Does long-term testosterone therapy cause tendon or ligament degeneration?

Long-Term Testosterone Use and Tendon/Ligament Injury Risk

Long-term testosterone therapy is associated with a significantly increased risk of tendon and ligament injuries, including tears and subsequent surgical repairs, with evidence showing 2-3 fold increased risk of ACL tears and up to 3.6 times greater risk of rotator cuff tears in patients on testosterone replacement therapy.

Evidence of Increased Tendon/Ligament Injury Risk

The most recent and highest quality evidence demonstrates clear associations between testosterone therapy and connective tissue injuries:

Anterior Cruciate Ligament (ACL) Injuries

Recent large database studies consistently show elevated ACL injury rates in testosterone users:

• Injectable testosterone within 1 year before ACL reconstruction resulted in a 17.05% revision rate compared to 5.17% in matched controls, yielding a 3.3-fold increased relative risk of revision surgery 1
• Patients prescribed testosterone for ≥3 months had 2.77 times higher odds of ACL injury within 2 years (0.35% vs 0.10% in controls), with incidence rates of 17.8 per 10,000 person-years versus 4.9 in controls 2
• A separate analysis found testosterone users had 2.46 times greater likelihood of ACL tears at 1 year and 2.22 times at 2 years 3

Critical finding: The timing matters—testosterone use within 1 year of surgery shows the strongest association with complications, while distant use >1 year showed weaker but still elevated trends 1.

Rotator Cuff Pathology

Testosterone therapy demonstrates even more dramatic effects on rotator cuff tissue:

• Patients on testosterone for ≥90 days had 3.6 times greater risk of rotator cuff tears (1.14% vs 0.19%) 4
• Among those with tears, testosterone users underwent repair at 1.6 times higher rates (46.4% vs 34.0%) 4
• Most striking: testosterone users had 26.7 times greater risk of subsequent rotator cuff repair within 1 year of primary repair 4

Broader Tendon Injury Patterns

A comprehensive analysis of patients initiating testosterone without documented low testosterone showed:

• 1.35 times higher odds of rotator cuff tears within 1 year 5
• 2.06-2.14 times higher odds of patellar tendon tears 5
• 1.59 times higher odds of quadriceps tendon tears 5
• 1.33 times higher odds of any tendon tear 5

These risks persisted through the second year of therapy 5.

Guideline Context: Absence of Tendon/Ligament Warnings

Important caveat: The comprehensive New England Journal of Medicine guideline on testosterone risks 6 and the American College of Physicians evidence report 7 do not list tendon or ligament injuries among recognized risks. Their focus was on cardiovascular events, prostate issues, erythrocytosis, and metabolic effects.

The FDA drug label for injectable testosterone 8 similarly does not mention tendon or ligament degeneration among its precautions, focusing instead on prostatic hypertrophy, priapism, and polycythemia.

This represents a significant gap: The recent research evidence (2023-2026) has emerged after these guidelines, revealing a previously unrecognized musculoskeletal consequence of testosterone therapy.

Mechanistic Considerations

While the exact mechanism remains under investigation, the research suggests:

• Direct tissue effects: One study examining patellar tendon biopsies found former testosterone abusers had significantly higher tendon deformation and strain at common force levels, though cross-sectional area and cell density were unchanged 9
• Altered tissue homeostasis: The combined evidence suggests testosterone may compromise tendon mechanical properties without obvious structural changes on imaging
• Dose-response relationship: The strongest associations occur with recent/ongoing use, with some normalization after cessation 1

Clinical Implications and Risk Stratification

High-Risk Scenarios

Avoid or strongly counsel against testosterone therapy in patients who:

• Participate in activities with high ligament stress (pivoting sports, heavy lifting)
• Have history of prior tendon/ligament injuries
• Are considering or recovering from ligamentous reconstruction surgery

Timing Considerations

• Perioperative period: Strongly consider discontinuing testosterone ≥1 year before elective ligament reconstruction 1
• Post-injury: Delay testosterone initiation if recent tendon/ligament injury occurred

Monitoring Strategy

For patients on testosterone therapy:

• Counsel explicitly about 2-3 fold increased tendon/ligament injury risk
• Maintain heightened suspicion for tendon pathology with activity-related pain
• Consider lower threshold for imaging evaluation of suspected tendon injuries
• Document this discussion for medicolegal purposes, as this risk is not yet in formal guidelines

Age and Sex Considerations

The ACL injury risk was significant across nearly all age groups (25-65+ years), with odds ratios ranging from 3.91 to 12.3 2. Both males (OR 3.13) and females (OR 1.94) showed elevated risk, though the effect was stronger in males 2.

Bottom line: This is not limited to young athletes—middle-aged and older patients on testosterone therapy face substantial tendon/ligament injury risk that should fundamentally influence prescribing decisions and patient counseling, particularly given that many of these patients may not have legitimate indications for testosterone therapy 5.