Transvaginal ultrasound measurement of endometrial thickness as a biomarker for estrogen exposure.
ABSTRACT 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.
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.
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.
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.
- SourceAvailable from: Ashley S Felix[Show abstract] [Hide abstract]
ABSTRACT: Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, we tested the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55-74, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We evaluated associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3-13.8 years). Compared to baseline endometrial thickness of 1.0 - 2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR: 2.00, 95% CI 1.15, 3.48) and endometrial (RR: 5.02, 95% CI 0.96, 26.36) carcinomas in models adjusted for menopausal hormone use and BMI. Our data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas.International Journal of Cancer 07/2013; · 6.20 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Currently available treatments for menopausal symptoms are associated with differing endometrial safety and endometrium-related tolerability profiles. This article reviews the differential endometrial effects associated with estrogen therapy, estrogen-progestin therapy (EPT), selective estrogen receptor modulators (SERMs), and tissue-selective estrogen complex (TSEC). Searches of electronic databases and of recent presentations at congresses were performed. Articles and abstracts relevant to the endometrial effects of estrogen therapy, EPT, SERMs, and TSECs were summarized in this interpretive literature review. Owing to their effects on the endometrium, cyclic and continuous-combined EPT can induce irregular uterine bleeding. Cyclic EPT may induce endometrial proliferation. Continuous-combined EPT reduces the incidence of endometrial cancer. In the endometrium, SERM activity ranges from essentially neutral to agonist, depending on the individual SERM. Raloxifene, tamoxifen, lasofoxifene, ospemifene, and bazedoxifene (BZA) demonstrated different degrees of endometrial tissue effects in preclinical and clinical studies. BZA inhibits the effects of conjugated estrogens on the endometrium. These effects are attributable to tissue-specific estrogen receptor degradation, which effectively diminishes the molecular target of estrogen activity in the endometrium. Conjugated estrogens/BZA, a TSEC, has a favorable endometrial profile, with incidences of hyperplasia and bleeding/spotting similar to those of placebo. Endometrial safety is a significant hurdle in the development of new hormone therapies for postmenopausal women. Preclinical and clinical findings suggest that BZA has an endometrial profile distinct from those of other SERMs. TSECs are a novel approach to providing relief of menopausal symptoms with adequate endometrial safety profile.Menopause (New York, N.Y.) 02/2014; · 3.08 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Cut-off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause.Annals of medical and health sciences research. 07/2014; 4(4):608-14.