Mathiesen Sidsel, Sørensen Kaspar, Ifversen Marianne, Hagen Casper P, Holm Petersen Jørgen, Juul Anders, Müller Klaus
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Endocr Connect. 2021 Oct 18;10(10):1352-1365. doi: 10.1530/EC-21-0154.
Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood.
This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from the time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated.
Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14 to 16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT.
Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.
需要对儿童造血干细胞移植(HSCT)后的睾丸功能进行纵向评估,以指导临床随访。我们研究了儿童HSCT后男性生殖激素的动态变化,重点关注青春期时间以及与成年期睾酮缺乏和无精子症的关联。
这项回顾性纵向研究纳入了39名儿童HSCT后中位时间为19年的幸存者。分析了HSCT时、青春期期间及成年期血清促黄体生成素(LH)、睾酮、促卵泡生成素(FSH)和抑制素B的浓度。将青春期时间(LH和睾酮升高)与112名健康男孩的参考队列进行比较。研究了青春期生殖激素水平与成年睾丸功能(包括精液质量)之间的关联。
6/26名在HSCT时处于青春期前的患者需要用睾酮诱导青春期。在其余患者中,青春期时间与参考队列相当。然而,9/33名患者(未进行青春期诱导)在成年早期出现睾酮缺乏,这与14至16岁时较高的LH水平有关。在18/26名未进行睾酮替代的患者中发现成年期无精子症。对于HSCT时处于青春期前的患者,青春期中期较高的FSH水平和较低的抑制素B水平与成年期无精子症有关。
我们的结果表明,儿童HSCT后睾丸功能恶化的风险很大,尽管青春期时间正常。尽管青春期中期的生殖激素水平可指示成年睾丸功能,但这些患者仍需要延长至成年期的随访,包括临床检查、生殖激素分析以及为有生育潜力需求的患者进行精液样本检查。