Association between Vitamin D Levels, Puberty Timing, and Age at Menarche

Abstract

Pubertal development represents the process of physical maturation where an adolescent reaches sexual maturity and attains reproductive function. The effects of vitamin D are mainly mediated by the vitamin D receptor (VDR), which is expressed in almost all body cells, including the ovary and human pituitary gland and animal hypothalamus. Thus, vitamin D has gained great interest as pathogenic factor of pubertal disorders and fertility. This narrative review aimed to provide a broad overview of the available literature regarding the association between vitamin D levels, puberty timing, and age at menarche. A review of the data on the involvement of micronutrient deficiency, as a modifiable cause of pubertal disorders, is important for the prediction and prevention of deficiencies as well as for fertility protection and should be considered a public health priority. Reported data support that vitamin D is a regulator of neuroendocrine and ovarian physiology and, more in detail, a deficiency of vitamin D is involved in altered pubertal timing. Considering the long-term consequences of early pubertal development and early menarche, the detection of modifiable causes is crucial in preventive strategies. Future studies in humans and with an increased scale are needed to elucidate the vitamin D role in sexual maturation and puberty development.

Keywords: age at menarche; early menarche; precocious puberty; pubertal disorders; timing of puberty; vitamin D; vitamin D deficiency.

Figure 1

Pathways of vitamin synthesis and function. Cholecalciferol derives from animal products and supplements. It originates from the conversion of 7-dehydrocholesterol to vitamin D3 through isomerization and thermo-conversion mediated by ultraviolet B radiation in epidermal and dermal keratinocytes and fibroblasts. Ergocalciferol derives from plants and supplements. It originates from the conversion of ergosterol in plants mediated by irradiation. Calcidiol derives from 25-hydroxylation of cholecalciferol and ergocalciferol in the liver mediated by vitamin D-25-hydroxylase (CYP2R1). Calcidiol reaches the kidneys and is converted into bioactive calcitriol through hydroxylation mediated by 25(OH)D-1alfa-hydroxylase (CYP27B1), which is activated by PTH and inhibited by FGF-23. Calcitriol modulates calcium–phosphorus balance: in response to low dietary calcium intake, calcitriol induces maturation of osteoclasts and calcium–phosphorus absorption by bone and reduces renal calcium and phosphate excretion [11,12,13,14] (created with biorender.com, accessed on 10 July 2023). UVB = ultraviolet type B; PTH = parathyroid hormone; FGF = Fibroblast Growth Factors.

Figure 2

Potential mechanisms linking vitamin D and pubertal timing. VDR = vitamin D receptor.