madman
Super Moderator
Testosterone therapy in children and adolescents: to whom, how, when? (2022)
Maria Camila Suarez A., Joseph M. Israeli, Eliyahu Kresch, Leon Telis, and Daniel E. Nassau
Male production of testosterone is crucial for the development of a wide range of functions. External and internal genitalia formation, secondary sexual characteristics, spermatogenesis, growth velocity, bone mass density, psychosocial maturation, and metabolic and cardiovascular profiles are closely dependent on testosterone exposure. Disorders in androgen production can present during all life stages, including childhood and adolescence, and testosterone therapy (TT) is in many cases the only treatment that can correct the underlying deficit. TT is controversial in the pediatric population as hypoandrogenism is difficult to classify and diagnose in these age groups, and standardized protocols of treatment and monitorization are still lacking. In pediatric patients, hypogonadism can be central, primary, or a combination of both. Testosterone preparations are typically designed for adults’ TT, and providers need to be aware of the advantages and disadvantages of these formulations, especially cognizant of supratherapeutic dosing. Monitoring of testosterone levels in boys on TT should be tailored to the individual patient and based on the anticipated duration of therapy. Although clinical consensus is lacking, an approximation of the current challenges and common practices in pediatric hypoandrogenism could help elucidate the broad spectrum of pathologies that lie behind this single hormone deficiency with wide-ranging implications.
INTRODUCTION
Testosterone, the male sex hormone, can be a challenge to detect deficits within and manage replacement in children and adolescents. Testosterone is produced primarily by the Leydig cells of the testes in response to gonadotropic stimulation from the pituitary gland, with some production from the zona reticularis within the adrenal glands [1]. Testosterone acts on a litany of processes including bone maturation [2], growth [3], development of secondary sexual characteristics [4], metabolism [5, 6], hematology [7], and psychosocial status [8]. Furthermore, hypoandrogenism throughout life is linked to increased metabolic cardiovascular complications, highlighting the need for proper diagnosis and treatment [9, 10].
Prior to adulthood, testosterone levels are relatively quiescent; however, there are three important developmental points in a child’s life when the absence of physiologic testosterone levels can have a lasting impact [4, 11]. During fetal development, testosterone production leads to normal male external genital development [12, 13]. Shortly after birth, between 3 and 6 months of life, a “mini-puberty” of infancy occurs, in which gonadotropins and testosterone levels rise temporarily, leading to penile growth and, although not well understood, neurocognitive and psychosocial development [14]. After these transient elevations, testosterone remains low throughout childhood until rising during pubertal development [15]. Unfortunately, clinical signs of hypogonadism can be subtle or absent prior to pubertal development, creating a challenge for clinicians for early diagnosis and treatment, and most often it is not until delayed or incomplete pubertal development that a defect in androgen production is uncovered.
Aside from the challenges of diagnosing hypogonadism in children and adolescents, controversy exists on when and how to initiate testosterone therapy (TT) in pediatric patients. The goal of TT is to replicate normal physiology as closely as possible, including the unique functions of testosterone in child and adolescent development. In this review, we will highlight testosterone functions in children/adolescents, classify the different types of pediatric hypogonadism and specific disorders within, and discuss strategies for diagnosis, treatment, and adverse effects of TT in this population.
*TESTOSTERONE FUNCTION IN CHILDREN/ADOLESCENTS
-Sexual development
-Growth–bone mineral density
-Psychosocial and neurocognitive
*CLASSIFICATION OF PEDIATRIC HYPOGONADISM
*DIAGNOSIS
-Clinical manifestations
-Hormone profile
-Genetic testing
*TESTOSTERONE REPLACEMENT INDICATIONS
*TESTOSTERONE PREPARATIONS: MEDICATION, DOSE, AND FREQUENCY
*ADVERSE EFFECTS
*MONITORING
FUTURE DIRECTIONS
There is a lack of literature and guidance for the initiation of testosterone therapy in adolescents and children. As mentioned earlier, little data exists on testosterone levels before and after therapy in the pediatric population. Future studies should focus on establishing standards for testing and monitoring these patients.
CONCLUSION
The diagnosis and management of hypoandrogenism in children are challenging. While testosterone plays a large role in male development, fetal and perinatal findings can be subtle or absent, leading to diagnosis when puberty is delayed or incomplete. TT is fundamental and definitive in the management of hypoandrogenism, especially when the testicles are unable to produce adequate testosterone, despite gonadotrophic signaling. Androgen supplementation can be administrated temporarily; however, lifelong treatment may be required in some men, highlighting the need for timely diagnosis and management. Unfortunately, although well developed for TT in adults, expert consensus and pediatric guidelines about diagnostic criteria, clinical indications, appropriate monitoring, and adequate age and regimens are lacking. A concerted effort to perform future studies in children and adolescents that address these gaps in knowledge should be pursued. A comprehensive approach, tailored to the individual patient should contribute to a timely manner diagnosis and treatment, preventing the deleterious long-term effects that could be caused due to testosterone deficiency.
Maria Camila Suarez A., Joseph M. Israeli, Eliyahu Kresch, Leon Telis, and Daniel E. Nassau
Male production of testosterone is crucial for the development of a wide range of functions. External and internal genitalia formation, secondary sexual characteristics, spermatogenesis, growth velocity, bone mass density, psychosocial maturation, and metabolic and cardiovascular profiles are closely dependent on testosterone exposure. Disorders in androgen production can present during all life stages, including childhood and adolescence, and testosterone therapy (TT) is in many cases the only treatment that can correct the underlying deficit. TT is controversial in the pediatric population as hypoandrogenism is difficult to classify and diagnose in these age groups, and standardized protocols of treatment and monitorization are still lacking. In pediatric patients, hypogonadism can be central, primary, or a combination of both. Testosterone preparations are typically designed for adults’ TT, and providers need to be aware of the advantages and disadvantages of these formulations, especially cognizant of supratherapeutic dosing. Monitoring of testosterone levels in boys on TT should be tailored to the individual patient and based on the anticipated duration of therapy. Although clinical consensus is lacking, an approximation of the current challenges and common practices in pediatric hypoandrogenism could help elucidate the broad spectrum of pathologies that lie behind this single hormone deficiency with wide-ranging implications.
INTRODUCTION
Testosterone, the male sex hormone, can be a challenge to detect deficits within and manage replacement in children and adolescents. Testosterone is produced primarily by the Leydig cells of the testes in response to gonadotropic stimulation from the pituitary gland, with some production from the zona reticularis within the adrenal glands [1]. Testosterone acts on a litany of processes including bone maturation [2], growth [3], development of secondary sexual characteristics [4], metabolism [5, 6], hematology [7], and psychosocial status [8]. Furthermore, hypoandrogenism throughout life is linked to increased metabolic cardiovascular complications, highlighting the need for proper diagnosis and treatment [9, 10].
Prior to adulthood, testosterone levels are relatively quiescent; however, there are three important developmental points in a child’s life when the absence of physiologic testosterone levels can have a lasting impact [4, 11]. During fetal development, testosterone production leads to normal male external genital development [12, 13]. Shortly after birth, between 3 and 6 months of life, a “mini-puberty” of infancy occurs, in which gonadotropins and testosterone levels rise temporarily, leading to penile growth and, although not well understood, neurocognitive and psychosocial development [14]. After these transient elevations, testosterone remains low throughout childhood until rising during pubertal development [15]. Unfortunately, clinical signs of hypogonadism can be subtle or absent prior to pubertal development, creating a challenge for clinicians for early diagnosis and treatment, and most often it is not until delayed or incomplete pubertal development that a defect in androgen production is uncovered.
Aside from the challenges of diagnosing hypogonadism in children and adolescents, controversy exists on when and how to initiate testosterone therapy (TT) in pediatric patients. The goal of TT is to replicate normal physiology as closely as possible, including the unique functions of testosterone in child and adolescent development. In this review, we will highlight testosterone functions in children/adolescents, classify the different types of pediatric hypogonadism and specific disorders within, and discuss strategies for diagnosis, treatment, and adverse effects of TT in this population.
*TESTOSTERONE FUNCTION IN CHILDREN/ADOLESCENTS
-Sexual development
-Growth–bone mineral density
-Psychosocial and neurocognitive
*CLASSIFICATION OF PEDIATRIC HYPOGONADISM
*DIAGNOSIS
-Clinical manifestations
-Hormone profile
-Genetic testing
*TESTOSTERONE REPLACEMENT INDICATIONS
*TESTOSTERONE PREPARATIONS: MEDICATION, DOSE, AND FREQUENCY
*ADVERSE EFFECTS
*MONITORING
FUTURE DIRECTIONS
There is a lack of literature and guidance for the initiation of testosterone therapy in adolescents and children. As mentioned earlier, little data exists on testosterone levels before and after therapy in the pediatric population. Future studies should focus on establishing standards for testing and monitoring these patients.
CONCLUSION
The diagnosis and management of hypoandrogenism in children are challenging. While testosterone plays a large role in male development, fetal and perinatal findings can be subtle or absent, leading to diagnosis when puberty is delayed or incomplete. TT is fundamental and definitive in the management of hypoandrogenism, especially when the testicles are unable to produce adequate testosterone, despite gonadotrophic signaling. Androgen supplementation can be administrated temporarily; however, lifelong treatment may be required in some men, highlighting the need for timely diagnosis and management. Unfortunately, although well developed for TT in adults, expert consensus and pediatric guidelines about diagnostic criteria, clinical indications, appropriate monitoring, and adequate age and regimens are lacking. A concerted effort to perform future studies in children and adolescents that address these gaps in knowledge should be pursued. A comprehensive approach, tailored to the individual patient should contribute to a timely manner diagnosis and treatment, preventing the deleterious long-term effects that could be caused due to testosterone deficiency.
