The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men: the Framingham Heart Study
Open accessAbstract
OBJECTIVE: Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors. DESIGN: Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005. PARTICIPANTS: A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships. MEASUREMENTS: Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status. RESULTS: Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG ) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48). CONCLUSION: Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.
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The genetic contribution to variability in muscle mass and strength may be explained by the equally high genetic contributions to circulating testosterone.
“Among the nonhormonal factors, genetics explains a large proportion [∼50% to 60% from pooled twin studies (156)] of the variability in muscle mass and strength (157, 158) and may be explained in turn by the equally high genetic contributions to circulating testosterone (37, 38).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [37]
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- Authors
- Travison, T. G., Zhuang, W. V., Lunetta, K. L., Karasik, D., Bhasin, S., Kiel, D. P., Coviello, A. D., & Murabito, J. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Creighton University (US)
- Harvard University (US)
- Boston University (US)
- Corresponding author
- Murabito, J. M.
- ORCID
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2013-06-27
- Volume
- 80
- Issue
- 2
- Pages
- 277-282
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- PMC
- PMC3825765
- OpenAlex
- W2020014896
- Cited by
- 41
- References
- 43
- Citations by year
- 2026: 3 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 3 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 6
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1, 5p30ag031679-15)
- National Institute on Aging (R01AG031206, 5 P30 AG031679, R01AR/AG 41398, P30-AG031679, R21AG032598)
- National Heart, Lung, and Blood Institute (N01‐HC25195, N01-HC-025195)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK092938)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041398)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- heritability, circulating testosterone, estradiol, estrone, sex hormone-binding globulin, free testosterone, sex steroids, genetic correlation, men, Framingham Heart Study
- MeSH terms
- Adult, Chromatography, Liquid, Cross-Sectional Studies, Estradiol, Estrone, Family Health, Humans, Male, Middle Aged, Sex Hormone-Binding Globulin, Testosterone, Fluoroimmunoassay, Genes, Y-Linked, Tandem Mass Spectrometry, Genetic Association Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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