Vitamin D effects on androgen levels in men

Main Article Content

I.V. Pankiv


Background. Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system. Considering the potential link between vitamin D and human fertility, authors performed this review summarizing current literature on vitamin D and possible mechanisms explaining the link of vitamin D with androgen metabolism in men. The purpose of this review was to provide an overview on the effects of vitamin D on androgen metabolism in men. Methods. Author performed a systematic literature search in PubMed for relevant English language publications published from January 2011 until September 2021. Results. The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues. In men, vitamin D status has been associated with androgen levels and hypogonadism. Further, there is some evidence for a favorable effect of vitamin D supplementation on testosterone concentrations, although others failed to show a significant effect on testosterone levels. Vitamin D might play an important role in androgen metabolism. Existing evidence from available trials evaluating the effect of vitamin D supplementation on androgen levels in men is insufficient to recommend measurement of 25(OH)D levels or vitamin D supplementation in hypogonadal men. We cannot exclude vitamin D effects on androgen levels in men with low TT levels or in men with severe vitamin D deficiency. This question remains to be answered in future investigations. Conclusions. Vitamin D deficiency is associated with adverse fertility outcomes including hypogonadism, but the evidence is insufficient to establish causality. High-quality trials are needed to further evaluate the effects of vitamin D supplementation on androgen levels in men.

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How to Cite
Pankiv, I. “Vitamin D Effects on Androgen Levels in Men”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 17, no. 8, Jan. 2022, pp. 646-50, doi:10.22141/2224-0721.17.8.2021.246801.
Literature Review


Trummer C, Pilz S, Schwetz V, Obermayer-Pietsch B, Lerchbaum E. Vitamin D, PCOS and androgens in men: a systematic review. Endocr Connect. 2018 Mar;7(3):R95-R113. doi:10.1530/EC-18-0009.

Chen Z, Lv X, Hu W, Qian X, Wu T, Zhu Y. Vitamin D Status and Its Influence on the Health of Preschool Children in Hangzhou. Front Public Health. 2021 May 17;9:675403. doi:10.3389/fpubh.2021.675403.

Muñoz-Garach A, García-Fontana B, Muñoz-Torres M. Vitamin D Status, Calcium Intake and Risk of Developing Type 2 Diabetes: An Unresolved Issue. Nutrients. 2019 Mar 16;11(3):642. doi:10.3390/nu11030642.

Aludwan M, Kobyliak N, Abenavoli L, et al. Vitamin D3 deficiency is associated with more severe insulin resistance and metformin use in patients with type 2 diabetes. Minerva Endocrinol. 2020 Sep;45(3):172-180. doi:10.23736/S0391-1977.20.03161-2.

Rai V, Agrawal DK. Role of Vitamin D in Cardiovascular Diseases. Endocrinol Metab Clin North Am. 2017 Dec;46(4):1039-1059. doi:10.1016/j.ecl.2017.07.009.

Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019 Jan;23(2):1-44. doi:10.3310/hta23020.

Jeon SM, Shin EA. Exploring vitamin D metabolism and function in cancer. Exp Mol Med. 2018 Apr 16;50(4):1-14. doi:10.1038/s12276-018-0038-9.

Heath AK, Kim IY, Hodge AM, English DR, Muller DC. Vitamin D Status and Mortality: A Systematic Review of Observational Studies. Int J Environ Res Public Health. 2019 Jan 29;16(3):383. doi:10.3390/ijerph16030383.

Pilz S, Zittermann A, Obeid R, et al. The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. Int J Environ Res Public Health. 2018 Oct 12;15(10):2241. doi:10.3390/ijerph15102241.

Grzechocinska B, Dabrowski FA, Cyganek A, Wielgos M. The role of vitamin D in impaired fertility treatment. Neuro Endocrinol Lett. 2013;34(8):756-62.

Babakhanzadeh E, Nazari M, Ghasemifar S, Khodadadian A. Some of the Factors Involved in Male Infertility: A Prospective Review. Int J Gen Med. 2020 Feb 5;13:29-41. doi:10.2147/IJGM.S241099.

Punab M, Poolamets O, Paju P, et al. Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod. 2017 Jan;32(1):18-31. doi:10.1093/humrep/dew284.

Fantus RJ, Chang C, Platz EA, et al. Serum Total Testosterone and Premature Mortality Among Men in the USA. Eur Urol Open Sci. 2021 Jun 7;29:89-92. doi:10.1016/j.euros.2021.05.008.

Holmboe SA, Skakkebæk NE, Juul A, et al. Individual testosterone decline and future mortality risk in men. Eur J Endocrinol. 2018 Jan;178(1):123-130. doi:10.1530/EJE-17-0280.

Lerchbaum E, Pilz S, Trummer C, et al. Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4292-4302. doi:10.1210/jc.2017-01428.

Snyder PJ, Bhasin S, Cunningham GR, et al; Testosterone Trials Investigators. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016 Feb 18;374(7):611-24. doi:10.1056/NEJMoa1506119.

Cunningham GR. Testosterone and metabolic syndrome. Asian J Androl. 2015 Mar-Apr;17(2):192-6. doi:10.4103/1008-682X.148068.

D'Amelio P. Vitamin D Deficiency and Risk of Metabolic Syndrome in Aging Men. World J Mens Health. 2021 Apr;39(2):291-301. doi:10.5534/wjmh.200189.

Nieschlag E, Nieschlag S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019 Jun 1;180(6):R201-R212. doi:10.1530/EJE-19-0071.

Maestro MA, Molnár F, Mouriño A, Carlberg C. Vitamin D receptor 2016: novel ligands and structural insights. Expert Opin Ther Pat. 2016 Nov;26(11):1291-1306. doi:10.1080/13543776.2016.1216547.

Campolina-Silva GH, Maria BT, Mahecha GAB, Oliveira CA. Reduced vitamin D receptor (VDR) expression and plasma vitamin D levels are associated with aging-related prostate lesions. Prostate. 2018 May;78(7):532-546. doi:10.1002/pros.23498.

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 Sep;18(3):285-305. doi:10.1007/s11154-017-9425-0.

Foresta C, Selice R, Di Mambro A, Strapazzon G. Testiculopathy and vitamin D insufficiency. Lancet. 2010 Oct 16;376(9749):1301. doi:10.1016/S0140-6736(10)61916-2.

De Toni L, De Filippis V, Tescari S, et al. Uncarboxylated osteocalcin stimulates 25-hydroxy vitamin D production in Leydig cell line through a GPRC6a-dependent pathway. Endocrinology. 2014 Nov;155(11):4266-74. doi:10.1210/en.2014-1283.

Saponaro F, Saba A, Zucchi R. An Update on Vitamin D Metabolism. Int J Mol Sci. 2020 Sep 8;21(18):6573. doi:10.3390/ijms21186573.

Mordan-McCombs S, Brown T, Wang WL, Gaupel AC, Welsh J, Tenniswood M. Tumor progression in the LPB-Tag transgenic model of prostate cancer is altered by vitamin D receptor and serum testosterone status. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):368-71. doi:10.1016/j.jsbmb.2010.03.062.

Hofer D, Münzker J, Schwetz V, et al. Testicular synthesis and vitamin D action. J Clin Endocrinol Metab. 2014 Oct;99(10):3766-73. doi:10.1210/jc.2014-1690.

Yılmazel FK, Karabulut İ, Yılmaz AH, Keskin E, Bedir F, Özbey İ. A review of hypogonadotropic hypogonadism cases followed up in our clinic in the last decade. Urologia. 2021 Feb;88(1):50-55. doi:10.1177/0391560319882231.

Rajakumar K, de las Heras J, Chen TC, Lee S, Holick MF, Arslanian SA. Vitamin D status, adiposity, and lipids in black American and Caucasian children. J Clin Endocrinol Metab. 2011 May;96(5):1560-7. doi:10.1210/jc.2010-2388.

Selva DM, Hirsch-Reinshagen V, Burgess B, et al. The ATP-binding cassette transporter 1 mediates lipid efflux from Sertoli cells and influences male fertility. J Lipid Res. 2004 Jun;45(6):1040-50. doi:10.1194/jlr.M400007-JLR200.

Nimptsch K, Platz EA, Willett WC, Giovannucci E. Association between plasma 25-OH vitamin D and testosterone levels in men. Clin Endocrinol (Oxf). 2012 Jul;77(1):106-12. doi:10.1111/j.1365-2265.2012.04332.x.

Lee DM, Tajar A, Pye SR, et al; EMAS study group. Association of hypogonadism with vitamin D status: the European Male Ageing Study. Eur J Endocrinol. 2012 Jan;166(1):77-85. doi:10.1530/EJE-11-0743.

Jorde R, Grimnes G, Hutchinson MS, Kjærgaard M, Kamycheva E, Svartberg J. Supplementation with vitamin D does not increase serum testosterone levels in healthy males. Horm Metab Res. 2013 Sep;45(9):675-81. doi:10.1055/s-0033-1345139.

Wang N, Han B, Li Q, et al. Vitamin D is associated with testosterone and hypogonadism in Chinese men: Results from a cross-sectional SPECT-China study. Reprod Biol Endocrinol. 2015 Jul 16;13:74. doi:10.1186/s12958-015-0068-2.

Heijboer AC, Oosterwerff M, Schroten NF, et al. Vitamin D supplementation and testosterone concentrations in male human subjects. Clin Endocrinol (Oxf). 2015 Jul;83(1):105-10. doi:10.1111/cen.12711.

Chin KY, Ima-Nirwana S, Wan Ngah WZ. Vitamin D is significantly associated with total testosterone and sex hormone-binding globulin in Malaysian men. Aging Male. 2015;18(3):175-9. doi:10.3109/13685538.2015.1034686.

Tak YJ, Lee JG, Kim YJ, et al. Serum 25-hydroxyvitamin D levels and testosterone deficiency in middle-aged Korean men: a cross-sectional study. Asian J Androl. 2015 Mar-Apr;17(2):324-8. doi:10.4103/1008-682X.142137.

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 Nov;164:11-17. doi:10.1016/j.jsbmb.2015.11.013.

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 Aug;85(2):258-66. doi:10.1111/cen.13062.

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 Aug;31(8):1875-85. doi:10.1093/humrep/dew152.

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 Feb;96:95-102. doi:10.1016/j.maturitas.2016.11.017.

Hammoud AO, Meikle AW, Peterson CM, Stanford J, Gibson M, Carrell DT. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J Androl. 2012 Nov;14(6):855-9. doi:10.1038/aja.2012.77.

Wulaningsih W, Van Hemelrijck M, Michaelsson K, et al. Association of serum inorganic phosphate with sex steroid hormones and vitamin D in a nationally representative sample of men. Andrology. 2014 Nov;2(6):967-76. doi:10.1111/andr.285.

Lerchbaum E, Pilz S, Trummer C, et al. Serum vitamin D levels and hypogonadism in men. Andrology. 2014 Sep;2(5):748-54. doi:10.1111/j.2047-2927.2014.00247.x.

Pilz S, Kienreich K, Tomaschitz A, et al. Vitamin D and cancer mortality: systematic review of prospective epidemiological studies. Anticancer Agents Med Chem. 2013 Jan;13(1):107-17.

Ferlin A, Selice R, Di Mambro A, et al. Role of vitamin D levels and vitamin D supplementation on bone mineral density in Klinefelter syndrome. Osteoporos Int. 2015 Aug;26(8):2193-202. doi:10.1007/s00198-015-3136-8.

Foresta C, Calogero AE, Lombardo F, Lenzi A, Ferlin A. Late-onset hypogonadism: beyond testosterone. Asian J Androl. 2015 Mar-Apr;17(2):236-8. doi:10.4103/1008-682X.135985.

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 Mar;20(1):9-16. doi:10.1080/13685538.2016.1271783.

Pilz S, Frisch S, Koertke H, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011 Mar;43(3):223-5. doi:10.1055/s-0030-1269854.

Lerchbaum E, Pilz S, Trummer C, et al. Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4292-4302. doi:10.1210/jc.2017-01428.

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