madman
Super Moderator
Puberty Induction in Adolescent Males: Current Practice (2022)
Mohammed S. Alenazi, Ali M. Alqahtani, Mohammad M. Ahmad, Eyad M. Almalki, Angham AlMutair, Mussa Almalki
Abstract
Puberty is a developmental stage characterized by the appearance of secondary sexual characteristics which leads to complete physical, psychosocial, and sexual maturation. The current practice of hormonal therapy to induce puberty in adolescent males is based on published consensus and expert opinion. Evidence-based guidelines on optimal timing and regimen in puberty induction in males are lacking, and this reflects some discrepancies in practice among endocrinologists. It is worth mentioning that the availability of various hormonal products in markets, their different routes of administration, and patients/parents’ preference also have an impact on clinical decisions. This review outlines the current clinical approach to delayed puberty in boys with an emphasis on puberty induction.
Introduction And Background
Delayed puberty in males is defined as the absence of testicular growth at an age that is 2 to 2.5 SD later than the population means (traditionally, the age of 14 years). However the onset of puberty varies by country, race, and ethnicity [1], and it is delayed in around 2%-3% of boys [2]. Normal pubertal development is the result of the increasing release of gonadotropin-releasing hormone (GnRH) by the hypothalamus, which in turn stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Transient activation of the hypothalamus-pituitary-gonadal axis starts from intrauterine life to the first few months of life, a process that has been described as “mini-puberty.” Subsequently, the hypothalamus-pituitary-gonadal (HPG) axis is inactivated by gamma-aminobutyric acid (GABA) until the beginning of pubertal maturation [3]. The exact trigger that initiates pulsatile GnRH secretion is not fully known but is thought to be influenced by multiple factors including genetics, nutrition, neurotransmitters, and hormones. It has been demonstrated that the major neurotransmitter responsible for activating the GnRH pulse generator are glutamate, neuropeptide Y, endorphins, opioids, and melatonin [4]. Furthermore, kisspeptin and its receptor regulate GnRH secretion [4]. Inactivating mutations in the genes encoding the human kisspeptin receptor leads to failure of puberty progression [5]. The gonadotropins stimulate the development of gonads and result in synthesis as well as the release of sex steroids estrogens and androgens, and this process leads to the physical and hormonal changes of puberty: gonadarche indicates pubertal onset and it is provoked by the GnRH release in a pulsatile fashion, which activates the HPG axis. In males, LH stimulates the Leydig cells to produce testosterone and maintain spermatogenesis, while FSH stimulates the Sertoli cells and initiates spermatogenesis [6,7]. Adrenarche (i.e., androgen production by adrenal glands leading to the development of the pubic and axillary hairs, the sebaceous and the apocrine glands) is a separate but usually parallel process and does not in itself indicate genuine puberty [7]. Premature adrenarche is the presence of secondary sexual hairs in boys younger than nine years old [8]. The normal physiology of puberty is illustrated in Figure 1.
Review
*When to suspect delayed puberty in boys?
*When and how to evaluate the patient with delayed puberty?
*Clinical history
*Physical examination
*Investigations
Puberty induction
-Goals
-Optimal Timing
Treatment options for adolescent boys with delayed puberty
-Testosterone
-Monitoring of Testosterone Therapy in Boys
*Potential adverse effects of testosterone replacement
*Gonadotropin
*Gonadotropin-releasing hormone
*Our suggested approach to patient delayed puberty
Conclusions
Adolescence is a critical period in human life, marking the transition from childhood to emerging adulthood and characterized by numerous challenges and developments in both the physical and social domains. Testosterone therapy in adolescent boys is primarily intended to increase linear growth and pubertal progression, but it may also improve bone mineral content, muscle function, metabolic profile, and psychological well-being. Some people may only need testosterone therapy for a short time, while others may need it for the rest of their lives, and therapy monitoring will thus depend on the underlying condition. Gonadotropin treatment can also be used to induce puberty in an adolescent male with hypogonadism. The stimulation of testicular growth and spermatogenesis with improvement in potential fertility is an additional benefit of gonadotropin treatment over testosterone treatment.
Mohammed S. Alenazi, Ali M. Alqahtani, Mohammad M. Ahmad, Eyad M. Almalki, Angham AlMutair, Mussa Almalki
Abstract
Puberty is a developmental stage characterized by the appearance of secondary sexual characteristics which leads to complete physical, psychosocial, and sexual maturation. The current practice of hormonal therapy to induce puberty in adolescent males is based on published consensus and expert opinion. Evidence-based guidelines on optimal timing and regimen in puberty induction in males are lacking, and this reflects some discrepancies in practice among endocrinologists. It is worth mentioning that the availability of various hormonal products in markets, their different routes of administration, and patients/parents’ preference also have an impact on clinical decisions. This review outlines the current clinical approach to delayed puberty in boys with an emphasis on puberty induction.
Introduction And Background
Delayed puberty in males is defined as the absence of testicular growth at an age that is 2 to 2.5 SD later than the population means (traditionally, the age of 14 years). However the onset of puberty varies by country, race, and ethnicity [1], and it is delayed in around 2%-3% of boys [2]. Normal pubertal development is the result of the increasing release of gonadotropin-releasing hormone (GnRH) by the hypothalamus, which in turn stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Transient activation of the hypothalamus-pituitary-gonadal axis starts from intrauterine life to the first few months of life, a process that has been described as “mini-puberty.” Subsequently, the hypothalamus-pituitary-gonadal (HPG) axis is inactivated by gamma-aminobutyric acid (GABA) until the beginning of pubertal maturation [3]. The exact trigger that initiates pulsatile GnRH secretion is not fully known but is thought to be influenced by multiple factors including genetics, nutrition, neurotransmitters, and hormones. It has been demonstrated that the major neurotransmitter responsible for activating the GnRH pulse generator are glutamate, neuropeptide Y, endorphins, opioids, and melatonin [4]. Furthermore, kisspeptin and its receptor regulate GnRH secretion [4]. Inactivating mutations in the genes encoding the human kisspeptin receptor leads to failure of puberty progression [5]. The gonadotropins stimulate the development of gonads and result in synthesis as well as the release of sex steroids estrogens and androgens, and this process leads to the physical and hormonal changes of puberty: gonadarche indicates pubertal onset and it is provoked by the GnRH release in a pulsatile fashion, which activates the HPG axis. In males, LH stimulates the Leydig cells to produce testosterone and maintain spermatogenesis, while FSH stimulates the Sertoli cells and initiates spermatogenesis [6,7]. Adrenarche (i.e., androgen production by adrenal glands leading to the development of the pubic and axillary hairs, the sebaceous and the apocrine glands) is a separate but usually parallel process and does not in itself indicate genuine puberty [7]. Premature adrenarche is the presence of secondary sexual hairs in boys younger than nine years old [8]. The normal physiology of puberty is illustrated in Figure 1.
Review
*When to suspect delayed puberty in boys?
*When and how to evaluate the patient with delayed puberty?
*Clinical history
*Physical examination
*Investigations
Puberty induction
-Goals
-Optimal Timing
Treatment options for adolescent boys with delayed puberty
-Testosterone
-Monitoring of Testosterone Therapy in Boys
*Potential adverse effects of testosterone replacement
*Gonadotropin
*Gonadotropin-releasing hormone
*Our suggested approach to patient delayed puberty
Conclusions
Adolescence is a critical period in human life, marking the transition from childhood to emerging adulthood and characterized by numerous challenges and developments in both the physical and social domains. Testosterone therapy in adolescent boys is primarily intended to increase linear growth and pubertal progression, but it may also improve bone mineral content, muscle function, metabolic profile, and psychological well-being. Some people may only need testosterone therapy for a short time, while others may need it for the rest of their lives, and therapy monitoring will thus depend on the underlying condition. Gonadotropin treatment can also be used to induce puberty in an adolescent male with hypogonadism. The stimulation of testicular growth and spermatogenesis with improvement in potential fertility is an additional benefit of gonadotropin treatment over testosterone treatment.
