title: Menopausal estrogen therapy and non-Hodgkin's lymphoma: A post-hoc analysis of women's health initiative randomized clinical trial.
abstract: Estrogens are important immunomodulators, exerting significant effects on cell proliferation, apoptosis, cytokine production and differentiation of hematopoietic cells. Estrogen receptors are expressed on normal B and T lymphocytes, bone marrow and in leukemia and lymphoma cell lines. Epidemiologic evidence for the association of menopausal hormone use with risk of non-Hodgkin's lymphoma (NHL) has been mixed; however, all of the investigations have been observational. We analyzed the data from Women's Health Initiative hormone therapy trials where conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 16,654) or CEE alone (women with prior hysterectomy) (n = 10,685) were tested against placebos and the intervention lasted a median of 5.6 years in the CEE + MPA trial and 7.2 years in the CEE alone trial. During 13 years of follow-up through September 20, 2013 383 incident NHL cases were identified. We used the intent-to-treat approach to calculate incidence rates of NHL, hazards ratios (HR) and 95% confidence intervals (CI) by treatment group. Incidence of NHL was virtually the same in the treatment and placebo groups. The HR was 1.02 (95%CI 0.74-1.39) for CEE alone, 0.98 (95% CI 0.76-1.28) for CEE+MPA, and 1.00 (95% CI 0.82-1.22) for both combined. There were no specific NHL subtypes associated with either type of the treatment, except a marginally decreased risk of plasma cell neoplasms (HR= 0.53 95% CI 0.27-1.03) in the CEE-alone group. These results do not support a role of estrogen alone or combined with progestin in the development of NHL among postmenopausal women.
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI.|Department of Pathology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kato
authors.affiliation: Division of Medical Oncology and Hematology, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angels Medical Center, Torrance, CA.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Department of Preventive Medicine and the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Evanston, IL.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Departments of Epidemiology and Environmental Health, University of Buffalo, Buffalo, NY.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Ray
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Judith
authors.initials: J
authors.lastname: Abrams
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Bock
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Pinkal
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
mesh_terms: D000368:Aged; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology*; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects; D008875:Middle Aged
chemical_list: D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate
keywords: Estrogen; Lymphoma; Progestogen; Randomized clinical trial