Testosterone Effects on Short-Term Physical, Hormonal, and Neurodevelopmental Outcomes in Infants with 47,XXY/Klinefelter Syndrome: The TESTO Randomized Controlled Trial.

Shanlee Davis, Susan Howell, Jennifer Janusz, Najiba Lahlou, Regina Reynolds, Talia Thompson, Karli Swenson, Rebecca Wilson, Judith Ross, Philip Zeitler, Nicole Tartaglia
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Abstract

Context: 47,XXY/Klinefelter syndrome (XXY) is associated with impaired testicular function and differences in physical growth, metabolism, and neurodevelopment. Clinical features of XXY may be attributable to inadequate testosterone during the mini-puberty period of infancy.

Objective: We tested the hypothesis that exogenous testosterone treatment positively effects short-term physical, hormonal, and neurodevelopmental outcomes in infants with XXY.

Design: Double-blind randomized controlled trial, 2017-2021.

Setting: US tertiary care pediatric hospital.

Patients: Infants 30-90 days of age with prenatally identified, non-mosaic 47,XXY (n=71).

Intervention: Testosterone cypionate 25mg intramuscular injections every 4 weeks for 3 doses.

Main outcome measures: The a priori primary outcomes were change in percent fat mass (%FM) z-scores and change in the total composite percentile on Alberta Infant Motor Scales (AIMS) assessment from baseline to 12 weeks.

Results: The between group difference in change in %FM z-scores was -0.57 [95% CI -1.1, -0.06], p=0.03), secondary to greater increases in lean mass in the testosterone-treated group (1.5±0.4 kg vs 1.2±0.4, p=0.001). Testosterone suppressed gonadotropins and inhibin B (p<0.001 for all). In contrast, there were no significant group differences in short term motor, cognitive, or language outcomes (p>0.15 for all).

Conclusions: In this double-blind randomized controlled trial in infants with XXY, testosterone injections resulted in physical effects attributable to systemic androgen exposure; however, there was no impact on neurodevelopmental outcomes and the hypothalamic-pituitary-gonadal axis was suppressed. These results do not support routine testosterone treatment in infants with XXY, however long term follow up on physical health, neurodevelopment and testicular function is needed.

睾丸激素对47,XXY/Klinefelter综合征婴儿短期生理、激素和神经发育结局的影响:TESTO随机对照试验
背景:47、XXY/Klinefelter综合征(XXY)与睾丸功能受损以及身体生长、代谢和神经发育的差异有关。XXY的临床特征可能与婴儿期小青春期睾酮不足有关。目的:我们验证了外源性睾酮治疗对XXY婴儿的短期身体、激素和神经发育结果有积极影响的假设。设计:双盲随机对照试验,2017-2021。地点:美国三级儿科医院。患者:30-90天的婴儿,产前鉴定,非马赛克47,XXY (n=71)。干预措施:每4周肌肉注射甲磺酸睾酮25mg,共3次。主要结果测量:先验的主要结果是从基线到12周,阿尔伯塔婴儿运动量表(AIMS)评估中脂肪质量百分比(%FM) z分数的变化和总复合百分位数的变化。结果:两组间%FM z-score变化差异为-0.57 [95% CI -1.1, - 0.06], p=0.03),其次是睾酮治疗组瘦体重增加(1.5±0.4 kg vs 1.2±0.4 kg, p=0.001)。睾酮抑制促性腺激素和抑制素B (p0.15)。结论:在这项针对XXY婴儿的双盲随机对照试验中,睾酮注射导致全身雄激素暴露的生理效应;然而,对神经发育结果没有影响,下丘脑-垂体-性腺轴受到抑制。这些结果不支持对患有XXY的婴儿进行常规睾酮治疗,但需要对身体健康、神经发育和睾丸功能进行长期随访。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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