Department of Pediatric Endocrinology and Diabetology, Children's Hospital of Eastern Switzerland, 9006 St. Gallen, Switzerland.
University of Muenster, 48149 Muenster, Germany.
Endocr Rev. 2024 Jul 12;45(4):460-492. doi: 10.1210/endrev/bnae003.
There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second-termed "mini-puberty"-in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications.
人生中有 3 个下丘脑-垂体-性腺（HPG）轴的生理波。第一个发生在胎儿期，第二个称为“迷你青春期”-出生后第一个月，第三个发生在青春期。青春期后，轴在整个成年期保持活跃。先天性促性腺激素低下性性腺功能减退症（CHH）是一种罕见的遗传性疾病，其特征是下丘脑促性腺激素释放激素（GnRH）分泌或作用不足。在严重的 CHH 病例中，所有 3 个 GnRH 脉冲波都不存在。胎儿 HPG 轴激活的缺失表现在大约 50%的小阴茎和/或未降睾丸（隐睾）的男性新生儿中。在这些男孩中，迷你青春期阶段的缺失加剧了睾丸不成熟。其特征是 Sertoli 细胞数量少，而 Sertoli 细胞对未来的生殖能力很重要。因此，迷你青春期缺失会对这些男性的后期生育能力产生不利影响。CHH 在婴儿期经常被漏诊，即使被识别，也没有关于最佳治疗管理的共识。在这里，我们回顾了生理性迷你青春期和中枢 HPG 轴紊乱的后果；提供了一种诊断方法，以允许早期识别这些情况；并回顾了目前用于治疗 CHH 男性婴儿迷你青春期替代的治疗选择。有小病例系列的证据表明，用促性腺激素替代以模拟男性的“迷你青春期”不仅可以使睾丸下降，而且可以使睾丸和阴茎大小正常化，可能会有有益的结果。此外，在紊乱的迷你青春期中，这种治疗替代方案可以解决生殖和非生殖问题。
