ArticleScientific reports2016
Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.
- Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.European journal of endocrinology · 2024Pooled it
- Prevalence and risk factors of erectile dysfunction in patients with liver cirrhosis: a systematic review and meta-analysis.Hepatology international · 2023Pooled it
- Hormonal profiles of men with highly elevated SHBG and primary testicular dysfunction support free hormone hypothesis.Journal of the Endocrine Society · 2026Article
- A novel model to study the impact of gender-affirming therapy on bone in young male mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Accurate Measurement of Serum Free Testosterone Levels via Liquid Chromatography‒Tandem Mass Spectrometry (LC‒MS/MS) has Predictive Value in the Diagnosis of Polycystic Ovary Syndrome and Associated Metabolic Disorders.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Impact of HCV infection on male reproductive hormones; a systematic review and meta-analysis.International journal of impotence research · 2026Review
- Association between serum vitamin D and sex hormones in women: a cross-sectional analysis using NHANES Data (2021-2023).International journal of impotence research · 2026Article
- Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.Nature genetics · 2026Article
- Sex steroids, SHBG and type 2 diabetes in women: what do we really know?Diabetologia · 2026Review
- Estrogen in skeletal muscle: metabolism, mechanisms, and exercise-induced changes.Journal of endocrinological investigation · 2026Review
- Hormonal and metabolic profiles in teenagers and young adults with polycystic ovary syndrome (PCOS).Endocrine · 2026Article
- SheVari4Food & nutrition research · 2026Article
- The causal effects of genetically predicted sex hormone-binding globulin and sarcopenia: A 2-sample Mendelian randomization study.Medicine · 2025Article
- Loss of Inhibin Negative Feedback to Pituitary Gonadotropes Leads to Enhanced Ovulation but Pregnancy Failure in Mice.Endocrinology · 2025Article
- Sex hormone-binding globulin restrains hepatic fibrosis via inhibition of Tgfβ expression.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Determination of Androgen Bioactivity by an In Vitro Assay During Pubertal Transition in Healthy Boys.Clinical endocrinology · 2025Article
- Associations of Serum Testosterone and SHBG With Incident Fractures in Middle-aged to Older Men.The Journal of clinical endocrinology and metabolism · 2025Article
- Ketosis suppression and ageing (KetoSAge): the effect of suppressing ketosis on SHBG and sex hormone profiles in healthy premenopausal women, and its implications for cancer risk and therapy.Frontiers in nutrition · 2025Article
- Genetic correlations of alcohol consumption and alcohol use disorder with sex hormone levels in females and males.Frontiers in psychiatry · 2025Article
- Regression and machine learning approaches identify potential risk factors for glioblastoma multiforme.Brain communications · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology.
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Registered trials
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 OpenQuestion graph.