The Effects of Gender Affirming Hormone Treatment on Transgender Mens Musculoskeletal Health: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis concludes that while masculinizing gender-affirming hormone treatment reliably increases lean mass and muscle strength in transgender men without significantly altering bone mineral density at key sites, the current evidence base remains methodologically weak and highly variable, underscoring the need for continued clinical monitoring and higher-quality longitudinal research.

The Gist

Imagine your body as a house. The bones are the sturdy beams and foundation, while the muscles are the workers who do the heavy lifting and keep the structure strong. For transgender men (people assigned female at birth who identify as men), taking Gender-Affirming Hormone Treatment (GAHT) is like hiring a new construction crew: Testosterone.

This new crew is very good at building muscle and adding weight, but the big question for doctors and patients has always been: "Is this crew also reinforcing the foundation, or are they accidentally weakening the beams?"

This paper is a massive "report card" that looked at dozens of studies to answer that question. Here is the breakdown in simple terms:

1. The Big Question: What happens to the bones?

For a long time, doctors worried that changing the body's hormone balance might make bones brittle, like dry wood.

• The Finding: The study found that taking testosterone for about 4 to 5 years does not break the foundation. The density of the bones in the hip and spine stayed mostly the same. They didn't get significantly stronger, but they didn't get weaker either.
• The Catch: The "report card" for this part of the study is a bit messy. The studies looked at the bones using different rulers (different machines and methods), and the results were all over the place. It's like trying to measure a room with a tape measure, a ruler, and a laser, all at the same time. Because the data was so mixed, the authors say, "We are pretty sure the bones aren't breaking, but we need better, more consistent tools to be 100% certain."

2. The Good News: The Muscle Factory is Open!

While the bones were just "holding steady," the muscles went into overdrive.

• The Finding: Testosterone is a powerful builder. The study showed a huge increase in muscle mass and strength. It's like the construction crew didn't just patch the roof; they added a whole new gym to the house.
• The Numbers: Muscle strength went up significantly. Fat-free mass (lean muscle) also went up. This is great news because stronger muscles actually help protect the bones by putting more "stress" on them, which signals the bones to stay strong.

3. The Weight Gain: Is it bad?

Many people worry about gaining weight on hormones.

• The Finding: Yes, body weight and BMI (Body Mass Index) went up slightly. But think of it this way: It's not just "fluff." Most of that weight gain was actually muscle, not fat. It's the difference between adding a heavy steel beam (good for structure) versus adding a pile of feathers (which just adds weight without strength).

4. The "Blind Spots" in the Research

The authors are very honest about the limitations. They compared the research on transgender men to the research on transgender women and found a gap.

• The Analogy: Imagine we have a high-definition, 4K camera for studying transgender women's bones, but for transgender men, we are still using a grainy, black-and-white film camera.
• The Problem: Most studies used standard X-rays (DXA), which are like taking a 2D photo of a 3D object. They can't see the tiny, honeycomb-like details inside the bone that determine if it will break. The authors are calling for "3D scanners" (a technology called HR-pQCT) to get a better look at the bone's internal architecture.

The Bottom Line (The Takeaway)

If you are a transgender man on testosterone:

1. Don't panic about your bones: The evidence suggests your bones are safe and aren't getting weaker.
2. Celebrate the strength: You are building a stronger, more muscular body, which is a major health benefit.
3. Keep an eye on things: Because the research isn't perfect yet, doctors should keep checking your bone health regularly, just to be safe.
4. Keep moving: Since your muscles are growing, keep doing strength training. It's the best way to make sure those new muscles protect your bones for the long haul.

In short: The hormone treatment is a great builder for your muscles and seems safe for your bones, but we need to build better "microscopes" to see exactly how those bones are changing over a lifetime.

Technical Summary

1. Problem Statement

Previous research, specifically a meta-analysis by Singh-Ospina et al. (2017), suggested that Gender Affirming Hormone Treatment (GAHT) does not significantly alter Bone Mineral Density (BMD) in transgender men. However, that review was limited by:

• Temporal constraints: It only included studies up to April 2015.
• Methodological limitations: It relied on the Der Simonian–Laird random effects model and lacked assessment of muscle health or advanced imaging (QCT).
• Evidence gaps: Emerging studies and advances in meta-analytic synthesis methods necessitated an updated evaluation to determine the long-term safety and physiological impact of masculinizing GAHT on the musculoskeletal system, particularly as transgender men age.

2. Methodology

The study adhered to PRISMA guidelines and was registered with PROSPERO (CRD42024573102).

• Data Sources: A systematic search was conducted across PubMed, Embase, and SportDiscus for studies published in English up to July 31, 2024, with cross-referencing completed in December 2024.
• Eligibility Criteria:
  • Population: Transgender men (assigned female at birth) aged ≥18 (adolescents were excluded to avoid puberty confounding).
  • Intervention: GAHT (testosterone administration) for >3 months.
  • Outcomes: Primary outcomes were longitudinal changes in BMD at the Femoral Neck (FN), Lumbar Spine (LS), and Total Hip (TH). Secondary outcomes included body composition (BMI, body mass, fat mass, fat-free mass) and muscle strength.
  • Study Design: Longitudinal observational studies, case series, and randomized trials.
• Data Analysis:
  • Effect Size: Hedges' g (standardized mean difference) adjusted for small sample sizes.
  • Pooling Model: The Inverse Heterogeneity (IVhet) model was used, chosen for its robustness over the Der Simonian–Laird method used in previous reviews.
  • Bias Assessment: Risk of bias was evaluated using ROBINS-I (for longitudinal studies) and JBI Critical Appraisal Tools (for cross-sectional studies). No studies were excluded based on bias; instead, sensitivity analyses were conducted.
  • Heterogeneity & Bias: Assessed via $I^2$, Cochran's $Q$, and the Luis Furuya-Kanamori (LFK) index for publication bias.
  • Evidence Quality: Graded using the GRADE framework.

3. Key Contributions

• Updated Evidence Base: This is the first meta-analysis to update the Singh-Ospina (2017) findings with data extending to 2024, incorporating 28 studies (2,361 transgender men participants) compared to the previous 13.
• Expanded Scope: Unlike prior reviews, this study comprehensively analyzed muscle strength and body composition (lean mass vs. fat mass) alongside bone density.
• Advanced Statistical Rigor: Utilization of the IVhet model and the LFK index provided more robust handling of heterogeneity and publication bias detection compared to traditional methods.
• Granular Analysis: Differentiated between longitudinal changes (within-subject) and cross-sectional comparisons (transgender men vs. cisgender women).

4. Key Results

A. Bone Mineral Density (BMD)

• Longitudinal Changes: GAHT was not associated with significant changes in BMD at any clinically relevant site over an average treatment duration of 4 ± 5 years.
  • Femoral Neck (FN): $g = -0.10$ ($p=0.54$). Note: High heterogeneity ($I^2=78\%$) and low evidence quality (GRADE).
  • Lumbar Spine (LS): $g = 0.06$ ($p=0.15$). Note: Low heterogeneity ($I^2=0\%$).
  • Total Hip (TH): $g = 0.00$ ($p=0.94$). Note: Moderate heterogeneity ($I^2=49\%$).
• Cross-Sectional: When compared to cisgender women, transgender men showed a statistically significant difference at the FN ($g = 1.00$, favoring cisgender women), but no significant difference at the LS.

B. Body Composition and Muscle Strength

• Fat-Free Mass (FFM): GAHT produced a large, statistically significant increase ($g = 0.59$, $p < 0.001$) with very low heterogeneity ($I^2=0\%$) and high-quality evidence.
• Muscle Strength: GAHT resulted in a substantial increase in strength ($g = 0.86$, $p < 0.001$). However, this finding had moderate heterogeneity ($I^2=68\%$) and low-quality evidence, largely due to inconsistent measurement tools (handgrip vs. isokinetic dynamometry vs. fitness tests).
• Body Mass & BMI: Statistically significant increases were observed in Body Mass ($g = 0.18$) and BMI ($g = 0.13$).
• Fat Mass: A non-significant trend toward reduction was observed ($g = -0.17$, $p=0.07$), with high-quality evidence.

C. Risk of Bias and Limitations

• Bias: 45% of studies were low risk, but 24% were critical risk. A major limitation is the inability to blind participants to GAHT.
• Imaging: The reliance on DXA (Dual-Energy X-ray Absorptiometry) limits the ability to assess bone microarchitecture. The authors note emerging HR-pQCT data suggesting preserved or enhanced bone microstructure, which DXA cannot detect.
• Heterogeneity: High variability in GAHT regimens (dosage, route of administration), duration, and physical activity levels across studies contributed to inconsistent findings, particularly for FN BMD and muscle strength.

5. Significance and Clinical Implications

• Bone Safety: The study confirms that masculinizing GAHT does not negatively impact BMD in the short-to-medium term (approx. 5 years). However, due to the low certainty of evidence and high heterogeneity, clinicians must continue routine bone health monitoring, especially for patients with additional risk factors.
• Anabolic Benefits: The treatment reliably increases lean mass and muscle strength, offering significant anabolic benefits. Clinicians should reassure patients that weight gain during therapy often reflects healthy lean tissue accumulation.
• Research Gaps: The field urgently requires:
  • Longitudinal studies with standardized strength assessments (moving beyond handgrip).
  • Integration of HR-pQCT to evaluate bone microarchitecture and fracture risk more accurately than DXA.
  • Better control for confounding variables (age, gonadectomy status, physical activity).
• Conclusion: While GAHT appears safe for bone density and beneficial for muscle, the current evidence base is methodologically weak. Future research must employ advanced imaging and rigorous designs to clarify long-term skeletal trajectories as the transgender population ages.