Reproductive Factors, Exogenous Hormone Use, and Risk of B-Cell Non-Hodgkin Lymphoma in a Cohort of Women From the European Prospective Investigation Into Cancer and Nutrition

Laura Costas; Leila Lujan-Barroso; Yolanda Benavente; Naomi E. Allen; Pilar Amiano; Eva Ardanaz; Caroline Besson; Heiner Boeing; Bas Bueno-de-Mesquita; Iris Cervenka; Renée T. Fortner; Agnès Fournier; Marc Gunter; Sophia Harlid; José María Huerta; Mats Jerkeman; Karin Jirström; Rudolf Kaaks; Anna Karakatsani; Kay-Tee Khaw; Anastasia Kotanidou; Eiliv Lund; Giovanna Masala; Amalia Mattiello; Beatrice Melin; Virginia Menéndez; Neil Murphy; Alexandra Nieters; Kim Overvad; Elio Riboli; Carlotta Sacerdote; Maria-Jose Sánchez; Julie A. Schmidt; Sabina Sieri; Anne Tjønneland; Antonia Trichopoulou; Rosario Tumino; Roel Vermeulen; Elisabete Weiderpass; Silvia de Sanjosé; Antonio Agudo; Delphine Casabonne


Am J Epidemiol. 2019;188(2):274-281. 

In This Article


The analytical cohort was followed for an average of 14 years, for a total of 4,792,436 person-years. Baseline characteristics of participants are presented in Web Table 1 (available at Overall, age at menarche, parity, and breastfeeding (Table 1), as well as oral contraceptive use and age at natural menopause (Table 2), were not statistically significantly associated with B-cell NHL risk.

Surgical menopause was significantly associated with B-cell NHL risk as compared with natural menopause (hazard ratio (HR) = 1.51, 95% confidence interval (CI): 1.17, 1.94; Table 2). Accordingly, women who had undergone both hysterectomy and oophorectomy had a 26% higher risk of B-cell NHL compared with women who had not (HR = 1.26, 95% CI: 1.01, 1.56). Associations were more pronounced among women who had undergone bilateral oophorectomy (HR = 1.51, 95% CI: 1.19, 1.91) than among women who had undergone unilateral oophorectomy (HR = 0.81, 95% CI: 0.59, 1.10), as compared with women with intact ovaries (data not shown). Postmenopausal hormone therapy was not associated with B-cell NHL (HR = 1.03, 95% CI: 0.91, 1.18) overall or by formulation (estrogen alone, progestin alone, or estrogen plus progestin). Among women with no postmenopausal hormone therapy use, having a surgical menopause was still associated with greater B-cell NHL risk than having a natural menopause (HR = 1.74, 95% CI: 1.19, 2.49; data not shown).

No consistent associations were found in the analyses by lymphoma subtype (Web Table 2 and Web Table 3). No significant heterogeneity was observed by subtype for any of the potential risk factors evaluated (data not shown). Results of analyses combining B-cell and T-cell subtypes and censoring multiple myeloma from the definition of lymphoma are provided in Web Table 4 and Web Table 5 for comparability with previous studies; results were similar.