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DOI: 10.1055/s-0045-1811952
Female Adipose Tissue Sex Steroid Biosynthesis
Authors
Funding None.

Abstract
Estrogens, including estradiol and estrone, and androgens, including testosterone, are locally produced in adipose tissue throughout a woman's lifespan. Already in fertile-aged women, subcutaneous and visceral adipose tissue produce notable amounts of estrogens despite ongoing ovarian estrogen synthesis. After menopause, adipose tissue becomes the most important producer of estrogens. A decrease in circulating estrogen concentrations coincides with a relative increase in the amount of visceral adipose tissue and an increased risk for metabolic disorders. Furthermore, local adipose tissue biosynthesis of sex steroids may regulate the distribution of adipose tissue between the subcutaneous and visceral depots. Further studies are needed to characterize the relation of local adipose tissue sex steroid milieu to local and circulating markers of adipose tissue and metabolic dysfunction. This can shed more light on the increasing adiposity and metabolic burden associated with menopause. Here, we discuss the roles estrogens and androgens play in adipose tissue distribution and function before and after menopause, and highlight the role of local sex steroid biosynthesis, or intracrinology, in determining local tissue sex steroid environments.
Publikationsverlauf
Artikel online veröffentlicht:
03. Oktober 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
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References
- 1 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89 (06) 2548-2556
- 2 Li J, Papadopoulos V, Vihma V. Steroid biosynthesis in adipose tissue. Steroids 2015; 103: 89-104
- 3 Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol 2001; 45 (3, suppl): S116-S124
- 4 Labrie F. All sex steroids are made intracellularly in peripheral tissues by the mechanisms of intracrinology after menopause. J Steroid Biochem Mol Biol 2015; 145: 133-138
- 5 Schiffer L, Arlt W, Storbeck KH. Intracrine androgen biosynthesis, metabolism and action revisited. Mol Cell Endocrinol 2018; 465: 4-26
- 6 Arlt W. Androgen therapy in women. Eur J Endocrinol 2006; 154 (01) 1-11
- 7 Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol 2003; 86 (3–5): 225-230
- 8 Hetemäki N, Robciuc A, Vihma V. et al. Adipose tissue sex steroids in postmenopausal women with and without menopausal hormone therapy. J Clin Endocrinol Metab 2025; 110 (02) 511-522
- 9 Hetemäki N, Savolainen-Peltonen H, Tikkanen MJ. et al. Estrogen metabolism in abdominal subcutaneous and visceral adipose tissue in postmenopausal women. J Clin Endocrinol Metab 2017; 102 (12) 4588-4595
- 10 Paatela H, Wang F, Vihma V. et al. Steroid sulfatase activity in subcutaneous and visceral adipose tissue: a comparison between pre- and postmenopausal women. Eur J Endocrinol 2016; 174 (02) 167-175
- 11 Kinoshita T, Honma S, Shibata Y. et al. An innovative LC-MS/MS-based method for determining CYP 17 and CYP 19 activity in the adipose tissue of pre- and postmenopausal and ovariectomized women using 13C-labeled steroid substrates. J Clin Endocrinol Metab 2014; 99 (04) 1339-1347
- 12 Yamatani H, Takahashi K, Yoshida T, Takata K, Kurachi H. Association of estrogen with glucocorticoid levels in visceral fat in postmenopausal women. Menopause 2013; 20 (04) 437-442
- 13 Waraich RS, Mauvais-Jarvis F. Paracrine and intracrine contributions of androgens and estrogens to adipose tissue biology: physiopathological aspects. Horm Mol Biol Clin Investig 2013; 14 (02) 49-55
- 14 Leeners B, Geary N, Tobler PN, Asarian L. Ovarian hormones and obesity. Hum Reprod Update 2017; 23 (03) 300-321
- 15 Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev 2013; 93 (01) 359-404
- 16 Ambikairajah A, Walsh E, Tabatabaei-Jafari H, Cherbuin N. Fat mass changes during menopause: a metaanalysis. Am J Obstet Gynecol 2019; 221 (05) 393-409.e50
- 17 Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444 (7121): 881-887
- 18 Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med 2013; 34 (01) 1-11
- 19 Neeland IJ, Ross R, Després JP. et al; International Atherosclerosis Society, International Chair on Cardiometabolic Risk Working Group on Visceral Obesity. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol 2019; 7 (09) 715-725
- 20 Blouin K, Veilleux A, Luu-The V, Tchernof A. Androgen metabolism in adipose tissue: recent advances. Mol Cell Endocrinol 2009; 301 (1–2): 97-103
- 21 Bracht JR, Vieira-Potter VJ, De Souza Santos R, Öz OK, Palmer BF, Clegg DJ. The role of estrogens in the adipose tissue milieu. Ann N Y Acad Sci 2020; 1461 (01) 127-143
- 22 Schiffer L, Arlt W, O'Reilly MW. Understanding the role of androgen action in female adipose tissue. Front Horm Res 2019; 53: 33-49
- 23 O'Reilly MW, House PJ, Tomlinson JW. Understanding androgen action in adipose tissue. J Steroid Biochem Mol Biol 2014; 143: 277-284
- 24 Mauvais-Jarvis F, Lindsey SH. Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations. J Clin Invest 2024; 134 (17) e180073
- 25 Maniyadath B, Zhang Q, Gupta RK, Mandrup S. Adipose tissue at single-cell resolution. Cell Metab 2023; 35 (03) 386-413
- 26 Ghaben AL, Scherer PE. Adipogenesis and metabolic health. Nat Rev Mol Cell Biol 2019; 20 (04) 242-258
- 27 Karastergiou K, Fried SK. Cellular mechanisms driving sex differences in adipose tissue biology and body shape in humans and mouse models. Adv Exp Med Biol 2017; 1043: 29-51
- 28 Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 2010; 11 (01) 11-18
- 29 Drolet R, Richard C, Sniderman AD. et al. Hypertrophy and hyperplasia of abdominal adipose tissues in women. Int J Obes (Lond) 2008; 32 (02) 283-291
- 30 Sakers A, De Siqueira MK, Seale P, Villanueva CJ. Adipose-tissue plasticity in health and disease. Cell 2022; 185 (03) 419-446
- 31 Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol 2015; 402: 113-119
- 32 Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 2000; 21 (06) 697-738
- 33 Tchkonia T, Thomou T, Zhu Y. et al. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17 (05) 644-656
- 34 Cypess AM. Reassessing human adipose tissue. Reply. N Engl J Med 2022; 386 (22) e61
- 35 Hwang I, Kim JB. Two faces of white adipose tissue with heterogeneous adipogenic progenitors. Diabetes Metab J 2019; 43 (06) 752-762
- 36 Brown KA, Scherer PE. Update on adipose tissue and cancer. Endocr Rev 2023; 44 (06) 961-974
- 37 Bray GA. Beyond BMI. Nutrients 2023; 15 (10) 2254
- 38 Rankinen T, Kim SY, Pérusse L, Després JP, Bouchard C. The prediction of abdominal visceral fat level from body composition and anthropometry: ROC analysis. Int J Obes Relat Metab Disord 1999; 23 (08) 801-809
- 39 Li X, Liu J, Zhou B. et al. Sex differences in the effect of testosterone on adipose tissue insulin resistance from overweight to obese adults. J Clin Endocrinol Metab 2021; 106 (08) 2252-2263
- 40 Liu X, He M, Li Y. Adult obesity diagnostic tool: a narrative review. Medicine (Baltimore) 2024; 103 (17) e37946
- 41 Camhi SM, Bray GA, Bouchard C. et al. The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity (Silver Spring) 2011; 19 (02) 402-408
- 42 Mauvais-Jarvis F. Sex differences in energy metabolism: natural selection, mechanisms and consequences. Nat Rev Nephrol 2024; 20 (01) 56-69
- 43 Karpe F, Pinnick KE. Biology of upper-body and lower-body adipose tissue–link to whole-body phenotypes. Nat Rev Endocrinol 2015; 11 (02) 90-100
- 44 Pi-Sunyer FX. The epidemiology of central fat distribution in relation to disease. Nutr Rev 2004; 62 (7 Pt 2): S120-S126
- 45 Schleinitz D, Krause K, Wohland T. et al. Identification of distinct transcriptome signatures of human adipose tissue from fifteen depots. Eur J Hum Genet 2020; 28 (12) 1714-1725
- 46 Heilbronn L, Smith SR, Ravussin E. Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. Int J Obes Relat Metab Disord 2004; 28 (Suppl. 04) S12-S21
- 47 Valenzuela PL, Carrera-Bastos P, Castillo-García A, Lieberman DE, Santos-Lozano A, Lucia A. Obesity and the risk of cardiometabolic diseases. Nat Rev Cardiol 2023; 20 (07) 475-494
- 48 Pernoud LE, Gardiner PA, Fraser SD, Dillon-Rossiter K, Dean MM, Schaumberg MA. A systematic review and meta-analysis investigating differences in chronic inflammation and adiposity before and after menopause. Maturitas 2024; 190: 108119
- 49 Juppi HK, Sipilä S, Cronin NJ. et al. Role of menopausal transition and physical activity in loss of lean and muscle mass: a follow-up study in middle-aged Finnish women. J Clin Med 2020; 9 (05) 1588
- 50 Abildgaard J, Pedersen AT, Green CJ. et al. Menopause is associated with decreased whole body fat oxidation during exercise. Am J Physiol Endocrinol Metab 2013; 304 (11) E1227-E1236
- 51 Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 2008; 32 (06) 949-958
- 52 Karppinen JE, Wiklund P, Ihalainen JK. et al. Age but not menopausal status is linked to lower resting energy expenditure. J Clin Endocrinol Metab 2023; 108 (11) 2789-2797
- 53 Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol 2012; 13 (08) 707-712
- 54 Corvera S. Cellular heterogeneity in adipose tissues. Annu Rev Physiol 2021; 83: 257-278
- 55 Li Q, Spalding KL. The regulation of adipocyte growth in white adipose tissue. Front Cell Dev Biol 2022; 10: 1003219
- 56 Goossens GH, Jocken JWE, Blaak EE. Sexual dimorphism in cardiometabolic health: the role of adipose tissue, muscle and liver. Nat Rev Endocrinol 2021; 17 (01) 47-66
- 57 Duerre DJ, Galmozzi A. Deconstructing adipose tissue heterogeneity one cell at a time. Front Endocrinol (Lausanne) 2022; 13: 847291
- 58 Bäckdahl J, Franzén L, Massier L. et al. Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin. Cell Metab 2021; 33 (11) 2301
- 59 Emont MP, Jacobs C, Essene AL. et al. A single-cell atlas of human and mouse white adipose tissue. Nature 2022; 603 (7903): 926-933
- 60 Blüher M. Understanding adipose tissue dysfunction. J Obes Metab Syndr 2024; 33 (04) 275-288
- 61 Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015; 36 (07) 461-470
- 62 Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011; 11 (02) 85-97
- 63 Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring) 2010; 18 (05) 884-889
- 64 Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001; 2 (04) 282-286
- 65 Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr 2007; 27: 79-101
- 66 Frayn KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia 2002; 45 (09) 1201-1210
- 67 Afshin A, Forouzanfar MH, Reitsma MB. et al; GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017; 377 (01) 13-27
- 68 Organization WH. World Health Statistics 2022: Monitoring Health for the SDGs,. Sustainable Development Goals; 2022
- 69 Chew NWS, Ng CH, Tan DJH. et al. The global burden of metabolic disease: Data from 2000 to 2019. Cell Metab 2023; 35 (03) 414-428.e3
- 70 Gu P, Xu A. Interplay between adipose tissue and blood vessels in obesity and vascular dysfunction. Rev Endocr Metab Disord 2013; 14 (01) 49-58
- 71 Herold J, Kalucka J. Angiogenesis in adipose tissue: the interplay between adipose and endothelial cells. Front Physiol 2021; 11: 624903
- 72 Morigny P, Houssier M, Mouisel E, Langin D. Adipocyte lipolysis and insulin resistance. Biochimie 2016; 125: 259-266
- 73 Gliniak CM, Pedersen L, Scherer PE. Adipose tissue fibrosis: the unwanted houseguest invited by obesity. J Endocrinol 2023; 259 (03) e230180
- 74 Poutanen M. Understanding the diversity of sex steroid action. J Endocrinol 2012; 212 (01) 1-2
- 75 Gruber CJ, Tschugguel W, Schneeberger C, Huber JC. Production and actions of estrogens. N Engl J Med 2002; 346 (05) 340-352
- 76 Kolatorova L, Vitku J, Suchopar J, Hill M, Parizek A. Progesterone: a steroid with wide range of effects in physiology as well as human medicine. Int J Mol Sci 2022; 23 (14) 7989
- 77 Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011; 32 (01) 81-151
- 78 Poutanen M, Hagberg Thulin M, Härkönen P. Targeting sex steroid biosynthesis for breast and prostate cancer therapy. Nat Rev Cancer 2023; 23 (10) 686-709
- 79 Storbeck KH, O'Reilly MW. The clinical and biochemical significance of 11-oxygenated androgens in human health and disease. Eur J Endocrinol 2023; 188 (04) R98-R109
- 80 Payne AH, Hales DB. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 2004; 25 (06) 947-970
- 81 Mauvais-Jarvis F, Clegg DJ, Hevener AL. The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev 2013; 34 (03) 309-338
- 82 Skiba MA, Bell RJ, Islam RM, Handelsman DJ, Desai R, Davis SR. Androgens during the reproductive years: what is normal for women?. J Clin Endocrinol Metab 2019; 104 (11) 5382-5392
- 83 Piltonen T, Koivunen R, Morin-Papunen L, Ruokonen A, Huhtaniemi IT, Tapanainen JS. Ovarian and adrenal steroid production: regulatory role of LH/HCG. Hum Reprod 2002; 17 (03) 620-624
- 84 Vuppaladhadiam L, Lager J, Fiehn O. et al. Human placenta buffers the fetus from adverse effects of perceived maternal stress. Cells 2021; 10 (02) 379
- 85 Olde B, Leeb-Lundberg LM. GPR30/GPER1: searching for a role in estrogen physiology. Trends Endocrinol Metab 2009; 20 (08) 409-416
- 86 Edwards DP. Regulation of signal transduction pathways by estrogen and progesterone. Annu Rev Physiol 2005; 67: 335-376
- 87 Morselli E, Santos RS, Criollo A, Nelson MD, Palmer BF, Clegg DJ. The effects of oestrogens and their receptors on cardiometabolic health. Nat Rev Endocrinol 2017; 13 (06) 352-364
- 88 O'Lone R, Frith MC, Karlsson EK, Hansen U. Genomic targets of nuclear estrogen receptors. Mol Endocrinol 2004; 18 (08) 1859-1875
- 89 Roepke TA, Malyala A, Bosch MA, Kelly MJ, Rønnekleiv OK. Estrogen regulation of genes important for K+ channel signaling in the arcuate nucleus. Endocrinology 2007; 148 (10) 4937-4951
- 90 Rizk J, Sahu R, Duteil D. An overview on androgen-mediated actions in skeletal muscle and adipose tissue. Steroids 2023; 199: 109306
- 91 Storbeck KH, Bloem LM, Africander D, Schloms L, Swart P, Swart AC. 11β-hydroxydihydrotestosterone and 11-ketodihydrotestosterone, novel C19 steroids with androgenic activity: a putative role in castration resistant prostate cancer?. Mol Cell Endocrinol 2013; 377 (1–2): 135-146
- 92 Vázquez-Martínez ER, Mendoza-Garcés L, Vergara-Castañeda E, Cerbón M. Epigenetic regulation of progesterone receptor isoforms: from classical models to the sexual brain. Mol Cell Endocrinol 2014; 392 (1–2): 115-124
- 93 Liu JH. The role of progestogens in menopausal hormone therapy. Clin Obstet Gynecol 2021; 64 (04) 772-783
- 94 Hammond GL. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol 2016; 230 (01) R13-R25
- 95 Wu CH, Motohashi T, Abdel-Rahman HA, Flickinger GL, Mikhail G. Free and protein-bound plasma estradiol-17 beta during the menstrual cycle. J Clin Endocrinol Metab 1976; 43 (02) 436-445
- 96 Goldman AL, Bhasin S, Wu FCW, Krishna M, Matsumoto AM, Jasuja R. A reappraisal of testosterone's binding in circulation: physiological and clinical implications. Endocr Rev 2017; 38 (04) 302-324
- 97 Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005; 8 (Suppl. 01) 3-63
- 98 Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA. The regulation of steroid action by sulfation and desulfation. Endocr Rev 2015; 36 (05) 526-563
- 99 Schiffer L, Barnard L, Baranowski ES. et al. Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review. J Steroid Biochem Mol Biol 2019; 194: 105439
- 100 Labrie F, Bélanger A, Luu-The V. et al. DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: its role during aging. Steroids 1998; 63 (5–6): 322-328
- 101 Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis–some new perspectives. Endocrinology 2001; 142 (11) 4589-4594
- 102 Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005; 90 (07) 3847-3853
- 103 Anderson LA, McTernan PG, Barnett AH, Kumar S. The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site. J Clin Endocrinol Metab 2001; 86 (10) 5045-5051
- 104 Cox-York KA, Erickson CB, Pereira RI, Bessesen DH, Van Pelt RE. Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women. J Cell Mol Med 2017; 21 (04) 677-684
- 105 Tchoukalova YD, Koutsari C, Karpyak MV, Votruba SB, Wendland E, Jensen MD. Subcutaneous adipocyte size and body fat distribution. Am J Clin Nutr 2008; 87 (01) 56-63
- 106 Tchoukalova YD, Koutsari C, Votruba SB. et al. Sex- and depot-dependent differences in adipogenesis in normal-weight humans. Obesity (Silver Spring) 2010; 18 (10) 1875-1880
- 107 Van Pelt RE, Gozansky WS, Schwartz RS, Kohrt WM. Intravenous estrogens increase insulin clearance and action in postmenopausal women. Am J Physiol Endocrinol Metab 2003; 285 (02) E311-E317
- 108 Ferrara CM, Lynch NA, Nicklas BJ, Ryan AS, Berman DM. Differences in adipose tissue metabolism between postmenopausal and perimenopausal women. J Clin Endocrinol Metab 2002; 87 (09) 4166-4170
- 109 Raison J, Basdevant A, Sitt Y, Guy-Grand B. Regional differences in adipose tissue lipoprotein lipase activity in relation to body fat distribution and menopausal status in obese women. Int J Obes (Lond) 1988; 12 (05) 465-472
- 110 Newell-Fugate AE. The role of sex steroids in white adipose tissue adipocyte function. Reproduction 2017; 153 (04) R133-R149
- 111 Foryst-Ludwig A, Kintscher U. Metabolic impact of estrogen signalling through ERalpha and ERbeta. J Steroid Biochem Mol Biol 2010; 122 (1–3): 74-81
- 112 Barros RP, Gustafsson JÅ. Estrogen receptors and the metabolic network. Cell Metab 2011; 14 (03) 289-299
- 113 Nilsson M, Dahlman I, Rydén M. et al. Oestrogen receptor alpha gene expression levels are reduced in obese compared to normal weight females. Int J Obes (Lond) 2007; 31 (06) 900-907
- 114 Tchernof A, Brochu D, Maltais-Payette I. et al. Androgens and the regulation of adiposity and body fat distribution in humans. Compr Physiol 2018; 8 (04) 1253-1290
- 115 Ofori EK, Conde Alonso S, Correas-Gomez L. et al. Thigh and abdominal adipose tissue depot associations with testosterone levels in postmenopausal females. Clin Endocrinol (Oxf) 2019; 90 (03) 433-439
- 116 Marchand GB, Carreau AM, Laforest S. et al. Circulating steroid levels as correlates of adipose tissue phenotype in premenopausal women. Horm Mol Biol Clin Investig 2018 34. 01
- 117 Hirschberg AL. Approach to investigation of hyperandrogenism in a postmenopausal woman. J Clin Endocrinol Metab 2023; 108 (05) 1243-1253
- 118 Yanes Cardozo LL, Romero DG, Reckelhoff JF. Cardiometabolic features of polycystic ovary syndrome: role of androgens. Physiology (Bethesda) 2017; 32 (05) 357-366
- 119 Stener-Victorin E, Teede H, Norman RJ. et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2024; 10 (01) 27
- 120 Sievers C, Klotsche J, Pieper L. et al. Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients. Eur J Endocrinol 2010; 163 (04) 699-708
- 121 Janssen I, Powell LH, Jasielec MS, Kazlauskaite R. Covariation of change in bioavailable testosterone and adiposity in midlife women. Obesity (Silver Spring) 2015; 23 (02) 488-494
- 122 Cao 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 (03) e58448
- 123 Joyner J, Hutley L, Cameron D. Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes. Horm Metab Res 2002; 34 (05) 223-228
- 124 Chazenbalk G, Singh P, Irge D, Shah A, Abbott DH, Dumesic DA. Androgens inhibit adipogenesis during human adipose stem cell commitment to preadipocyte formation. Steroids 2013; 78 (09) 920-926
- 125 Blouin K, Nadeau M, Perreault M. et al. Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women. Clin Endocrinol (Oxf) 2010; 72 (02) 176-188
- 126 Dai W, Li Y, Zheng H. Estradiol/testosterone imbalance: impact on coronary heart disease risk factors in postmenopausal women. Cardiology 2012; 121 (04) 249-254
- 127 Spoletini I, Vitale C, Pelliccia F, Fossati C, Rosano GM. Androgens and cardiovascular disease in postmenopausal women: a systematic review. Climacteric 2014; 17 (06) 625-634
- 128 Schiffer L, Kempegowda P, Sitch AJ. et al. Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation. Eur J Endocrinol 2023; 188 (01) lvac017
- 129 Nanba AT, Rege J, Ren J, Auchus RJ, Rainey WE, Turcu AF. 11-oxygenated C19 steroids do not decline with age in women. J Clin Endocrinol Metab 2019; 104 (07) 2615-2622
- 130 O'Brien SN, Welter BH, Mantzke KA, Price TM. Identification of progesterone receptor in human subcutaneous adipose tissue. J Clin Endocrinol Metab 1998; 83 (02) 509-513
- 131 Zhang Y, Nadeau M, Faucher F. et al. Progesterone metabolism in adipose cells. Mol Cell Endocrinol 2009; 298 (1–2): 76-83
- 132 Wawrzkiewicz-Jałowiecka A, Lalik A, Soveral G. Recent update on the molecular mechanisms of gonadal steroids action in adipose tissue. Int J Mol Sci 2021; 22 (10) 5226
- 133 Harlow SD, Gass M, Hall JE. et al; STRAW + 10 Collaborative Group. Executive summary of the stages of reproductive aging workshop + 10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 2012; 97 (04) 1159-1168
- 134 Hall JE. Endocrinology of the menopause. Endocrinol Metab Clin North Am 2015; 44 (03) 485-496
- 135 Santoro N, Roeca C, Peters BA, Neal-Perry G. The menopause transition: signs, symptoms, and management options. J Clin Endocrinol Metab 2021; 106 (01) 1-15
- 136 Sherman BM, West JH, Korenman SG. The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women. J Clin Endocrinol Metab 1976; 42 (04) 629-636
- 137 Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr Rev 2009; 30 (05) 465-493
- 138 Davis SR, Baber RJ. Treating menopause - MHT and beyond. Nat Rev Endocrinol 2022; 18 (08) 490-502
- 139 Charatcharoenwitthaya N, Khosla S, Atkinson EJ, McCready LK, Riggs BL. Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women. J Bone Miner Res 2007; 22 (05) 724-729
- 140 Menazza S, Murphy E. The expanding complexity of estrogen receptor signaling in the cardiovascular system. Circ Res 2016; 118 (06) 994-1007
- 141 Barton M, Meyer MR. Postmenopausal hypertension: mechanisms and therapy. Hypertension 2009; 54 (01) 11-18
- 142 Lee CG, Carr MC, Murdoch SJ. et al. Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. J Clin Endocrinol Metab 2009; 94 (04) 1104-1110
- 143 Sites CK, Brochu M, Tchernof A, Poehlman ET. Relationship between hormone replacement therapy use with body fat distribution and insulin sensitivity in obese postmenopausal women. Metabolism 2001; 50 (07) 835-840
- 144 El Khoudary SR, Greendale G, Crawford SL. et al. The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN). Menopause 2019; 26 (10) 1213-1227
- 145 Grundy SM. What is the contribution of obesity to the metabolic syndrome?. Endocrinol Metab Clin North Am 2004; 33 (02) 267-282
- 146 Cherubini A, Ostadreza M, Jamialahmadi O. et al; EPIDEMIC Study Investigators. Interaction between estrogen receptor-α and PNPLA3 p.I148M variant drives fatty liver disease susceptibility in women. Nat Med 2023; 29 (10) 2643-2655
- 147 Depypere H, Inki P. The levonorgestrel-releasing intrauterine system for endometrial protection during estrogen replacement therapy: a clinical review. Climacteric 2015; 18 (04) 470-482
- 148 Simon JA. Estrogen replacement therapy: effects on the endogenous androgen milieu. Fertil Steril 2002; 77 (Suppl. 04) S77-S82
- 149 Shifren JL, Rifai N, Desindes S, McIlwain M, Doros G, Mazer NA. A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. J Clin Endocrinol Metab 2008; 93 (05) 1702-1710
- 150 Vigneswaran K, Hamoda H. Hormone replacement therapy - current recommendations. Best Pract Res Clin Obstet Gynaecol 2022; 81: 8-21
- 151 Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab 2006; 8 (05) 538-554
- 152 Szmuilowicz ED, Stuenkel CA, Seely EW. Influence of menopause on diabetes and diabetes risk. Nat Rev Endocrinol 2009; 5 (10) 553-558
- 153 Xu Y, Lin J, Wang S, Xiong J, Zhu Q. Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus. Kaohsiung J Med Sci 2014; 30 (07) 350-361
- 154 DiStefano JK. NAFLD and NASH in postmenopausal women: implications for diagnosis and treatment. Endocrinology 2020; 161 (10) bqaa134
- 155 Weidlinger S, Winterberger K, Pape J. et al. Impact of estrogens on resting energy expenditure: a systematic review. Obes Rev 2023; 24 (10) e13605
- 156 Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism 1991; 40 (12) 1323-1326
- 157 Boardman HM, Hartley L, Eisinga A. et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015; 2015 (03) CD002229
- 158 “The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2022 hormone therapy position statement of the North American Menopause Society. Menopause 2022; 29 (07) 767-794
- 159 Scarabin PY. Progestogens and venous thromboembolism in menopausal women: an updated oral versus transdermal estrogen meta-analysis. Climacteric 2018; 21 (04) 341-345
- 160 Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364: k4810
- 161 Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008; 107 (01) 103-111
- 162 Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F. et al. Use of postmenopausal hormone therapy and risk of Alzheimer's disease in Finland: nationwide case-control study. BMJ 2019; 364: l665
- 163 Davis SR, Baber R, Panay N. et al. Global consensus position statement on the use of testosterone therapy for women. J Clin Endocrinol Metab 2019; 104 (10) 4660-4666
- 164 Casiano Evans EA, Hobson DTG, Aschkenazi SO. et al. Nonestrogen therapies for treatment of genitourinary syndrome of menopause: a systematic review. Obstet Gynecol 2023; 142 (03) 555-570
- 165 Rubinow KB. An intracrine view of sex steroids, immunity, and metabolic regulation. Mol Metab 2018; 15: 92-103
- 166 Simpson E, Rubin G, Clyne C. et al. The role of local estrogen biosynthesis in males and females. Trends Endocrinol Metab 2000; 11 (05) 184-188
- 167 Labrie F. Intracrinology. Mol Cell Endocrinol 1991; 78 (03) C113-C118
- 168 Stocco C. Tissue physiology and pathology of aromatase. Steroids 2012; 77 (1–2): 27-35
- 169 Labrie F, Bélanger A, Pelletier G, Martel C, Archer DF, Utian WH. Science of intracrinology in postmenopausal women. Menopause 2017; 24 (06) 702-712
- 170 Forney JP, Milewich L, Chen GT. et al. Aromatization of androstenedione to estrone by human adipose tissue in vitro. Correlation with adipose tissue mass, age, and endometrial neoplasia. J Clin Endocrinol Metab 1981; 53 (01) 192-199
- 171 Dalla Valle L, Toffolo V, Nardi A. et al. Tissue-specific transcriptional initiation and activity of steroid sulfatase complementing dehydroepiandrosterone sulfate uptake and intracrine steroid activations in human adipose tissue. J Endocrinol 2006; 190 (01) 129-139
- 172 Hetemäki N, Mikkola TS, Tikkanen MJ. et al. Adipose tissue estrogen production and metabolism in premenopausal women. J Steroid Biochem Mol Biol 2021; 209: 105849
- 173 Bélanger C, Luu-The V, Dupont P, Tchernof A. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res 2002; 34 (11–12): 737-745
- 174 Ostinelli G, Laforest S, Denham SG. et al. Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction. J Clin Endocrinol Metab 2022; 107 (08) e3330-e3342
- 175 Vihma V, Wang F, Savolainen-Peltonen H. et al. Quantitative determination of estrone by liquid chromatography-tandem mass spectrometry in subcutaneous adipose tissue from the breast in postmenopausal women. J Steroid Biochem Mol Biol 2016; 155 (Pt A): 120-125
- 176 Savolainen-Peltonen H, Vihma V, Leidenius M. et al. Breast adipose tissue estrogen metabolism in postmenopausal women with or without breast cancer. J Clin Endocrinol Metab 2014; 99 (12) E2661-E2667
- 177 Tchernof A, Mansour MF, Pelletier M, Boulet MM, Nadeau M, Luu-The V. Updated survey of the steroid-converting enzymes in human adipose tissues. J Steroid Biochem Mol Biol 2015; 147: 56-69
- 178 Siiteri PK. Adipose tissue as a source of hormones. Am J Clin Nutr 1987; 45 (1, suppl): 277-282
- 179 Baglietto L, English DR, Hopper JL. et al. Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition. Breast Cancer Res Treat 2009; 115 (01) 171-179
- 180 McTiernan A, Wu L, Chen C. et al; Women's Health Initiative Investigators. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 2006; 14 (09) 1662-1677
- 181 Penell JC, Kushnir MM, Lind L. et al. Concentrations of nine endogenous steroid hormones in 70-year-old men and women. Endocr Connect 2021; 10 (05) 511-520
- 182 Ronconi V, Turchi F, Bujalska IJ, Giacchetti G, Boscaro M. Adipose cell-adrenal interactions: current knowledge and future perspectives. Trends Endocrinol Metab 2008; 19 (03) 100-103
- 183 Campos DB, Palin MF, Bordignon V, Murphy BD. The ‘beneficial’ adipokines in reproduction and fertility. Int J Obes (Lond) 2008; 32 (02) 223-231
- 184 Reed MJ, Purohit A, Woo LW, Newman SP, Potter BV. Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr Rev 2005; 26 (02) 171-202
- 185 Thomas MP, Potter BV. The structural biology of oestrogen metabolism. J Steroid Biochem Mol Biol 2013; 137: 27-49
- 186 Wang J, Feng Y, Liu B, Xie W. Estrogen sulfotransferase and sulfatase in steroid homeostasis, metabolic disease, and cancer. Steroids 2024; 201: 109335
- 187 Hanson SR, Best MD, Wong CH. Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew Chem Int Ed 2004; 43 (43) 5736-5763
- 188 Strott CA. Steroid sulfotransferases. Endocr Rev 1996; 17 (06) 670-697
- 189 Ihunnah CA, Wada T, Philips BJ. et al. Estrogen sulfotransferase/SULT1E1 promotes human adipogenesis. Mol Cell Biol 2014; 34 (09) 1682-1694
- 190 Rižner TL, Gjorgoska M. Steroid sulfatase and sulfotransferases in the estrogen and androgen action of gynecological cancers: current status and perspectives. Essays Biochem 2024; 68 (04) 411-422
- 191 Santner SJ, Feil PD, Santen RJ. In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab 1984; 59 (01) 29-33
- 192 Moeller G, Adamski J. Integrated view on 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 2009; 301 (1–2): 7-19
- 193 Poirier D. Recent advances in the development of 17beta-hydroxysteroid dehydrogenase inhibitors. Steroids 2025; 213: 109529
- 194 Tsachaki M, Odermatt A. Subcellular localization and membrane topology of 17β-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 2019; 489: 98-106
- 195 Moeller G, Adamski J. Multifunctionality of human 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 2006; 248 (1–2): 47-55
- 196 Saloniemi T, Jokela H, Strauss L, Pakarinen P, Poutanen M. The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models. J Endocrinol 2012; 212 (01) 27-40
- 197 Poutanen M, Penning TM. Biology and clinical relevance of hydroxysteroid (17beta) dehydrogenase enzymes. Mol Cell Endocrinol 2019; 489: 1-2
- 198 Blouin 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 (02) E244-E255
- 199 Wang F, Vihma V, Soronen J. et al. 17β-Estradiol and estradiol fatty acyl esters and estrogen-converting enzyme expression in adipose tissue in obese men and women. J Clin Endocrinol Metab 2013; 98 (12) 4923-4931
- 200 Bellemare V, Laberge P, Noël S, Tchernof A, Luu-The V. Differential estrogenic 17beta-hydroxysteroid dehydrogenase activity and type 12 17beta-hydroxysteroid dehydrogenase expression levels in preadipocytes and differentiated adipocytes. J Steroid Biochem Mol Biol 2009; 114 (3–5): 129-134
- 201 Luu-The V. Analysis and characteristics of multiple types of human 17beta-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 2001; 76 (1–5): 143-151
- 202 Fouad Mansour M, Blanchette S, Pelletier M, Poirier D, Tchernof A. 17β-hydroxysteroid dehydrogenase type 2 activity, expression and cellular localization in abdominal adipose tissues from women. Clin Endocrinol (Oxf) 2023; 98 (02) 229-237
- 203 Marchais-Oberwinkler S, Henn C, Möller G. et al. 17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development. J Steroid Biochem Mol Biol 2011; 125 (1–2): 66-82
- 204 Labrie F, Luu-The V, Lin SX, Simard J, Labrie C. Role of 17 beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues. Trends Endocrinol Metab 2000; 11 (10) 421-427
- 205 Simpson ER, Mahendroo MS, Means GD. et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994; 15 (03) 342-355
- 206 Ackerman GE, Smith ME, Mendelson CR, MacDonald PC, Simpson ER. Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 1981; 53 (02) 412-417
- 207 Price T, Aitken J, Head J, Mahendroo M, Means G, Simpson E. Determination of aromatase cytochrome P450 messenger ribonucleic acid in human breast tissue by competitive polymerase chain reaction amplification. J Clin Endocrinol Metab 1992; 74 (06) 1247-1252
- 208 Simpson ER, Zhao Y, Agarwal VR. et al. Aromatase expression in health and disease. Recent Prog Horm Res 1997; 52: 185-213 , discussion 213–214
- 209 Zhao Y, Mendelson CR, Simpson ER. Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes. Mol Endocrinol 1995; 9 (03) 340-349
- 210 Killinger DW, Perel E, Danilescu D, Kharlip L, Lindsay WR. Influence of adipose tissue distribution on the biological activity of androgens. Ann N Y Acad Sci 1990; 595: 199-211
- 211 Bulun SE, Simpson ER. Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 1994; 78 (02) 428-432
- 212 Cleland WH, Mendelson CR, Simpson ER. Effects of aging and obesity on aromatase activity of human adipose cells. J Clin Endocrinol Metab 1985; 60 (01) 174-177
- 213 Misso ML, Jang C, Adams J. et al. Adipose aromatase gene expression is greater in older women and is unaffected by postmenopausal estrogen therapy. Menopause 2005; 12 (02) 210-215
- 214 Edman CD, MacDonald PC. Effect of obesity on conversion of plasma androstenedione to estrone in ovulatory and anovulator young women. Am J Obstet Gynecol 1978; 130 (04) 456-461
- 215 MacDonald PC, Edman CD, Hemsell DL, Porter JC, Siiteri PK. Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. Am J Obstet Gynecol 1978; 130 (04) 448-455
- 216 Battisti S, Guida FM, Coppa F. et al. Modification of abdominal fat distribution after aromatase inhibitor therapy in breast cancer patients visualized using 3-D computed tomography volumetry. Clin Breast Cancer 2014; 14 (05) 365-370
- 217 Jones ME, Thorburn AW, Britt KL. et al. Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. J Steroid Biochem Mol Biol 2001; 79 (1–5): 3-9
- 218 Savolainen-Peltonen H, Vihma V, Wang F. et al. Estrogen biosynthesis in breast adipose tissue during menstrual cycle in women with and without breast cancer. Gynecol Endocrinol 2018; 34 (12) 1039-1043
- 219 GBD 2021 Demographics Collaborators. Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950-2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021. Lancet 2024; 403 (10440): 1989-2056
- 220 HUS Helsinki University Hospital Laboratory, HUS Diagnostic Center (HUSLAB) Test Catalog, Helsinki, Finland. Accessed 2/15/2024. https://huslab.fi/ohjekirja/
- 221 Mayo Clinic Laboratories Test Catalog, Rochester, MN, USA. Accessed 2/15/2024. https://www.mayocliniclabs.com/test-catalog/
- 222 Edlefsen KL, Jackson RD, Prentice RL. et al. The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women. Menopause 2010; 17 (03) 622-629
- 223 Rothman MS, Carlson NE, Xu M. et al. Reexamination of testosterone, dihydrotestosterone, estradiol and estrone levels across the menstrual cycle and in postmenopausal women measured by liquid chromatography-tandem mass spectrometry. Steroids 2011; 76 (1–2): 177-182
- 224 Davis SR, Bell RJ, Robinson PJ. et al; ASPREE Investigator Group. Testosterone and estrone increase from the age of 70 years: findings from the sex hormones in older women study. J Clin Endocrinol Metab 2019; 104 (12) 6291-6300
- 225 Mezzullo M, Pelusi C, Fazzini A. et al. Female and male serum reference intervals for challenging sex and precursor steroids by liquid chromatography - tandem mass spectrometry. J Steroid Biochem Mol Biol 2020; 197: 105538
- 226 Ensrud KE, Larson JC, Guthrie KA. et al. Changes in serum endogenous estrogen concentrations are mediators of the effect of low-dose oral estradiol on vasomotor symptoms. Menopause 2022; 29 (09) 1014-1020
- 227 Verdonk SJE, Vesper HW, Martens F, Sluss PM, Hillebrand JJ, Heijboer AC. Estradiol reference intervals in women during the menstrual cycle, postmenopausal women and men using an LC-MS/MS method. Clin Chim Acta 2019; 495: 198-204
- 228 Slater CC, Hodis HN, Mack WJ, Shoupe D, Paulson RJ, Stanczyk FZ. Markedly elevated levels of estrone sulfate after long-term oral, but not transdermal, administration of estradiol in postmenopausal women. Menopause 2001; 8 (03) 200-203
- 229 Labrie F, Cusan L, Gomez JL. et al. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol 2008; 111 (3–5): 178-194
- 230 Kleider C, Calderón Giraldo J, Pemp D, Esch HL, Lehmann L. Validation of a GC- and LC-MS/MS based method for the quantification of 22 estrogens and its application to human plasma. Steroids 2022; 186: 109077
- 231 Labrie F, Bélanger A, Bélanger P. et al. Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. J Steroid Biochem Mol Biol 2006; 99 (4–5): 182-188
- 232 Eisenhofer G, Peitzsch M, Kaden D. et al. Reference intervals for plasma concentrations of adrenal steroids measured by LC-MS/MS: Impact of gender, age, oral contraceptives, body mass index and blood pressure status. Clin Chim Acta 2017; 470: 115-124
- 233 Wang F, Koskela A, Hämäläinen E. et al. Quantitative determination of dehydroepiandrosterone fatty acyl esters in human female adipose tissue and serum using mass spectrometric methods. J Steroid Biochem Mol Biol 2011; 124 (3–5): 93-98