Human Reproduction, 2025, 00(0), 1–9

https://doi.org/10.1093/humrep/deaf023
Original Article

Reproductive epidemiology

Semen quality and lifespan: a study of 78 284 men

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

followed for up to 50 years
1,2,� 3,4
L. Priskorn , R. Lindahl-Jacobsen , T.K. Jensen1,2,5, S.A. Holmboe 1,2
, L.S. Hansen 1,2
, M. Kriegbaum 6
, B.S. Lind 7
,
6 6,8 1,2
V. Siersma , C.L. Andersen , and N. Jørgensen
1
Department of Growth and Reproduction, Copenhagen University Hospital—Rigshospitalet, Copenhagen, Denmark
2
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen
University Hospital—Rigshospitalet, Copenhagen, Denmark
3
Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark
4
Interdisciplinary Centre on Population Dynamics (CPop), University of Southern Denmark, Odense, Denmark
5
Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark
6
The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
7
Department of Clinical Biochemistry, Copenhagen University Hospital—Hvidovre, Hvidovre, Denmark
8
Department of Hematology, Copenhagen University Hospital—Rigshospitalet, Copenhagen, Denmark

�Correspondence address. Department of Growth and Reproduction and EDMaRC, Copenhagen University Hospital—Rigshospitalet, Blegdamsvej 9, DK-2100
Copenhagen, Denmark. Tel: þ45-35455064; Fax: þ45-35457950. E-mail: laerke.priskorn@regionh.dk https://orcid.org/0000-0002-9152-1893

ABSTRACT
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 evalu­
ation. Thus, some men with impaired semen quality may experience less healthy ageing than men with better semen quality and

Received: December 02, 2024. Revised: January 09, 2025. Editorial decision: January 31, 2025.
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved.
For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our
RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
2 | Priskorn et al.

could benefit from being identified at the time of semen quality evaluation. However, finding relevant biomarkers to identify the sub­
groups 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.

Keywords: semen quality / testicular function / lifespan / survival / mortality

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

Introduction morbidity and shorter life expectancy, even at levels above the
cut-off values usually used for the diagnosis of male factor infer­
Male infertility is a critical clinical problem for couples facing dif­
tility, thus semen quality may be a universal biomarker of mor­
ficulties conceiving but the public health relevance of semen
bidity and mortality, also of relevance for men with proven and
quality may extend beyond fertility and reproduction. There is a
untested fertility.
growing body of evidence suggesting that male infertility and se­
Thus, based on a large semen quality database with up to
men quality are associated with a higher lifetime incidence of
50 years of register follow-up, we have investigated the associa­
certain diseases and shorter life expectancy (Murshidi et al., 2020;
tion between semen quality and all-cause mortality, taking into
Fallara et al., 2024). One study found higher mortality in men
account hospital diagnoses received during the 10 years prior to
with male factor infertility compared to men in infertile couples
semen testing.
without a male factor (Eisenberg et al., 2014), while others have
reported higher mortality only in men with azoospermia and not
in those with oligozoospermia (Glazer et al., 2019; Del Giudice Materials and methods
et al., 2021). Semen quality has, however, been linked to mortality Study population and design
in a dose-dependent manner, suggesting that a concern of im­
This register follow-up study is based on the Danish Semen
paired health is not limited to only men with azoospermia. A
Quality Database (DaSe), which consists of men delivering a se­
long-term follow-up among 43 277 men without azoospermia but
men sample from 1963 to 2015 at the public semen analysis labo­
referred for couple infertility (a subset of the population in the
ratory in the Copenhagen area, The Copenhagen General Practice
present study) showed that mortality decreased with higher
Laboratory. These data have been cleansed, validated, and stored
sperm concentrations up to a threshold of 40 million/ml, a value
in the CopLab database (Kriegbaum et al., 2024). Men had been re­
which is substantially higher than the current World Health
ferred to the laboratory by a general practitioner, urologist, or
Organization’s lower reference limit of 16 million/ml (World
gynaecologist for screening of semen quality due to self-reported
Health Organization, 2021). Mortality also decreases as the per­
couple infertility and before determination of additionally
centages of motile and morphologically normal spermatozoa in­
needed diagnostics or treatments. Semen results, therefore, rep­
crease (Jensen et al., 2009).
resent a broad spectrum of semen quality, from men with azoo­
Most infertile men present without any major comorbidities
spermia to men having very good semen quality. Men were
at the time of their fertility assessment, as they are still relatively included in the current study if they delivered a semen sample
young. However, it is well established that on a group level, infer­ from 1965 (there were only a few observations before that), if
tile men have more comorbidities at the time of fertility evalua­ they were between 18 and 65 years old at the time of sample de­
tion than comparable fertile men (Salonia et al., 2009; Eisenberg livery, and if the database included information on at least their
et al., 2015; Ventimiglia et al., 2015). When studying the associa­ sperm concentration and period of abstinence. In total, 78 284
tion between fertility and mortality among men evaluated for in­ men with relevant data from DaSe could be identified in the
fertility, Eisenberg et al. (2014) adjusted for comorbidities at the Danish Civil Registration System and are included in the present
time of fertility evaluation in a subset of the population, which study with registry data on follow-up. In addition, a subpopula­
attenuated the observed association. This indicates that poorer tion with health data available for at least 10 years before semen
health in infertile men at the time of infertility diagnosis could sample delivery included men delivering samples from 1987 on­
partly explain the observed long-term association between se­ wards (N ¼ 59 657). Details are presented in a flow chart in
men quality and mortality. However, with a mean follow-up time Supplementary Fig. S1.
of 7.7 years, this study only included 69 cases with a mean age of Data on a subset of the population in the present study
death of 44.1 years, and it remains to be seen what roles the diag­ (N ¼ 43 277), who delivered a semen sample before 2001 and
noses prior to semen quality assessment play in the long-term where men with azoospermia were excluded, have been pub­
association between semen quality and mortality. lished previously (Jensen et al., 2009). In the present study, the
Furthermore, the majority of studies examining the associa­ follow-up has been expanded considerably with the end of
tion of male fertility with mortality have only evaluated indica­ follow-up moving from 2001 to 2023; additionally, the men with
tors of male reproductive function, such as fatherhood azoospermia (N ¼ 4829) were included after careful individual
(Eisenberg et al., 2011; Elenkov et al., 2020), infertility diagnosis or data evaluation of causes of referral and notes about the semen
type of fertility treatment (Eisenberg et al., 2014; Glazer et al., findings to ensure that they did not deliver semen samples for an
2019; Lundberg et al., 2019; Del Giudice et al., 2020), or the couple assessment after a vasectomy procedure.
fecundity marker, time-to-pregnancy (Ahrenfeldt et al., 2021;
Lindahl-Jacobsen et al., 2024); only a few studies have evaluated Exposure assessment (semen quality)
the impact of semen quality (Groos et al., 2006; Jensen et al., Reporting of semen quality assessment is conducted according to
2009). Semen quality is relevant to consider since growing evi­ the recommended specifications (Bjo€ rndahl et al., 2016). Before
dence suggests that semen parameters are related to increased delivery of the semen sample to the laboratory, the men had
 Semen quality and lifespan | 3

been asked to keep an ejaculation abstinence period of 3–4 days, We retrieved information on all diagnoses received within the
and the actual abstinence period was recorded. The semen sam­ 10 years prior to semen sample delivery. Diagnoses were grouped
ples were produced at the laboratory or at home with instruc­ via a grouping of 99 diagnoses, further combined into 15 relevant
tions to bring the sample to the laboratory protected from main groups as defined by Statistics Denmark (2023). For the sta­
extreme temperatures within 1 h after ejaculation. The labora­ tistical analyses, dummy variables were constructed for these
tory used standardized analysis methods throughout the collec­ main groups.
tion period. From 1980, the methods relied on the World Health
Organization guidelines (World Health Organization, 1980), Statistical analyses
which were in accordance with the methods used up to this time Basic description
point. Briefly, all specimens were analysed within 1 h of ejacula­ Basic characteristics and semen parameters were described with

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

tion into a standard tube. Immediately after receipt and no later medians and 5–95 percentiles or frequencies for the total study
than 2 h after ejaculation, the grade of motility was assessed by population and stratified by period of sample delivery (before
counting the motile and immotile spermatozoa using a light mi­ 1987 or from 1987 and onwards). Similarly, educational level and
croscope with ×600 magnification (Bostofte et al., 1982a,b; Jensen prior diagnoses were described for the subpopulation delivering a
et al., 2009). Until 2012, morphology was assessed according to semen sample 1987–2015.
the original WHO criteria (World Health Organization, 1980) and,
after that, according to strict criteria (Menkveld et al., 1990; Restricted mean survival time
World Health Organization, 1999). Total sperm count was calcu­ Using the non-parametric restricted mean survival time (RMST)
lated by multiplying semen volume and sperm concentration, analysis, absolute measures of life expectancy until age 90 years
and the total motile sperm count was calculated as total sperm and according to semen quality were illustrated for each semen
count multiplied by the proportion of motile sperm. parameter category. The mean survival time calculations were
Some men delivered several semen samples, but only the first conditioned on having survived until the age of sample delivery.
sample from each man is included in the present study. For sta­
tistical analyses, all semen parameters were categorized (see Cox regression analyses
Fig. 1 for the specific categorizations). To allow for morphology The longitudinal associations between categorized semen
results, assessed with different criteria, to be analysed together, parameters and all-cause mortality were analysed using Cox re­
men were divided into six groups based on percentiles (<5, 5–25, gression to estimate the hazard ratios (HRs) and 95% CIs. All men
25–50, 50–75, 75–95, or >95 percentile) of their sperm morphol­ were followed from the age at delivery of their first semen sam­
ogy, calculated separately for the two assessment criteria, after ple until age at death, emigration, or end of follow-up, whichever
which the similar categories were combined. came first. In the basic Model 1, used to analyse data from the to­
tal population and repeated for the subpopulation, age was used
Outcome assessment (all-cause mortality)
as the underlying time scale and strata of the period of sample
Information from the first semen sample (considered baseline)
delivery in 5-year intervals were included to account for calendar
from each man was included and linked to Danish registers using
effects (Canchola et al., 2003), with further adjustment for the pe­
the personal identification number, which was first given to all
riod of abstinence. The main Model 2, used to analyse data for
Danish citizens alive in 1968 and to all newborns and immigrants
men delivering a semen sample between 1987 and 2015, was con­
after that (Pedersen, 2011). This allowed us to have accurate
structed as described above with further adjustment for educa­
and efficient individual data linkage between the DaSe and the
tional level as a proxy for socioeconomic status and the health
registers used in the present study. The Centralized Civil Register
status of the men defined by all diagnoses registered in the
provided follow-up information on vital status and date of
National Patient Register in the 10 years before semen quality as­
death or emigration from 1965 until the end of follow-up, 31
sessment (included as dummy variables as previously described).
December 2023.
The proportional hazards assumption was checked visually by
Covariate assessment plotting the Schoenfeld residuals according to time (Grambsch
The period of abstinence before sample delivery was recorded, and Therneau, 1994).
and the variable was categorized for statistical analyses (≤1, 1–
Sensitivity analyses
≤2, 2–≤3, 3–≤4, 4–≤5, 5–≤6, and >6 days). The period (year) of
(i) To assess the robustness of adjustments and any modifying ef­
sample delivery was categorized into 5-year groups, and the age
at sample delivery was calculated. fect of health, analyses were repeated in the two strata consisting
Educational level was available from the Population of men with and without any registered diagnoses in the 10 years
Education register from 1980 (Statistics Denmark, 2024). The prior to baseline, respectively. (ii) To elucidate the influence of
highest level of education that each man had completed at the potential undiagnosed diseases before and at baseline, which
time of sample delivery was obtained. If no information was could affect both semen quality and mortality risk, the main
available in the baseline year, the earliest information from the Model 2 was repeated after introducing a 5-year immortality pe­
following years was used. According to the International riod from baseline (thus only deaths occurring more than 5 years
Standard of Education (ISCED), the educational level was grouped after baseline were included). (iii) To examine how follow-up
into low (ISCED levels 0–2), medium (ISCED levels 3–4), and high time influenced the results, analyses in Model 1 were repeated
(ISCED level 5þ) educational levels. for total motile sperm count, stratified by 10-year periods of
The National Patient Register (Schmidt et al., 2015) contains all study entry. The number of men delivering samples between
contacts to somatic hospital departments since 1977 and was 1965 and 1975 was limited, and therefore this period was com­
used to identify diagnoses prior to semen quality assessment. bined with the following. (iv) Finally, morphology analyses, in
Diagnoses are registered by WHO International Classification of which categorization was based on percentiles due to a shift in
Diseases (ICD) codes, with the eighth revision (ICD-8) used before assessment method, were repeated after excluding counts based
1994 and subsequently the 10th revision (ICD-10) was used. on strict criteria.
4 | Priskorn et al.

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

Figure 1. Expected age of death (restricted mean survival time) according to semen quality, based on the total population of 78 284 men. Bars
represent the mean expected age of death within each category.

Statistical analyses were conducted in SAS (version 9.4 M8), data. All information was anonymized prior to statistical
the statistical software package SAS Institute (SAS Institute Inc, analysis.
Cary, NC, USA).

Results
Basic description
Ethical approval The total study population consisted of 78 284 men, of whom
The study was approved by the Danish Data Protection Agency 8600 (11.0%) died during follow-up (median follow-up time:
and registered in the data processing inventory of the University 23 years). The men had a median age of 32 years at time of deliv­
of Copenhagen (J. no. 514-0460/20-3000). Danish law does not re­ ery of the semen sample (Table 1). Median sperm concentration
quire informed consent for registry studies using administrative was 46 million/ml (5–95 percentile: 0–182 million/ml). See Table 2
 Semen quality and lifespan | 5

Table 1. Basic description of study population (total and subpopulations with sample delivery 1965–1986 and 1987–2015, respectively).

Sample delivery 1965– Sample delivery 1987–

Total population (N ¼ 78 284) 1986 (N ¼ 18 627) 2015 (N ¼ 59 657)
Age, years 32 (24–44) 30 (23–42) 32 (24–44)
Birth year 1964 (1944–1982) 1949 (1937–1959) 1969 (1952–1983)
Sample year 1997 (1977–2014) 1980 (1975–1986) 2002 (1988–2014)
Follow-up time, years 23 (8–45) 40 (9–47) 20 (8–35)
Deaths, % (n) 11.0 (8600) 29.8 (5541) 5.1 (3059)

Data are illustrated as median (5–95 percentile) or frequency (N).

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

for a description of other semen parameters. The subpopulation In the adjusted analyses, compared to the reference with a total
of men delivering a semen sample from 1987 to 2015 also had a motile count >120 million, all other groups had significantly
median age of 32 years at baseline and was followed for a median higher mortality risk with no apparent threshold (azoospermia:
of 20 years with 3059 (5.1%) deaths occurring (Table 1). Semen HR ¼ 1.39 (95% CI: 1.05; 1.85), >0–5 million: HR ¼ 1.61 (95% CI:
parameters in this subpopulation were similar to those of the en­ 1.42; 1.83), >5–10 million: HR ¼ 1.38 (95% CI: 1.14; 1.68), >10–40
tire population, although sperm concentration and total sperm million: HR ¼ 1.27 (95% CI: 1.13; 1.42), >40–80 million: HR ¼ 1.16
count were slightly higher (Table 2). In the subpopulation, 20.7% (95% CI: 1.03; 1.29), and >80–120 million: HR ¼ 1.19 (95% CI: 1.06;
had received a diagnosis (any) in a hospital setting in the 10 years 1.34)) (Fig. 2B and Supplementary Table S1).
before baseline, most frequently related to fractures and ill-
defined conditions (10.4% and 6.1%, respectively), while only a Sensitivity analyses
few had another diagnosis, e.g. malignancies (0.6%) or nutritional When stratifying analyses on men with and without any prior di­
and metabolic related diagnoses (0.4%). See Table 3 for the fre­ agnoses, results based on men without prior diagnoses were very
quency of diagnoses in all disease groups. Men with a prior diag­ similar to the adjusted results. The group of men with prior diag­
nosis tended to have a higher sperm concentration than those noses was limited in size, and thus, CIs for the estimates were
without (median: 51 vs 47 million/ml). Still, the sperm concentra­ wider. However, the overall impression was that associations be­
tion was lower for the specific subgroups of men with prior ma­ tween semen quality parameters and all-cause mortality were
lignancies (median: 35 million/ml), diseases related to the more pronounced in men with prior diagnoses (Supplementary
circulatory system (median: 44 million/ml) or the genitourinary Table S2).
system (median: 43 million/ml) compared to those without these When limiting events to deaths occurring more than 5 years
diagnoses (median: 48 million/ml). after baseline, the overall results did not change, and HRs were
of similar magnitude as in the main Model 2 (data not shown).
Semen quality and restricted mean survival time Repeated analyses, stratified by period of sample delivery to
In absolute terms, men with azoospermia or a total motile count explore the role of length of follow-up, revealed no clear pattern
>0–5 million had a life expectancy of 78.0 and 77.6 years, respec­ (data not shown).
tively, while it was 80.3 years for men with a total motile count Results for morphology excluding counts assessed with strict
>120 million, corresponding to a reduction in life expectancy of criteria were comparable to those from the main analysis (data
2.3 and 2.7 years (P < 0.001). Similar differences between the low­ not shown).
est and highest semen quality categories were observed for the
other semen parameters (Fig. 1).
Discussion
Semen quality and all-cause mortality In this large study combining semen quality and register data,
For the total population (N ¼ 78 284), all semen parameters were following men for up to 50 years, we observed that lower semen
negatively associated with all-cause mortality in a dose–response quality was associated with increased all-cause mortality in a
manner (P-trend <0.001 for all semen parameters). However, the dose–response manner for all semen parameters. In absolute
higher mortality risk for men with azoospermia tended to numbers, men with a total motile count >120 million had a
be slightly less pronounced than for the next category of men 2.7-year longer life expectancy than men with a total motile
(with sperm concentration >0–5 million/ml, total sperm count count >0–5 million. The association between semen quality and
>0–10 million or total motile sperm count >0–5 million). Men mortality was not explained by diseases present at the time of se­
with azoospermia had an HR ¼ 1.28 (95% CI: 1.12; 1.46), while men men sampling, which could affect both semen quality and long-
with a total motile sperm count of >0–5 million had an HR ¼ 1.46 term survival. Our study, measuring semen quality rather than
(95% CI: 1.35; 1.59) compared to the reference of men with a total crude categorizations such as fatherhood or infertility diagnosis,
motile count >120 million (Fig. 2A and Supplementary Table S1). clearly demonstrated that semen quality parameters as a marker
Results based on the subpopulation delivering a semen sam­ for long-term survival are relevant even at semen quality levels
ple from 1987 to 2015 (N ¼ 59 657) showed similar trends as for much higher than the cut-off values usually used for diagnosis of
the total population, but the estimates were more pronounced male factor infertility.
(Supplementary Table S1). For example, in this sample, men Results from our prior study (Jensen et al., 2009) and this
with azoospermia had an HR ¼ 1.52 (95% CI: 1.15; 2.02), while study, expanding the study population and follow-up time of our
men with a total motile sperm count of >0–5 million had an previous study considerably and including health information
HR ¼ 1.70 (95% CI: 1.50; 1.93) compared to the reference. After ad­ prior to semen sampling, are consistent overall. Our results also
justment for educational status and diagnoses before baseline, align with prior studies finding that male reproductive function
the observed differences in survival persisted (P-trend <0.001 for is a biomarker of long-term survival (Groos et al., 2006;
all semen parameters), but most HRs were slightly attenuated. Jensen et al., 2009; Eisenberg et al., 2014; Glazer et al., 2019;
6 | Priskorn et al.

Table 2. Semen quality of study population (total and subpopulations with sample delivery 1965–1986 and 1987–2015, respectively).

Total population Sample delivery Sample delivery

(N ¼ 78 284) 1965–1986 (N ¼ 18 627) 1987–2015 (N ¼ 59 657)

Median Median Median

N (5–95 percentile) N (5–95 percentile) N (5–95 percentile)
Period of abstinence, days 78 284 3.5 (2.0–5.0) 18 627 3.5 (2.0–4.5) 59 657 3.5 (2.0–5.5)
Semen volume, ml 78 190 3.2 (1.2–6.2) 18 602 3.2 (1.1–6.3) 59 588 3.2 (1.4–6.2)
Sperm concentration, million/ml 78 284 46 (0–182) 18 627 37 (0–163) 59 657 48 (0.2–188)
Total sperm count, million 78 190 144 (0–566) 18 602 113 (0–508) 59 588 154 (0.5–580)

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

Motile sperm, %a 73 393 68 (30–81) 15 841 66 (17–82) 57 552 68 (33–81)
Total motile count, milliona 73 310 105 (1–414) 15 819 95 (0.3–389) 57 491 108 (2–420)
Morphology until 2011, %a,b 64 308 63 (25–85) 14 861 66 (28–84) 49 447 61 (24–86)
Morphology, strict criteria, %a,b 7574 4 (1–11) 0 – 7574 4 (1–11)

Data are illustrated as median (5–95 percentile).

a
Men with azoospermia are not included, explaining the lower numbers.
b
From 2012, morphology was assessed using strict criteria (WHO 2010).

Table 3. Educational status and registered hospital diagnoses of study reported that men with a sperm concentration of 0–5 mil­
the subpopulation with sample delivery 1987–2015. lion/ml were, on average, hospitalized 7 years earlier than men
with a sperm concentration of 195–200 million/ml (Latif et al.,
Sample delivery 1987–
2015 (N ¼ 59 657) 2017), underlining that men with impaired semen quality as a
group not only can expect to die earlier but also to live fewer
Education, % (n)
Low 16.4 (9752) healthy years.
Medium 41.3 (24 616) Del Giudice et al. (2021) reported that the observed association
High 40.2 (23 960) between oligozoospermia and mortality remained after exclud­
Unknown 2.2 (1329) ing prevalent cardiovascular and malignant disease (i.e. within
Any diagnosis before baseline, % (n)a 20.7 (12 331)
Infections 0.8 (473)
1 year of the index date determining categorization as infertile or
Malignancies 0.6 (345) not). Similarly, in our study, the associations remained and were
Nutritional and metabolic 0.4 (213) only slightly attenuated after considering the educational status
Blood and blood forming organs 0.1 (55) and any hospital diagnoses received within the 10 years before
Mental disorders 0.2 (89)
Nervous system and sensory organs 1.3 (765)
semen quality testing, and even in sensitivity analyses excluding
Circulatory system 0.7 (421) deaths within 5 years after baseline, supporting that the associa­
Respiratory organs 1.2 (702) tion is not due to reverse causality (already identified poor health
Digestive system 1.4 (856) causing impaired semen quality). However, the association may
Genitourinary system 1.0 (615)
Skin and subcutaneous tissue 0.9 (517)
be due to unrecognized poorer health or a common risk factor for
Musculoskeletal and connective tissue 2.8 (1643) poor health and reproductive function. Thus, the fertility work-
Congenital malformations 0.2 (133) up may be a window of opportunity for preventive initiatives if
Ill-defined 6.1 (3618) we can identify the subgroup of men at increased risk of impaired
Fractures etc. 10.4 (6182)
health in the future. Men with severely impaired semen quality
Data are illustrated as frequency (N).
a
due to current or prior disease (or its treatment) are likely rather
Any registered diagnosis within the 10 years prior to baseline. Men can
have more than one diagnosis. Thus, the sum of specific diagnoses exceeds sick and at increased risk of dying per se, and this may explain
the number of men with any diagnosis before baseline. the results of our sensitivity analysis indicating that the excess
mortality in men with impaired semen quality was even larger in
men with registered diagnoses before semen analysis than in
Del Giudice et al., 2020; Elenkov et al., 2020; Ahrenfeldt et al., men without prior diagnoses. Thus, the major preventive poten­
2021). In contrast, a large register-based Swedish study observed tial may lie in the group of men without such prior diseases. We
no overall increased mortality risk among infertile men com­ have previously shown that in young Danish men (median age
pared to men without such a diagnosis (Lundberg et al., 2019), but 19 years), who are considered healthy, semen quality and repro­
in general, couples who are diagnosed as infertile are a selected ductive hormones were associated with minor differences in car­
population with lower mortality than the general population and diometabolic health markers (Hansen et al., 2023). Similarly, Hart
thus, external comparisons can be difficult. Our previous study et al. (2019) reported that a significant minority of 20-year-old
also reported lower mortality in the total population of men de­ Australian men presented with features of metabolic syndrome,
livering a semen sample at the public semen analysis laboratory and that adverse cardiometabolic features were associated with
in the Copenhagen area than in the age-standardized general impaired testicular function. Whether these differences will de­
population of Danish men. However, within the studied popula­ velop into overt health differences is yet unknown.
tion, an association between semen quality and mortality was
still observed (Jensen et al., 2009). Strengths and limitations
To our knowledge, our results are the first to describe the as­ The study has several strengths. It is based on, by far, the largest
sociation between semen quality and life expectancy, in contrast semen quality database available, which can be linked with
to our previous publication, which only reported relative differ­ health information from valid registers and with an extended
ences in mortality risk (Jensen et al., 2009). Thus, there are no follow-up of up to 50 years for the earliest included men with al­
other publications available for a direct comparison, but one most no loss-to-follow-up. In contrast to other proxies of male
 Semen quality and lifespan | 7

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

Figure 2. All-cause mortality according to semen quality. Analyses are based on (A) the total population of 78 284 men studied from 1965 to 2015 and
(B) the more recent subpopulation of 59 657 men studied from 1987 to 2015. Data are presented as adjusted hazard ratios with 95% CIs. Results are
from Cox regression analyses. Results in panel (A) are based on the basic Model 1, with attained age as the underlying time scale, including strata of
period of semen sampling (5-year intervals), and adjusted for period of abstinence. Results in panel (B) are based on the main Model 2, constructed as
described above with further adjustment for educational status and any diagnoses prior to baseline.

reproductive function, such as fertility treatment and father­ Lastly, no genetic data, data on reproductive hormone levels, or
hood, semen quality is not affected by fertility intentions, which biobank material were available, which could be used to elabo­
might be a significant confounding factor in other studies, com­ rate on mechanisms behind observed associations.
plicating the process of selecting a relevant comparison group in We did not observe the highest mortality risk in the group of men
contrast to the present study which relied on internal compari­ with azoospermia as has been reported in other studies (Glazer et al.,
sons. It is well known that the population seeking fertility treat­ 2019; Del Giudice et al., 2021) but rather among men with very few
ment is healthier than the background population, which may spermatozoa in their sample (below 5 million/ml). Although we ex­
hamper the generalizations of the observed associations. cluded men who delivered semen samples for assessment after a va­
Although the included men are well-described based on regis­ sectomy procedure, it cannot completely be excluded that some of
ter data, a limitation is that information exceeding what can be these had been misclassified as fertility patients. However, a more
obtained from the registers is lacking, e.g. information on health likely explanation is that the group of men with azoospermia con­
behaviours which could confound the studied associations. sists of two subgroups, i.e. men with obstructive azoospermia and
However, educational level was included as a crude proxy for so­ basically well-functioning spermatogenesis as well as men with non-
cioeconomic status and thus health behaviour, and adjustment obstructive azoospermia with severely impaired or completely
did not change the associations. In addition, a prior study has ceased spermatogenesis. The first subgroup would attenuate the as­
shown that smoking, BMI and educational level do not modify sociation between azoospermia and mortality.
the association between semen quality and hospitalizations
(Latif et al., 2018). Unfortunately, information regarding father­
hood status of the included men was not available either but, in
Conclusion
our previous study, this did not explain the observed association In conclusion, semen quality was found to be a strong marker of
between semen quality and mortality (Jensen et al., 2009). mortality. Men with very good semen quality could expect to live,
Furthermore, assessment of the health of men prior to semen on average, more than 2 years longer than men with severely im­
sampling was based on diagnoses registered in the National paired semen quality. The dose–response association between
Patient Register, and presence of diagnoses from the general semen quality and mortality was observed for all included semen
practitioner or undiagnosed health issues cannot be ruled out. parameters, and diagnosed diseases or educational levels at the
8 | Priskorn et al.

time of semen quality assessment did not explain the associa­ male infertility and overall male health: a systematic review of
tions. Before preventive initiatives can be initiated, further stud­ the literature. Investig Clin Urol 2020;61:355–371.
ies are needed to identify late-occurring morbidities associated Del Giudice FD, Kasman AM, Li S, Belladelli F, Ferro M, Cobelli O D,
with semen quality. Thus, future studies should focus on disease Berardinis ED, Busetto GM, Eisenberg ML. Increased mortality
trajectories according to semen quality as well as early bio­ among men diagnosed with impaired fertility: analysis of US
markers that could be relevant disease markers in infertile men. claims data. Urology 2021;147:143–149.
Eisenberg ML, Li S, Behr B, Cullen MR, Galusha D, Lamb DJ, Lipshultz
LI. Semen quality, infertility and mortality in the USA. Hum
Supplementary data Reprod 2014;29:1567–1574.
Supplementary data are available at Human Reproduction online. Eisenberg ML, Li S, Behr B, Pera RR, Cullen MR. Relationship between

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

semen production and medical comorbidity. Fertil Steril 2015;
103:66–71.
Data availability Eisenberg ML, Park Y, Hollenbeck AR, Lipshultz LI, Schatzkin A, Pletcher
The data underlying this article cannot be shared publicly due to MJ. Fatherhood and the risk of cardiovascular mortality in the NIH-
data protection rules. The data will be shared on reasonable re­ AARP Diet and Health Study. Hum Reprod 2011;26:3479–3485.
quest to the corresponding author after relevant permissions Elenkov A, Giwercman A, Tøttenborg SS, Bonde JPE, Glazer CH,
have been obtained. Haervig KK, Bungum AB, Nilsson PM. Male childlessness as inde­
pendent predictor of risk of cardiovascular and all-cause mortal­
ity: a population-based cohort study with more than 30 years
Authors’ roles follow-up. PLoS One 2020;15:e0237422.
Substantial contribution to conception and design: all authors. Fallara G, Pozzi E, Belladelli F, Boeri L, Capogrosso P, Corona G,
Data acquisition: L.P., R.L.-J., M.K., B.S.L., V.S., C.L.A., and N.J. D’Arma A, Alfano M, Montorsi F, Salonia A. A systematic review
Data analysis: L.P., R.L.-J., and N.J. Data interpretation: all and meta-analysis on the impact of infertility on men’s general
authors. Drafting the article: L.P. and N.J. Critical revision of the health. Eur Urol Focus 2024;10:98–106.
article for important intellectual content: all authors. All authors Glazer CH, Eisenberg ML, Tøttenborg SS, Giwercman A, Flachs EM,
have approved the final version of article and agree to be ac­ € uner EV, Vassard D, Pinborg A, Schmidt L, Bonde JP. Male fac­
Bra
countable for all aspects of the work. tor infertility and risk of death: a nationwide record-linkage
study. Hum Reprod 2019;34:2266–2273.
Grambsch PM, Therneau TM. Proportional hazards tests and diag­
Funding
nostics based on weighted residuals. Biometrika 1994;81:515–526.
Johan and Hanne Weimann, F. Seedorff’s grant (F-24230-01), Groos S, Krause W, Mueller UO. Men with subnormal sperm counts
Research Fund of the Capital Region of Denmark (R-153-A6176). live shorter lives. Soc Biol 2006;53:46–60.
None of the funders had any role in the study design, collection, Hansen LS, Priskorn L, Holmboe SA, Jensen TK, Hansen AH,
analysis or interpretation of data, writing of the article, or publication Andersson AM, Jørgensen N. Testicular function is associated
decisions. The authors declare they have no competing interests. with cardiometabolic health markers: a cross-sectional study of
2289 young men. Andrology 2023;11:561–574.
Hart RJ, Doherty DA, Mori TA, Adams LA, Huang RC, Minaee N,
Conflict of interest
Handelsman DJ, McLachlan R, Norman RJ, Dickinson JE et al.
The authors declare no conflicts of interest. Features of the metabolic syndrome in late adolescence are asso­
ciated with impaired testicular function at 20 years of age. Hum
Reprod 2019;34:389–402.
References Jensen TK, Jacobsen R, Christensen K, Nielsen NC, Bostofte E. Good
€ ller S, Wensink MJ, Eisenberg ML, Christensen K,
Ahrenfeldt LJ, Mo semen quality and life expectancy: a cohort study of 43,277 men.
Jensen TK, Lindahl-Jacobsen R. Impaired fecundity as a marker Am J Epidemiol 2009;170:559–565.
of health and survival: a Danish twin cohort study. Hum Reprod Kriegbaum M, Lind BS, Grand MK, Andersen CL. The Copenhagen
2021;36:2309–2320. Primary Care Laboratory (CopLab) Database. Clin Epidemiol 2024;
€ rndahl L, Barratt CLR, Mortimer D, Jouannet P. ‘How to count
Bjo 16:155–163.
sperm properly’: checklist for acceptability of studies based on Latif T, Jensen TK, Mehlsen J, Holmboe SA, Brinth L, Pors K, Skouby
human semen analysis. Hum Reprod 2016;31:227–232. SO, Jørgensen N, Lindahl-Jacobsen R. Semen quality as a predic­
Bostofte E, Serup J, Rebbe H. Relation between morphologically ab­ tor of subsequent morbidity: a Danish Cohort Study of 4,712 men
normal spermatozoa and pregnancies obtained during a twenty- with long-term follow-up. Am J Epidemiol 2017;186:910–917.
year follow-up period. Int J Androl 1982a;5:379–386. Latif T, Lindahl-Jacobsen R, Mehlsen J, Eisenberg ML, Holmboe SA,
Bostofte E, Serup J, Rebbe H. Relation between sperm count and se­ Pors K, Brinth L, Skouby SO, Jørgensen N, Jensen TK. Semen qual­
men volume, and pregnancies obtained during a twenty-year fol­ ity associated with subsequent hospitalizations—can the effect
low-up period. Int J Androl 1982b;5:267–275. be explained by socio-economic status and lifestyle factors?
Canchola AJ, Stewart SL, Bernstein L, West DW, Ross RK, Deapen D, Andrology 2018;6:428–435.
Reynolds P, Wright W, Anton-Culver H, Peel D et al. Different Lindahl-Jacobsen R, Tavlo Petersson M, Priskorn L, Skakkebæk NE,
time scales in COX regression. In: West Users SAS Software. San Juul A, Kristensen DM, Eisenberg ML, Jensen TK. Time to preg­
Francisco (CA), 2003,1–6. https://www.lexjansen.com/wuss/ nancy and life expectancy: a cohort study of 18 796 pregnant
2003/DataAnalysis/i-cox_time_scales.pdf (11 February 2025, date couples. Hum Reprod 2024;39:595–603.
last accessed). Lundberg FE, Johansson ALV, Ludvigsson JF. Mortality in 43,598 men
Del Giudice FD, Kasman AM, Ferro M, Sciarra A, Berardinis ED, with infertility—a Swedish nationwide population-based cohort
Belladelli F, Salonia A, Eisenberg ML. Clinical correlation among study. Clin Epidemiol 2019;11:645–657.
 Semen quality and lifespan | 9

Menkveld R, Stander FS, Kotze TJ, Kruger TF, Zyl, JA, van. Define.asp?MainTable=INDL01&PLanguage=1&PXSId=0&wsid=cftree
The evaluation of morphological characteristics of human sper­ (11 February 2025, date last accessed).
matozoa according to stricter criteria. Hum Reprod 1990; Statistics Denmark. Statistics on Educational Attainment. 2024. https://www.
5:586–592. dst.dk/en/Statistik/dokumentation/documentationofstatistics/high
Murshidi MM, Choy JT, Eisenberg ML. Male infertility and somatic est-education-attained (11 February 2025, date last accessed).
health. Urol Clin North Am 2020;47:211–217. Ventimiglia E, Capogrosso P, Boeri L, Serino A, Colicchia M, Ippolito
Pedersen CB. The Danish Civil Registration System. Scand J Public S, Scano R, Papaleo E, Damiano R, Montorsi F et al. Infertility as a
Health 2011;39:22–25. proxy of general male health: results of a cross-sectional survey.
Salonia A, Matloob R, Gallina A, Abdollah F, Sacca � A, Briganti A, Fertil Steril 2015;104:48–55.
Suardi N, Colombo R, Rocchini L, Guazzoni G et al. Are infertile World Health Organization. Laboratory Manual for the Examination of

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025

men less healthy than fertile men? Results of a prospective case- Human Semen and Semen-Cervical Mucus Interaction. Singapore:
control survey. Eur Urol 2009;56:1025–1031. Press Concern, 1980.
Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, World Health Organization. WHO Laboratory Manual for the
Sørensen HT. The Danish National patient registry: a review of Examination of Human Semen and Sperm-Cervical Mucus Interaction,
content, data quality, and research potential. Clin Epidemiol 2015; 4th edn. Cambridge (UK): Cambridge University Press, 1999.
7:449–490. World Health Organization. WHO Laboratory Manual for the
Statistics Denmark. IND01: Admissions by Region, Diagnosis (99 Groups), Age Examination and Processing of Human Semen, 6th edn. Geneva:
and Sex. 2023. https://sdg.statistikbank.dk/statbank5a/SelectVarVal/ World Health Organization, 2021.
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved.
For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through
our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Human Reproduction, 2025, 00, 1–12
https://doi.org/10.1093/humrep/deaf023
Original Article

Downloaded from https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaf023/8051460 by guest on 09 March 2025