Semen quality and lifespan: a study of 78 284 men followed for up to 50 years.

Study Question: Is semen quality associated with the lifespan of men?

Summary Answer: Men with a total motile sperm count of >120 million could expect to live 2.7 years longer than men with total motile sperm count of >0-5 million.

What Is Known Already: Male infertility and semen quality have been suggested to be markers of morbidity and thus mortality, but the role of underlying disease present at time of semen quality evaluation has not been thoroughly assessed. The aim of this study was to determine the association between semen quality and mortality, and to assess the impact of the health of the man prior to semen quality assessment.

Study Design, Size, Duration: The study was based on 78 284 men who had their semen quality assessed between 1965 and 2015 at the public semen analysis laboratory in the Copenhagen area, Denmark, due to reported couple infertility. Thus, the included men covered a wide range of semen quality. Semen quality assessment included semen volume, sperm concentration, and the proportion of motile and morphologically normal sperm, from which the total sperm count and the total motile sperm count were calculated. Utilizing the unique Danish national registers, follow-up of the men regarding all-cause mortality was performed with a median follow-up of 23 years (5-95th percentile: 8-45 years) during which 8600 deaths occurred, accounting for 11.0% of the total population.

Participants/materials, Setting, Methods: Life expectancy was calculated according to semen quality. Furthermore, the relative differences in mortality were estimated using Cox regression analyses and presented as hazard ratios (HRs) with 95% CIs. A more recent subpopulation of 59 657 men delivered semen samples between 1987 and 2015, a period in which information on educational level and diseases prior to semen sampling was available and adjusted for in Cox regression analyses.

Main Results And The Role Of Chance: Men with a total motile count of >120 million could expect to live 80.3 years, compared to 77.6 years among men with total motile count of >0-5 million. In Cox regression analyses, all semen parameters were negatively associated with mortality in a dose-response manner both in the total population and the more recent subpopulation (P-trend for all semen parameters <0.001), and adjustment for educational levels and prior diagnoses did not change the estimates in the latter. Looking at total motile sperm count as an example, men with a total motile sperm count >120 million served as the reference, and the adjusted HRs for all-cause mortality in the more recent subpopulation were: azoospermia: 1.39, >0-5 million: 1.61, >5-10 million: 1.38, >10-40 million: 1.27, >40-80 million: 1.16, >80-120 million: 1.19, P-trend < 0.001.

Limitations, Reasons For Caution: The study was well-powered and included a unique database of results from semen analyses combined with register follow-up. However, we did not have information on health behaviours, and assessment of the health of men prior to semen sampling was limited to diagnoses obtained from the National Patient Register, and only applied to a subpopulation of men. A further limitation is that the group of men with azoospermia represents a heterogeneous group regarding testicular function as they could not be stratified into those having obstructive azoospermia and those having non-obstructive azoospermia.

Wider Implications Of The Findings: We observed clear negative dose-response associations between all semen parameters and all-cause mortality. The associations were not explained by educational levels or diseases registered at the time of semen evaluation. Thus, some men with impaired semen quality may experience less healthy ageing than men with better semen quality and could benefit from being identified at the time of semen quality evaluation. However, finding relevant biomarkers to identify the subgroups of men at increased risk will be key to initiating relevant prevention strategies.

Study Funding/competing Interest(s): Funding for this study was received from Johan and Hanne Weimann, F. Seedorff's grant (F-24230-01), and the Research Fund of the Capital Region of Denmark (R-153-A6176). None of the funders had any role in the study design, collection, analysis or interpretation of data, writing of the article, or publication decisions. The authors declare they have no competing interests.

Trial Registration Number: N/A.