Risk Factors for Uterine Fibroids: A Case Control Study
Condition: Uterine Fibroids
MeSH terms: Leiomyoma; Myofibroma
Study type: Observational

Summary: 
      The proposed study is designed to estimate the proportion of 35-49 year-old women in a large
      urban health plan who have had fibroids. The membership of the health plan is approximately
      45% black, so estimates for black and white women can be compared. Risk factors for the
      condition will be studied, and uterine tissue from women having hysterectomies or
      myomectomies will be studied to identify genetic, hormonal, and protein mediators of tumor
      growth.

      A randomly selected sample of about 1800 women age 35-49 who are members of the George
      Washington University Health Plan will be invited to participate. Presence of leiomyomas for
      premenopausal participants with no prior diagnosis of leiomyoma will be determined by an
      ultrasound examination. Presence of leiomyomas for premenopausal women who report a prior
      diagnosis of fibroids will be determined by ultrasound evidence in their medical record when
      available, and by self-report when not available. History of fibroids in postmenopausal women
      will be based on pathology records for those with surgical menopause and on radiology records
      or self-report for the small number of naturally postmenopausal women. Estimates of the
      proportion who have or have had fibroids will be compared for blacks and whites.

      To examine risk factors for leiomyoma we will conduct a case-control analysis. Cases will be
      those women identified with leiomyoma from the random sample, supplemented by women in the
      same age range who have hysterectomies or myomectomies during the study period and hose
      excised uteri show evidence of fibroids on standard pathology examination. Women from the
      random sample with ultrasound or pathology evidence showing no uterine fibroids will
      constitute the control group. Controls will be compared to cases grouped by size of largest
      fibroid and grouped by clinical.

      A telephone interview and self-administered questionnaire will provide information on
      demographic factors, medical history, dietary intake, reproductive history, life style
      factors, and occupational/environmental exposures. Blood will be collected from premenopausal
      women to measure lipids, insulin, and potential susceptibility genes. Urine will also be
      collected from premenopausal women early in their menstrual cycles to measure gonadotropin
      levels. Blood pressure, heart rate, weight, height, and waist-to-hip ration will be measured.
      Tissue from surgical specimens will be use by collaborators at NIEHS to measure cell
      proliferation and apoptosis, genetic factors, estrogen and progesterone receptor levels,
      protein markers of estrogen action, and growth factors.
    

Detailed description: 
      Uterine leiomyomas are the leading cause of hysterectomy in the United States, accounting for
      over 200,000 procedures each year. Leiomyoma is a common condition with many tumors being
      asymptomatic. It is not known which women who have fibroids will develop clinical symptoms.
      In 1996-1999 the NIEHS Uterine Fibroid Study enrolled 1245 randomly selected premenopausal
      women, aged 35 to 49, who had been randomly selected from the membership roles of George
      Washington University Health Plan, a large prepaid health plan in Washington, D.C. Slightly
      over half of the participants were African American. Participants were asked about prior
      diagnoses of uterine leiomyomas, and 87% were examined by abdominal/transvaginal ultrasound
      to screen for uterine leiomyoma. Sixty-two percent of the 1245 had either had a prior
      diagnosis of leiomyoma or had sonogram evidence of the condition.

      Study Objectives:

        1. Monitor fibroid-related symptoms over time (Two follow-ups over a five-year period).

        2. Measure the proportion of women who undergo major medical intervention (hysteroscopic
           resection, uterine artery embolization, laser coagulation, myomectomy, or hysterectomy).

        3. Identify risk factors for increased symptom severity.

        4. Identify risk factors for treatment intervention.

      Methods: Premenopausal participants in the Uterine Fibroid Study (1996-1999) will be
      recontacted twice during the years 2001 - 2005 to obtain information about leiomyoma-related
      symptoms and medical or surgical treatments. Data will be collected with a computer-assisted
      telephone interview. Medical records of ultrasound or MRI examinations and major medical or
      surgical interventions will be abstracted to verify medical follow-up and treatment.

      Significance: The presence of leiomyomas can be identified with ultrasound screening when the
      condition is asymptomatic. However, no data are available that allow clinicians to predict
      which women will experience morbidity. This longitudinal study will trace disease
      progression, and identify factors related to increased symptom severity and medical/surgical
      treatment. The findings could then be used to develop a systematic scoring system that can be
      used to identify women at high risk.
    

Observational model: Case-Control
Time perspective: Other
Keywords: Leiomyomas; Ultrasound; Hysterectomy; Epidemiology; Hyperinsulinemia