Are infertile men at a higher risk of morbidity and early mortality?

Increasing evidence supports the role of male infertility as a harbinger of broader health issues, given that infertile men often exhibit higher rates of chronic conditions later in life. Infertile men have double the risk of developing testicular and breast cancer and an increased risk of high-grade prostate cancer, are more likely to develop ischemic heart disease, hypertension, heart disease, and hyperlipidemia, and have higher cardiovascular mortality compared to fertile men. The risk of developing Type 2 diabetes seems to increase with the severity of the spermatogenic dysfunction, and metabolic abnormalities such as insulin resistance, increased visceral adiposity, and systemic inflammation are often reported in men with male factor infertility. The relative risk of developing autoimmune diseases such as rheumatoid arthritis, psoriasis, systemic lupus erythematosus, and thyroiditis is significantly higher in infertile compared to fertile men, although the absolute risk is low. Male infertility also confers a 26% increased risk of early mortality, and the risk is even increased for men with azoospermia. On the other hand, a linear relationship between all semen parameters and life expectancy was found in a recent study. To explain the relationship between male infertility and increased risk of morbidity and mortality, hormonal, lifestyle/behavior, and genetic factors have been previously called into question. In the present mini review, the immune system alteration and the epigenetic hypotheses are exposed in more detail. The proposed evidence suggest that health screening for related conditions should be offered as part of the routine male infertility workup, to facilitate earlier detection and preventative care, and to position reproductive evaluations as a pivotal moment for long-term health intervention.