Skip to main content

Advertisement

SpringerLink
Log in

Androgens and Hypertension in Men and Women: a Unifying View

  • Hypertension and Metabolic Syndrome (J Sperati, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality.

Recent Findings

Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension.

Summary

Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be a major determinant of the increased prevalence of hypertension. The relationship between androgen signalling and NF-kB might explain the pathophysiological mechanism leading to the development of endothelium dysfunction and hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of Importance •• Of Major Importance

  1. Maranon R, Reckelhoff JF. Sex and gender differences in control of blood pressure. Clin Sci (Lond). 2013;125(7):311–8.

    Article  Google Scholar 

  2. Himmelmann A, Svensson A, Hansson L. Influence of sex on blood pressure and left ventricular mass in adolescents: the hypertension in pregnancy offspring study. J Hum Hypertens. 1994;8(7):485–90.

    CAS  PubMed  Google Scholar 

  3. Stamler J, Stamler R, Riedlinger WF, Algera G, Roberts RH. Hypertension screening of 1 million Americans. Community hypertension evaluation clinic (CHEC) program, 1973 through 1975. JAMA. 1976;235(21):2299–306.

    Article  CAS  PubMed  Google Scholar 

  4. Yanes LL, Reckelhoff JF. A new piece in the hypertension puzzle: central blood pressure regulation by sex steroids. Am J Physiol Heart Circ Physiol. 2009;297(5):H1583–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. • Reckelhoff JF, Roman RJ. Androgens and hypertension: role in both males and females? Hypertension. 2011;57(4):681–2. The study explores the potential mechanisms by which androgens could increase BP and why prevalence of hypertension in men is greater than in women during the reproductive age while incidence of hypertension increases in women until it exceeds that in men.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Festa A, D’Agostino R Jr, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study (IRAS). Circulation. 2000;102(1):42–7.

    Article  CAS  PubMed  Google Scholar 

  7. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291(16):1978–86.

    Article  CAS  PubMed  Google Scholar 

  8. Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl). 2011;89(7):667–76.

    Article  CAS  Google Scholar 

  9. Odegaard JI, Chawla A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science. 2013;339(6116):172–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cai JJ, Wen J, Jiang WH, Lin J, Hong Y, Zhu YS. Androgen actions on endothelium functions and cardiovascular diseases. J Geriatr Cardiol. 2016;13(2):183–96.

    PubMed  PubMed Central  Google Scholar 

  11. Kienitz T, Quinkler M. Testosterone and blood pressure regulation. Kidney Blood Press Res. 2008;31(2):71–9.

    Article  CAS  PubMed  Google Scholar 

  12. Chen YF, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992;19(5):456–63.

    Article  CAS  PubMed  Google Scholar 

  13. Ellison KE, Ingelfinger JR, Pivor M, Dzau VJ. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J Clin Invest. 1989;83(6):1941–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hestiantoro A, Swaab DF. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer’s disease neuropathology. J Clin Endocrinol Metab. 2004;89(4):1912–25.

    Article  CAS  PubMed  Google Scholar 

  15. Sartori-Valinotti JC, Iliescu R, Fortepiani LA, Yanes LL, Reckelhoff JF. Sex differences in oxidative stress and the impact on blood pressure control and cardiovascular disease. Clin Exp Pharmacol Physiol. 2007;34(9):938–45.

    Article  CAS  PubMed  Google Scholar 

  16. Vikan T, Johnsen SH, Schirmer H, Njølstad I, Svartberg J. Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromsø study. Eur J Epidemiol. 2009;24(6):289–95.

    Article  CAS  PubMed  Google Scholar 

  17. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68–75.

    Article  CAS  PubMed  Google Scholar 

  18. Dixit KCS, Wu J, Smith LB, Hadoke PWF, Wu FCW. Androgens and coronary artery disease. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-2015.

    Google Scholar 

  19. Moulana M, Lima R, Reckelhoff JF. Metabolic syndrome, androgens, and hypertension. Curr Hypertens Rep. 2011;13(2):158–62.

    Article  CAS  PubMed  Google Scholar 

  20. Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev. 2003;24(3):313–40.

    Article  CAS  PubMed  Google Scholar 

  21. Mah PM, Wittert GA. Obesity and testicular function. Mol Cell Endocrinol. 2010;316(2):180–6.

    Article  CAS  PubMed  Google Scholar 

  22. Mårin P, Holmäng S, Gustafsson C, Jönsson L, Kvist H, Elander A, Eldh J, Sjöström L, Holm G, Björntorp P. Androgen treatment of abdominally obese men. Obes Res. 1993;1(4):245–51.

    Article  PubMed  Google Scholar 

  23. Zitzmann M. Mechanisms of disease: pharmacogenetics of testosterone therapy in hypogonadal men. Nat Clin Pract Urol. 2007;4(3):161–6.

    Article  CAS  PubMed  Google Scholar 

  24. Reckelhoff JF, Yanes LL, Iliescu R, Fortepiani LA, Granger JP. Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease. Am J Physiol Renal Physiol. 2005;289(5):F941–8.

    Article  CAS  PubMed  Google Scholar 

  25. Yanes LL, Sartori-Valinotti JC, Iliescu R, Romero DG, Racusen LC, Zhang H, Reckelhoff JF. Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats. Am J Physiol Renal Physiol. 2009;296(4):F771–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. •• Navarro G, Allard C, Xu W, Mauvais-Jarvis F. The role of androgens in metabolism, obesity, and diabetes in males and females. Obesity (Silver Spring). 2015;23(4):713–9. This review discusses the possibility that the effects of androgens on metabolic syndrome and its sequelae may differ between males and females.

    Article  CAS  Google Scholar 

  27. • Francomano D, Ilacqua A, Bruzziches R, Lenzi A, Aversa A. Effects of 5-year treatment with testosterone undecanoate on lower urinary tract symptoms in obese men with hypogonadism and metabolic syndrome. Urology. 2014;83(1):167–73. This study investigates the effects of TRT during 5 years of treatment for hypogonadism associated with metabolic syndrome and its impact on urinary function and symptoms.

    Article  PubMed  Google Scholar 

  28. Collins L, Basaria S. Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications. Asian J Androl. 2012;14(2):222–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. •• Choi SM, Kam SC. Metabolic effects of androgen deprivation therapy. Korean J Urol. 2015;56(1):12–8. In this study metabolic and cardiovascular complications of androgen deprivation therapy (ADT) are evaluated. ADT, the main treatment method for metastatic prostate cancer, increases the risk for cardiovascular events.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hakimian P, Blute M Jr, Kashanian J, Chan S, Silver D, Shabsigh R. Metabolic and cardiovascular effects of androgen deprivation therapy. BJU Int. 2008;102(11):1509–14.

    Article  PubMed  Google Scholar 

  31. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89(7):3313–8.

    Article  CAS  PubMed  Google Scholar 

  32. Cohen PG. Obesity in men: the hypogonadal-estrogen receptor relationship and its effect on glucose homeostasis. Med Hypotheses. 2008;70(2):358–60.

    Article  CAS  PubMed  Google Scholar 

  33. Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84(10):3673–80.

    CAS  PubMed  Google Scholar 

  34. •• Dubois V, Laurent MR, Jardi F, Antonio L, Lemaire K, Goyvaerts L, Deldicque L, Carmeliet G, Decallonne B, Vanderschueren D, Claessens F. Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice. Endocrinology. 2016;157(2):648–65. In this paper the importance of a healthy diet in a clinical context of androgen deficiency is stressed. It may have implications for the prevention of metabolic alterations in hypogonadal men.

    Article  CAS  PubMed  Google Scholar 

  35. Salam R, Kshetrimayum AS, Keisam R. Testosterone and metabolic syndrome: the link. Indian J Endocrinol Metab. 2012;16(Suppl 1):S12–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yanes LL, Reckelhoff JF. Postmenopausal hypertension. Am J Hypertens. 2011;24(7):740-9.

  37. Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci U S A. 1994;91(11):5212–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nickenig G, Böhm M. Interaction between insulin and AT1 receptor. Relevance for hypertension and arteriosclerosis. Basic Res Cardiol. 1998;93(Suppl 2):135–9.

    Article  CAS  PubMed  Google Scholar 

  39. Xue B, Singh M, Guo F, Hay M, Johnson AK. Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide. Am J Physiol Heart Circ Physiol. 2009;297(5):H1638–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. • Huang CK, Lee SO, Chang E, Pang H, Chang C. Androgen receptor (AR) in cardiovascular diseases. J Endocrinol. 2016;229(1):R1–R16. This paper underlines that androgen deficiency causes elevated lipid accumulation enhancing atherosclerosis, and that AR plays an important role in contributing to obesity and insulin/leptin resistance to increase the metabolic syndrome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lobo RA, Carmina E. The importance of diagnosing the polycystic ovary syndrome. Ann Intern Med. 2000;132:989–93.

    Article  CAS  PubMed  Google Scholar 

  42. Carmina E, Napoli N, Longo RA, Rini GB, Lobo RA. Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS. Eur J Endocrinol. 2006;154:141–5.

    Article  CAS  PubMed  Google Scholar 

  43. • Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists, American College of Endocrinology, and androgen excess and PCOS society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 1. Endocr Pract. 2015;21(11):1291–300. A review of recent findings that clarifies the clinical practice for PCOS treatment, considering metabolic alteration, insulin resistance and cardiovascular risk.

    Article  PubMed  Google Scholar 

  44. Jovanovic VP, Carmina E, Lobo RA. Not all women diagnosed with PCOS share the same cardiovascular risk profiles. Fertil Steril. 2010;94:826–32.

    Article  PubMed  Google Scholar 

  45. Guastella E, Longo RA, Carmina E. Clinical and endocrine characteristics of the main PCOS phenotypes. Fertil Steril. 2010;94:2197–201.

    Article  CAS  PubMed  Google Scholar 

  46. Carmina E. Obesity, Adipokines and metabolic syndrome in polycystic ovary syndrome. Front Horm Res. 2013;40:40–50.

    Article  CAS  PubMed  Google Scholar 

  47. • Sarray S, Madan S, Saleh LR, Mahmoud N, Almawi WY. Validity of adiponectin-to-leptin and adiponectin-to-resistin ratios as predictors of polycystic ovary syndrome. Fertil Steril. 2015;104(2):460–6. This study shows that adiponectin/leptin and adiponectin/resistin ratios play an important role in metabolic syndrome and hypertension in women affected with PCOS.

    Article  CAS  PubMed  Google Scholar 

  48. Vasan RS, Larson MG, Leip EP, Evans JC, O’Donnell CJ, Kannel WB, Levy D. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345(18):1291–7.

    Article  CAS  PubMed  Google Scholar 

  49. Ong KL, Tso AW, Lam KS, Cheung BM. Gender difference in blood pressure control and cardiovascular risk factors in Americans with diagnosed hypertension. Hypertension. 2008;51(4):1142–8.

    Article  CAS  PubMed  Google Scholar 

  50. Wiinberg N, Høegholm A, Christensen HR, Bang LE, Mikkelsen KL, Nielsen PE, Svendsen TL, Kampmann JP, Madsen NH, Bentzon MW. 24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender. Am J Hypertens. 1995;8(10 Pt 1):978–86.

    Article  CAS  PubMed  Google Scholar 

  51. Laughlin GA, Barrett-Connor E. Sexual dimorphism in the influence of advanced aging on adrenal hormone levels: the rancho Bernardo study. J Clin Endocrinol Metab. 2000;85(10):3561–8.

    CAS  PubMed  Google Scholar 

  52. Labrie F, Bélanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. JCEM. 1997;82:2386–92.

    Google Scholar 

  53. Piltonen T, Koivunen R, Ruokonen A, Tapanainen JS. Ovarian age-related responsiveness to human chorionic gonadotropin. JCEM. 2003;88:3327–32.

    CAS  PubMed  Google Scholar 

  54. 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;90:3847–53.

    Article  CAS  PubMed  Google Scholar 

  55. Carmina E, Campagna AM, Lobo RA. A 20-year follow-up of young women with polycystic ovary syndrome. Obstet Gynecol. 2012;119:263–9.

    Article  PubMed  Google Scholar 

  56. •• Rutkowski K, Sowa P, Rutkowska-Talipska J, Kuryliszyn-Moskal A, Rutkowski R. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. 2014;74(11):1195–207. This paper underlines that in women after menopause the relative androgen deficiency is related to metabolic dysfunction and visceral fat depot increasing CVD

    Article  CAS  PubMed  Google Scholar 

  57. Carmina E, Chu MC, Moran C, Tortoriello D, Vardhana P, Tena G, Preciado R, Lobo R. Subcutaneous and omental fat expression of adiponectin and leptin in women with polycystic ovary syndrome. Fertil Steril. 2008;89:642–8.

    Article  CAS  PubMed  Google Scholar 

  58. Ely DL, Salisbury R, Hadi D, Turner M, Johnson ML. Androgen receptor and the testes influence hypertension in a hybrid rat model. Hypertension. 1991;17(6 Pt 2):1104–10.

    Article  CAS  PubMed  Google Scholar 

  59. Rayet B, Gélinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18(49):6938–47.

    Article  CAS  PubMed  Google Scholar 

  60. Pentikäinen V, Suomalainen L, Erkkilä K, Martelin E, Parvinen M, Pentikäinen MO, Dunkel L. Nuclear factor-kappa B activation in human testicular apoptosis. Am J Pathol. 2002;160(1):205–18.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Baud V, Karin M. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov. 2009;8(1):33–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. •• Baker RG, Hayden MS, Ghosh S. NF-κB, inflammation, and metabolic disease. Cell Metab. 2011;13(1):11–22. In this review the role of NF-kB in endothelial dysfunction and foam cells biogenesis in metabolic syndrome is discussed.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y, Ogawa Y. Role of the toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol. 2007;27(1):84–91.

    Article  CAS  PubMed  Google Scholar 

  64. Chang I, Kim S, Kim JY, Cho N, Kim YH, Kim HS, Lee MK, Kim KW, Lee MS. Nuclear factor kappaB protects pancreatic beta-cells from tumor necrosis factor-alpha-mediated apoptosis. Diabetes. 2003;52(5):1169–75.

    Article  CAS  PubMed  Google Scholar 

  65. Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA, Neumeier D. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest. 1996;97(7):1715–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gareus R, Kotsaki E, Xanthoulea S, van der Made I, Gijbels MJ, Kardakaris R, Polykratis A, Kollias G, de Winther MP, Pasparakis M. Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. Cell Metab. 2008;8(5):372–83.

    Article  CAS  PubMed  Google Scholar 

  67. •• Zhang L, Altuwaijri S, Deng F, Chen L, Lal P, Bhanot UK, Korets R, Wenske S, Lilja HG, Chang C, Scher HI, Gerald WL. NF-kappaB regulates androgen receptor expression and prostate cancer growth. Am J Pathol. 2009;175(2):489–99. The study concerns the implications of the transcription factor NF-kB in tumorigenesis and how it may promote AR transcription activation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UOC of Endocrinology and Diabetes, TorVergata University of Rome, Reproductive Endocrinology Section, San Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy

    Costanzo Moretti

  2. Department Experimental Medicine-Medical Physiopathology, Food Science and Endocrinology Section, “Sapienza” University of Rome, Rome, Italy

    Giulia Lanzolla & Lucio Gnessi

  3. Laboratory of Molecular Oncology, Department of Molecular Medicine, “Sapienza” University of Rome, Rome, Italy

    Marta Moretti

  4. Department of Health Sciences and Mother and Child Care, University of Palermo, Palermo, Italy

    Enrico Carmina

Authors
  1. Costanzo Moretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giulia Lanzolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marta Moretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucio Gnessi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Enrico Carmina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Enrico Carmina.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Hypertension and Metabolic Syndrome

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moretti, C., Lanzolla, G., Moretti, M. et al. Androgens and Hypertension in Men and Women: a Unifying View. Curr Hypertens Rep 19, 44 (2017). https://doi.org/10.1007/s11906-017-0740-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-017-0740-3

Keywords

Search

Navigation