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 5 16,654) or CEE alone (women with prior hysterectomy) (n 5 10,685) were tested against placebos and the intervention lasted a median of 5.6 years in the CEE 1 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 CEE1MPA, 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 (HR5 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.Lymphoid neoplasms, including lymphoma, myeloma and lymphocytic leukemia, comprise the 5th most commonly diagnosed cancer in the United States, 1 following breast, prostate, lung and colorectal cancers. Although lymphoid neoplasms are clinically and etiologically heterogeneous, to a large extent, severe disruption of immune function has been

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Lymphoma in Australian Border Collies: survey results and pedigree analyses

“…Furthermore, the common practice of desexing in Australia most likely explains the small number of entire dogs in this study, making interpretation of this information difficult. In people, being female and the use of hormone therapy with oestrogen and/or progestin have been associated with a decreased risk of non‐Hodgkin's lymphoma, although another study did not show the same relationship …”

Female reproductive factors and risk of lymphoid neoplasm: The Japan Public Health Center‐based Prospective Study

“…Regarding the use of exogenous hormones such as oral contraceptives and hormone therapy, previous findings have yielded inconsistent results. 3,6 The substantial change in exogenous hormone availability and pattern of use over the years prevents comparison of associations with various defined exogenous hormones across studies. For this reason, we were also unable to provide estimations by formulation of exogenous hormones or duration of usage.…”

“…Although the reason for this discrepancy is not clear, one possible explanation is immune‐mediated associations of sex hormones with lymphomagenesis . In particular, estrogens have important immunomodulatory roles, including a biphasic effect on regulating immune responses, release of relevant cytokines, induction of B‐cell differentiation, and induction of proliferation or apoptosis through hormone receptors …”

“…[3][4][5] In particular, estrogens have important immunomodulatory roles, including a biphasic effect on regulating immune responses, release of relevant cytokines, induction of B-cell differentiation, and induction of proliferation or apoptosis through hormone receptors. [5][6][7][8] Previous studies have hypothesized that there is a link between lymphomagenesis and female reproductive factors through long-term and high exposure to female sex hormones. 2,3 Although attention has focused on pregnancy as a protective factor against the risk of non-Hodgkin lymphoma (NHL) owing to its dramatic alternations in female sex hormones and immune response, a recent systematic review and a meta-analysis suggested only a weak or null association.…”