How hormonal differences influence ligament strength, joint stability, and injury risk.
By Dr. John A. Robinson, NMD, and Dr. Cristina Romero-Bosch, NMD | RegeneZone®
Why are women more likely than men to tear certain ligaments, even when participating in the same sports?
The anterior cruciate ligament (ACL) provides a striking example. Female athletes experience ACL injuries at approximately two to eight times the rate of male athletes in some comparable sports and populations.
Anatomical differences, knee alignment, and muscle activation help explain this disparity. But another important factor is hormonal biology: estrogen, testosterone, and relaxin influence collagen metabolism, ligament properties, and joint stability.
At RegeneZone®, we believe these differences deserve greater attention when evaluating women's orthopedic health.
1. Are Women's Ligaments Biologically Different?
Ligaments consist primarily of type I collagen, organized into dense fibers that stabilize joints and resist mechanical stress.
Research has identified several sex-related differences:
Ligament size: Women generally have smaller ACL cross-sectional areas, potentially reducing total load-bearing capacity.
Ligament stiffness: Female ACLs may demonstrate lower stiffness and greater elongation under load.
Joint laxity: Women, on average, exhibit greater ligamentous flexibility.
Collagen metabolism: Male and female connective tissues respond differently to sex hormones.
Muscle strength: Men generally possess greater absolute muscle mass and strength, providing additional joint stabilization.
Ligament resilience depends on collagen quantity, fiber organization, and crosslinking—the molecular bonds that strengthen connective tissue.
Hormones influence several of these characteristics.
2. Estrogen: Does It Make Ligaments More Vulnerable?
Estrogen is essential for bone, muscle, and connective tissue health. However, its effects on ligament strength are complex.
Ligament fibroblasts—the cells responsible for producing collagen—contain estrogen receptors. Laboratory research demonstrates that estradiol can influence several important processes:
Collagen synthesis: Estradiol has been shown to reduce type I and III procollagen production in ACL fibroblasts under certain experimental conditions.
Collagen crosslinking: Estrogen may influence the molecular bonds responsible for collagen stiffness and tensile strength.
Ligament laxity: Hormonal signaling may alter connective tissue compliance, potentially influencing joint stability.
These findings suggest that estrogen can affect the structural properties of ligaments. However, human studies have not consistently demonstrated that menstrual-cycle estrogen fluctuations increase knee laxity or directly cause ACL injuries.
The distinction is important: estrogen is essential for musculoskeletal health, but its effects on ligament collagen may differ substantially from those of testosterone.
3. Testosterone: Why Male Ligaments May Have an Advantage
Men generally have circulating testosterone concentrations approximately 10–20 times higher than women.
Testosterone influences musculoskeletal strength through three important pathways.
Collagen production and remodeling
Experimental research suggests that androgen signaling influences fibroblast activity, collagen turnover, and extracellular matrix remodeling.
These processes may contribute to connective tissue adaptation, although direct evidence that testosterone increases human ligament tensile strength remains limited.
Tissue stiffness
Studies of tendon biology suggest that androgens can influence collagen content and mechanical stiffness.
Greater stiffness can help connective tissue resist deformation under load, although tendon findings cannot automatically be applied to ligaments.
Muscle strength and joint stabilization
Testosterone's most established musculoskeletal benefit is its anabolic effect on skeletal muscle.
Greater muscle mass and strength improve active joint stabilization and help distribute mechanical forces.
For example, strong hamstrings and coordinated muscle activation can reduce forces that stress the ACL during cutting, jumping, and landing.
Testosterone may therefore influence ligament protection through both connective tissue biology and the muscular system surrounding the joint. Its muscular effects are well established; direct ligament protection remains under investigation.
4. Relaxin: A Potential Contributor to Female Ligament Injury Risk
Relaxin is best known for its role during pregnancy, but it also circulates outside pregnancy and influences connective tissue metabolism.
Researchers have identified relaxin receptors in female ACL tissue.
Relaxin can stimulate matrix metalloproteinases (MMPs), enzymes involved in collagen degradation and extracellular matrix remodeling.
Experimental research suggests that relaxin may:
Increase collagen breakdown.
Reduce collagen production.
Increase ligament compliance and reduce stiffness.
One prospective study of collegiate female athletes associated elevated relaxin concentrations with approximately fourfold greater ACL injury risk.
Although this finding requires confirmation, it raises the possibility that relaxin contributes to sex-related differences in ligament vulnerability.
The interaction among estrogen, testosterone, and relaxin may be particularly important because these hormones influence overlapping collagen-remodeling pathways.
5. New Research: Differences at the Cellular Level
A 2026 study published in The Journal of Bone and Joint Surgery identified sex-based differences in ACL cell populations and gene expression.
Researchers observed that certain fibroblast progenitor-like cells in female ACL tissue demonstrated greater expression of genes associated with collagen dysregulation and degradation than corresponding male cells.
These findings suggest that male and female ligaments may differ not only anatomically but also in the cellular processes responsible for maintaining and remodeling collagen.
This raises an important possibility: sex-specific ligament biology may influence how connective tissue responds to mechanical stress, injury, and repair.
Further research is needed to determine how these cellular differences translate into clinical injury risk.
6. Could Testosterone Replacement Therapy Help Women Protect Their Ligaments?
If testosterone supports muscle development and influences connective tissue remodeling, could testosterone replacement therapy (TRT) improve ligament resilience in women?
There are several biologically plausible benefits:
Muscular stabilization: Supporting muscle mass and strength may improve joint stability and load distribution.
Collagen remodeling: Androgen signaling may influence fibroblast function and extracellular matrix adaptation.
Physical function: Appropriate hormonal care may support aspects of musculoskeletal health during aging.
However, clinical trials have not established that testosterone therapy prevents ACL tears, increases ligament tensile strength, or accelerates ligament healing in women.
Excessive androgen exposure may also create a mismatch between increasing muscle strength and the slower adaptation of connective tissue.
Current clinical guidelines do not recommend testosterone therapy specifically for ligament injury prevention.
At RegeneZone®, we believe hormonal health deserves consideration in a comprehensive orthopedic evaluation, particularly in women experiencing menopausal changes, muscle loss, or recurrent musculoskeletal problems.
Treatment decisions must nevertheless be based on established indications, individualized risk assessment, and the available evidence.
7. The RegeneZone® Approach: Looking Beyond the Injured Ligament
A ligament injury is rarely just about the ligament itself.
At RegeneZone®, we evaluate the broader factors influencing joint health and recovery:
Hormonal health: Estrogen, testosterone, and menopausal status when clinically relevant.
Connective tissue biology: Collagen metabolism, tissue remodeling, and recovery capacity.
Muscle and biomechanics: Strength, neuromuscular control, and individualized physical therapy.
Metabolic and inflammatory health: Conditions that may affect tissue function and recovery.
Precision diagnostics: Clinical examination and appropriate imaging, including musculoskeletal ultrasound.
When appropriate, we also discuss regenerative orthopedic procedures, their potential limitations, and the available clinical evidence.
Our goal is to understand not only what was injured, but also the biological and mechanical factors that may have contributed to the injury.
Conclusion: Hormones Are Part of the Ligament Strength Equation
Women experience higher rates of certain ligament injuries than men, particularly noncontact ACL tears.
Anatomical and biomechanical differences contribute to this disparity, but sex hormones may also influence ligament vulnerability.
Estrogen affects collagen synthesis and remodeling. Relaxin can promote extracellular matrix degradation. Testosterone supports muscle strength and may influence connective tissue adaptation.
Emerging research further suggests that male and female ligament cells differ in their underlying biological activity.
These findings support a more comprehensive approach to women's orthopedic health—one that considers hormones, collagen biology, muscle function, and biomechanics together.
At RegeneZone®, we believe stronger joints begin with understanding the entire biological environment—not simply treating the injured ligament.
Scientific References
The Effect of Sex Hormones on Joint Ligament Properties: A Systematic Review and Meta-analysis. American Journal of Sports Medicine. 2025. PubMed.
Sexual Dimorphisms in Anterior Cruciate Ligament Injury: A Current Concepts Review. Orthopaedic Journal of Sports Medicine. 2021. Full text.
Sex Differences in Common Sports Injuries. Full text.
Sex Hormones and Tendon. 2016. PubMed.
Sex-Based Differences in Cell Types and Gene Expression within the Anterior Cruciate Ligament. Journal of Bone and Joint Surgery. 2026. PubMed.
Non-contact ACL Injuries in Female Athletes: An International Olympic Committee Current Concepts Statement. British Journal of Sports Medicine. Full text.
