Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

Spaziani, Matteo; Tarantino, C.; Pozza, Carlotta; Anzuini, Antonella; Panimolle, Francesca; Papi, Giampaolo; Gianfrilli, Daniele; Lenzi, Andrea; Radicioni, A.

doi:10.1007/s40618-020-01452-w

Cited by 4 publications

(3 citation statements)

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“…Testosterone treatment includes different strategies, based on the age of patient: early hormonal treatment (EHT), from 4 to 60 months of age; hormonal booster treatment (HBT), from 5 to 8 years of age and finally testosterone replacement therapy (TRT), from puberty to the rest of life [ 21 ]. Patients with high grade aneuploidies that underwent an early treatment with testosterone show persistent suppression of testicular secretory function [ 53 ]. In 2020, Gropman et al [ 17 ], demonstrated that affected patients treated with HRT obtained higher scores on the Bayley Scales of Infant Development (BSID-III), compared with untreated patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical, Cognitive and Neurodevelopmental Profile in Tetrasomies and Pentasomies: A Systematic Review

et al. 2022

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Background: Sex chromosome aneuploidies (SCAs) are a group of disorders characterised by an abnormal number of sex chromosomes. Collective prevalence rate of SCAs is estimated to be around 1 in 400–500 live births; sex chromosome trisomies (e.g., XXX, XXY, XYY) are most frequent, while tetra- and pentasomies (e.g., XXXX, XXXXX, XXXY, XXXXY) are rarer, and the most common is 48, XXYY syndrome. The presence of additional X and/or Y chromosomes is believed to cause neurodevelopmental differences, with increased risk for developmental delays, language-based learning disabilities, cognitive impairments, executive dysfunction, and behavioural and psychological disorders. Aim of the Study: Our review has the purpose of analysing the neurocognitive, linguistical and behavioural profile of patients affected by sex chromosomes supernumerary aneuploidies (tetrasomy and pentasomy) to better understand the specific areas of weakness, in order to provide specific rehabilitation therapy. Methods: The literature search was performed by two authors independently. We used MEDLINE, PubMed, and PsycINFO search engines to identify sources of interest, without year or language restrictions. At the end of an accurate selection, 16 articles fulfilled the inclusion and exclusion criteria. Results and Conclusions: International literature has described single aspects of the neuropsychological profile of 48, XXYY and 49, XXXXY patients. In 48, XXYY patients, various degrees of psychosocial/executive functioning issues have been reported and there is an increased frequency of behavioural problems in childhood. Developmental delay and behavioural problems are the most common presenting problems, even if anxiety, depression and oppositional defiant disorder are also reported. They also show generalized difficulties with socialization and communication. Cognitive abilities are lower in measures of verbal IQ than in measures of performance IQ. Visuospatial skills are a relative strength compared to verbal skills. In patients with 49, XXXXY, both intellectual and adaptive functioning skills fall into the disability range, with better non-verbal cognitive performance. Speech and language testing reveals more deficits in expressive language than receptive language and comprehension. Anxiety, thought problems, internalizing and externalizing problems, and deficits in social cognition and communication are reported. Behavioural symptoms lessen from school age to adolescence, with the exception of thought problems and anxiety. Individuals affected by sex chromosome aneuploidies show testosterone deficiency, microorchidism, lack of pubertal progression and infertility. Hormone replacement therapy (HRT) is usually recommended for these patients: different studies have found that testosterone-based HRT benefit a wide range of areas initiated in these disorders, affecting not only neuromotor, cognitive and behavioural profile but also structural anomalies of the brain (i.e., increase of volume of grey temporal lobe matter). In conclusion, further studies are needed to better understand the neuropsychological profile with a complete evaluation, including neurocognitive and psychosocial aspects and to establish the real impact of HRT on improving the cognitive and behavioural profile of these patients.

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Section: Discussionmentioning

confidence: 99%

Clinical, Cognitive and Neurodevelopmental Profile in Tetrasomies and Pentasomies: A Systematic Review

et al. 2022

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“… 66 – 68 These results cannot be applied to patients with higher grade sex chromosome aneuploidies, such as 48, XXXY, 48, XXYY or 49, XXXXY, in whom testosterone treatment resulted in an earlier and persistent suppression of testicular hormone production. 103 …”

Section: Pharmacotherapy For Male Hypogonadismmentioning

confidence: 99%

“…[66][67][68] These results cannot be applied to patients with higher grade sex chromosome aneuploidies, such as 48, XXXY, 48, XXYY or 49, XXXXY, in whom testosterone treatment resulted in an earlier and persistent suppression of testicular hormone production. 103 One study assessed the effect of r-FSH treatment on 3 boys with central hypogonadism. 12 The underlying rationale was that FSH is important to provoke Sertoli cell proliferation before pubertal maturation induced by intratesticular testosterone.…”

Section: Pharmacotherapy In Childhoodmentioning

confidence: 99%

Recent advancement in the treatment of boys and adolescents with hypogonadism

Rey

2022

Therapeutic Advances in Endocrinology

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Clinical manifestations and the need for treatment varies according to age in males with hypogonadism. Early foetal-onset hypogonadism results in disorders of sex development (DSD) presenting with undervirilised genitalia whereas hypogonadism established later in foetal life presents with micropenis, cryptorchidism and/or micro-orchidism. After the period of neonatal activation of the gonadal axis has waned, the diagnosis of hypogonadism is challenging because androgen deficiency is not apparent until the age of puberty. Then, the differential diagnosis between constitutional delay of puberty and central hypogonadism may be difficult. During infancy and childhood, treatment is usually sought because of micropenis and/or cryptorchidism, whereas lack of pubertal development and relative short stature are the main complaints in teenagers. Testosterone therapy has been the standard, although off-label, in the vast majority of cases. However, more recently alternative therapies have been tested: aromatase inhibitors to induce the hypothalamic-pituitary-testicular axis in boys with constitutional delay of puberty and replacement with GnRH or gonadotrophins in those with central hypogonadism. Furthermore, follicle-stimulating hormone (FSH) priming prior to hCG or luteinizing hormone (LH) treatment seems effective to induce an enhanced testicular enlargement. Although the rationale for gonadotrophin or GnRH treatment is based on mimicking normal physiology, long-term results are still needed to assess their impact on adult fertility.

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Serum prokineticin-2 in prepubertal and adult Klinefelter individuals

Fiore

Tarani

Radicioni

et al. 2022

Can. J. Physiol. Pharmacol.

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The prokineticin-2 (PROK2) is a small peptide belonging to the prokineticin family. In humans and rodents this chemokine is primarily involved in the control of central and peripheral reproductive processes. Klinefelter's syndrome (KS) is the first cause of male genetic infertility, due to an extra X chromosome, which may occur with a classical karyotype (47, XXY) or mosaic forms (46, XY/47, XXY). In affected subjects, pubertal maturation usually begins at an adequate chronological age, but when development is almost complete, they display a primary gonadal failure, with early spermatogenesis damage, and later onset of testosterone insufficiency. Thus, the main aim of the present study was to investigate the serum levels of PROK2 in prepubertal and adult KS patients, comparing them with healthy subjects. We showed for the first time the presence of PROK2 in the children serum but with significant changes in KS individuals. Indeed, compared to healthy subjects characterized by PROK2 serum elevation during the growth, KS individuals showed constant serum levels during the sexual maturation phase (higher during the prepubertal phase but lower during the adult age). In conclusion, these data indicate that in KS individuals PROK2 may be considered a biomarker for investigating the SK infertility process.

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Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

Cited by 4 publications

References 43 publications

Clinical, Cognitive and Neurodevelopmental Profile in Tetrasomies and Pentasomies: A Systematic Review

Clinical, Cognitive and Neurodevelopmental Profile in Tetrasomies and Pentasomies: A Systematic Review

Recent advancement in the treatment of boys and adolescents with hypogonadism

Serum prokineticin-2 in prepubertal and adult Klinefelter individuals

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