Male Infertility and Reduced Life Expectancy: Epidemiology, Mechanisms, and Clinical Implications
Abstract
:1. Introduction
2. Epidemiological Links Between Male Infertility and Mortality
3. Common Comorbidities in Infertile Men
3.1. Cardiovascular Disease and Metabolic Syndrome
3.2. Oncologic Concerns
3.3. Endocrine and Autoimmune Disorders
3.4. Genetic Syndromes
3.5. Other Health Issues
4. Biological and Hormonal Mechanisms Connecting Infertility with Systemic Disease
4.1. Genetic Pleiotropy and Developmental Pathways
4.2. Hormonal Imbalances
4.3. Shared Risk Factors and Organ Reserve
4.4. Molecular and Cellular Mechanisms
5. Psychosocial Impact of Infertility on Mental Health
6. Lifestyle, Socioeconomic Status, and Environmental Exposures
6.1. Lifestyle Behaviors
6.2. Socioeconomic Determinants and Health Inequalities
6.3. Environmental and Occupational Exposures
6.4. The Role of Social and Relationship Factors
7. Clinical Implications and Recommendations
7.1. Comprehensive Health Screeing
7.2. Hormonal Evalutation and Management Strategies
7.3. Cancer Surveillance
7.4. Intergrating Mental Health Support into Fertility Support
7.5. Lifestyle Interventions
7.6. Long-Term Follow-up
7.7. Patient Education and Counseling
7.8. Interdisciplinary Collaboration
7.9. Public Health Strategies and Awareness as a Window to Health
8. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Study | Population Size (N) | Fertility Status | Mortality Risk (HR/RR) | Key Findings |
---|---|---|---|---|
Fallara et al. (2024) [15] | 3,173,122 fertile vs. 212,791 infertile men | Infertile vs. fertile men | All-cause mortality: HR = 1.37 (95% CI: 1.04–1.81); Testicular cancer: RR = 1.86 (95% CI: 1.41–2.45); Prostate cancer: RR = 1.66 (95% CI: 1.06–2.61); Melanoma: RR = 1.30 (95% CI: 1.08–1.56); Diabetes: HR = 1.39 (95% CI: 1.09–1.71); Cardiovascular events: HR = 1.20 (95% CI: 1.00–1.44) | Infertile men had significantly increased risks of all-cause mortality, specific cancers (testicular, prostate, melanoma), diabetes, and cardiovascular events compared to fertile men, supporting infertility as a marker for general health risks. |
Del Giudice et al. (2021) [14] | Total: 202,456 (infertility cohorts); 59,291 (semen parameters cohorts) | Infertile vs. fertile men; Oligo/Azoospermic vs. Normospermic | HR = 1.26 (95% CI: 1.01–1.59); RR = 1.67 (95% CI: 1.26–2.21) for Oligo/Azoospermic vs. Normospermic | Infertile men had a 26% higher all-cause mortality compared to fertile men. Those with combined oligo- and azoospermia had a 67% higher risk of death compared to normospermic men. Azoospermic men specifically had over twofold risk (HR = 2.17, 95% CI: 1.55–3.04) compared to normospermic controls. |
Behboudi-Gandevani et al. (2021) [19] | 168,327 infertile men; 2,252,806 controls | Infertility vs. Fertility | OR = 1.43 (95% CI 1.25–1.64) | Infertile men had approximately 43% higher risk of developing any cancer compared to fertile men. Specifically elevated risks were noted for testicular cancer (OR = 1.91, 95% CI: 1.52–2.42), prostate cancer (OR = 1.48, 95% CI: 1.05–2.08), and melanoma (OR = 1.31, 95% CI: 1.06–1.62). Male infertility was concluded to be a significant independent risk factor for future cancer development. |
Elenkov et al. (2020) [18] | 22,444 men from Malmö Preventive Project | Childless vs. Fathers (proxy for infertility) | HR (CVD mortality) = 1.33 (95% CI: 1.18–1.49); HR (all-cause mortality) = 1.23 (95% CI: 1.14–1.33) | Childless men exhibited significantly higher cardiovascular mortality (33% increased risk) and all-cause mortality (23% increased risk) compared to fathers. Childless men also had a worse baseline metabolic profile with increased odds of high triglycerides (OR 1.24), high fasting glucose (OR 1.23), and hypertension (OR 1.28). Suggests childlessness (likely related to infertility) independently predicts increased cardiovascular and metabolic risks. |
Al-Jebari et al. (2019) [20] | 1,181,490 fathers (20,618 IVF; 14,882 ICSI; 1,145,990 natural conception) | ICSI/IVF vs. Natural conception | HR = 1.64 (95% CI: 1.25–2.15) for ICSI; HR = 1.33 (95% CI: 1.06–1.66) for IVF; HR = 1.86 (95% CI: 1.25–2.77) for early-onset prostate cancer (ICSI) | Men fathering via ICSI had a 64% higher overall risk of prostate cancer compared with natural conception. ICSI-treated men had an 86% increased risk of early-onset prostate cancer (diagnosed before age 55). Fathers conceiving via IVF had a 33% higher risk of prostate cancer compared to natural conception. Severe male-factor infertility thus appears strongly associated with elevated long-term prostate cancer risks, particularly for early-onset disease. |
Lundberg et al. (2019) [17] | 43,598 men with infertility diagnosis; 57,733 men with infertility-related diagnosis; 2,762,254 controls | Infertility and infertility-related diagnoses vs. controls | HR = 0.98 (95% CI: 0.89–1.08) for infertility diagnosis; HR = 1.23 (95% CI: 1.17–1.30) for infertility-related diagnoses; HR = 3.26 (95% CI: 2.42–4.41) for mortality before age 30 in infertile men | Overall, men diagnosed with infertility did not have significantly higher mortality compared to controls. However, significantly higher mortality occurred among those with infertility-related diagnoses and particularly among infertile men under 30, largely due to cancers diagnosed before infertility evaluation. A slightly elevated suicide risk (HR = 1.18; 95% CI: 1.01–1.37) was also observed, indicating possible psychosocial implications. |
Eisenberg et al. (2016) [16] | 13,027 infertile men; 23,860 fertility-tested controls; 79,099 vasectomized men | Male infertility vs. fertility-tested and vasectomized men | Increased risk: Diabetes (HR 1.30, 95% CI 1.10–1.53), Ischemic heart disease (HR 1.48, 95% CI 1.19–1.84), Hypertension (HR 1.09, 95% CI 1.02–1.17), Renal disease (HR 1.60, 95% CI 1.14–2.24), Liver disease (HR 1.53, 95% CI 1.31–1.80), Peripheral vascular disease (HR 1.52, 95% CI 1.12–2.07) | Infertile men had significantly increased risks of developing chronic medical conditions including diabetes, ischemic heart disease, hypertension, renal and liver diseases, and peripheral vascular disease compared to fertile (vasectomized) men. Findings suggest infertility evaluation may identify men at increased risk for chronic health conditions later in life. |
Eisenberg et al. (2014) [12] | 11,935 infertile men | Normal vs. Abnormal semen parameters | HR = 2.29 (95% CI: 1.12–4.65) for men with ≥2 semen abnormalities | Over ~8 years follow-up, men with two or more abnormal semen parameters had more than double the risk of death compared to those with normal semen parameters. Study confirms that more severe sperm abnormalities predict higher risks of premature mortality. |
Jensen et al. (2009) [11] | 43,277 men | Normospermic vs. Oligo-/Azoospermic | Dose-response decrease in mortality with increasing sperm concentration (up to 40 million/mL), motility, and normal morphology (p < 0.05) | Men with higher sperm counts and greater percentages of motile and morphologically normal spermatozoa had significantly lower mortality rates. Mortality decreased steadily with improving semen quality parameters up to a concentration of 40 million/mL, supporting the concept of semen quality as a fundamental biomarker of overall male health and life expectancy. |
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Kaltsas, A.; Koumenis, A.; Stavropoulos, M.; Kratiras, Z.; Deligiannis, D.; Adamos, K.; Chrisofos, M. Male Infertility and Reduced Life Expectancy: Epidemiology, Mechanisms, and Clinical Implications. J. Clin. Med. 2025, 14, 3930. https://doi.org/10.3390/jcm14113930
Kaltsas A, Koumenis A, Stavropoulos M, Kratiras Z, Deligiannis D, Adamos K, Chrisofos M. Male Infertility and Reduced Life Expectancy: Epidemiology, Mechanisms, and Clinical Implications. Journal of Clinical Medicine. 2025; 14(11):3930. https://doi.org/10.3390/jcm14113930
Chicago/Turabian StyleKaltsas, Aris, Andreas Koumenis, Marios Stavropoulos, Zisis Kratiras, Dimitrios Deligiannis, Konstantinos Adamos, and Michael Chrisofos. 2025. "Male Infertility and Reduced Life Expectancy: Epidemiology, Mechanisms, and Clinical Implications" Journal of Clinical Medicine 14, no. 11: 3930. https://doi.org/10.3390/jcm14113930
APA StyleKaltsas, A., Koumenis, A., Stavropoulos, M., Kratiras, Z., Deligiannis, D., Adamos, K., & Chrisofos, M. (2025). Male Infertility and Reduced Life Expectancy: Epidemiology, Mechanisms, and Clinical Implications. Journal of Clinical Medicine, 14(11), 3930. https://doi.org/10.3390/jcm14113930