Relationship Between Low Levels of Anabolic Hormones and 6-year Mortality in Older Men: the Aging in the Chianti Area (InCHIANTI) Study

Overview

Journal Arch Intern Med

Specialty General Medicine

Date 2007 Nov 14

PMID 17998499

Citations 73

Authors

Marcello Maggio

Fulvio Lauretani

Gian Paolo Ceda

Stefania Bandinelli

Shari M Ling

E Jeffrey Metter

Andrea Artoni

Laura Carassale

Anna Cazzato

Graziano Ceresini

Jack M Guralnik

Shehzad Basaria

Giorgio Valenti

Luigi Ferrucci

Affiliations

Soon will be listed here.

Abstract

Background: Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders.

Methods: Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowest-quartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 microg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hormones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis.

Results: Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dysregulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.88-2.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.12-4.68), respectively (test for trend, P <.001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P <.001).

Conclusions: Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons.

Citing Articles

The brain-body energy conservation model of aging.

Shaulson E, Cohen A, Picard M Nat Aging. 2024; 4(10):1354-1371.

PMID: 39379694 DOI: 10.1038/s43587-024-00716-x.

Can longer lifespan be associated with gut microbiota involvement in lipid metabolism?.

Sardzikova S, Gajewska M, Galka N, Stefanek M, Balaz A, Garaiova M FEMS Microbiol Ecol. 2024; 100(11).

PMID: 39354675 PMC: 11503954. DOI: 10.1093/femsec/fiae135.

A Cross-Sectional Study on Metabolic Syndrome Parameters, the Nutritional Index, and Physical Status Associated with or Without the Possible Diagnosed Sarcopenia in Older Women Using A Propensity Score Matching Method.

Iida T, Aoi S, Kunishige M, Kawane Y, Obata Y, Nishigaki M J Frailty Sarcopenia Falls. 2024; 9(2):142-150.

PMID: 38835622 PMC: 11145093. DOI: 10.22540/JFSF-09-142.

The treatment of chronic anemia in heart failure: a global approach.

Bianchi V, von Haehling S Clin Res Cardiol. 2023; 113(8):1117-1136.

PMID: 37660308 DOI: 10.1007/s00392-023-02275-4.

Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control.

Sakr H, Sirasanagandla S, Das S, Bima A, Elsamanoudy A Biomedicines. 2023; 11(8).

PMID: 37626767 PMC: 10452601. DOI: 10.3390/biomedicines11082271.

References

Valenti G, Bossoni S, Giustina A, Maugeri D, Motta M, Vigna G . Consensus Document on substitution therapy with testosterone in hypoandrogenic elderly men. Aging Clin Exp Res. 2003; 14(6):439-64. DOI: 10.1007/BF03327345. View

Laughlin G, Barrett-Connor E, Criqui M, Kritz-Silverstein D . The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004; 89(1):114-20. DOI: 10.1210/jc.2003-030967. View

Cappola A, Xue Q, Walston J, Leng S, Ferrucci L, Guralnik J . DHEAS levels and mortality in disabled older women: the Women's Health and Aging Study I. J Gerontol A Biol Sci Med Sci. 2006; 61(9):957-62. PMC: 2645634. DOI: 10.1093/gerona/61.9.957. View

Morley J, Kaiser F, Perry 3rd H, Patrick P, Morley P, Stauber P . Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997; 46(4):410-3. DOI: 10.1016/s0026-0495(97)90057-3. View

Ferrucci L, Maggio M, Bandinelli S, Basaria S, Lauretani F, Ble A . Low testosterone levels and the risk of anemia in older men and women. Arch Intern Med. 2006; 166(13):1380-8. PMC: 2645631. DOI: 10.1001/archinte.166.13.1380. View

Jankowska E, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M . Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006; 114(17):1829-37. DOI: 10.1161/CIRCULATIONAHA.106.649426. View

Ceda G, DallAglio E, Magnacavallo A, Vargas N, Fontana V, Maggio M . The insulin-like growth factor axis and plasma lipid levels in the elderly. J Clin Endocrinol Metab. 1998; 83(2):499-502. DOI: 10.1210/jcem.83.2.4548. View

Maggio M, Lauretani F, Ceda G, Bandinelli S, Basaria S, Ble A . Association between hormones and metabolic syndrome in older Italian men. J Am Geriatr Soc. 2007; 54(12):1832-8. PMC: 2653255. DOI: 10.1111/j.1532-5415.2006.00963.x. View

Van den Berghe G, BAXTER R, Weekers F, Wouters P, Bowers C, Veldhuis J . A paradoxical gender dissociation within the growth hormone/insulin-like growth factor I axis during protracted critical illness. J Clin Endocrinol Metab. 2000; 85(1):183-92. DOI: 10.1210/jcem.85.1.6316. View

10.

Simpson H, Jackson N, Shojaee-Moradie F, Jones R, Russell-Jones D, Sonksen P . Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but no effect on lipid metabolism in type 1 diabetes. J Clin Endocrinol Metab. 2004; 89(1):425-32. DOI: 10.1210/jc.2003-031274. View

11.

Shores M, Matsumoto A, Sloan K, Kivlahan D . Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006; 166(15):1660-5. DOI: 10.1001/archinte.166.15.1660. View

12.

Anker S, Clark A, Kemp M, Salsbury C, Teixeira M, Hellewell P . Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. J Am Coll Cardiol. 1997; 30(4):997-1001. DOI: 10.1016/s0735-1097(97)00262-3. View

13.

Roubenoff R, Parise H, Payette H, Abad L, DAgostino R, Jacques P . Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med. 2003; 115(6):429-35. DOI: 10.1016/j.amjmed.2003.05.001. View

14.

Vermeulen A, Verdonck L, Kaufman J . A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999; 84(10):3666-72. DOI: 10.1210/jcem.84.10.6079. View

15.

Roth G, Lane M, Ingram D, Mattison J, Elahi D, Tobin J . Biomarkers of caloric restriction may predict longevity in humans. Science. 2002; 297(5582):811. DOI: 10.1126/science.1071851. View

16.

Trivedi D, Khaw K . Dehydroepiandrosterone sulfate and mortality in elderly men and women. J Clin Endocrinol Metab. 2001; 86(9):4171-7. DOI: 10.1210/jcem.86.9.7838. View

17.

Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifai N, Nelson W . Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2007; 30(2):234-8. DOI: 10.2337/dc06-1579. View

18.

Maggio M, Cappola A, Ceda G, Basaria S, Chia C, Valenti G . The hormonal pathway to frailty in older men. J Endocrinol Invest. 2006; 28(11 Suppl Proceedings):15-9. View

19.

Barrett-Connor E, Khaw K, Yen S . A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986; 315(24):1519-24. DOI: 10.1056/NEJM198612113152405. View

20.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View