series and highlight the need for adequately powered, prospective studies with systematic HRT characterization.