Title : Musculoskeletal and orthopedic implications of Gender-Affirming Hormone Therapy (GAHT): A PRISMA-Guided systematic narrative review
Abstract:
Background: GAHT is a cornerstone of care for TGD patients and modifies bone remodeling, body composition, and hematologic parameters—determinants of fracture risk, implant fixation, perioperative thrombosis, and functional recovery. Orthopedic-specific guidance is scarce.
Objectives: Provide a PRISMA-guided synthesis of musculoskeletal outcomes under GAHT; translate endocrine findings into perioperative and rehabilitative recommendations; define evidence gaps and a research agenda.
Methods: PRISMA 2020 protocol. Databases: PubMed, Scopus, Web of Science, Cochrane (inception–Aug 2025). Inclusion: peer-reviewed human studies with GAHT exposure (feminizing/masculinizing; with/without prior GnRHa) and at least one musculoskeletal/orthopedic endpoint (BMD, bone turnover markers [BTMs], body composition/strength, fracture incidence, perioperative/VTE outcomes). Two-reviewer screening in Covidence; NIH Study Quality/ROBINS-I bias tools. Of 540 records, 65 met criteria. Exploratory pooling was attempted for homogeneous measures; narrative synthesis otherwise, stratified by identity (TF/TM), age (adolescent/adult), GAHT route/dose, gonadectomy status, and duration.
Results:
-BMD: In TF adults, estrogen generally maintains or modestly increases lumbar-spine BMD; hip/femoral-neck responses are variable. Baseline low BMD is common pre-GAHT. HR-pQCT reveals microarchitectural differences (lower trabecular density, higher cortical porosity) despite normal aBMD in some TF cohorts. In TM adults, testosterone maintains or slightly increases BMD at spine and hip, likely via aromatization and increased mechanical loading. GnRHa in adolescents reduces BMD accrual; subsequent GAHT partially restores deficits, more in TM than TF youth.
-BTMs: Estrogen reduces resorption (e.g., CTX) in TF; testosterone increases formation (e.g., P1NP) in TM without parallel resorption rise—an anabolic remodeling signature.
-Body composition & strength: Estrogen increases fat mass and reduces lean mass/strength in TF; testosterone increases lean mass/strength and decreases fat mass in TM—findings with direct rehabilitation implications.
-Fracture risk: Registry data show higher fracture risk in older TF adults vs cis men, approximating cis women; TM cohorts show no excess risk.
-Perioperative/VTE: Oral estrogen is associated with higher VTE risk; transdermal estradiol appears safer and may be preferable perioperatively in high-risk TF patients. Current data do not demonstrate excess thrombotic risk with testosterone.
Clinical translation:
-Preop screening: Document GAHT history; obtain DXA in TF patients with risk factors (e.g., low BMI, prior GnRHa, fracture). Consider BTMs in complex revision/non-union.
-Fixation/implants: Anticipate reduced bone quality in subsets of TF patients; plan fixation accordingly.
-Rehabilitation: Mitigate sarcopenia/falls in TF; manage rapid strength gains and tendon load in TM.
-VTE protocols: For TF on oral estrogen, consider route modification to transdermal and risk-stratified chemoprophylaxis.
Evidence gaps: No controlled data on tendon/ligament/cartilage biology, fracture healing, or implant fixation under GAHT; limited adolescent long-term outcomes after GnRHa+GAHT. Research agenda: Delphi consensus on periop/rehab algorithms; multicenter EHR/registry analyses stratified by GAHT route/dose/gonadectomy; prospective harmonized cohorts linking endocrine metrics to orthopedic endpoints.
Conclusions: GAHT effects on bone, body composition, and thrombosis are predictable and clinically actionable. Embedding GAHT-aware screening, fixation strategy, rehab planning, and VTE management into orthopedic workflows can improve outcomes and equity for TGD patients.
Keywords: transgender; gender-affirming hormone therapy; orthopedics; bone mineral density; fracture risk; venous thromboembolism; perioperative optimization; rehabilitation.
