2024 | Julia Rohayem, Emma C. Alexander, Sabine Heger, Anna Nordenström, and Sasha R. Howard
Mini-puberty is the second physiological wave of activation of the hypothalamic-pituitary-gonadal (HPG) axis, occurring in the first months after birth. In males, it is most prominent at 2-3 months postnatal age and ends at around 6 months. This period is crucial for testicular and penile development, with increased Sertoli cell numbers, which are essential for future reproductive capacity. In females, mini-puberty is less critical for reproductive capacity as the oocyte pool is already complete at birth. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In severe CHH, all three waves of GnRH pulsatility are absent, leading to testicular immaturity and reduced fertility. Diagnosis of CHH is often missed in infants, and treatment is typically testosterone therapy, which promotes penile growth but does not address testicular descent or Sertoli cell development. Gonadotropin therapy to mimic mini-puberty may offer additional benefits, including testicular descent, increased Sertoli cell pool, and long-term fertility improvements. Early diagnosis and treatment are crucial for optimal outcomes in males with CHH. The review discusses the physiological development of the reproductive axis, the role of the HPG axis, and the potential for therapeutic replacement of mini-puberty in males with CHH. It also highlights the importance of early identification of red flags and the need for further research into optimal therapeutic strategies. The review includes a description of the physiological development of the reproductive tract, the pathophysiology of GnRH deficiency, and the associated hormonal changes during mini-puberty in health and in conditions of congenital GnRH deficiency. It also discusses the consequences for affected individuals in adolescence and later life, and provides a possible approach to the clinical assessment of males suspected to be affected by GnRH deficiency at infancy. The review aims to provide a comprehensive understanding of the physiological and therapeutic aspects of mini-puberty and its importance in the development of reproductive capacity.Mini-puberty is the second physiological wave of activation of the hypothalamic-pituitary-gonadal (HPG) axis, occurring in the first months after birth. In males, it is most prominent at 2-3 months postnatal age and ends at around 6 months. This period is crucial for testicular and penile development, with increased Sertoli cell numbers, which are essential for future reproductive capacity. In females, mini-puberty is less critical for reproductive capacity as the oocyte pool is already complete at birth. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In severe CHH, all three waves of GnRH pulsatility are absent, leading to testicular immaturity and reduced fertility. Diagnosis of CHH is often missed in infants, and treatment is typically testosterone therapy, which promotes penile growth but does not address testicular descent or Sertoli cell development. Gonadotropin therapy to mimic mini-puberty may offer additional benefits, including testicular descent, increased Sertoli cell pool, and long-term fertility improvements. Early diagnosis and treatment are crucial for optimal outcomes in males with CHH. The review discusses the physiological development of the reproductive axis, the role of the HPG axis, and the potential for therapeutic replacement of mini-puberty in males with CHH. It also highlights the importance of early identification of red flags and the need for further research into optimal therapeutic strategies. The review includes a description of the physiological development of the reproductive tract, the pathophysiology of GnRH deficiency, and the associated hormonal changes during mini-puberty in health and in conditions of congenital GnRH deficiency. It also discusses the consequences for affected individuals in adolescence and later life, and provides a possible approach to the clinical assessment of males suspected to be affected by GnRH deficiency at infancy. The review aims to provide a comprehensive understanding of the physiological and therapeutic aspects of mini-puberty and its importance in the development of reproductive capacity.