Transvaginal Ultrasound Measurement of Endometrial Thickness as a Biomarker for Estrogen Exposure Anita S.Y. Sit, 1 Francesmary Modugno, 1 Lyndon M. Hill, 2 Jerry Martin, 2 and Joel L. Weissfeld 1 1 Graduate School of Public Health and 2 Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Women’s Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania Abstract Objective: In clinical settings, transvaginal ultrasound has been used to evaluate abnormal vaginal bleeding. Because the endometrium responds to estrogens, en- dometrial 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: En- dometrial thickness measurements ranged from 1 to 32 mm (median 3.0 mm). The frequencies of thicker endometrium (z3.0 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 associ- ations were not seen in analyses limited to current HRT users (n = 461). In multiple variable analysis (R 2 = 0.08), current HRT use (P < 0.0001) and higher BMI (P < 0.0001) were independently associated with thicker endometri- um. 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. (Cancer Epide- miol Biomarkers Prev 2004;13(9):1459 – 65) Introduction Transvaginal ultrasound is a noninvasive diagnostic tool commonly used to evaluate women with postmenopaus- al uterine bleeding. The ultrasound examination for endometrial pathology includes a measurement of endometrial thickness. In clinical studies, endometrial malignancy is uncommon in women with an endometrial thickness measurement <5 mm (1, 2). In contrast, this study specifically evaluates trans- vaginal ultrasound measurements of endometrial thick- ness in generally asymptomatic postmenopausal women, not selected for symptoms of uterine pathology. Because the endometrium contains estrogen receptors and responds to circulating estrogens (3), endometrial thick- ness constitutes a potential biological marker of estrogen status even in postmenopausal women. To the extent that transvaginal ultrasound effectively measures endometri- al thickness and estrogen status, endometrial thickness measurements may function as a useful biomarker for study of hormone-related malignancy, including breast, ovarian, endometrial, and even colon cancer. However, because the endometrium atrophies after menopause, errors associated with the transvaginal ultrasound measurement of endometrial thickness may be large relative to the variation in endometrial thickness observable across postmenopausal women at risk for estrogen-related malignancy. To address this concern, this study aimed to validate the transvaginal ultrasound measurement of endometrial thickness in generally asymptomatic, postmenopausal women by demonstrat- ing relationships between endometrial thickness meas- urements and factors known to be associated with estrogen exposure. Methods Study Population. The study group included female participants at the Pittsburgh Center for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (4, 5). PLCO is a National Cancer Institute Received 5/23/03; revised 4/5/04; accepted 4/13/04. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Anita S.Y. Sit, Department of Obstetrics and Gynecology, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128. Phone: 408-885-5550; Fax: 408-885-5577. E-mail: anitabenma@yahoo.com Copyright D 2004 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention 1459 Cancer Epidemiol Biomarkers Prev 2004;13(9). September 2004 Downloaded from http://aacrjournals.org/cebp/article-pdf/13/9/1459/2244151/1459-1465.pdf by guest on 14 June 2022