Testosterone Therapy in Adult Males with Hypogonadism

A non-systematic review says testosterone therapy is safe and effective, but cites no funding or conflicts

Journal: European Urology | Published: 2025-12-24 | Type: Journal Article, Review, Letter | PMID: 41448986 Authors: Boeri Luca (IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan); Masterson Thomas (University of Miami); Antonio Leen (KU Leuven); Corona Giovanni (Azienda USL Bologna); Khera Mohit (Baylor College of Medicine); Salonia Andrea (IRCCS Ospedale San Raffaele, Milan); Mulhall John P (Memorial Sloan Kettering Cancer Center) Funding/COI: Not listed

Summary

This is a narrative review, not a study — the authors read existing literature on testosterone deficiency (TD) and testosterone therapy (TTh) and summarized their own interpretation of it, without a systematic search protocol or new data. They conclude TTh is "safe and effective" for symptomatic men with confirmed low testosterone, improving sexual function, body composition, metabolic markers, and bone density. No original patient cohort, no new trial data, no quantitative synthesis of the studies it draws on.

Claims

• TD symptoms are described as mild and nonspecific: sexual dysfunction, fatigue, mood changes, reduced muscle and bone mass
• TTh is characterized as improving sexual function, body composition, metabolic profile, and bone mineral density
• The review states TTh does not increase risk of major cardiovascular events or prostate cancer, without giving effect sizes, confidence intervals, or citing specific trials in the abstract
• Recommended target range for treatment: mid-normal testosterone, 450-600 ng/dL
• Suggested monitoring schedule: follow-up at 3 months, then every 6-12 months, tracking hematocrit, PSA, and metabolic parameters

Study Quality

The authors explicitly label this a "nonsystematic literature review" — there's no PRISMA-style search strategy, no inclusion/exclusion criteria, and no way for a reader to verify which studies were considered versus omitted. That matters because the cardiovascular and prostate cancer safety claims are exactly where the TTh literature has been most contested for the past decade, with meta-analyses reaching different conclusions depending on which trials they include and how cardiovascular events are defined. A narrative review lets the authors selectively cite studies that support their existing clinical view.

The abstract provides no sample sizes, no confidence intervals, and no breakdown of which specific trials underlie the safety and efficacy claims. "Evidence indicates" is doing a lot of work in this abstract without pointing to what that evidence actually is.

Red Flags

• No funding source or conflict-of-interest disclosure listed, despite the sensitivity of TTh research to industry sponsorship and several authors' documented history of testosterone-industry consulting relationships in prior publications
• Nonsystematic methodology means selection bias in which studies got included cannot be ruled out
• The safety conclusions on cardiovascular events and prostate cancer — the two biggest historical concerns with TTh — are stated as settled without citing specific trial data in the abstract
• Classified partly as "Letter" in the article type, an unusual designation for what's presented as a full clinical review

Strengths

• Author group includes clinicians from multiple major academic urology and endocrinology centers across the US and Europe, suggesting broad clinical experience informing the synthesis
• Provides concrete, actionable monitoring parameters (testosterone target range, follow-up intervals, labs to track) that are useful context for understanding current guideline-based practice
• Addresses a genuinely evolving area of clinical practice where guidance has shifted over the past two decades

Verdict

This reads as a clinical opinion piece dressed up as a review — useful for understanding where mainstream urology currently stands on TTh, but it's not evidence in itself. Without a systematic methodology, funding disclosure, or citations to the specific trials behind its safety claims, there's no way to independently check whether "TTh doesn't increase cardiovascular or prostate cancer risk" reflects a genuine consensus or a curated reading of the literature. Treat this as a snapshot of expert opinion, not as new data resolving the debate.