Pediatric Research Center, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Clin Endocrinol (Oxf). 2023 Dec;99(6):552-558. doi: 10.1111/cen.14974. Epub 2023 Sep 29.
We designed a longitudinal study to investigate the association between the ages of central pubertal activation and the appearance of clinical signs of puberty and determined total luteinizing hormone (LH) immunoreactivity in daytime- and nocturnal sleeptime-excreted urine samples.
Thirty healthy volunteers (17 boys and 13 girls, aged 3.4-15.2 years and 4.3-14.3 years, respectively, at the beginning of the study) were included. Male and female subjects were followed for an average of 15 visits during 5.5 and 5.8 years on average, respectively. At each visit, subjects provided 24-h urine samples divided into nocturnal sleeptime and waketime portions according to the participant's sleep-and-wake rhythm. Total urinary LH (U-LH) concentrations were measured in duplicate by Delfia® IFMA (Wallac), which has been designed specifically to detect intact LH as well as the beta subunit and its core fragment, but not the human chorionic gonadotropin.
The initial increases in nocturnal sleeptime total U-LH concentrations over the cutoff value of 0.7 IU/L occurred at around the same time (around 9-10 years of age) in both sexes, which could not be detected in waketime urine samples. The mean first age for the nocturnal sleeptime total U-LH concentrations to reach or surpass the cutoff was 10.7 years (range: 10.2-11.6 years) in boys and 11.8 years (range: 10.7-13.4 years) in girls, showing no statistically significant difference between the sexes (p = .15). The mean time span from the age at which sleeptime total U-LH concentration first exceeded the 0.7 IU/L level to observing pubertal stage 2 was 1.5 years in boys and 0.1 years in girls.
Findings in our population with a limited sample size suggest that the timing of central pubertal activation is a sex-independent phenomenon, which can be observed by monitoring the nocturnal sleeptime total LH concentrations in urine. The lag time from central pubertal activation of gonadotropin secretion to the clinical onset of puberty is significantly longer in boys.
我们设计了一项纵向研究,旨在探讨中枢性青春期启动的年龄与青春期临床征象出现之间的关系,并确定昼夜间睡眠时尿液中总黄体生成素(LH)免疫活性。
纳入 30 名健康志愿者(男 17 名,女 13 名,分别于研究开始时年龄为 3.4-15.2 岁和 4.3-14.3 岁)。男性和女性受试者分别平均随访 15 次,平均随访时间分别为 5.5 年和 5.8 年。每次就诊时,受试者根据自身的睡眠-觉醒节律提供 24 小时尿液样本,分为夜间睡眠时间和觉醒时间部分。采用 Delfia® IFMA(Wallac)双份检测总尿 LH(U-LH)浓度,该方法专门设计用于检测完整的 LH 以及β亚单位及其核心片段,但不检测人绒毛膜促性腺激素。
男女两性的夜间睡眠时间总 U-LH 浓度超过 0.7IU/L 的初始升高时间大致相同(约 9-10 岁),而在觉醒时间尿液样本中无法检测到。夜间睡眠时间总 U-LH 浓度达到或超过截定点的首次平均年龄在男孩中为 10.7 岁(范围:10.2-11.6 岁),在女孩中为 11.8 岁(范围:10.7-13.4 岁),两性之间无统计学显著性差异(p=0.15)。从睡眠时间总 U-LH 浓度首次超过 0.7IU/L 水平到观察到青春期 2 期的时间间隔在男孩中为 1.5 年,在女孩中为 0.1 年。
在我们的人群中,由于样本量有限,研究结果表明中枢性青春期启动的时间是一种与性别无关的现象,可以通过监测尿液中夜间睡眠时间总 LH 浓度来观察。从促性腺激素分泌的中枢性青春期启动到青春期临床发病的时间间隔在男孩中明显更长。