Endometrial thickness and pathology in postmenopausal women with bleeding on transdermal 17β-estradiol plus body-identical progesterone.

Objective: The primary objective was to explore the relationship between endometrial thickness and transdermal 17β-estradiol/micronised progesterone dose in postmenopausal women with unscheduled bleeding on menopausal hormone therapy (MHT). The prevalence of endometrial pathology was also assessed.

Methods: Retrospective analysis of a consecutive case series. Postmenopausal women attending a private menopause clinic were included if they presented with unscheduled bleeding on transdermal 17β-estradiol plus micronised progesterone between 1st June 2022 and 31st May 2024, and attended for an in-house ultrasound scan.

Results: 235 women were included (mean age 57 years, 49.37% overweight or obese). 173 women (73.62%) received on-label transdermal estradiol doses. Most women (n = 220 women, 93.62%) used continuous progesterone. On ultrasound examination, 173 women (73.62%) had a normal endometrium, 48 (20.43%) had a thickened endometrium, and 14 (5.96%) had an inadequately visualised endometrium. High BMI (> 25 kg/m²) was significantly associated with increased endometrial thickness (ET) (mean ET normal BMI vs overweight: 3.84 mm vs 4.52 mm, p = 0.07; mean ET normal BMI vs obese: 3.84 mm vs 4.50 mm, p = 0.04). There was no evidence that ET differed according to transdermal estradiol dose (on- vs off-label, p = 0.53), or by progesterone dose (low vs normal vs high, p = 0.61) or route (oral vs vaginal, p = 0.26). In multivariable analyses, there was evidence of an association between ET and MHT regimen (continuous vs sequential, p = 0.03). Amongst women with a measured serum estradiol concentration (n = 92), there was no evidence of an association between ET and serum estradiol level (p = 0.21). There were no cases of endometrial hyperplasia or cancer.

Conclusions: In the study cohort, endometrial thickness in women with unscheduled bleeding on transdermal 17β-estradiol plus micronised progesterone was not associated with MHT dose. The prevalence of endometrial pathology was low, including in women using off-label estradiol doses. Our findings suggest that progesterone dose should be clinically guided for optimal efficacy and to minimise risks. More research is needed to confirm our findings and prospectively evaluate endometrial outcomes in different patient populations over longer time periods, and to enable a more personalised approach to menopause care.