Men with low testosterone often take replacement therapy to feel better. But a new analysis of many trials asks a hard question: does this treatment make bones weaker? The answer is yes for overall fractures. When researchers looked at all the data together, men on testosterone replacement therapy faced a significantly higher risk of breaking a bone than those on a placebo. The risk was 55 percent higher in the treatment group. This finding comes from a massive review that combined results from 2,711 men across multiple studies. It is important to note that the data did not show a difference for major osteoporotic fractures or specific types like hip or spine breaks. The wide range of numbers suggests the results for these specific breaks were not clear. While the overall fracture risk is a real concern, the picture for specific bone breaks remains uncertain. This review helps doctors weigh the benefits of feeling better against the potential cost of more frequent breaks.
Meta-analysis shows testosterone replacement therapy increases clinical fracture risk in hypogonadal men compared to placeboTestosterone therapy raises fracture risk in hypogonadal men
AI-generated summary of the cited source, checked by automated accuracy review. How we work
Key Takeaway
Testosterone replacement therapy is associated with a significantly increased risk of clinical fractures in hypogonadal men based on this meta-analysis.
This systematic review and meta-analysis evaluated the impact of testosterone replacement therapy on fracture risk among men with hypogonadism. The analysis pooled data from randomized controlled trials involving a total of 2,711 participants to assess safety and efficacy regarding bone health outcomes.
The primary analysis revealed a concerning increase in the risk of clinical fractures for patients receiving testosterone compared to those on placebo. The relative risk was 1.55, with a 95% confidence interval ranging from 1.21 to 1.97, indicating a statistically significant elevation in fracture incidence. This finding suggests a potential safety concern that clinicians must weigh against the benefits of treatment.
However, when examining specific fracture types, the results were more nuanced. There was no significant difference observed for major osteoporotic fractures, vertebral fractures, or hip fractures. The confidence intervals for these subtypes were wide, often crossing the null value, which implies uncertainty in the estimates for these specific outcomes. Despite the lack of significance in these subgroups, the overall clinical fracture signal remains the most critical takeaway.
What this means for you:
Men with low testosterone on replacement therapy had a 55 percent higher risk of clinical fractures. More on Hypogonadism
Adding docetaxel to ADT and RT cuts mortality in high-risk prostate cancer with normal testosterone
Adding chemo to hormone therapy for prostate cancer may depend on testosterone levels
This RCT subgroup analysis found that adding docetaxel to radiation and ADT significantly reduced all-cause mortality in nonmetastatic high-…
Adding chemo to standard therapy for high-risk prostate cancer may only help men with normal testosterone levels, a long-term study suggests…
Systematic review evaluates saliva, DBS, and urine testosterone testing versus serum monitoring during transdermal TRT
Stop guessing your testosterone levels
This systematic review examined the accuracy of alternative testosterone assays compared to serum testing in patients receiving transdermal …
Saliva tests often show perfect results while you still feel terrible because gels create a false picture of your health that blood tests re…
Triple therapy for CHH shows lower hCG dose but similar spermatogenesis rates in small RCT
Can a triple-hormone approach help men with a rare fertility condition?
A randomized trial in 45 adult males with congenital hypogonadotropic hypogonadism compared triple therapy (hCG, FSH, testosterone) to combi…
Men with a rare fertility condition using three hormones together needed lower weekly doses of one drug and reported better quality of life …
GAHT in transgender men shows no significant BMD changes but increases muscle strength and body composition
Does hormone therapy affect bone health and strength for transgender men?
A systematic review with meta-analysis of transgender men found gender affirming hormone treatment was not associated with significant longi…
After four years of gender-affirming hormone therapy, transgender men show no bone loss at key sites while gaining muscle strength and lean …
View Original Abstract ↓
OBJECTIVE: Testosterone replacement therapy is the treatment of choice in men with hypogonadism. Although its beneficial effect on bone mineral density is well established, the evidence regarding its impact on fracture risk remains inconclusive. The purpose of this study was to systematically review and meta-analyze the highest-quality available evidence regarding the effect of TRT on fracture risk in hypogonadal men.
STUDY DESIGN: A systematic literature search was conducted in PubMed, Scopus and Cochrane databases from inception through 30 September 2025. Only randomized controlled trials were eligible for inclusion. Outcomes were summarized as relative risk (RR), with a 95% confidence interval (CI). The I index was used in order to quantify heterogeneity.
RESULTS: The initial search yielded 1145 results after removal of duplicates; seven papers underwent full-text assessment. Finally, two studies were included in the qualitative and quantitative analysis (n = 2711). TRT was associated with increased risk of clinical fractures compared with placebo (RR 1.55, 95% CI 1.21-1.97, p < 0.0001, I 0%). However, no difference between groups was observed when the analysis was restricted to major osteoporotic fractures (hip, spine, wrist, and arm) (RR 0.62, 95% CI 0.12-3.35, p = 0.58, I 63%). This was also the case for vertebral (RR 0.87, 95% CI 0.29-2.58, p = 0.80, I 9%) and hip fractures (RR 1.02, 95% CI 0.33-3.09, p = 0.98, I 0%), when analyzed separately.
CONCLUSION: TRT is associated with an increased incidence of predominantly non-major fractures, while the risk of major osteoporotic fractures, including hip and vertebral fractures, was not increased.
Low-intensity pulsed ultrasound shows a 0.79 healing rate in nonunion fractures across observational studies
Trial results show mixed success for ultrasound on nonunion fractures
Related in Orthopedics & Sports Medicine
Heart rate and GPS metrics are commonly used but lack specific validation for water sports
Monitoring Methods for High Level Surface Water Sports Athletes
This scoping review of 22 papers maps monitoring methods for high-level non-motorized surface water sports athletes. Findings indicate that …
New research maps how elite athletes in sailing and canoeing are monitored, highlighting a need for better data for women and youth competit…
Strategic leadership in sport organizations involves contingent governance, culturally mediated leadership, and configurational performance systems
Strategic leadership in sports varies across cultures, review finds
This systematic review of 38 empirical studies characterizes strategic leadership within international sports competitions. The authors iden…
A review of 38 studies finds strategic leadership in sports depends on culture and governance, not a one-size-fits-all approach.
Chlorinated pool air exposure is linked to mucosal irritation and asthma-like symptoms in swimmers
Chlorinated pool air may cause asthma like symptoms in swimmers
This mini review synthesizes evidence regarding the impact of chlorinated pool air on competitive swimmers and workers. The authors conclude…
Swimming in chlorinated pools can lead to lung irritation and inflammation, posing a risk for athletes with sensitive airways.
Badminton training exposure and mid-to-late adolescence may increase injury risk in youth players
High training volume increases injury risk for young badminton players
This scoping review synthesizes observational data regarding musculoskeletal injuries among youth and adolescent badminton players. Findings…
Younger badminton players face higher injury risks as they move into late adolescence and increase their training hours.
From Other Specialties
Bortezomib, cyclophosphamide, and dexamethasone achieved remission in a patient with AL amyloidosis and POEMS syndrome
Treatment shows success for heart failure and rare blood diseases
This case report and literature review describes the treatment of an elderly male with concurrent AL amyloidosis and POEMS syndrome. The pat…
A new look at a complex case reveals how a specific drug combination helped an elderly man with multiple rare conditions.
Current molecular and cellular phenotypes do not yet support clinical subtype identification for recurrent pregnancy loss
New research looks at why some pregnancies end early
This mini review examines maternal-fetal interface abnormalities in patients with unexplained recurrent pregnancy loss (URPL). The authors c…
Doctors are looking for better ways to understand and treat the reasons behind repeated pregnancy loss.
TNF inhibitors may be effective for juvenile idiopathic arthritis in patients with DiGeorge syndrome
Biologic treatments show promise for children with DiGeorge syndrome
This case report and literature review examines the management of juvenile idiopathic arthritis (JIA) in children with DiGeorge syndrome (DG…
Children with both DiGeorge syndrome and juvenile idiopathic arthritis may find relief from joint pain using specific biologic medications.
mHealth apps reduce HbA1c by 0.39% in type 2 diabetes across 19 RCTs
Mobile Health Apps Help Manage Blood Sugar in Type 2 Diabetes
This meta-analysis of 19 RCTs with 2,166 participants found that mobile health (mHealth) app interventions significantly reduced HbA1c (MD -…
Using mobile health applications can help people with type 2 diabetes lower their blood sugar levels and improve their overall quality of li…