Relationship between serum vitamin D concentration and parameters of gonadal function in infertile male patients

Abstract

Background: Vitamin D (vitD) deficiency could affect male reproductive function. Our objective was to investigate the relationship between serum vitD concentrations and hormonal and seminal parameters in infertile patients and to compare the results with those in healthy controls.

Materials and methods: Infertile patients (n = 29) and normozoospermic healthy donors (n = 27) were recruited for the study. Serum concentrations of vitD, total testosterone, estradiol, and sex hormone-binding globulin were determined using chemiluminescence assays, and free testosterone concentration was determined by radioimmunoassay. Semen analysis was performed as suggested by the World Health Organization. Statistical analysis was conducted using Student’s t test, contingency tables, and linear regression studies.

Results: VitD concentrations were lower in patients than in controls (p < 0.001). A significant association (p < 0.001) was observed between vitD concentrations <20ng/mL and infertility. In the control group, significant correlations were reported between vitD concentrations >30 ng/mL and the concentrations of testosterone (p < 0.05), free testosterone (p < 0.01), and estradiol (p < 0.05). A direct correlation was found between vitD concentration and percentage of sperm vitality (p = 0.01). VitD also positively correlated with the percentage of progressive sperm motility (p <0.05) and sex hormone-binding globulin concentrations (p < 0.01).

Conclusions: VitD may affect male reproductive parameters, and its deficiency could be associated with infertility.

Keywords

Infertility / Male / Spermatozoa / Testosterone / Vitamin D

Acknowledgments

We thank Siemens Healthineers S.A. Argentina for the donation of part of the reagents for hormonal determination tests performed in this study.

Statement of ethics

This study has been approved by the Ethical Board of the Facultad de Ciencias Bioquímicas y Farmacéuticas from Universidad Nacional de Rosario (res. 835/2018). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all the study participants.

Conflict of interest statement

The authors report no conflict of interest.

Funding source

None.

Author contributions

MH and EM contributed substantially to the acquisition and analysis of data, drafting the article, and final approval of the version to be published. SG managed the project and contributed substantially to the study design, the analysis of data, drafting the article, and final approval of the version to be published.

Data availability

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

References

[1] Jungwirth A, Giwercman A, Tournaye H, et al. European Association of Urology guidelines on male infertility: The 2012 update. Eur Urol 2012; 62(2):324-332.

[2] Eisenberg ML, Lathi RB, Baker VL, Westphal LM, Milki AA, Nangia AK. Frequency of the male infertility evaluation: Data from the national survey of family growth. J Urol 2013; 189(3):1030-1034.

[3] Chen Y, Zhi X. Roles of vitamin D in reproductive systems and assisted reproductive technology. Endocrinology 2020; 161(4):bqaa023.

[4] Arab A, Hadi A, Moosavian SP, Askari G, Nasirian M. The association between serum vitamin D, fertility and semen quality: A systematic review and meta-analysis. Int J Surg 2019;71:101-109.

[5] Chu J, Gallos I, Tobias A, Tan B, Eapen A, Coomarasamy A. Vitamin D and assisted reproductive treatment outcome: A systematic review and meta-analysis. Hum Reprod 2018; 33(1):65-80.

[6] Holick MF. Vitamin D deficiency. NEnglJMed 2007; 357(3):266-281.

[7] Mousa A, Abell S, Scragg R, de Courten B. Vitamin D in reproductive health and pregnancy. Semin Reprod Med 2016; 34(2):e1-e13.

[8] Ryan JW, Anderson PH, Morris HA. Pleiotropic activities of vitamin D receptors: Adequate activation for multiple health outcomes. Clin Biochem Rev 2015; 36(2):53-61.

[9] Mazzaferro S, Pasquali M. Vitamin D: A dynamic molecule. How relevant might the dynamism for a vitamin be? Nephrol Dial Transplant 2016; 31(1):23-30.

[10] Corbett ST, Hill O, Nangia AK. Vitamin D receptor found in human sperm. Urology 2006; 68(6):1345-1349.

[11] Foresta C, Selice R, Di Mambro A., Strapazzon G. Testiculopathy and vitamin D insufficiency. Lancet 2010; 376(9749):1301.

[12] Blomberg Jensen M, Nielsen JE, Jorgensen A, et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod 2010; 25(5):1303-1311.

[13] Keane KN, Cruzat VF, Calton EK, et al. Molecular actions of vitamin D in reproductive cell biology. Reproduction 2017; 153(1):R29-R42.

[14] Boisen IM, Bollehuus Hansen L, Mortensen LJ, Lanske B, Juul A, Blomberg Jensen M. Possible influence of vitamin D on male reproduction. J Steroid Biochem Mol Biol 2017;173:215-222.

[15] World Health Organization WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th Edition Geneva: WHO Press; 2010.

[16] Sartorius G, Ly LP, Sikaris K, McLachlan R, Handelsman DJ. Predictive accuracy and sources of variability in calculated free testosterone estimates. Ann Clin Biochem 2009; 46(Pt 2):137-143.

[17] Ayala C, Steinberger E, Smith DP. The influence of semen analysis parameters on the fertility potential of infertile couples. J Androl 1996; 17 (6):718-725.

[18] Tartagni M, Matteo M, Baldini D, et al. Males with low serum levels of vitamin D have lower pregnancy rates when ovulation induction and timed intercourse are used as a treatment for infertile couples: Results from a pilot study. Reprod Biol Endocrinol 2015;13:127.

[19] Blomberg Jensen M, Gerner Lawaetz J, Andersson AM, et al. Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men. Hum Reprod 2016; 31(8):1875-1885.

[20] Akhavizadegan H, Karbakhsh M. Comparison of serum vitamin D between fertile and infertile men in a vitamin D deficient endemic area: A case-control study. Urologia 2017; 84(4):218-220.

[21] Sun W, Chen L, Zhang W, Wang R, Goltzman D, Miao D. Active vitamin D deficiency mediated by extracellular calcium and phosphorus results in male infertility in young mice. Am J Physiol Endocrinol Metab 2015; 308(1):E51-E62.

[22] Zanatta AP, Brouard V, Gautier C, et al. Interactions between oestrogen and 1a,25(OH)₂-vitamin D₃ signalling and their roles in spermatogenesis and spermatozoa functions. Basic Clin Androl 2017;27:10.

[23] Shahreza FD, Hajian M, Gharagozloo P, Drevet JR, Nasr-Esfahani MH. Impact of vitamin D deficiency on mouse sperm structure and function. Andrology 2020; 8(5):1442-1455.

[24] Fu L, Chen YH, Xu S, et al. Vitamin D deficiency impairs testicular development and spermatogenesis in mice. Reprod Toxicol 2017; 73:241-249.

[25] Jueraitetibaike K, Ding Z, Wang DD, et al. The effect of vitamin D on sperm motility and the underlying mechanism. Asian J Androl 2019; 21(4):400-407.

[26] de Angelis C, Galdiero M, Pivonello C, et al. The role of vitamin D in male fertility: A focus on the testis. Rev Endocr Metab Disord 2017; 18(3):285-305.

[27] Blomberg Jensen M, Bjerrum PJ, Jessen TE, et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod 2011; 26(6):1307-1317.

[28] Ciccone IM, Costa EM, Pariz JR, et al. Serum vitamin D content is associated with semen parameters and serum testosterone levels in men. Asian J Androl 2021; 23(1):52-58.

[29] Wadhwa L, Priyadarshini S, Fauzdar A, Wadhwa SN, Arora S. Impact of vitamin D supplementation on semen quality in vitamin D-deficient infertile males with oligoasthenozoospermia. J Obstet Gynaecol India 2020; 70(1):44-49.

[30] Anic GM, Albanes D, Rohrmann S, et al. Association between serum 25- hydroxyvitamin D and serum sex steroid hormones among men in NHANES. Clin Endocrinol (Oxf) 2016; 85(2):258-266.

[31] Zhao D, Ouyang P, de Boer IH, et al. Serum vitamin D and sex hormones levels in men and women: The multi-ethnic study of atherosclerosis (MESA). Maturitas 2017;96:95-102.

[32] Välimäki VV, Alfthan H, Ivaska KK, et al. Serum estradiol, testosterone, and sex hormone-binding globulin as regulators of peak bone mass and bone turnover rate in young Finnish men. J Clin Endocrinol Metab 2004; 89(8):3785-3789.

[33] Rehman R, Lalani S, Baig M, Nizami I, Rana Z, Gazzaz ZJ. Association between vitamin D, reproductive hormones and sperm parameters in infertile male subjects. Front Endocrinol (Lausanne) 2018;9:607.

[34] Rafiq R, van Schoor NM, Sohl E, et al. Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men. J Steroid Biochem Mol Biol 2016;164:11-17.

[35] Lerchbaum E, Pilz S, Trummer C, et al. Serum vitamin D levels and hypogonadism in men. Andrology 2014; 2(5):748-754.

[36] Pilz S, Frisch S, Koertke H, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res 2011; 43(3):223-225.

[37] Hofer D, Münzker J, Schwetz V, et al. Testicular synthesis and vitamin D action. J Clm Endocrinol Metab 2014; 99(10):3766-3773.

[38] Canguven O, Talib RA, El Ansari W, Yassin DJ, Al Naimi A. Vitamin D treatment improves levels of sexual hormones, metabolic parameters and erectile function in middle-aged vitamin D deficient men. Aging Male 2017; 20(1):9-16.

[39] Hosseini Marnani E, Mollahosseini M, Gheflati A, Ghadiri-Anari A, Nadjarzadeh A. The effect of vitamin D supplementation on the androgenic profile in men: A systematic review and meta-analysis of clinical trials. Andrologia 2019; 51(9):e13343.

[40] Santos HO, Howell S, Nichols K, Teixeira FJ. Reviewing the evidence on vitamin D supplementation in the management of testosterone status and its effects on male reproductive system (testis and prostate): Mechanistically dazzling but clinically disappointing. Clin Ther 2020; 42(6):e101-e114.

[41] Hess R, Cooke P. Estrogen in the male: A historical perspective. Biol Reprod 2018; 99(1):27-44.

[42] Blomberg Jensen M, Lieben L, Nielsen JE, et al. Characterization of the testicular, epididymal and endocrine phenotypes in the Leuven VDR-deficient mouse model: Targeting estrogen signalling. Mol Cell Endocrinol 2013; 377(1-2):93-102.

[43] Grzechocinska B, Dabrowski FA, Cyganek A, Wielgos M. The role of vitamin D in impaired fertility treatment. Neuro Endocrinol Lett 2013; 34(8):756-762.

[44] Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jørgensen N. Effects of vitamin D supplementation on semen quality, reproductive hormones, and live birth rate: A randomized clinical trial. J Clin Endocrinol Metab 2018; 103(3):870-881.