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Elevated testosterone, estrogen levels increase uterine fibroid risk
Women who have high levels of both testosterone and estradiol in midlife have an increased risk for developing incident uterine fibroids compared with women with low levels of the hormones, according to research in The Journal of Clinical Endocrinology & Metabolism.
“Our research suggests women undergoing the menopausal transition who have higher testosterone levels have an increased risk of developing fibroids, particularly if they also have higher estrogen levels,” Jason Y.Y. Wong, ScD, of Stanford University School of Medicine, said in a press release. “This study is the first longitudinal investigation of the relationship between androgen and estrogen levels and the development of uterine fibroids.”
Wong and colleagues analyzed data from 3,240 women aged 42 to 52 years with an intact uterus and at least one ovary (mean age, 46 years; 46.6% white; 52.3% premenopausal; 45.3% early perimenopausal) participating in the Study of Women’s Health Around the Nation (SWAN), a 13-year longitudinal study of women undergoing menopause beginning in 1996. Women completed questionnaires and interviews approximately every 12 months and self-reported the diagnosis of any uterine fibroids at each visit; blood samples were collected at visits to measure estradiol, total testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone and sex hormone-binding globulin levels (43.6% completed follow-up visits). Sex hormone levels above the baseline median were characterized as “high,” and hormone levels below the baseline median were characterized as “low.”
Within the cohort, 512 women reported a single incidence of fibroids; 478 women reported recurrent uterine fibroids. The median baseline total estradiol level was 55.1 pg/mL; the median baseline total testosterone level was 41.5 ng/dL.
Women with elevated testosterone levels had significantly higher odds of developing incident uterine fibroids (OR = 1.33; 95% CI, 1.01-1.76) vs. women with low testosterone levels; those odds increased for women with high levels of both testosterone and estradiol (adjusted OR = 1.52; 95% CI, 1.07-2.17). Testosterone was not significantly associated with fibroid recurrence in women with a history of fibroids at baseline, according to researchers.
Researchers also found that women with high levels of both hormones were less likely to have recurrent uterine fibroids vs. women with low levels of the hormones (adjusted OR = 0.5; 95% CI, 0.26-0.96).
“Our findings are particularly interesting because testosterone was previously unrecognized as a factor in the development of uterine fibroids,” Jennifer S. Lee, MD, PhD, of Stanford University School of Medicine and Veterans Affairs Palo Alto Health Care System in Palo Alto, California, said in a press release. “The research opens up new lines of inquiry regarding how fibroids develop and how they are treated. Given that managing uterine fibroids costs an estimated $34.4 billion in annual medical expenditures nationwide, it is important to identify new ways to better treat this common condition.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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This longitudinal study of self-reported fibroid development in premenopausal and perimenopausal women enrolled in the Study of Women’s Health Across the Nation (SWAN) confirms relationships between sex steroids and fibroid development and also raises interesting questions as to a possible difference in the development of new vs. recurrent fibroids. Previously held beliefs are substantiated, including increased risk for fibroids with ethnicity, BMI, use of estrogen/progestin and progestin-only hormones and premenopausal status. Also appreciated, women with high bioavailable testosterone and estradiol (E2) have increased odds of new fibroid development. Unanticipated was the observation of no relationship of increased bioavailable testosterone to recurrent fibroids and a lower odds of recurrent fibroids with high bioavailable estradiol compared with low bioavailable estradiol. It is difficult to explain this discrepancy based on current knowledge of sex steroid effects on fibroids and may be due to limitations of self-reporting and heterogeneity of the study population. But, it also stimulates thoughts of how one fibroid within a uterus affects the development and growth of other fibroids in the same uterus, an area of much needed research.