Uterine leiomyomata (UL) have a substantial impact on women’s health, but relatively few studies have identified opportunities for primary prevention of these neoplasms. Most established risk factors are not modifiable, including premenopausal age, African ancestry, age at menarche, and childbearing history. The main challenge in studying UL is that a large proportion of tumors are asymptomatic. Herein, we review the epidemiology of UL from published studies to date. We highlight the advantages of ultrasound screening studies and the ways in which their innovative methods have helped clarify the etiology of disease. We conclude with a discussion of promising new hypotheses.

It has been hypothesized that breast cancer risk is influenced by prenatal hormone levels. Diethylstilbestrol (DES), a synthetic estrogen, was widely used by pregnant women in the 1950s and 1960s. Women who took the drug have an increased risk of breast cancer, but whether risk is also increased in the daughters who were exposed in utero is less clear. We assessed the relation of prenatal DES exposure to risk of breast cancer in a cohort of DES-exposed and unexposed women followed since the 1970s by mailed questionnaires. Eighty percent of both exposed and unexposed women completed the most recent questionnaire. Self-reports of breast cancer were confirmed by pathology reports. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for prenatal DES exposure relative to no exposure. During follow-up, 102 incident cases of invasive breast cancer occurred, with 76 among DES-exposed women (98,591 person-years) and 26 among unexposed women (35,046 person-years). The overall age-adjusted IRR was 1.40 [95% confidence interval (95% CI), 0.89-2.22]. For breast cancer occurring at ages ≥40 years, the IRR was 1.91 (95% CI, 1.09-3.33) and for cancers occurring at ages ≥50 years, it was 3.00 (95% CI, 1.01-8.98). Control for calendar year, parity, age at first birth, and other factors did not alter the results. These results, from the first prospective study on the subject, suggest that women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years. The findings support the hypothesis that prenatal hormone levels influence breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1509–14)

Recent studies have shown that both female and male obesity may delay time-to-pregnancy (TTP). Little is known about central adiposity or weight gain and fecundability in women. We examined the association between anthropometric factors and TTP among 1651 Danish women participating in an internet-based prospective cohort study of pregnancy planners (2007–2008). We categorized body mass index (BMI = kg/m²) as underweight (<20), normal weight (20–24), overweight (25–29), obese (30–34) and very obese (≥35). We used discrete-time Cox regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CI), controlling for potential confounders. We found longer TTPs for overweight (FR = 0.83, 95% CI = 0.70–1.00), obese (FR = 0.75, 95% CI = 0.58–0.97), and very obese (FR = 0.61, 95% CI = 0.42–0.88) women, compared with normal weight women. After further control for waist circumference, FRs for overweight, obese, and very obese women were 0.72 (95% CI = 0.58–0.90), 0.60 (95% CI = 0.42–0.85) and 0.48 (95% CI = 0.31–0.74), respectively. Underweight was associated with reduced fecundability among nulliparous women (FR = 0.82, 95% CI = 0.63–1.06) and increased fecundability among parous women (FR = 1.61, 95% CI = 1.08–2.39). Male BMI was not materially associated with TTP after control for female BMI. Compared with women who maintained a stable weight since age 17 (−5 to 4 kg), women who gained ≥15 kg had longer TTPs (FR = 0.72, 95% CI = 0.59–0.88) after adjustment for BMI at age 17. Associations of waist circumference and waist-to-hip ratio with TTP depended on adjustment for female BMI: null associations were observed before adjustment for BMI and weakly positive associations were observed after adjustment for BMI. Our results confirm previous studies showing reduced fertility in overweight and obese women. The association between underweight and fecundability varied by parity.

The authors assessed the risk of uterine leiomyomata in relation to reproductive factors and hormonal contraception in a prospective cohort study of US Black women. From March 1997 through March 2001, the authors followed 22,895 premenopausal women with intact uteri and no prior self-reported diagnosis of uterine leiomyomata. The authors used age- and time-stratified Cox regression models to estimate incidence rate ratios for self-reported uterine leiomyomata, confirmed by ultrasound or hysterectomy, in association with selected reproductive and hormonal factors. During 76,711 person-years of follow-up, 2,279 new cases of ultrasound- or hysterectomy-confirmed uterine leiomyomata were self-reported. After adjustment for age, body mass index, smoking, alcohol intake, and other reproductive covariates, the risk of ultrasound- or hysterectomy-confirmed leiomyomata was inversely associated with age at menarche, parity, and age at first birth and positively associated with years since last birth. Overweight or obesity appeared to attenuate the inverse association between parity and uterine leiomyomata. Current use of progestin-only injectables was inversely associated with risk. No consistent patterns were observed for other forms of hormonal contraception. Reproductive history is an important determinant of leiomyomata risk in premenopausal US Black women. Progestin-only injectables may reduce risk.