Uterine Leiomyomas

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. Uterine leiomyomas are histologically identifiable as benign smooth muscle tumors with varying amounts of associated fibrous tissue. Many women have more than one uterine leiomyoma, but each appears to be clonally distinct. MED12 mutations that appear to cause gain of function are found in the majority of tumors and are likely triggers for tumorigenesis. Several specific cytogenetic changes have also been identified in tumor tissue, but most tumors show no chromosomal abnormalities. These benign tumors are hormone-dependent. They develop after puberty and regress after menopause. Both estrogen and progesterone are considered important stimulants, or at least permissive factors for tumor growth. To address the research needs in this field we have designed four studies. The first, the NIEHS Uterine Fibroid Study, is a large epidemiologic study of black and white women, aged 35-49, in which the randomly selected participants were screened for fibroids with ultrasound. The second study (Fibroid Growth Study, Shyamal Peddada, PI) is a clinical study of fibroids designed to describe fibroid growth. The third study, Postpartum Uterine Regression, monitored fibroid change with pregnancy and postpartum uterine regression. The fourth study, is a prospective study of fibroid incidence and growth. We continue to analyze data from the NIEHS Uterine Fibroid Study. We began enrolment in a prospective study of fibroids in November, 2010, and completed recruitment of nearly 1700 African American women, aged 23-34 by the end of 2012. Any prior diagnosis of fibroids was an exclusion criterion. The Study of Environment, Lifestyle & Fibroids (SELF) is based in the Detroit, Michigan area with collaboration from Henry Ford Health System. Participants are screened for fibroids with ultrasound at enrollment (detection limit of lesion = 0.5 cm diameter). There are three subsequent clinic visits at approximately 20-month intervals to monitor fibroids by ultrasound examinations in order to identify onset time. Those found to have fibroids at enrollment (newly detected, not previously clinically diagnosed), as well as those who develop fibroids during the study, will be followed in the same manner to assess development of additional new fibroids and to measure fibroid growth. We collected risk factor and symptom data at enrollment and at each 20-month visit for five years. The study is designed to collect a broad spectrum of exposure data including recognized risk factors for fibroids (age of menarche, pregnancy history, alcohol use, body mass index) and potential risk factors for which there has been only suggestive data. Three primary hypotheses will be tested. (1) Vitamin D deficiency is a risk factor for fibroids, (2) Reproductive tract infections are risk factors for fibroids, and (3) A higher proportion of African ancestry is associated with increased fibroid risk (African ancestry measured by informative SNPs known to have very different frequencies between Europeans and Africans). We have completed participant-visits for the 3rd and final follow-up. Our participation at the 5-year follow-up was 90% of those enrolled. Enrollment activities included: orientation to study, pre-enrollment self-administered questionnaire, web-based questionnaire, food-frequency questionnaire, computer-assisted telephone interview, clinic visit with ultrasound. measure of blood pressure, weight, height, skin reflectance, specimen collection (blood, urine, vaginal swabs), menstrual cycle diary to prospectively record at least one menstrual cycle and bleeding pattern, and an early life questionnaire that the participant administers to her mother (if available). The enrollment data have been analyzed to examine the associations of the following exposures with prevalent fibroids: keloid scars, being fed soy formula as an infant, Depo Provera use, and reproductive tract infections. We are continuing to collect data on the last group of participants, including relevant medical-record retrieval and menstrual diary processing (forms that are mailed in to provide data on timing of next menstrual cycle and menstrual characteristics. We also have quality control checks to do on the ultrasound data. We will be developing data files for both the prospective incidence and the files for analyzing fibroid growth. Biospecimens are also being assayed: e.g., vitamin D as reflected by 25(OH)D, metals, bacterial vaginosis so that the impact of exposures can be assessed. We have begun to analyze fibroid incidence and growth during the first 20-month interval of observation. We find that about 10% of fibroid-free women at baseline had developed fibroids by the first follow-up. The young women were less likely to develop fibroids than the older women, supporting the earlier modeled data indicating that fibroid development is about 10 years earlier in African Americans compared to whites. Growth was based on volume change over an 18-month interval analyzed on a log scale but converted to percent increase indexed to an 18-month interval. Average growth was nearly a 90% increase in volume per 18 months. The growth rate estimate for small fibroids (<1cm in diameter) was twice that of the average, while the rate for large fibroids (4+ cm in diameter) was lower (55% increase in volume per 18 months). As the data become available, we will be examining the associations for vitamin D and bacterial vaginosis with fibroid incidence and growth to begin to address our first two primary study hypotheses. I also collaborate with Kathie Hartmann on the Right From the Start Study, a pregnancy study that screens participants for fibroids with ultrasound early in their pregnancies. with ultrasound early in their pregnancies.