Estradiol and metabolic syndrome in older italian men: The InCHIANTI Study.

The increasing prevalence of metabolic syndrome (MS) with age in older men has been linked with decreasing testosterone levels. Interestingly, while testosterone levels decline with age, estradiol (E2) levels remain relatively stable, resulting in a decreased testosterone:E2 ratio. Because E2 levels tend to be elevated in morbid obesity, insulin resistance, and diabetes, it is reasonable to hypothesize that high E2 levels are associated with MS in older men. We studied the relationship of total and free E2 with MS after adjustment for multiple confounders, including age, BMI, smoking, alcohol consumption, physical activity, interleukin-6 (IL-6), fasting insulin, and testosterone. Men 65 years or older (age range, 65-96; n = 452) had complete data on E2, testosterone, fasting insulin, sex hormone-binding globulin, IL-6, and albumin. Concentrations of free E2 and free testosterone were calculated using the mass action equations. MS was defined according to Adult Treatment Panel III (ATP-III). Participants with MS had significantly higher serum free and total E2 (P < .001) (P = .003). After adjusting for confounders, including age, smoking, alcohol consumption, physical activity, log(IL-6), and log(insulin), participants with higher log(total E2) (odds ratio [OR], 2.31; 95% confidence interval [95% CI], 1.39-4.70; P = .02) and higher log(free E2) (OR, 2.69; 1.38-5.24; P < .001) had an increased risk of having MS. Log(free E2) (P = .04) maintained significant correlation with MS, even after further adjustment for BMI. In older men, high E2 is independently associated with MS. Whether confirmed in other studies, assessment of E2 should be also considered in older men. Whether changes in this hormonal pattern play a role in the development of MS should be further tested in longitudinal studies.

[1]  S. Bandinelli,et al.  Estradiol and inflammatory markers in older men. , 2009, The Journal of clinical endocrinology and metabolism.

[2]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[3]  A. Silman,et al.  Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. , 2008, The Journal of clinical endocrinology and metabolism.

[4]  P. Cohen Obesity in men: the hypogonadal-estrogen receptor relationship and its effect on glucose homeostasis. , 2008, Medical hypotheses.

[5]  E. Metter,et al.  Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. , 2007, The Journal of clinical endocrinology and metabolism.

[6]  D. Grobbee,et al.  Association of endogenous sex hormone with C‐reactive protein levels in middle‐aged and elderly men , 2007, Clinical endocrinology.

[7]  P. Wilson,et al.  Serum estradiol and risk of stroke in elderly men , 2007, Neurology.

[8]  S. Bandinelli,et al.  Association Between Hormones and Metabolic Syndrome in Older Italian Men , 2006, Journal of the American Geriatrics Society.

[9]  S. Maggi,et al.  Components of the metabolic syndrome and incidence of diabetes in elderly Italians: the Italian Longitudinal Study on Aging. , 2006, Atherosclerosis.

[10]  S. Maggi,et al.  Metabolic syndrome, diabetes, and cardiovascular disease in an elderly Caucasian cohort: the Italian Longitudinal Study on Aging. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[11]  S. Cummings,et al.  Testosterone and estradiol among older men. , 2006, The Journal of clinical endocrinology and metabolism.

[12]  E. Ding,et al.  Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. , 2006, JAMA.

[13]  R. Krauss,et al.  Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement , 2005, Current opinion in cardiology.

[14]  Fernando Costa,et al.  Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. , 2005, Circulation.

[15]  D. Grobbee,et al.  Endogenous sex hormones and metabolic syndrome in aging men. , 2005, The Journal of clinical endocrinology and metabolism.

[16]  Vinjar Fønnebø,et al.  Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromsø Study. , 2004, The Journal of clinical endocrinology and metabolism.

[17]  D. Grobbee,et al.  Endogenous Sex Hormones and Progression of Carotid Atherosclerosis in Elderly Men , 2004, Circulation.

[18]  L. Niskanen,et al.  Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. , 2004, Diabetes care.

[19]  J. Morley The metabolic syndrome and aging. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[20]  Reubin Andres,et al.  Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness. , 2003, Journal of the American College of Cardiology.

[21]  Diederick E Grobbee,et al.  Endogenous sex hormones in men aged 40-80 years. , 2003, European journal of endocrinology.

[22]  W. Dietz,et al.  Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. , 2002, JAMA.

[23]  J. Kaufman,et al.  Estradiol in elderly men , 2002, The aging male : the official journal of the International Society for the Study of the Aging Male.

[24]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[25]  Luigi Ferrucci,et al.  Subsystems Contributing to the Decline in Ability to Walk: Bridging the Gap Between Epidemiology and Geriatric Practice in the InCHIANTI Study , 2000, Journal of the American Geriatrics Society.

[26]  W. Crowley,et al.  Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. , 2000, The Journal of clinical endocrinology and metabolism.

[27]  D. Grobbee,et al.  Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. , 2000, The Journal of clinical endocrinology and metabolism.

[28]  E. Barrett-Connor,et al.  Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. , 2000, Diabetes care.

[29]  A. Vermeulen,et al.  A critical evaluation of simple methods for the estimation of free testosterone in serum. , 1999, The Journal of clinical endocrinology and metabolism.

[30]  E. Barrett-Connor,et al.  Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. , 1998, American journal of epidemiology.

[31]  F Berrino,et al.  Relative validity and reproducibility of a food frequency dietary questionnaire for use in the Italian EPIC centres. , 1997, International journal of epidemiology.

[32]  Tumor necrosis factor-alpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4. , 1996, Molecular endocrinology.

[33]  B. Pinkernell,et al.  The association of hyperestrogenemia with coronary thrombosis in men. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[34]  J. Goméz,et al.  Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. , 1994, The Journal of clinical endocrinology and metabolism.

[35]  Y. Ito,et al.  Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. , 1994, Endocrine reviews.

[36]  J. Kaufman,et al.  Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. , 1993, The Journal of clinical endocrinology and metabolism.

[37]  J F Sallis,et al.  Compendium of physical activities: classification of energy costs of human physical activities. , 1993, Medicine and science in sports and exercise.

[38]  E. Barrett-Connor,et al.  The influence of aging on plasma sex hormones in men: the Telecom Study. , 1992, American journal of epidemiology.

[39]  J. Mckinlay,et al.  Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. , 1991, The Journal of clinical endocrinology and metabolism.

[40]  D. Kiel,et al.  Sex hormones and lipoproteins in men. , 1989, The American journal of medicine.

[41]  E. Barrett-Connor,et al.  Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. , 1988, Circulation.

[42]  T. Bäckström,et al.  Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. , 1982, Journal of steroid biochemistry.

[43]  R. Berkowitz,et al.  Increased estrogen production in obese men. , 1979, The Journal of clinical endocrinology and metabolism.