Relationship between semen production and medical comorbidity

Men with medical comorbidities have a higher rate of abnormal semen parameters.

Michael L. Eisenberg, M.D., Shufeng Li, M.S., Barry Behr, Ph.D., Renee Reijo Pera, Ph.D., Mark R. Cullen, M.D.

Volume 103, Issue 1, Pages 66-71


To study the relationship between semen quality and current health status in a cohort of men evaluated for infertility.

Cross-sectional study.

Fertility clinic.

Nine thousand three hundred eighty-seven men evaluated for infertility between 1994 and 2011.


Main Outcome Measure(s):
Charlson comorbidity index, medical diagnoses by organ system.

At the time of evaluation, 9,387 men with a mean age of 38 years had semen data available. Of these men, 44% had at least one medical diagnosis unrelated to infertility. When stratifying the cohort by the Charlson comorbidity index (CCI), differences in all measured semen parameters were identified. Men with a higher CCI had lower semen volume, concentration, motility, total sperm count, and morphology scores. In addition, men with diseases of the endocrine, circulatory, genitourinary, and skin diseases all showed significantly higher rates of semen abnormalities. Upon closer examination of diseases of the circulatory system, men with hypertensive disease, peripheral vascular and cerebrovascular disease, and nonischemic heart disease all displayed higher rates of semen abnormalities.

The current report identified a relationship between medical comorbidites and male semen production. Although genetics help guide a man’s sperm production, his current condition and health play an important role.

  • This article demonstrates the potential global impact of overall health upon fertility status. Given the obesity epidemic that is prevalent in our adolescents and young adults, this is going to be a significant issue in their child bearing years. This should serve as a wake up call to the pediatricians and primary care providers. We also need to be involved in educating our colleagues and patients on the ramifications of poor overall health.

    This also brings up a huge challenge in the treatment of these chronic diseases. Should we as practitioners just throw medications to control HTN, DM, HLD, etc. which is the easier pathway in this day and age of capitation and the ACA. OR should we encourage lifestyle modification, which takes much more effort on the part of the patient, but may bring on much more lasting change and improvement in the long run?

  • ranjithrama

    Mike Eisenberg adds to the series of studies that indicate an association between men with abnormal semen parameters and comorbidity and mortality. How should urologists counsel an infertile man with abnormal semen parameters beyond the fertility evaluation? Can we make a case for checking BP / HbA1c / fasting lipid panels in men with infertility?

  • wbgrant

    Low 25-hydroxyvitamin D concentrations may explain the link between semen production and medical comorbidity

    The recent paper by Eisenberg and colleagues found that poor
    semen quality and infertility were associated with increased risk of endocrine
    disease, nutritional and metabolic disorders, genitourinary diseases, and skin
    disorders, but not with several other diseases (1). They noted that diabetes
    mellitus impacts male fertility through ejaculatory and erectile impairments,
    and that men with infertility have reduced circulating testosterone levels
    compared to fertile men. They did not provide a comprehensive hypothesis to
    explain their findings. I would like to propose that low 25-hydroxyvitamin D
    [25(OH)D] concentrations may explain their findings and related ones discussed
    in the paper.

    There are several different ways to study the link between
    vitamin D and health outcomes. At present, observational studies based on
    25(OH)D concentrations have provided the largest set of supportive findings
    (2). Results from randomized controlled trials (RCTs) have been largely
    inconclusive due the fact that most such trials were poorly designed, often
    enrolling people with 25(OH)D concentrations too high to find an effect of the
    low vitamin D doses often used (3). Thus, this letter will use examples
    primarily from observational studies. In support, it is noted that mechanisms
    have been identified to explain most of the vitamin D-health outcome relations.

    Here are the findings from the literature. In terms of male fertility, low 25(OH)D concentrations were associated with poor semen quality in infertile men (4). A review found vitamin D signalling has a positive effect on semen quality (5). Low 25(OH)D
    concentrations are also associated with erectile dysfunction related to endothelial factors (6, 7).

    25(OH)D concentrations have been found inversely correlated with risk of cardiovascular disease (8, 9), peripheral arterial disease (8), cerebrovascular disease (8, 10), hypertension (8), diabetes mellitus (8, 11), and erectile dysfunction (12, 13). The link between 25(OH)D concentrations and risk of cardiovascular disease is considered causal based on Hill’s criteria for causality in a biological system (14). A vitamin D RCT found that vitamin D supplementation lowered blood pressure (15). Another vitamin D RCT found that vitamin D supplementation increased testosterone levels (16).

    If blood samples are available from some of the men studied in Ref. 1, 25(OH)D concentrations could be measured to evaluate the vitamin D-infertility-medical comorbidity hypothesis. If not, an additional study could easily be mounted.

    Meanwhile, men who are infertile could be advised to have their 25(OH)D concentration measured and, if low, raise it by ultraviolet-B exposure or vitamin D supplements to about 30-60 ng/mL (17).


    1. Eisenberg ML, Li S, Behr B, Reijo Pera R, Cullen MR. Relationship between semen production and medical comorbidity. Fertility and Sterility. Published online: December 9, 2014

    2. Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al. Vitamin D and risk of cause specific death: systematic review and
    meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.

    3. Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014;72:48-54.

    4. Yang B, Sun H, Wan Y, Wang H, Qin W, Yang L, et al. Associations between testosterone, bone mineral density, vitamin D and semen quality in fertile and infertile Chinese men. Int J Androl. 2012;35:783-92.

    5. Blomberg Jensen M. Vitamin D and male reproduction. Nat Rev Endocrinol. 2014;10:175-86.

    6. Sorenson M, Grant WB. Does vitamin D deficiency contribute to erectile dysfunction? Dermatoendocrinol. 2012;4:128-36.

    7. Barassi A, Pezzilli R, Colpi GM, Corsi Romanelli MM, Melzi d’Eril GV. Vitamin D and erectile dysfunction. J Sex Med. 2014;11:2792-800.

    8. Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106:963-8.

    9. Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: A meta-analysis of
    prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5:819-29.

    10. Brøndum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M. 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol. 2013;73:38-47.

    11. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB.
    Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis
    of prospective studies. Diabetes Care. 2013;36:1422-8.

    12. Sorenson M, Grant WB. Does vitamin D deficiency contribute to erectile dysfunction? Dermatoendocrinol. 2012;4:128-36.

    13. Barassi A, Pezzilli R, Colpi GM, Corsi Romanelli MM, Melzi d’Eril GV. Vitamin d and erectile dysfunction. J Sex Med. 2014;11:2792-800.

    14. Weyland PG, Grant WB, Howie-Esqauivel J. Does sufficient evidence exist to support a causal association between vitamin D status and cardiovascular disease risk? An assessment using Hill’s criteria for causality. Nutrients. 2014;6:3403-30.

    15. Mozaffari-Khosravi H, Loloei S, Mirjalili MR, Barzegar K. The effect of vitamin D supplementation on blood pressure in patients with elevated blood pressure and vitamin D deficiency: a randomized, double-blind, placebo-controlled trial. Blood Press Monit. 2014 Oct 27. [Epub ahead of print]

    16. Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann A. Effect of vitamin D supplementation on testosterone levels in men.
    Horm Metab Res. 2011;43:223-5.

    17. Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality- a review of recent evidence. Autoimmun Rev. 2013;12:976-89.

    I receive funding from Bio-Tech Pharmacal (Fayetteville, AR), the Sunlight Research Forum (Veldhoven), and Medi-Sun Engineering, LLC (Highland Park, IL).

    • Michael Eisenberg

      The etiology for the association between a man’s fertility and his overall health is uncertain. Genetic, hormonal, in utero, and lifestyle factors have all been proposed. It is likely that all contribute to some extent. Dr. Grant makes a compelling argument that vitamin D may provide another link in the causal pathway.

      • Jason Kovac

        It is interesting to note that numerous male multi-vitamins have different levels of vitamin D in them. Indeed, some have none. Should we be advocating for patients using those products that contain higher levels of vitamin D?

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