Efficacy and Safety of Testosterone Replacement in Testicular Cancer Survivors With Treatment-Influenced Hypogonadism: A Systematic Review.

Ten analyses encompassing 332 testicular cancer survivors with treatment-influenced hypogonadism were included, with 238 patients receiving testosterone replacement.

• Systematic review conducted according to PRISMA standards.
• Databases searched included Embase, PubMed/MEDLINE, Cochrane Central, Web of Science Core Collection, Korean Journal Index, SciELO, and Global Index Medicus.
• Search was conducted in June 2024.
• Participants included both bilateral and unilateral testicular cancer survivors.

Eight of the 10 analyses assessed participants without poor quality-of-life metrics, metabolic factors, and bone mineral density at baseline and only found a significant benefit in fat distribution metrics with testosterone supplementation.

• These 8 analyses did not show significant benefits in QOL metrics, most metabolic factors, or BMD with testosterone supplementation.
• Fat distribution metrics were the only area where a significant benefit was identified among participants with normal baseline metrics.
• This represents the majority of analyses reviewed (8 of 10).

Two analyses evaluating participants with poor quality-of-life metrics or bone mineral density at baseline showed improvements in QOL or BMD with testosterone supplementation.

• Improvements in QOL or BMD were observed specifically in participants who had impaired baseline values.
• These findings suggest that baseline status may be a key determinant of response to testosterone replacement therapy.
• Only 2 of the 10 included analyses specifically assessed participants with poor baseline QOL or BMD metrics.

There is robust evidence regarding the efficacy and safety of testosterone replacement in hypogonadal individuals generally, but limited evidence specifically evaluating supplementation in testicular cancer survivors with treatment-influenced hypogonadism.

• The authors distinguished between evidence in the general hypogonadal population versus the specific subpopulation of testicular cancer survivors.
• The limited number of included analyses (n=10) and patients (n=332 total, 238 receiving testosterone) reflects this evidence gap.
• The review highlights the need for more targeted research in this specific patient population.

Routine testosterone supplementation for all testicular cancer survivors with treatment-influenced hypogonadism lacks efficacy support.

• Results suggest testosterone replacement is not universally beneficial across this patient population.
• The evidence supports a targeted approach to supplementation based on baseline impairment in QOL metrics, metabolic factors, and BMD.
• This conclusion is derived from the finding that the majority of analyses (8 of 10) did not demonstrate broad benefit in participants without poor baseline metrics.