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      Androgen Treatment in Adolescent Males With Hypogonadism

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          Abstract

          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.

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          Most cited references86

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          Activation of the Hypothalamic-Pituitary-Gonadal Axis in Infancy: Minipuberty

          The hypothalamic-pituitary-gonadal (HPG) axis is active in the midgestational foetus but silenced towards term because of the negative feedback effects mediated by the placental hormones. This restraint is removed at birth, leading to reactivation of the axis and an increase in gonadotrophin levels. Gonadotrophin levels are high during the first 3 months of life but decrease towards the age of 6 months except for FSH levels in girls that remain elevated until 3-4 years of age. After this, the HPG axis remains quiescent until puberty. The postnatal gonadotrophin surge results in gonadal activation in both sexes. In boys, testosterone levels rise to a peak at 1-3 months of age and then decline following LH levels. Postnatal HPG axis activation is associated with penile and testicular growth and therefore considered important for the development of male genitalia. In girls, elevated gonadotrophin levels result in the maturation of ovarian follicles and in an increase in oestradiol levels. Biological significance and possible long-term consequences of this minipuberty remain elusive, as do the mechanisms that silence the HPG axis until puberty. However, the first months of life provide a ‘window of opportunity' for functional studies of the HPG axis prior to pubertal development.
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            Clinical practice. Delayed puberty.

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              Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology

              Although first identified over 70 years ago, Klinefelter syndrome (KS) continues to pose substantial diagnostic challenges, as many patients are still misdiagnosed, or remain undiagnosed. In fact, as few as 25% of patients with KS are accurately diagnosed and most of these diagnoses are not made until adulthood. Classic characteristics of KS include small testes, infertility, hypergonadothropic hypogonadism, and cognitive impairment. However, the pathophysiology behind KS is not well understood, although genetic effects are also thought to play a role. For example, recent developments in genetics and genomics point to a fundamental change in our understanding of KS, with global epigenetic and RNA expression changes playing a central role for the phenotype. KS is also associated with more general health markers, including higher morbidity and mortality rates and lower socioeconomic status (which likely affect both morbidity and mortality). In addition, hypogonadism is associated with greater risk of metabolic syndrome, type 2 diabetes, cardiovascular disease, breast cancer, and extragonadal germ cell tumors. Medical treatment typically focuses on testosterone replacement therapy (TRT), although the effects of this therapy have not been studied rigorously, and future studies need to evaluate the effects of TRT on metabolic risk and neurocognitive outcomes. This review presents a comprehensive interdisciplinary examination of recent developments in genetic, endocrine, and neurocognitive science, including the study of animal models. It provides a number of recommendations for improving the effectiveness of research and clinical practice, including neonatal KS screening programs, and a multidisciplinary approach to KS treatment from childhood until senescence.
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                Author and article information

                Journal
                Am J Mens Health
                Am J Mens Health
                JMH
                spjmh
                American Journal of Men's Health
                SAGE Publications (Sage CA: Los Angeles, CA )
                1557-9883
                1557-9891
                23 May 2020
                May-Jun 2020
                : 14
                : 3
                : 1557988320922443
                Affiliations
                [1 ]Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina
                [2 ]Departamento de Biología Celular, Histología, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires, Argentina
                Author notes
                [*]Rodolfo A. Rey, MD, PhD, Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Buenos Aires C1425EFD, Argentina. Email: rodolforey@ 123456cedie.org.ar
                Author information
                https://orcid.org/0000-0002-1100-3843
                Article
                10.1177_1557988320922443
                10.1177/1557988320922443
                7249582
                32448030
                f544c2e7-00a9-43c2-b5ba-aae3dd38c768
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 30 January 2020
                : 25 March 2020
                : 27 March 2020
                Funding
                Funded by: Fondo para la Investigación Científica y Tecnológica, FundRef https://doi.org/10.13039/501100006668;
                Award ID: PICT 2016-0993 and PICT 2017-0032
                Funded by: Consejo Nacional de Investigaciones Científicas y Técnicas, FundRef https://doi.org/10.13039/501100002923;
                Award ID: Fondo para la Investigación Científica y Tecnol
                Funded by: Consejo Nacional de Investigaciones Científicas y Técnicas, FundRef https://doi.org/10.13039/501100002923;
                Award ID: PIP 11220130100687
                Categories
                Review
                Custom metadata
                May-June 2020
                ts1

                anorchidism,cryptorchidism,delayed puberty,disorders of sex development,gonadal dysgenesis,kallmann syndrome,klinefelter syndrome,testicular failure

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