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.

Association between 25-hydroxyvitamin D concentrations and pubertal timing: 6–14-year-old children and adolescents in the NHANES 2015–2016

“…Puberty is the physiological process whereby adolescents reach sexual maturity and become capable of reproduction. Puberty onset varies naturally among individuals; in addition to genetic and environmental factors, the importance of nutritional factors, such as iron, zinc, calcium, and vitamin D, increases during puberty ( 4 ). 25(OH)D is a key regulator of neuroendocrine and ovarian physiology ( 5 ).…”

“…For example, in one study, the probability of menarche was twice as high in vitamin D-deficient girls than in girls who were vitamin D sufficient. In girls, vitamin D deficiency has been shown to decrease the age of menarche by ∼10 months compared with that in girls with sufficient vitamin D ( 4 , 22 ). A systematic meta-analysis of six studies showed that vitamin D-deficient individuals were more likely to develop precocious puberty (OR = 2.02 [95% confidence interval 1.65–2.46]) ( 4 , 23 ).…”

“…In girls, vitamin D deficiency has been shown to decrease the age of menarche by ∼10 months compared with that in girls with sufficient vitamin D ( 4 , 22 ). A systematic meta-analysis of six studies showed that vitamin D-deficient individuals were more likely to develop precocious puberty (OR = 2.02 [95% confidence interval 1.65–2.46]) ( 4 , 23 ). One retrospective study collected data from 221 girls with idiopathic central precocious puberty (ICPP) and 144 girls without ICPP, and the serum 25(OH)D levels in the ICPP group were significantly lower than those in the non-ICPP group (p < 0.001).…”

“…One retrospective study collected data from 221 girls with idiopathic central precocious puberty (ICPP) and 144 girls without ICPP, and the serum 25(OH)D levels in the ICPP group were significantly lower than those in the non-ICPP group (p < 0.001). A low serum 25(OH)D is an independent risk factor for ICPP ( 4 , 24 ). Another meta-analysis showed that the average serum vitamin D concentration in individuals with precocious puberty was 1.16 ng/mL, which was lower than that in the control group ( 12 ).…”

“…Vitamin D and vitamin D receptor (VDR)-activating enzymes are expressed throughout the hypothalamus–pituitary–gonadal (HPG) axis ( 1 , 2 ), and vitamin D is metabolized in the developing gonads ( 1 , 3 ), suggesting a local role for vitamin D during development. The serum 25-hydroxyvitamin D (25(OH)D) concentration is used to evaluate individual vitamin D status and is the best indicator of vitamin D stores; indeed, it is the main circulating form of vitamin D and has a half-life of 2–3 weeks ( 4 ). The biological actions of vitamin D are mediated through the VDR, which is distributed across various tissues, including the skeleton and parathyroid glands, as well as reproductive tissues.…”