Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols.
Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols.
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DOI：
10.1297/cpe.24.37
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发表时间：
2015-04-01
期刊：
影响因子：
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通讯作者：
Tanaka, Toshiaki
中科院分区：
文献类型：
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作者：
Sato, Naoko;Hasegawa, Tomonobu;Tanaka, Toshiaki
男性性腺激素减退症(MHH)是一种与不育症相关的疾病，采用睾酮替代疗法(TRT)和/或促性腺激素替代疗法(GRT)(TRT和GRT，以及HRT激素替代疗法)进行治疗。在日本，已经制定了青春期治疗指南。由于骨龄迅速成熟的风险，已使用低剂量的睾酮或促性腺激素。然而，治疗干预的最佳时机和方法尚未确定。这项研究的目的是调查日本MHH儿童的治疗现状，并回顾日本儿科内分泌学学会理事参与的初步调查和从26个进行HRT的机构获得的第二次调查。受试者为55例HRT后达到成年身高的MHH患者。其中Kallmann综合征7例，单纯性促性腺激素缺乏6例，颅内、垂体肿瘤所致获得性垂体功能低下18例，臀位分娩所致经典型特发性垂体功能低下22例，Charge综合征2例。HRT开始时的平均年龄为15.7岁，平均身高为157.2厘米。成人平均身高19.4岁，平均身高171.0 cm。HRT开始年龄晚于正常青春期年龄，与青春期身高增长呈显著负相关，与成年身高无相关性。在生精方面，hCG-rFSH联合治疗的患者中，76%的患者显示阳性，但程度不一；部分先天性MHH患者生精功能受损，获得性MHH患者均有良好的生精功能。因此，我们建议通过将受试者分成两组来确定不同的治疗方案，即后天性和先天性MHH，并在更接近青春期开始的时间，即接近初中入学的时候，来建立开始使用低剂量睾酮或低剂量促性腺激素的治疗方案。我们还提出了一种新的HRT方案，在GRT之前使用预防性FSH治疗，旨在实现先天性MHH患者未来的生育能力。
Male hypogonadotropic hypogonadism (MHH), a disorder associated with infertility, is treated with testosterone replacement therapy (TRT) and/or gonadotropins replacement therapy (GRT) (TRT and GRT, together with HRT hormone replacement therapy). In Japan, guidelines have been set for treatment during adolescence. Due to the risk of rapid maturation of bone age, low doses of testosterone or gonadotropins have been used. However, the optimal timing and methods of therapeutic intervention have not yet been established. The objective of this study was to investigate the current situation of treatment for children with MHH in Japan and to review a primary survey involving councilors of the Japanese Society for Pediatric Endocrinology and a secondary survey obtained from 26 facilities conducting HRT. The subjects were 55 patients with MHH who reached their adult height after HRT. The breakdown of the patients is as follows: 7 patients with Kallmann syndrome, 6 patients with isolated gonadotropin deficiency, 18 patients with acquired hypopituitarism due to intracranial and pituitary tumor, 22 patients with classical idiopathic hypopituitarism due to breech delivery, and 2 patients with CHARGE syndrome. The mean age at the start of HRT was 15.7 yrs and mean height was 157.2 cm. The mean age at reaching adult height was 19.4 yrs, and the mean adult height was 171.0 cm. The starting age of HRT was later than the normal pubertal age and showed a significant negative correlation with pubertal height gain, but it showed no correlation with adult height. As for spermatogenesis, 76% of the above patients treated with hCG-rFSH combined therapy showed positive results, though ranging in levels; impaired spermatogenesis was observed in some with congenital MHH, and favorable spermatogenesis was observed in all with acquired MHH. From the above, we propose the establishment of a treatment protocol for the start low-dose testosterone or low-dose gonadotropins by dividing subjects into two groups to determine different treatment protocols, acquired and congenital MHH, and to conduct them at a timing closer to the onset of puberty, namely, at a timing near entrance to junior high school. We also propose a new HRT protocol using preemptive FSH therapy prior to GRT aimed at achieving future fertility in patients with congenital MHH.