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. What's new? Non-Hodgkin lymphoma (NHL) is linked etiologically to disrupted immune function, and in women, that disruption may be attributed in part to the immunomodulatory activities of estrogens. Here, the relationship between estrogen and NHL was explored in a randomized clinical trial of postmenopausal women on hormone therapy that consisted of either estrogen alone or estrogen plus progesterone. NHL incidence rate was about the same for women taking either form of hormone therapy. Women taking only estrogen experienced a modest reduction in risk of plasma cell neoplasm. Overall, the findings suggest that NHL risk is largely unaffected by estrogens.
Original language | English (US) |
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Pages (from-to) | 604-611 |
Number of pages | 8 |
Journal | International Journal of Cancer |
Volume | 138 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 2016 |
Funding
National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), U.S. Department of Health and Human Services (WHI program); Grant numbers: N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221; Grant sponsor: National Cancer Institute (NIH through the Cancer Center Support Grant); Grant number: P30CA022453 Authors thank the following: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg Investigators and Academic Centers: (Brigham and Women''s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker Women''s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.
Keywords
- Estrogen
- Lymphoma
- Progestogen
- Randomized clinical trial
ASJC Scopus subject areas
- Oncology
- Cancer Research