Boutros Andrea, Idan Amanda, Sleiman Sue, Bacha Feyrous, Zhang Ting, Jayadev Veena, Menzies Alexander M, Long Georgina V, Handelsman David J
Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy.
Clin Endocrinol (Oxf). 2025 Nov;103(5):721-728. doi: 10.1111/cen.70001. Epub 2025 Jul 14.
To investigate the effects of immune-checkpoint inhibitors (ICIs) on spermatogenesis and testicular endocrine function in reproductive-age men with melanoma.
Prospective, mixed longitudinal and cross-sectional cohort study.
Twenty-nine men aged 19-46 years undergoing ICI therapy for melanoma at two Australian centres between 2019 and 2024. Three patients were excluded due to subsequent gonadotoxic therapies. The remaining 26 were evaluable.
Semen analysis and serum hormone levels (FSH, LH, testosterone) were assessed at baseline and after ICI exposure. Patients with prior cytotoxic chemotherapy or pelvic radiotherapy were excluded.
Among 26 evaluable patients, one man developed persistent azoospermia with marked serum FSH elevation. Overall, median total sperm output per ejaculate declined by 34% (193-127 million per ejaculate) and sperm concentration by 30% (61-43 million/mL), neither statistically significant before or after excluding the case of presumed autoimmune orchitis. On treatment, serum LH and testosterone remained stable while the increase in serum FSH (p = 0.04) was no longer significant after excluding the single man with auto-immune orchitis.
ICI treatment may be associated with minimal spermatogenic dysfunction, as reflected by modest reductions in sperm output and increased serum FSH levels, despite preserved serum LH and testosterone concentrations, but mostly due to a rare (4% prevalence) case of autoimmune orchitis. The unpredictability of these effects supports routine fertility preservation counselling in young men before ICI initiation.
探讨免疫检查点抑制剂（ICIs）对黑色素瘤育龄男性精子发生和睾丸内分泌功能的影响。
前瞻性、混合纵向和横断面队列研究。
2019年至2024年期间，在澳大利亚两个中心接受ICI治疗黑色素瘤的29名年龄在19 - 46岁之间的男性。3名患者因随后的性腺毒性治疗被排除。其余26名患者可进行评估。
在基线和ICI暴露后评估精液分析和血清激素水平（促卵泡激素、促黄体生成素、睾酮）。排除既往接受过细胞毒性化疗或盆腔放疗的患者。
在26名可评估的患者中，1名男性出现持续性无精子症，血清促卵泡激素显著升高。总体而言，每次射精的总精子输出中位数下降了34%（从每次射精1.93亿降至1.27亿），精子浓度下降了30%（从6100万/毫升降至4300万/毫升），在排除疑似自身免疫性睾丸炎病例前后，这两个变化均无统计学意义。在治疗过程中，血清促黄体生成素和睾酮保持稳定，而排除患有自身免疫性睾丸炎的唯一一名男性后，血清促卵泡激素的升高（p = 0.04）不再显著。
ICI治疗可能与最小程度的生精功能障碍有关，表现为精子输出略有减少和血清促卵泡激素水平升高，尽管血清促黄体生成素和睾酮浓度保持不变，但这主要归因于一例罕见的（患病率4%）自身免疫性睾丸炎病例。这些影响的不可预测性支持在年轻男性开始ICI治疗前进行常规的生育力保存咨询。
