Disorders of puberty and neurodevelopment: A shared etiology?

Abstract

The neuroendocrine control of puberty and reproduction is fascinatingly complex, with up- and down-regulation of key reproductive hormones during fetal, infantile, and later childhood periods that determine the correct function of the hypothalamic-pituitary-gonadal axis and the timing of puberty. Neuronal development is a vital element of these processes, and multiple conditions of disordered puberty and reproduction have their etiology in abnormal neuronal migration or function. Although there are numerous documented cases across multiple conditions wherein patients have both neurodevelopmental disorders and pubertal abnormalities, this has mostly been described ad hoc and the associations are not clearly documented. In this review, we aim to describe the overlap between these two groups of conditions and to increase awareness to ensure that puberty and reproductive function are carefully monitored in patients with neurodevelopmental conditions, and vice versa. Moreover, this commonality can be explored for clues about the disease mechanisms in these patient groups and provide new avenues for therapeutic interventions for affected individuals.

Keywords: autistic spectrum disorder; disordered puberty; hormone therapy; neurodevelopment; precocious puberty.

FIGURE 1

Distribution of age of menarche in girls with Williams syndrome (n = 86, closed circles) with healthy girls from northern Germany (n = 759, open circles). Distributions were significantly different (p < 0.001), with two peaks in the population of girls with Williams syndrome, corresponding to early puberty and normal puberty. Source: Partsch et al.^{[ 94 ]}

FIGURE 2

Risk of neurodevelopmental conditions in patients with hypogonadotropic hypogonadism and delayed puberty in a Swedish national cohort compared to matched controls. Shown are risks of autism spectrum disorder (ASD), attention‐deficit hyperactivity disorder (ADHD), and intellectual disability (ID) represented as odds ratios and corresponding 95% confidence intervals. CI, confidence intervals; OR, odds ratio. Source: Ohllson Gotby et al.^{[ 104 ]}