Endocrine & Hormone Panel - References

Endocrine & Hormone Panel — Literature Dossier

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Landmark Peer-Reviewed Studies

1. Yeap et al. (2024) — Sex Hormones, SHBG, and Mortality in Men (IPD Meta-Analysis)

• Citation: Yeap, B. B., Marriott, R. J., Antonio, L., Raj, S., Dwivedi, G., Reid, C. M., … & Wu, F. C. W. (2024). Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men: Individual Participant Data Meta-analyses. Annals of Internal Medicine, 177(6), 768–781.
• Identifiers: DOI: 10.7326/M23-2781 (DOI · SciDB · Scholar) | PMID: 38739921 (PubMed · Europe PMC)
• Study Design & Cohort: Two-stage individual participant data (IPD) meta-analysis of 11 prospective cohort studies measuring sex steroids strictly by mass spectrometry ($N=24,109$ community-dwelling men; $>255,000$ person-years of follow-up).
• Quantitative Findings & Diagnostic Thresholds:
  • Non-linear threshold for Total Testosterone: Men with concentrations $<7.4\text{ nmol/L}$ ($<213\text{ ng/dL}$) had significantly elevated all-cause mortality ($\text{HR }1.29–1.55$) and cardiovascular mortality ($\text{HR }1.36–1.72$); risk flattened across the optimal upper range ($400–850\text{ ng/dL}$).
  • Free Testosterone: Men with calculated Free Testosterone $<220\text{ pmol/L}$ ($<6.3\text{ ng/dL}$) exhibited progressively higher all-cause mortality ($\text{HR }1.22\text{ to }1.48$).
  • SHBG: Lower SHBG concentrations were inversely associated with lower all-cause mortality after adjusting for Total T, whereas excessively high SHBG ($>55\text{ nmol/L}$) tracked with reduced bioavailable androgen action and higher mortality.

2. Jankowska et al. (2009) — The Male Estradiol U-Shaped Survival Curve

• Citation: Jankowska, E. A., Rozentryt, P., Ponikowska, B., Hartmann, O., Kustrzycka-Kratochwil, D., Reczuch, K., … & Poole-Wilson, P. A. (2009). Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA, 301(18), 1892–1901.
• Identifiers: DOI: 10.1001/jama.2009.639 (DOI · SciDB · Scholar) | PMID: 19436016 (PubMed · Europe PMC)
• Study Design & Cohort: Prospective observational cohort ($N=501$ men with chronic heart failure followed for 3 years), establishing the canonical male estradiol U-curve later replicated in community cohorts.
• Quantitative Findings & Diagnostic Thresholds:
  • Compared with Quintile 3 (optimal male estradiol $21.80–30.11\text{ pg/mL}$):
    • Quintile 1 (low estradiol $<12.90\text{ pg/mL}$): Multivariable-adjusted 3-year mortality $\text{HR }4.17$ ($95\%\text{ CI }2.33–7.45$, $p<0.001$).
    • Quintile 5 (elevated estradiol $\ge 37.40\text{ pg/mL}$): Multivariable-adjusted 3-year mortality $\text{HR }2.33$ ($95\%\text{ CI }1.30–4.18$, $p=0.006$).

3. Mukama et al. (2023) — IGF-1 U-Shaped Association with Mortality in UK Biobank

• Citation: Mukama, T., Srour, B., Johnson, T., Katzke, V., & Kaaks, R. (2023). IGF-1 and Risk of Morbidity and Mortality From Cancer, Cardiovascular Diseases, and All Causes in Epic-Heidelberg and the UK Biobank. The Journal of Clinical Endocrinology & Metabolism, 108(10), e1092–e1105.
• Identifiers: DOI: 10.1210/clinem/dgad212 (DOI · SciDB · Scholar) | PMID: 37071841 (PubMed · Europe PMC) | PMCID: PMC10505543 (PMC Full Text)
• Study Design & Cohort: Prospective cohort analysis in the UK Biobank ($N=407,555$ participants, median follow-up 11.5 years, $27,328$ deaths) and EPIC-Heidelberg.
• Quantitative Findings & Diagnostic Thresholds:
  • Confirmed a strong U-shaped relationship between circulating IGF-1 and all-cause mortality, with the nadir of mortality risk centered around the median physiological range ($115–160\text{ ng/mL}$ or $15–21\text{ nmol/L}$).
  • Low IGF-1 (Lowest Decile vs. Mid-Quintile): All-cause mortality $\text{HR }1.33$ ($95\%\text{ CI }1.27–1.39$); cardiovascular mortality $\text{HR }1.43$.
  • High IGF-1 (Highest Decile vs. Mid-Quintile): All-cause mortality $\text{HR }1.12$ ($95\%\text{ CI }1.07–1.17$); driven by elevated cancer mortality and mitogenic signaling.

4. Phillips et al. (2010) — Cortisol : DHEA-S Ratio and All-Cause Mortality

• Citation: Phillips, A. C., Carroll, D., Gale, C. R., Lord, J. M., Arlt, W., & Batty, G. D. (2010). Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study. European Journal of Endocrinology, 163(2), 285–292.
• Identifiers: DOI: 10.1530/EJE-10-0299 (DOI · SciDB · Scholar) | PMID: 20498139 (PubMed · Europe PMC) | PMCID: PMC2910427 (PMC Full Text)
• Study Design & Cohort: Prospective cohort study ($N=4,255$ US veterans followed for 15 years).
• Quantitative Findings & Diagnostic Thresholds:
  • Low DHEA-S was inversely related to all-cause mortality ($\text{HR }1.42$), while a high Cortisol : DHEA-S ratio independently predicted 15-year all-cause mortality ($\text{HR }1.24$ per 1-SD increment, $95\%\text{ CI }1.11–1.38$) and cancer/other-cause mortality.