Reproductive factors and non-Hodgkin lymphoma: A systematic review

• Incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors.
• A higher proportion of studies reported protective associations when they evaluated gravidity compared to parity, usually showing a J-shaped pattern.
• Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design.
• Based on the available data, the evidence for a relationship between reproductive factors and NHL seems at best moderate.

Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive factors, as incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors. Although the evidence is not compelling, some studies show an inverse association with gravidity. Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design. Inconsistencies in the results are likely due to the complex relationship between reproductive, biological, and sociodemographic factors, as well as to study limitations. Elucidating the role of hormonal factors should provide clues for therapeutic options and public health decisions. We provide an overview of the available evidence on reproductive factors in NHL etiology, underscoring potential sources of discrepancies and bias.