Nelson Vergel
Founder, ExcelMale.com
Executive Summary
This briefing document details the findings of a retrospective cohort study investigating the association between prescription testosterone use and postoperative outcomes in male patients undergoing primary total shoulder arthroplasty (TSA). The analysis, based on data from the MarketScan Commercial Claims Database (2017–2021), identifies prescription testosterone as a significant independent risk factor for both infection-related and all-cause reoperations.Critical Takeaways:
- Increased Infection Risk: Men prescribed testosterone within 12 months prior to surgery faced a fourfold increase in the risk of infection-related reoperation (OR=4.1).
- Elevated All-Cause Reoperation: Testosterone use was associated with more than double the risk of reoperation for any reason (OR=2.2).
- Sustained Impact: The cumulative incidence of reoperations remained significantly higher for testosterone users across one-, two-, and three-year postoperative milestones.
- Clinical Significance: While traditional risk factors like age and comorbidities (e.g., diabetes, obesity) did not show significant associations in this specific analysis, testosterone therapy emerged as a distinct, independent driver of adverse outcomes.
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Study Overview and Methodology
The investigation utilized a robust, real-world dataset to clarify the previously uncertain relationship between testosterone therapy and surgical outcomes following TSA.Patient Cohort and Matching
- Initial Population: 54,850 primary TSAs identified between 2017 and 2021.
- Refined Study Group: Following exclusions (e.g., malignancy, previous shoulder arthroplasty, gender dysphoria), a final cohort of 10,017 TSAs was established.
- Matched Analysis:To ensure internal validity, the study utilized a 2:1 matching design (Mahalanobis nearest neighbor matching).
- Testosterone Group: 481 men with a testosterone prescription within 12 months pre-surgery.
- Control Group: 962 men with no such prescription.
- Matching Criteria: Age, setting (inpatient vs. outpatient), comorbidities (diabetes, hypertension, hyperlipidemia, obesity, smoking, alcohol use), and Charlson Comorbidity Index (CCI) scores.
Statistical Analysis of Reoperation Risks
The study found that testosterone use was the only significant risk factor identified in multivariate models for both infection-related and all-cause reoperations.Infection-Related Reoperations
The cumulative incidence of reoperation due to infection was consistently higher in the testosterone group:| Postoperative Timeframe | Testosterone Group | Control Group | p-value |
| 1 Year | 1.4% | 0.0% | <0.001 |
| 2 Years | 1.4% | 0.2% | 0.003 |
| 3 Years | 1.4% | 0.7% | 0.03 |
All-Cause Reoperations
The trend of increased risk extended to reoperations for any clinical reason:| Postoperative Timeframe | Testosterone Group | Control Group | p-value |
| 1 Year | 3.0% | 1.2% | 0.03 |
| 2 Years | 4.3% | 1.6% | 0.01 |
| 3 Years | 4.3% | 2.5% | 0.02 |
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Biological and Clinical Context
The study proposes several mechanisms and contextual factors to explain the observed correlation between testosterone and increased surgical complications.Biological Mechanisms
- Microbial Proliferation: Testosterone enhances sebaceous gland activity and sebum production, creating lipid-rich conditions that favor the growth of Cutibacterium acnes (C. acnes). High dermal loads of C. acnes are strongly associated with periprosthetic joint infection (PJI) in shoulder surgery.
- Immune Modulation: Androgens may suppress the systemic immune response by downregulating key inflammatory mediators (IL-1β, IL-6, TNF-α, CRP) and reducing the activity of macrophages and neutrophils.
- Delayed Wound Healing: Testosterone may inhibit keratinocyte proliferation and migration (via Wnt/β-catenin and TGF-β1 signaling), limit angiogenesis (via VEGF downregulation), and disrupt collagen synthesis.
Potential Contextual Factors
- Bone Mineral Density: While testosterone can improve bone density, patients prescribed it for hypogonadism may have lower baseline density, increasing the risk of osteoporosis-related implant complications.
- Activity Levels: Patients opting for elective testosterone supplementation may be more physically active, potentially placing higher mechanical stress on surgical implants.
Discussion of Findings and Literature Comparison
The findings align with some existing research while contradicting others, highlighting the complexity of the issue.- Consistency with Prior Research: These results support studies by Su et al., which linked testosterone use within six months of TSA to higher infection rates (3.4% vs 2.4%), and Schiffman et al., which found serum testosterone levels independently predicted high skin C. acnes loads.
- Contradictions in Reverse TSA: In contrast, a study by Parmar et al. on reverse total shoulder arthroplasty (rTSA) found no significant difference in revision or infection rates. This suggests that the impact of testosterone may vary between anatomic TSA and rTSA populations.
- Ambiguity in Orthopedic Benefits: While some randomized controlled trials suggest perioperative testosterone can improve clinical metrics like bone mineral density, those studies did not specifically evaluate reoperation risks.
Limitations and Future Research
The study authors emphasize that these findings should be considered hypothesis-generating due to several inherent limitations:- Low Event Volume: The absolute number of infection-related reoperations was small (n=9), leading to wide confidence intervals and a potential risk of type I error.
- Database Constraints: The MarketScan database lacks clinical granularity regarding infection severity, microbiology, surgical approach, and patient adherence to medication.
- Exposure Definition: The study identified testosterone use based on a prescription within 12 months but lacked data on dosage, formulation, or the specific indication (e.g., hypogonadism vs. elective performance enhancement).
Recommendations for Clinical Practice and Future Study
- Preoperative Screening: Clinicians should identify testosterone use during preoperative evaluations to inform risk stratification and shared decision-making.
- Prospective Validation: Future research is required to determine if the association is causal and to evaluate whether preoperative cessation of testosterone reduces risk.
- Broader Demographics: Future studies should investigate the effects of testosterone therapy in women and patients receiving different types of orthopedic implants.
