Circulating 5α-dihydrotestosterone, abdominal obesity and adipocyte characteristics in women
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Julie A. Côté
Abstract
Background: The association between circulating androgen levels and fat distribution in women has been widely inconsistent among existing studies.
Objective: We sought to investigate the relation between plasma adrenal and gonadal androgen levels and body fat distribution, as well as abdominal adipocyte characteristics.
Methods: Paired omental and subcutaneous adipose tissue samples were surgically obtained from 60 women (age, 47±5 years; body mass index, 26±5 kg/m2) undergoing gynecological surgery. Body composition and fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography, respectively. Adipocyte diameter, basal lipolysis, and heparin-releasable lipoprotein lipase activity were measured. Steroids were quantified using high-performance gas chromatography and mass spectrometry.
Results: Significant negative associations were found between plasma dihydrotestosterone (DHT) levels and total adiposity (body mass index, r=–0.35, p<0.05; fat mass, r=–0.31, p<0.05) as well as computed tomography assessments of abdominal adiposity (r=–0.30, p<0.05 and r=–0.44, p<0.005 for subcutaneous and visceral adipose tissue area, respectively). The association between DHT levels and visceral adipose tissue area was independent of total body fat mass. A significant negative association was also observed between plasma DHT and omental adipocyte diameter (r=–0.27, p<0.05). When expressed as the omental/subcutaneous ratio, heparin-releasable lipoprotein lipase activity was negatively and significantly related to plasma DHT, androstenedione, and dehydroepiandrosterone (DHEA) levels.
Conclusion: Abdominally obese women with large, metabolically active omental adipocytes appear to be characterized by reduced endogenous levels of DHT. The assumption that high androgen levels are associated with an android body fat distribution pattern in women should be critically re-examined.
J.A.C. is a recipient of a studentship from the Fonds de la recherche en santé du Québec. We thank Dr. Karine Blouin for her contribution to the literature review and initial analyses of the dataset.
Disclosure
The authors have nothing to disclose.
References
1. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774–800.10.1210/edrv.18.6.0318Suche in Google Scholar
2. Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH. Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab 1983;57:304–10.10.1210/jcem-57-2-304Suche in Google Scholar
3. Evans DJ, Barth JH, Burke CW. Body fat topography in women with androgen excess. Int J Obes 1988;12:157–62.Suche in Google Scholar
4. Hauner H, Ditschuneit HH, Pal SB, Moncayo R, Pfeiffer EF. Fat distribution, endocrine and metabolic profile in obese women with and without hirsutism. Metabolism 1988;37:281–6.10.1016/0026-0495(88)90109-6Suche in Google Scholar
5. Kaye SA, Folsom AR, Soler JT, Prineas RJ, Potter JD. Associations of body mass and fat distribution with sex hormone concentrations in postmenopausal women. Int J Epidemiol 1991;20:151–6.10.1093/ije/20.1.151Suche in Google Scholar
6. Pasquali R, Casimirri F, Cantobelli S, Labate AM, Venturoli S, Paradisi R, Zannarini L. Insulin and androgen relationships with abdominal body fat distribution in women with and without hyperandrogenism. Horm Res 1993;39:179–87.10.1159/000182732Suche in Google Scholar
7. Armellini F, Zamboni M, Castelli S, Robbi R, Mino A, Todesco T, Bergamo-Andreis IA, Bosello O. Interrelationships between intraabdominal fat and total serum testosterone levels in obese women. Metabolism 1994;43:390–5.10.1016/0026-0495(94)90110-4Suche in Google Scholar
8. De Pergola G, Triggiani V, Giorgino F, Cospite MR, Garruti G, Cignarelli M, Guastamacchia E, Giorgino R. 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;18:659–64.Suche in Google Scholar
9. Zamboni M, Armellini F, Turcato E, de Pergola G, Todesco T, Bissoli L, Bergamo Andreis IA, Bosello O. Relationship between visceral fat, steroid hormones and insulin sensitivity in premenopausal obese women. J Intern Med 1994;236:521–7.10.1111/j.1365-2796.1994.tb00839.xSuche in Google Scholar PubMed
10. Pedersen SB, Borglum JD, Brixen K, Richelsen B. Relationship between sex hormones, body composition and metabolic risk parameters in premenopausal women. Eur J Endocrinol 1995;133:200–6.10.1530/eje.0.1330200Suche in Google Scholar PubMed
11. Cigolini M, Targher G, Bergamo Andreis IA, Tonoli M, Filippi F, Muggeo M, De Sandre G. Moderate alcohol consumption and its relation to visceral fat and plasma androgens in healthy women. Int J Obes Relat Metab Disord 1996;20:206–12.Suche in Google Scholar
12. De Pergola G, Zamboni M, Sciaraffia M, Turcato E, Pannacciulli N, Armellini F, Giorgino F, Perrini S, Bosello O, Giorgino R. Body fat accumulation is possibly responsible for lower dehydroepiandrosterone circulating levels in premenopausal obese women. Int J Obes Relat Metab Disord 1996;20:1105–10.Suche in Google Scholar
13. Turcato E, Zamboni M, De Pergola G, Armellini F, Zivelonghi A, Bergamo-Andreis IA, Giorgino R, Bosello O. Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women. J Intern Med 1997;241:363–72.10.1046/j.1365-2796.1997.120129000.xSuche in Google Scholar PubMed
14. Garaulet M, Perex-Llamas F, Fuente T, Zamora S, Tebar FJ. Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-α, sex hormone-binding globulin and sex hormones. Eur J Endocrinol 2000;143:657–66.10.1530/eje.0.1430657Suche in Google Scholar PubMed
15. De Simone M, Verrotti A, Iughetti L, Palumbo M, Farello G, Di Cesare E, Bernabei R, Rosato T, Lozzi S, Criscione S. Increased visceral adipose tissue is associated with increased circulating insulin and decreased sex hormone binding globulin levels in massively obese adolescent girls. J Endocrinol Invest 2001;24:438–44.10.1007/BF03351044Suche in Google Scholar PubMed
16. Dixon JB, O’Brien PE. Neck circumference a good predictor of raised insulin and free androgen index in obese premenopausal women: changes with weight loss. Clin Endocrinol (Oxf) 2002;57:769–78.10.1046/j.1365-2265.2002.01665.xSuche in Google Scholar
17. Carranza-Lira S, Velasco Diaz G, Olivares A, Chan Verdugo R, Herrera J. Correlation of Kupperman’s index with estrogen and androgen levels, according to weight and body fat distribution in postmenopausal women from Mexico City. Int J Fertil Womens Med 2006;51:83–8.Suche in Google Scholar
18. Phillips GB, Jing T, Heymsfield SB. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women. Metabolism 2008;57:838–44.10.1016/j.metabol.2008.01.029Suche in Google Scholar
19. Casson PR, Toth MJ, Johnson JV, Stanczyk FZ, Casey CL, Dixon ME. Correlation of serum androgens with anthropometric and metabolic indices in healthy, nonobese postmenopausal women. J Clin Endocrinol Metab 2010;95:4276–82.10.1210/jc.2009-2390Suche in Google Scholar
20. Keller JL, Casson PR, Toth MJ. Relationship of androgens to body composition, energy and substrate metabolism and aerobic capacity in healthy, young women. Steroids 2011;76:1247–51.10.1016/j.steroids.2011.06.001Suche in Google Scholar
21. Seidell JC, Cigolini M, Charzewska J, Ellsinger BM, Di Biase G, Bjorntorp P, Hautvast JG, Contaldo F, Szostak V, Scuro LA. Androgenicity in relation to body fat distribution and metabolism in 38-year-old women – the European Fat Distribution Study. J Clin Epidemiol 1990;43:21–34.10.1016/0895-4356(90)90052-QSuche in Google Scholar
22. Ivandic A, Prpic-Krizevac I, Sucic M, Juric M. Hyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity. Metabolism 1998;47:13–9.10.1016/S0026-0495(98)90186-XSuche in Google Scholar
23. Ivandic A, Prpic-Krizevac I, Bozic D, Barbir A, Peljhan V, Balog Z, Glasnovic M. Insulin resistance and androgens in healthy women with different body fat distributions. Wien Klin Wochenschr 2002;114:321–6.Suche in Google Scholar
24. Glintborg D, Andersen M, Hagen C, Frystyk J, Hulstrom V, Flyvbjerg A, Hermann AP. Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls. Eur J Endocrinol 2006;155:337–45.10.1530/eje.1.02207Suche in Google Scholar
25. Yucel A, Noyan V, Sagsoz N. The association of serum androgens and insulin resistance with fat distribution in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2006;126:81–6.10.1016/j.ejogrb.2005.11.012Suche in Google Scholar
26. Pasquali R, Antenucci D, Melchionda N, Fabbri R, Venturoli S, Patrono D, Capelli M. Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition. J Endocrinol Invest 1987;10:345–50.10.1007/BF03348145Suche in Google Scholar
27. Korhonen S, Hippelainen M, Vanhala M, Heinonen S, Niskanen L. The androgenic sex hormone profile is an essential feature of metabolic syndrome in premenopausal women: a controlled community-based study. Fertil Steril 2003;79:1327–34.10.1016/S0015-0282(03)00347-9Suche in Google Scholar
28. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007;92:405–13.10.1210/jc.2006-1864Suche in Google Scholar
29. Deschenes D, Couture P, Dupont P, Tchernof A. Subdivision of the subcutaneous adipose tissue compartment and lipid-lipoprotein levels in women. Obes Res 2003;11:469–76.10.1038/oby.2003.64Suche in Google Scholar
30. Labrie F, Belanger A, Belanger P, Berube R, Martel C, Cusan L, Gomez J, Candas B, Chaussade V, Castiel I, Deloche C, Leclaire J. Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol Biol 2007;103:178–88.10.1016/j.jsbmb.2006.09.034Suche in Google Scholar
31. Leblanc M, Labrie C, Belanger A, Candas B, Labrie F. Bioavailability and pharmacokinetics of dehydroepiandrosterone in the cynomolgus monkey. J Clin Endocrinol Metab 2003;88: 4293–302.10.1210/jc.2003-022012Suche in Google Scholar
32. Leblanc M, Labrie C, Belanger A, Candas B, Labrie F. Pharmacokinetics of oral dehydroepiandrosterone (DHEA) in the ovariectomised cynomolgus monkey. J Steroid Biochem Mol Biol 2002;81:159–64.10.1016/S0960-0760(02)00059-6Suche in Google Scholar
33. Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964;239:375–80.10.1016/S0021-9258(18)51687-2Suche in Google Scholar
34. Kather H, Schroder F, Simon B. Microdetermination of glycerol using bacterial NADH-linked luciferase. Clin Chim Acta 1982;120:295–300.10.1016/0009-8981(82)90370-9Suche in Google Scholar
35. Taskinen MR, Nikkila EA, Huttunen JK, Hilden H. A micromethod for assay of lipoprotein lipase activity in needle biopsy samples of human adipose tissue and skeletal muscle. Clin Chim Acta 1980;104:107–17.10.1016/0009-8981(80)90140-0Suche in Google Scholar
36. Yang HP, Black A, Falk RT, Brinton LA, Potischman N, Wentzensen N, Faupel-Badger JM, Sherman ME. Association of serum sex steroid hormone hemodilution and body mass index among healthy postmenopausal women. Ann Epidemiol 2011;21:466–71.10.1016/j.annepidem.2011.01.003Suche in Google Scholar PubMed PubMed Central
37. Mahabir S, Baer DJ, Johnson LL, Hartman TJ, Dorgan JF, Campbell WS, Clevidence BA, Taylor PR. Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2006;15:2502–7.10.1158/1055-9965.EPI-06-0499Suche in Google Scholar PubMed
38. Blouin K, Nadeau M, Perreault M, Veilleux A, Drolet R, Marceau P, Mailloux J, Luu-The V, Tchernof A. Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women. Clin Endocrinol (Oxf) 2010;72:176–88.10.1111/j.1365-2265.2009.03645.xSuche in Google Scholar
39. Blouin K, Nadeau M, Mailloux J, Daris M, Lebel S, Luu-The V, Tchernof A. Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis. Am J Physiol Endocrinol Metab 2009; 296:E244–55.10.1152/ajpendo.00039.2008Suche in Google Scholar
40. Blouin K, Veilleux A, Luu-The V, Tchernof A. Androgen metabolism in adipose tissue: recent advances. Mol Cell Endocrinol 2009;301:97–103.10.1016/j.mce.2008.10.035Suche in Google Scholar
41. Uemura M, Tamura K, Chung S, Honma S, Okuyama A, Nakamura Y, Nakagawa H. Novel 5 α-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci 2008;99:81–6.10.1111/j.1349-7006.2007.00656.xSuche in Google Scholar
42. Gruber DM, Sator MO, Kirchengast S, Joura EA, Huber JC. Effect of percutaneous androgen replacement therapy on body composition and body weight in postmenopausal women. Maturitas 1998;29:253–9.10.1016/S0378-5122(98)00031-0Suche in Google Scholar
43. Lovejoy JC, Bray GA, Bourgeois MO, Macchiavelli R, Rood JC, Greeson C, Partington C. Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women – a clinical research center study. J Clin Endocrinol Metab 1996;81:2198–203.10.1210/jcem.81.6.8964851Suche in Google Scholar
44. Blouin K, Boivin A, Tchernof A. Androgens and body fat distribution. J Steroid Biochem Mol Biol 2008;108:272–80.10.1016/j.jsbmb.2007.09.001Suche in Google Scholar
45. Hajamor S, Despres JP, Couillard C, Lemieux S, Tremblay A, Prud’homme D, Tchernof A. Relationship between sex hormone-binding globulin levels and features of the metabolic syndrome. Metabolism 2003;52:724–30.10.1016/S0026-0495(03)00066-0Suche in Google Scholar
46. De Pergola G, Giagulli VA, Garruti G, Cospite MR, Giorgino F, Cignarelli M, Giorgino R. Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index. Metabolism 1991;40:187–90.10.1016/0026-0495(91)90172-SSuche in Google Scholar
47. Barrett-Connor E, Ferrara A. Dehydroepiandrosterone, dehydroepiandrosterone sulfate, obesity, waist-hip ratio, and noninsulin-dependent diabetes in postmenopausal women: the Rancho Bernardo Study. J Clin Endocrinol Metab 1996;81:59–64.10.1210/jc.81.1.59Suche in Google Scholar
48. Tchernof A, Labrie F. Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies. Eur J Endocrinol 2004;151:1–14.10.1530/eje.0.1510001Suche in Google Scholar PubMed
49. Labrie F, Belanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab 1997;82:2396–402.10.1210/jcem.82.8.4160Suche in Google Scholar PubMed
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