Intravesical therapies for non-muscle-invasive bladder cancer, particularly BCG, have been associated with transient impairments in semen parameters and sexual function in men, while reproductive hormone levels generally remain stable, suggesting a localized rather than systemic effect.
Key Findings
Results
BCG intravesical therapy has been associated with transient impairments in semen parameters and sexual function in men with NMIBC.
Impairments in semen parameters following BCG therapy appear to be transient rather than permanent.
Sexual function was also affected following BCG therapy.
Reproductive hormone levels generally remained stable following BCG therapy.
The pattern of effects suggests a localized rather than systemic mechanism of action.
Clinical data supporting these findings are described as limited.
Results
Preclinical studies have demonstrated that exposure to intravesical agents may result in reversible testicular damage.
Evidence for reversible testicular damage comes from preclinical (animal/laboratory) studies.
The reversible nature of the damage was noted as a key characteristic in preclinical findings.
This preclinical evidence contrasts with the limited clinical data available in human populations.
Results
Intravesical chemotherapy exhibits minimal systemic absorption, but concerns regarding its potential gonadotoxicity persist.
Despite minimal systemic absorption, the gonadotoxic potential of intravesical chemotherapy agents cannot be dismissed.
Clinical data on the impact of intravesical chemotherapy on male reproductive health remain limited.
This knowledge gap means definitive conclusions about reproductive safety cannot yet be drawn.
Results
Newly approved intravesical agents for NMIBC currently lack fertility-related safety data.
Nadofaragene and nogapendekin alfa inbakicept-pmln are identified as newly approved agents for NMIBC.
No fertility-related safety data currently exist for either of these agents.
This represents a gap in safety knowledge for patients of reproductive age receiving these newer therapies.
Results
Genitourinary complications following intravesical therapy may further compromise male reproductive tract integrity and exacerbate fertility risks.
Specific complications identified include epididymo-orchitis and prostatitis.
These complications are recognized as potential sequelae of intravesical therapy.
Such complications may compound direct effects of the therapeutic agents on fertility.
The authors describe these as potentially exacerbating fertility risks beyond the direct drug effects.
Conclusions
With fatherhood increasingly occurring beyond age 40, uro-oncologists are advised to consider the potential effects of intravesical therapy on male fertility and sexual function.
The trend of delayed fatherhood beyond age 40 is cited as a clinically relevant demographic shift.
The authors recommend that uro-oncologists incorporate reproductive counseling into NMIBC management.
A structured PubMed search was conducted covering studies published in English between 2000 and 2025.
Outcomes related to semen parameters, hormonal changes, and sexual function were extracted from selected studies.
The authors call for expanding research into reproductive outcomes among NMIBC patients to support more informed counseling.
What This Means
This research review examined what is currently known about how bladder cancer treatments delivered directly into the bladder (intravesical therapy) affect men's reproductive health and sexual function. The most common treatments — BCG immunotherapy and chemotherapy drugs placed directly in the bladder — are primarily used to prevent bladder cancer from coming back or spreading, but their effects on fertility and sexual health have not been well studied. The researchers searched medical literature published between 2000 and 2025 to compile available evidence.
The review found that BCG therapy appears to temporarily reduce sperm quality and negatively affect sexual function, but hormone levels in the blood largely stay normal, suggesting the effects are local to the reproductive organs rather than body-wide. Lab and animal studies suggest these effects may be reversible. Chemotherapy drugs used this way have very little absorption into the bloodstream, but the possibility of harm to sperm-producing tissue has not been ruled out. Two newer approved treatments for this type of bladder cancer have no published data at all regarding their effects on fertility. Additionally, infections of the testicles, epididymis, or prostate that can occur as complications of these treatments may further harm a man's reproductive health.
This research suggests that because more men are becoming fathers after age 40 — an age group that overlaps considerably with bladder cancer diagnoses — doctors who treat bladder cancer should discuss potential fertility and sexual health effects with their patients before starting treatment. The authors highlight a significant gap in the medical literature and call for more research specifically studying reproductive outcomes in men receiving these treatments, so that patients can make better-informed decisions about their care.
Abou Chakra M, Duquesne I, Mima M, Ohlander S, Kemp A, O'Donnell M. (2025). Male reproductive and sexual health outcomes following intravesical therapy for non-muscle invasive bladder cancer.. World journal of urology. https://doi.org/10.1007/s00345-025-06056-8