Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females
Emmanuel K. Ofori
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorSonia Conde Alonso
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorLorena Correas-Gomez
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorElvis A. Carnero
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorKarin Zwygart
Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research, University of Bern, Bern, Switzerland
Search for more papers by this authorHenry Hugues
Clinical Chemistry Laboratory, University Hospital (CHUV), Lausanne, Switzerland
Search for more papers by this authorDaniel Bardy
Clinical Chemistry Laboratory, University Hospital (CHUV), Lausanne, Switzerland
Search for more papers by this authorDidier Hans
Center for Bone Diseases, University Hospital (CHUV), Lausanne, Switzerland
Search for more papers by this authorCorresponding Author
Andrew A. Dwyer
Service of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), Lausanne, Switzerland
William F. Connell School of Nursing, Boston College, Boston, Massachusetts
Andrew A. Dwyer and Francesca Amati shared senior co-authorship.Correspondence
Andrew A. Dwyer, William F. Connell School of Nursing, Boston College, Chestnut Hill, MA.
Email: [email protected]
and
Francesca Amati, University of Lausanne, Lausanne, Switzerland.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Francesca Amati
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Service of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), Lausanne, Switzerland
Institute of Sport Sciences (ISSUL), University of Lausanne, Lausanne, Switzerland
Andrew A. Dwyer and Francesca Amati shared senior co-authorship.Correspondence
Andrew A. Dwyer, William F. Connell School of Nursing, Boston College, Chestnut Hill, MA.
Email: [email protected]
and
Francesca Amati, University of Lausanne, Lausanne, Switzerland.
Email: [email protected]
Search for more papers by this authorEmmanuel K. Ofori
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorSonia Conde Alonso
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorLorena Correas-Gomez
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorElvis A. Carnero
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Search for more papers by this authorKarin Zwygart
Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research, University of Bern, Bern, Switzerland
Search for more papers by this authorHenry Hugues
Clinical Chemistry Laboratory, University Hospital (CHUV), Lausanne, Switzerland
Search for more papers by this authorDaniel Bardy
Clinical Chemistry Laboratory, University Hospital (CHUV), Lausanne, Switzerland
Search for more papers by this authorDidier Hans
Center for Bone Diseases, University Hospital (CHUV), Lausanne, Switzerland
Search for more papers by this authorCorresponding Author
Andrew A. Dwyer
Service of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), Lausanne, Switzerland
William F. Connell School of Nursing, Boston College, Boston, Massachusetts
Andrew A. Dwyer and Francesca Amati shared senior co-authorship.Correspondence
Andrew A. Dwyer, William F. Connell School of Nursing, Boston College, Chestnut Hill, MA.
Email: [email protected]
and
Francesca Amati, University of Lausanne, Lausanne, Switzerland.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Francesca Amati
Aging and Muscle Metabolism Laboratory, Department of Physiology, School of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Service of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), Lausanne, Switzerland
Institute of Sport Sciences (ISSUL), University of Lausanne, Lausanne, Switzerland
Andrew A. Dwyer and Francesca Amati shared senior co-authorship.Correspondence
Andrew A. Dwyer, William F. Connell School of Nursing, Boston College, Chestnut Hill, MA.
Email: [email protected]
and
Francesca Amati, University of Lausanne, Lausanne, Switzerland.
Email: [email protected]
Search for more papers by this authorSummary
Objective
Research findings on the relationship between serum androgens and adipose tissue in older females are inconsistent. We aimed to clarify the relationship using state-of-the-art techniques to evaluate associations between body fat distribution and plasma testosterone (T) levels in older postmenopausal women.
Design
Observational, cross-sectional study of healthy, community dwelling postmenopausal women.
Patients and Measurements
Postmenopausal women (60-80 years old) were included in this study. Overall body composition was evaluated by dual-energy X-ray absorptiometry. Abdominal and thigh fat depots were measured by magnetic resonance imaging. Circulating T concentrations were analysed by liquid chromatography-tandem mass spectrometry.
Results
Thirty-five women (66.6 ± 0.8 years) participated in this study. T levels were positively associated with clinical proxy measures of adiposity including weight (ρ = 0.39), BMI (ρ = 0.43) and waist circumference (ρ = 0.39) (all P < 0.05). Fat mass and % body fat were correlated with T levels (ρ = 0.42 and 0.38 respectively, both P < 0.05). T correlated with overall and superficial abdominal fat (ρ = 0.34 and 0.37 respectively, both P < 0.05) but not with visceral adipose tissue. T increased with greater thigh fat (ρ = 0.49, P < 0.05) in both superficial and deep depots (ρ = 0.50 and 0.35 respectively, both P < 0.05).
Conclusion
Our results suggest that postmenopausal women with higher circulating T levels have both higher regional and overall body adiposity. These findings underscore the sexual dimorphism in the relationship between serum androgen levels and adiposity.
CONFLICT OF INTEREST
Nothing to declare.
REFERENCES
- 1Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low–normal gonadal status. J Gerontol A Biol Sci Med Sci. 2003; 58(7): M618-M625.
- 2Dobs AS, Nguyen T, Pace C, Roberts CP. Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women. J Clin Endocrinol Metab. 2002; 87(4): 1509-1516.
- 3Monroe AK, Dobs AS. The effect of androgens on lipids. Curr Opin Endocrinol Diabetes Obes. 2013; 20(2): 132-139.
- 4Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002; 77: 34-41.
- 5Amanatkar HR, Chibnall JT, Seo B-W, Manepalli JN, Grossberg GT. Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials. Ann Clin Psychiatry. 2014; 26(1): 19-32.
- 6He Z, Rankinen T, Leon AS, Skinner JS, Tchernof A, Bouchard C. Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training. Int J Obes (Lond). 2018.
- 7Bann D, Wu FC, Keevil B, et al. Changes in testosterone related to body composition in late midlife: findings from the 1946 British birth cohort study. Obesity. 2015; 23(7): 1486-1492.
- 8Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002; 87(2): 589-598.
- 9Cashdan E. Hormones, sex, and status in women. Horm Behav. 1995; 29(3): 354-366.
- 10Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG. The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol. 1989; 129(6): 1120-1131.
- 11Horstman AM, Dillon EL, Urban RJ, Sheffield-Moore M. The role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci. 2012; 67(11): 1140-1152.
- 12Vázquez-Vela M, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res. 2008; 39(8): 715-728.
- 13Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004; 89(6): 2548-2556.
- 14Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010; 316(2): 129-139.
- 15Quinkler M, Sinha B, Tomlinson JW, Bujalska IJ, Stewart PM, Arlt W. Androgen generation in adipose tissue in women with simple obesity–a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5. J Endocrinol. 2004; 183(2): 331-342.
- 16O'Reilly MW, Kempegowda P, Walsh M, et al. AKR1C3-mediated adipose androgen generation drives lipotoxicity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017; 102(9): 3327-3339.
- 17O'Reilly M, Gathercole L, Capper F, Arlt W, Tomlinson J. Effect of insulin on AKR1C3 expression in female adipose tissue: in-vivo and in-vitro study of adipose androgen generation in polycystic ovary syndrome. Lancet. 2015; 385(Suppl 1): S16.
- 18Fouad Mansour M, Pelletier M, Boulet MM, et al. Oxidative activity of 17beta-hydroxysteroid dehydrogenase on testosterone in male abdominal adipose tissues and cellular localization of 17beta-HSD type 2. Mol Cell Endocrinol. 2015; 414: 168-176.
- 19Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol. 2015; 402: 113-119.
- 20Nedungadi TP, Clegg DJ. Sexual dimorphism in body fat distribution and risk for cardiovascular diseases. Cardiovasc Transl Res. 2009; 2(3): 321-327.
- 21Manolopoulos K, Karpe F, Frayn K. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes (Lond). 2010; 34(6): 949.
- 22Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues–the biology of pear shape. Biol Sex Differ. 2012; 3(1): 13.
- 23Goodpaster BH, Krishnaswami S, Harris TB, et al. Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med. 2005; 165(7): 777-783.
- 24Amati F, Pennant M, Azuma K, et al. Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance. Obesity (Silver Spring). 2012; 20(5): 1115-1117.
- 25Blouin K, Boivin A, Tchernof A. Androgens and body fat distribution. J Steroid Biochem Mol Biol. 2008; 108(3): 272-280.
- 26Navarro G, Allard C, Xu W, Mauvais-Jarvis F. The role of androgens in metabolism, obesity, and diabetes in males and females. Obesity. 2015; 23(4): 713-719.
- 27Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997; 18(6): 774-800.
- 28Hoffman LK, Ehrmann DA. Cardiometabolic features of polycystic ovary syndrome. Nat Rev Endocrinol. 2008; 4(4): 215.
- 29Pitteloud N, Mootha VK, Dwyer AA, et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care. 2005; 28(7): 1636-1642.
- 30Kapoor D, Aldred H, Clark S, Channer KS, Jones TH. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care. 2007; 30(4): 911-917.
- 31Patel SM, Ratcliffe SJ, Reilly MP, et al. Higher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 2009; 94(12): 4776-4784.
- 32McTiernan A, Rajan KB, Tworoger SS, et al. Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol. 2003; 21(10): 1961-1966.
- 33De Pergola G, Triggiani V, Giorgino F, et al. The free testosterone to dehydroepiandrosterone sulphate molar ratio as a marker of visceral fat accumulation in premenopausal obese women. Int J Obes Relat Metab Disord. 1994; 18(10): 659-664.
- 34Cao Y, Zhang S, Zou S, Xia X. The relationship between endogenous androgens and body fat distribution in early and late postmenopausal women. PLoS ONE. 2013; 8(3): e58448.
- 35Akin F, Bastemir M, Alkış E, Kaptanoglu B. SHBG levels correlate with insulin resistance in postmenopausal women. Eur J Intern Med. 2009; 20(2): 162-167.
- 36Bruce SJ, Rey F, Béguin A, Berthod C, Werner D, Henry H. Discrepancy between radioimmunoassay and high performance liquid chromatography tandem-mass spectrometry for the analysis of androstenedione. Anal Biochem. 2014; 455: 20-25.
- 37Büttler RM, Martens F, Fanelli F, et al. Comparison of 7 published LC-MS/MS methods for the simultaneous measurement of testosterone, androstenedione, and dehydroepiandrosterone in serum. Clin Chem. 2015; 61(12): 1475-1483.
- 38Legro RS, Schlaff WD, Diamond MP, et al. Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism. J Clin Endocrinol Metab. 2010; 95(12): 5305-5313.
- 39Buehler T, Ramseier N, Machann J, Schwenzer NF, Boesch C. Magnetic resonance imaging based determination of body compartments with the versatile, interactive sparse sampling (VISS) method. J Magn Reson Imaging. 2012; 36(4): 951-960.
- 40Roberts N, Cruz-orive L, Reid N, Brodie D, Bourne M, Edwards R. Unbiased estimation of human body composition by the Cavalieri method using magnetic resonance imaging. J Microsc. 1993; 171(3): 239-253.
- 41Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB. Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr. 2007; 85(2): 377-384.
- 42Sled JG, Zijdenbos AP, Evans AC. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging. 1998; 17(1): 87-97.
- 43Bermon S, Garnier PY, Hirschberg AL, et al. Serum androgen levels in elite female athletes. J Clin Endocrinol Metab. 2014; 99(11): 4328-4335.
- 44Gates MA, Mekary RA, Chiu GR, Ding EL, Wittert GA, Araujo AB. Sex steroid hormone levels and body composition in men. J Clin Endocrinol Metab. 2013; 98(6): 2442-2450.
- 45Finkelstein JS, Lee H, Burnett-Bowie S-AM, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013; 369(11): 1011-1022.
- 46Marchand GB, Carreau A-M, Weisnagel SJ, et al. Increased body fat mass explains the positive association between circulating estradiol and insulin resistance in postmenopausal women. Am J Physiol Endocrinol Metab. 2018; 314(5): E448–E456.
- 47Janssen I, Powell LH, Kazlauskaite R, Dugan SA. Testosterone and visceral fat in midlife women: the Study of Women's Health Across the Nation (SWAN) fat patterning study. Obesity. 2010; 18(3): 604-610.
- 48Jensen MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008; 93(11 Suppl 1): s57-s63
- 49Lee M-J, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med. 2013; 34(1): 1-11.
- 50Snijder MB, Visser M, Dekker JM, et al. Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The Health ABC Study. Diabetologia. 2005; 48(2): 301-308.
- 51Goss AM, Gower BA. Insulin sensitivity is associated with thigh adipose tissue distribution in healthy postmenopausal women. Metabolism. 2012; 61(12): 1817-1823.
- 52Goodpaster BH, Thaete FL, Simoneau J-A, Kelley DE. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997; 46(10): 1579-1585.
- 53Yim J, Heshka S, Albu J, et al. Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk. Int J Obes (Lond). 2007; 31(9): 1400.
- 54Liedtke S, Schmidt ME, Vrieling A, et al. Postmenopausal sex hormones in relation to body fat distribution. Obesity. 2012; 20(5): 1088-1095.
- 55Kirschner M, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N. Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab. 1990; 70(2): 473-479.
- 56Guthrie JR, Dennerstein L, Taffe JR, et al. Central abdominal fat and endogenous hormones during the menopausal transition. Fertil Steril. 2003; 79(6): 1335-1340.
- 57Lovejoy J, Bray G, Bourgeois M, et al. Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women–a clinical research center study. J Clin Endocrinol Metab. 1996; 81(6): 2198-2203.
- 58Turcato E, Zamboni M, De Pergola G, et al. Interrelationships between weight loss, body fat distribution and sex hormones in pre-and postmenopausal obese women. J Intern Med. 1997; 241(5): 363-372.
- 59Stanczyk FZ, Lee JS, Santen RJ. Standardization of steroid hormone assays: why, how, and when? Cancer Epidemiol Biomarkers Prev. 2007; 16(9): 1713-1719.
- 60Marzetti M, Brunton T, McCreight L, Pearson E, Docherty S, Gandy SJ. Quantitative MRI evaluation of whole abdomen adipose tissue volumes in healthy volunteers-validation of technique and implications for clinical studies. Br J Radiol. 2018; 91(1087): 20180025.
- 61Blouin K, Nadeau M, Mailloux J, et al. Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis. Am J Physiol Endocrinol Metab. 2009; 296(2): E244-E255.
Citing Literature
