Transvaginal ultrasound measurement of endometrial thickness as a biomarker for estrogen exposure.

Objective: In clinical settings, transvaginal ultrasound has been used to evaluate abnormal vaginal bleeding. Because the endometrium responds to estrogens, endometrial thickness may constitute a biomarker of estrogen status in postmenopausal women. This study aimed to validate the transvaginal ultrasonographic measurement of endometrial thickness as an estrogen biomarker in asymptomatic, postmenopausal women by demonstrating an association between endometrial thickness and risk factors known to be associated with estrogen exposure.

Method: Endometrial thickness was measured in 1,271 women ages 55 to 74 years who underwent transvaginal ultrasound screening as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A questionnaire, completed before screening, provided risk factor information, including reproductive and hormone use histories.

Results: Endometrial thickness measurements ranged from 1 to 32 mm (median 3.0 mm). The frequencies of thicker endometrium (> or =3.0 mm), according to body mass index (BMI) quartile, were 55.2%, 66.1%, 69.7%, and 76.7% (P < 0.0001). The frequencies of thicker endometrium were 57.8%, 58.3%, and 82.6% among never users, ex-users, and current users of hormone replacement therapy (HRT), respectively (P < 0.0001). Other factors associated with thicker endometrium included age, marital status, history of uterine fibroids, years since menopause, and history of hypertension. Statistically significant associations were not seen in analyses limited to current HRT users (n = 461). In multiple variable analysis (R2 = 0.08), current HRT use (P < 0.0001) and higher BMI (P < 0.0001) were independently associated with thicker endometrium.

Conclusion: In postmenopausal women, factors reflecting exogenous (current HRT use) and endogenous (BMI) estrogen exposure were associated with increased endometrial thickness as measured during screening transvaginal ultrasound. Practical limitations related to screening transvaginal ultrasound include measurement variability, lack of information regarding type or dose of HRT, and problems of differentiating true endometrial thickening from unrecognized endometrial polyps or fluid accumulations. Constrained by these limitations, these results partially validate a transvaginal ultrasound measurement of endometrial thickness as a potential biomarker related to estrogen status.