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Testicular Function After Immune-Checkpoint Inhibitors Treatment
Andrea Boutros1,2, Amanda Idan3, Sue Sleiman4
1Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Objective:
To investigate the effects of immune-checkpoint inhibitors (ICIs) on spermatogenesis and testicular endocrine function in reproductive-age men with melanoma.
Design:
Prospective, mixed longitudinal and cross-sectional cohort study.
Patients:
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.
Measurements:
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.
Results:
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.
Conclusions:
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.
Insights
Immune-checkpoint inhibitors (ICIs) may cause mild testicular dysfunction in men with melanoma, with potential impacts on sperm production. Fertility preservation counseling is recommended before starting ICI therapy due to unpredictable effects.
Area of Science:
- Reproductive Endocrinology
- Oncology
- Immunology
Background:
- Immune-checkpoint inhibitors (ICIs) are increasingly used for melanoma treatment.
- Potential impacts of ICIs on male reproductive health, specifically spermatogenesis and testicular endocrine function, require investigation.
Purpose of the Study:
- To assess the effects of ICIs on sperm production and hormone levels in men with melanoma.
- To determine the prevalence and nature of testicular dysfunction associated with ICI therapy.
Main Methods:
- Prospective cohort study involving 26 men with melanoma undergoing ICI therapy.
- Semen analysis and serum hormone levels (FSH, LH, testosterone) were measured at baseline and post-treatment.
- Exclusion of patients with prior gonadotoxic therapies or radiotherapy.
Main Results:
- A modest, though not statistically significant, decline in sperm output and concentration was observed.
- One patient developed persistent azoospermia with elevated FSH, presumed autoimmune orchitis.
- Serum LH and testosterone remained stable; FSH elevation was primarily linked to the single autoimmune orchitis case.
Conclusions:
- ICI treatment may lead to minimal spermatogenic dysfunction and transient FSH increases, largely influenced by rare autoimmune orchitis.
- The unpredictable nature of these effects underscores the importance of fertility preservation counseling for young men initiating ICIs.
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