Longitudinal hormonal dynamics during minipuberty and exploratory associations with vitamin D status in healthy term male infants
DOI:
https://doi.org/10.15584/ejcem.2026.2.14Keywords:
corticosterone, minipuberty, neonates, testicular volume, testosterone, vitamin DAbstract
Introduction and aim. Minipuberty, the transient postnatal reactivation of the hypothalamic-pituitary-gonadal axis, is a critical window for male reproductive maturation. The study prospectively characterized hormonal dynamics during minipuberty and explored associations between 25-hydroxyvitamin D [25(OH)D] and gonadal hormones, adrenal corticosterone, and genital growth parameters.
Material and methods. Sixty healthy term male babies were enrolled; 52 completed follow-up. Testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), corticosterone, and 25(OH)D were measured on day 3 and at 3 months by LC-MS/MS and chemiluminescence immunoassay. Penile length and testicular volume were recorded at both visits.
Results. Testosterone increased from 47.18 to 142.62 ng/dL, LH from 1.31 to 2.46 mIU/mL, and FSH from 1.22 to 2.10 mIU/L (all p<0.001), while corticosterone decreased from 211.19 to 86.25 ng/dL (p<0.001). Several nominal associations were observed before multiple comparison correction; however, after Bonferroni correction, only the inverse association between 25(OH)D and corticosterone at 3 months (r=−0.576, p<0.001) remained statistically significant. All other associations should be considered exploratory.
Conclusion. Only the inverse association between vitamin D and corticosterone remained statistically significant after correction, while other associations were exploratory and require confirmation in larger studies.
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References
Kuiri-Hänninen T, Sankilampi U, Dunkel L. Activation of the hypothalamic-pituitary-gonadal axis in infancy: minipuberty. Horm Res Paediatr. 2014;82(2):73-80. doi:10.1159/000362414
Main KM, Schmidt IM, Skakkebaek NE. A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak. J Clin Endocrinol Metab. 2000;85(12):4905-4907. doi:10.1210/jcem.85.12.7058
Grinspon RP, Rey RA. Mini-puberty and true puberty: differences in testicular function. Ann Endocrinol (Paris). 2014;75(2):58-63. doi:10.1016/j.ando.2014.03.001
Kuiri-Hänninen T, Koskenniemi J, Dunkel L, et al. Postnatal testicular activity in healthy boys and boys with cryptorchidism. Front Endocrinol (Lausanne). 2019;10:489. doi:10.3389/fendo.2019.00489
Blomberg Jensen M, Nielsen JE, Jørgensen 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. doi:10.1093/humrep/deq024
Blomberg Jensen M. Vitamin D and male reproduction. Nat Rev Endocrinol. 2014;10(3):175-186. doi:10.1038/nrendo.2013.262
Kinuta K, Tanaka H, Moriwake T, et al. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology. 2000;141(4):1317-1324. doi:10.1210/endo.141.4.7403
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. doi:10.1055/s-0030-1269854
Wehr E, Pilz S, Boehm BO, et al. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf). 2010;73(2):243-248. doi:10.1111/j.1365-2265.2009.03777.x
Seth A, Marwaha RK, Singla B, et al. Vitamin D nutritional status of exclusively breast fed infants and their mothers. J Pediatr Endocrinol Metab. 2009;22(3):241-246.
Agarwal N, Faridi MM, Aggarwal A, Singh O. Vitamin D status of term exclusively breastfed infants and their mothers from India. Acta Paediatr. 2010;99(11):1671-1674. doi:10.1111/j.1651-2227.2010.01921.x
Harinarayan CV, Ramalakshmi T, Prasad UV, et al. High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr. 2007;85(4):1062-1067. doi:10.1093/ajcn/85.4.1062
Kılınç S, Atay E, Ceran Ö, Atay Z. Evaluation of vitamin D status and its correlation with gonadal function in children at minipuberty. Clin Endocrinol (Oxf). 2019;90(1):122-128. doi:10.1111/cen.13864
Villar J, Cheikh Ismail L, Victora CG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014;384(9946):857-868. doi:10.1016/S0140-6736(14)60932-6
World Health Organization. WHO Child Growth Standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. Geneva, Switzerland: World Health Organization; 2006.
Khadilkar A, Khadilkar V, Chinnappa J, et al. Prevention and treatment of vitamin D and calcium deficiency in children and adolescents: Indian Academy of Pediatrics guidelines. Indian Pediatr. 2017;54(7):567-573. doi:10.1007/s13312-017-1090-y
Hofer D, Münzker J, Schwetz V, et al. Testicular synthesis and vitamin D action. J Clin Endocrinol Metab. 2014;99(10):3766-3773. doi:10.1210/jc.2014-1575
Sharpe RM, McKinnell C, Kivlin C, Fisher JS. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction. 2003;125(6):769-784. doi:10.1530/rep.0.1250769
Rey RA, Grinspon RP. Normal male sexual differentiation and aetiology of disorders of sex development. Best Pract Res Clin Endocrinol Metab. 2011;25(2):221-238. doi:10.1016/j.beem.2010.08.001
Sippell WG, Dörr HG, Bidlingmaier F, Knorr D. Plasma levels of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone during infancy and childhood. Pediatr Res. 1980;14(1):39-46. doi:10.1203/00006450-198001000-00009
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. doi:10.1056/NEJMra070553
Ciardo F, Gambineri A, Fazzini A, et al. Vitamin D and adrenal gland: myth or reality? A systematic review. Front Endocrinol (Lausanne). 2022;13:1001065. doi:10.3389/fendo.2022.1001065
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