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American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Frontiers in Endocrinology 2023Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to...
Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in in 15 patients. encodes two distinct isoforms. In the adult mouse, expression of both isoform1 and isoform2 was detected in the brain, pituitary, and gonads. However, only isoform1 was detected in mouse primary GnRH cells and three immortalized GnRH cell lines, two mouse and one human. To date, the function of isoform2 has been verified as a transcription factor, while the function of isoform1 has been unknown. In the present report, bioinformatics and cell assays on a human-derived GnRH cell line reveal a novel function for isoform1, demonstrating it can act as a transcriptional regulator, decreasing expression. In addition, the impact of the two most prevalent variants, identified in five IHH patients, that were located at/or close to the DNA-binding domain was examined. Notably, one of these mutations prevented the repression of GnRH transcripts by isoform1. Normally, GnRH transcription increases as GnRH cells mature as they near migrate into the brain. Augmentation earlier during development can disrupt normal GnRH cell migration, consistent with some POU6F2 variants contributing to the IHH pathogenesis.
Topics: Animals; Humans; Mice; Brain; Gonadotropin-Releasing Hormone; Mutation, Missense; POU Domain Factors; Hypogonadism
PubMed: 37600690
DOI: 10.3389/fendo.2023.1203542 -
Pediatric Rheumatology Online Journal Mar 2021Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150... (Review)
Review
Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10-20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient's bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
Topics: Adolescent; Arthritis, Juvenile; Child; Growth Disorders; Humans; Puberty
PubMed: 33712046
DOI: 10.1186/s12969-021-00521-5 -
Transplantation and Cellular Therapy Aug 2022Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development,...
Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development, sexual dysfunction, and infertility. However, no systematic review exists regarding prevalence and risk factors in relation to different treatment regimens. We aimed to systematically evaluate the current evidence regarding the prevalence of male gonadal dysfunction after pediatric HSCT, related risk factors, and the diagnostic value of surrogate markers of spermatogenesis in this patient group. We searched PubMed and Embase using a combination of text words and subject terms. The eligibility screening was conducted using predefined criteria. Data were extracted corresponding to the Leydig cell compartment involved in testosterone production and the germ cell compartment involved in spermatogenesis, respectively. Subsequently, data synthesis was performed. Of 2369 identified records, 25 studies were eligible. The studies were heterogeneous in terms of included diagnoses, gonadotoxic therapy, follow-up time, and definitions of gonadal dysfunction. The data synthesis revealed a preserved Leydig cell function in patients treated with non-total body irradiation (TBI) regimens, whereas the evidence regarding the impact of TBI conditioning on Leydig cell function was conflicting. Based on surrogate markers of spermatogenesis and only limited data on semen quality, the germ cell compartment was affected in half of the patients treated with non-TBI regimens and in nearly all patients treated with TBI conditioning. Testicular irradiation as part of front-line therapy before referral to HSCT led to complete Leydig cell failure and germ cell failure. Evidence regarding the impact of diagnosis, pubertal stage at HSCT, and chronic graft-versus-host disease is limited, as is the evidence of the diagnostic value of surrogate markers of spermatogenesis. Testicular irradiation as part of front-line therapy and TBI conditioning are the main risk factors associated with male gonadal dysfunction after pediatric HSCT; however, impaired spermatogenesis is also observed in half of the patients treated with non-TBI regimens. Methodological shortcomings limit existing evidence, and future studies should include semen quality analyses, follow-up into late adulthood, and evaluation of the cumulative exposure to gonadotoxic therapy.
Topics: Adult; Child; Gonadal Disorders; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Semen Analysis; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 35644480
DOI: 10.1016/j.jtct.2022.05.036 -
Frontiers in Endocrinology 2022Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are... (Review)
Review
Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.
Topics: Humans; Male; Female; Fertility Preservation; beta-Thalassemia; Quality of Life; Semen; Counseling; Anemia, Sickle Cell; Ovarian Hyperstimulation Syndrome
PubMed: 36353243
DOI: 10.3389/fendo.2022.985525 -
Endocrine Connections Nov 2023Hypogonadism is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed... (Review)
Review
Hypogonadism is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed growth and delayed pubertal maturation. Hypogonadism may arise from gonadal disease (primary hypogonadism), dysfunction of the hypothalamic-pituitary axis (secondary hypogonadism) or functional hypogonadism. Disrupted puberty (delayed or absent) leading to hypogonadism can have a significant impact on both the physical and psychosocial well-being of adolescents with lasting effects. The diagnosis of hypogonadism in teenagers can be challenging as the most common cause of delayed puberty in both sexes is self-limited, also known as constitutional delay of growth and puberty (CDGP). Although an underlying congenital cause should always be considered in a teenager with hypogonadism, acquired conditions such as obesity, diabetes mellitus, other chronic diseases and medications have all been associated with low sex steroid hormone levels. In this review, we highlight some forms of functional hypogonadism in adolescents and the clinical challenges to differentiate normal variants from pathological states.
PubMed: 37615381
DOI: 10.1530/EC-23-0190 -
Indian Pediatrics Jul 2021To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT).
OBJECTIVES
To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT).
METHODS
In this cross-sectional study from a tertiary teaching hospital in Delhi, records of adolescents aged 17-19 years with TDT on regular transfusion at thalassemia day-care centre were reviewed. Pubertal development and its determinants were assessed.
RESULTS
Records of 58 (33 male) adolescents with TDT were reviewed. Among them, 42 (72.4%) had normal/delayed onset with spontaneous progression of puberty, while 16 (27.6%) had pubertal arrest/failure and received hormonal replacement therapy (HRT). Short stature was observed in all adolescents on HRT. Amongst other endocrinopathies, only hypoparathyroidism was found to be significantly higher in the HRT group. On multivariate analysis, serum ferritin (OR-1.005, 95% CI 1.002, 1.009) was observed to be the only significant determinant of pubertal arrest/failure.
CONCLUSIONS
A significant proportion of adolescents with TDT continue to have pubertal arrest/failure. High systemic iron load is the key determinant for this.
Topics: Adolescent; Blood Transfusion; Cross-Sectional Studies; Endocrine System Diseases; Humans; Male; Puberty; Thalassemia; beta-Thalassemia
PubMed: 33772533
DOI: No ID Found -
Reproductive Sciences (Thousand Oaks,... Jun 2021Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including... (Review)
Review
Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including ovarian failure and infertility, in women of reproductive age. Infertility following cancer treatment can have significant adverse effects on the quality of life. However, established methods for fertility preservation, including embryo or oocyte cryopreservation, are not always suitable for female cancer patients because of complicated individual conditions and treatment methods. Ovarian tissue cryopreservation and transplantation is a promising option for fertility preservation in pre-pubertal girls and adult patients with cancer who require immediate treatment, or who are not eligible to undergo ovarian stimulation. This review introduces various methods and strategies to improve ovarian tissue cryopreservation and transplantation outcomes, to help patients and clinicians choose the best option when considering the potential complexity of a patient's situation. Effective multidisciplinary oncofertility strategies, involving the inclusion of a highly skilled and experienced oncofertility team that considers cryopreservation methods, thawing processes and devices, surgical procedures for transplantation, and advances in technologies, are necessary to provide high-quality care to a cancer patient.
Topics: Adolescent; Adult; Antineoplastic Agents; Cryopreservation; Female; Fertility Preservation; Graft Survival; Humans; In Vitro Oocyte Maturation Techniques; Infertility, Female; Neoplasms; Ovary; Radiotherapy; Stem Cells; Transplantation, Autologous; Young Adult
PubMed: 33791995
DOI: 10.1007/s43032-021-00517-2