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Postmenopausal estrogen and progestogen therapy and the risk of uterine leiomyomas

Reed, Susan D. MD, MPH1 2 3; Cushing-Haugen, Kara L. MS3; Daling, Janet R. PhD3 4; Scholes, Delia PhD4 5; Schwartz, Stephen M. PhD3 4

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Objective: Leiomyomas are common benign neoplasms. Although hormone therapy is the most common and effective treatment for menopausal symptoms, little is known about its effect on leiomyomas. We examined the risk of a first diagnosis of leiomyomas in peri- and postmenopausal women associated with prior use of estrogen and progestogen therapy (EPT).

Design: A case-control study was conducted among enrollees from a nonprofit health plan. Cases had a first diagnosis of leiomyomas confirmed by surgery or ultrasound. Controls were women of the same age range without a diagnosis of leiomyomas selected at random from membership and outpatient files. Participants were interviewed regarding prior use of exogenous hormones, medical history, and reproductive history. This analysis was restricted to cases (n = 256) and controls (n = 276) who were peri- or postmenopausal and more than 40 years of age. Adjusted odds ratios (OR) and 95% CIs were estimated using logistic regression models.

Results: EPT use for more than 5 years was associated with a 1.7-fold increased risk of leiomyomas (95% CI, 0.9–3.3). Associations with EPT use were only present among women with a body mass index less than 24 kg/m2; OR (ever-use), 2.3 (95% CI, 1.2–4.3); and OR (≥ 5 years use), 4.0 (95% CI, 1.6–10.3).

Conclusion: Among peri- and postmenopausal women, prior EPT use was associated with an increased risk of a subsequent leiomyomas. This association seemed limited to the subset of women with low body mass index. Exogenous sources of estrogen and progestin in the setting of low adiposity may contribute to the development of leiomyomas.

From the 1Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington; 2Harborview Medical Center, Seattle, Washington; 3Fred Hutchinson Cancer Research Center, Seattle, Washington; 4Department of Epidemiology, University of Washington, Seattle, Washington; and the 5Center for Health Studies, Group Health Cooperative, Seattle, Washington.

Received February 18, 2003; revised and accepted May 22, 2003.

Address correspondence to: Susan D. Reed, MD, MPH, Assistant Professor, Department of Obstetrics and Gynecology, Harborview Medical Center, Box 359865, 325 9th Ave., Seattle, WA 98104. E-mail: reeds@u.washington.edu.

©2004The North American Menopause Society