Wood Claire L, Hollingsworth Kieren G, Bokaie Edrina, Hughes Eric, Muni-Lofra Robert, Mayhew Anna, Mitchell Rod T, Guglieri Michela, McElvaney Joseph, Cheetham Timothy D, Straub Volker
C Wood, Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom of Great Britain and Northern Ireland.
K Hollingsworth, Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom of Great Britain and Northern Ireland.
Endocr Connect. 2023 Sep 1;12(12). doi: 10.1530/EC-23-0245.
Glucocorticoids (GC) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown.
To assess hypothalamic-pituitary-gonadal axis, muscle volume and function 5 years after pubertal induction.
A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2y) then evaluated at +2.5y and +5y (final follow-up~ 3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function and limb muscle MRI.
Participants were 18.7 years (SD 1.6) at final follow-up and had been on GC for 11.2 years (SD 2.2). Testosterone levels were similar at +2.5y (8.6nmol/l (SD 3.4) and 5y (11.0 nmol/l (SD 6.1). TV increased from 2.8 mls (SD 0.9) at +2y to 7.1 mls (SD 1.8) then 10.6 mls (SD 3.5) at +2.5y and +5.0y(p<0.001). Inhibin B levels increased from 55.6 pg/ml (SD 47.0) at baseline to 158.2 pg/ml (SD 87.6), p=0.004 at 5y but remained lower than reference values (mean 305 pg/ml). Muscle contractile bulk decreased.
Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in Inhibin B, TV and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle and wellbeing, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.
糖皮质激素（GC）可减轻杜氏肌营养不良症（DMD）男孩的炎症并维持肌肉功能，但会导致青春期延迟。建议使用睾酮进行青春期诱导，但长期结果尚不清楚。
评估青春期诱导5年后下丘脑-垂体-性腺轴、肌肉体积和功能。
对一项临床研究进行前瞻性观察随访。15名接受GC治疗的DMD男性接受递增睾酮治疗2年（治疗结束后+2年），然后在+2.5年和+5年（最后一次注射后约3年进行最终随访）进行评估。收集的数据包括睾丸体积（TV）、促性腺激素、睾酮、抑制素B、肌肉功能和肢体肌肉MRI。
最终随访时参与者年龄为18.7岁（标准差1.6），接受GC治疗11.2年（标准差2.2）。睾酮水平在+2.5年（8.6nmol/l（标准差3.4））和5年（11.0nmol/l（标准差6.1））时相似。TV从+2年时的2.8毫升（标准差0.9）增加到+2.5年时的7.1毫升（标准差1.8），然后在+5.0年时增加到10.6毫升（标准差3.5）（p<0.001）。抑制素B水平从基线时的55.6pg/ml（标准差47.0）增加到5年时的158.2pg/ml（标准差87.6），p=0.004，但仍低于参考值（平均305pg/ml）。肌肉收缩体积减少。
DMD患者使用睾酮进行青春期诱导与下丘脑-垂体-性腺轴激活以及抑制素B、TV和睾酮浓度持续升高有关。一些患者的水平正常，这对未来生育能力很有希望。鉴于睾酮对骨骼健康、肌肉和幸福感有有益影响，监测该人群的睾酮水平并补充次优水平很重要。
