Evidence map›Paper›PMID 40663115›Full record

Observational studyOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2025

Testosterone, sex hormone-binding globulin, and fracture risk in men: evidence from observational and Mendelian randomization analyses.

Zhixiong Luo, Anping Feng, Anton Tyurin, Qingmei Cui, Khusainova Rita, Zhaomin Xie, Minniakhmetov Ildar, Ran An, Siqi Chen, Yidan Zhang and 4 more

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Zhixiong Luo *School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Anping Feng *Global Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Anton TyurinInternal Medicine Department, Bashkir State Medical University, Ufa, Russia.
Qingmei CuiGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Khusainova RitaEndocrinology Research Centre, Moscow, Russia.
Zhaomin XieGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Minniakhmetov IldarEndocrinology Research Centre, Moscow, Russia.
Ran AnGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Siqi ChenGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Yidan ZhangGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Lingyan DaiGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China.
Tracy E MadsenDepartment of Epidemiology and Centre for Global Cardiometabolic Health, School of Public Health, Brown University, Providence, RI, USA.
Simin LiuGlobal Health Research Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Sciences, Southern Medical University, Guangzhou, China. simil10@uci.edu.
Jie LiSchool of Medicine, South China University of Technology, Guangzhou, 510006, China. lijie4863@gdph.org.cn.ORCID http://orcid.org/0000-0002-7529-6040

Funding

National Natural Science Foundation of China 82473620
6 · The paper itself

Abstract

Both observational and factorial Mendelian randomization analysis revealed that the combined exposure to higher TT and lower SHBG was associated with decreased risk of fracture. These findings suggest that considering both TT and SHBG-rather than focusing on testosterone alone-may improve fracture risk assessment. PURPOSE: Lower total testosterone (TT) levels have been associated with increased fracture risk in aging men, yet the benefits of testosterone supplementation remain uncertain. This study aimed to assess the joint contributions of TT and sex hormone-binding globulin (SHBG) to fracture risk using both observational and genetic approaches.

methodsWe included 162,786 men from the UK Biobank, with baseline serum TT and SHBG measurements and genetic data. Cox proportional hazards models were used to estimate associations of TT and SHBG with incident fractures. A 2 × 2 factorial Mendelian randomization (MR) analysis was conducted to evaluate the combined genetic effects of increased TT and decreased SHBG on fracture risk.

resultsThe median age at baseline was 59.0 years, and 7493 men experienced fractures during 13.3 years follow-up. The association between serum TT levels and incident fracture was significantly affected by adjustment for SHBG. Compared to the lowest quintile of Bio-T levels, the adjusted hazard ratio (HR) for total fracture in the highest quintile was 0.72 (95% CI: 0.67, 0.78). In factorial MR analysis, men with genetically higher TT and lower SHBG had significantly lower odds of total fracture (OR: 0.87, 95% CI: 0.80-0.95) compared to those with genetically lower TT and higher SHBG. No association was observed in groups with only high TT or only low SHBG.

conclusionOur findings suggest that the interplay between TT and SHBG is important in determining fracture risk, highlighting the potential clinical value of jointly assessing them to improve fracture risk stratification in men.

Indexed as

Osteoporotic FracturesSex Hormone-Binding GlobulinTestosteroneAgedHumansMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideRisk AssessmentRisk FactorsSex Hormone-Binding GlobulinSHBG protein, humanTestosteroneFactorial Mendelian randomizationFractureMenSHBGTestosterone

Identifiers

PMID40663115

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.