Abstract
Androgen excess (AE) was approximated to be present in 7 % of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5–7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.
Similar content being viewed by others
References
Azziz R, Sanchez LA, Knochenhauer ES et al (2004) Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 89:453–462
Carmina E, Rosato F, Janni A, Rizzo M, Longo RA (2006) Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 91:2–6
Diamanti-Kandarakis E, Kouli CR, Bergiele AT et al (1999) A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 84:4006–4011
Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF (2000) A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 85:2434–2438
Sanchon R, Gambineri A, Alpanes M, Martinez-Garcia MA, Pasquali R, Escobar-Morreale HF (2012) Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors. Hum Reprod 27:1209–1216
Laughlin GA, Goodell V, Barrett-Connor E (2010) Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women. J Clin Endocrinol Metab 95:740–747
Ouyang P, Vaidya D, Dobs A et al (2009) Sex hormone levels and subclinical atherosclerosis in postmenopausal women: the Multi-Ethnic Study of atherosclerosis. Atherosclerosis 204:255–261
Mäki-Petäjä KM, Wilkinson IB (2012) Inflammation and large arteries: potential mechanisms for inflammation-induced arterial stiffness potential mechanisms for inflammation-induced arterial stiffness. Artery Res 6:59–64
Wang L, Szklo M, Folsom AR, Cook NR, Gapstur SM, Ouyang P (2012) Endogenous sex hormones, blood pressure change, and risk of hypertension in postmenopausal women: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 224:228–234
Diamanti-Kandarakis E, Dunaif A (2012) Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 33:981–1030
Despres JP (2006) Intra-abdominal obesity: an untreated risk factor for Type 2 diabetes and cardiovascular disease. J Endocrinol Invest 29:77–82
Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA, Chrousos GP (2007) Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 18:280–285
Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H (2007) Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 92:405–413
Christakou C, Diamanti-Kandarakis E (2013) Structural, biochemical and non-traditional cardiovascular risk markers in PCOS. Curr Pharm Des 19:5764–5774
Toulis KA, Goulis DG, Mintziori G et al (2011) Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum Reprod Update 17:741–760
Carmina E, Campagna AM, Lobo RA (2013) Emergence of ovulatory cycles with aging in women with polycystic ovary syndrome (PCOS) alters the trajectory of cardiovascular and metabolic risk factors. Hum Reprod 28:2245–2252
Shaw LJ, Bairey Merz CN, Azziz R et al (2008) Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health-National Heart, Lung, and Blood Institute sponsored Women’s Ischemia Syndrome Evaluation. J Clin Endocrinol Metab 93:1276–1284
Kurdoglu Z, Ozkol H, Tuluce Y, Koyuncu I (2012) Oxidative status and its relation with insulin resistance in young non-obese women with polycystic ovary syndrome. J Endocrinol Invest 35:317–321
Diamanti-Kandarakis E, Alexandraki K, Piperi C et al (2006) Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur J Clin Invest 36:691–697
Legro RS, Kunselman AR, Dunaif A (2001) Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 111:607–613
Macut D, Panidis D, Glisic B et al (2008) Lipid and lipoprotein profile in women with polycystic ovary syndrome. Can J Physiol Pharmacol 86:199–204
Liu Y, Ding J, Bush TL et al (2001) Relative androgen excess and increased cardiovascular risk after menopause: a hypothesized relation. Am J Epidemiol 154:489–494
Rizzo M, Longo RA, Guastella E, Rini GB, Carmina E (2011) Assessing cardiovascular risk in Mediterranean women with polycystic ovary syndrome. J Endocrinol Invest 34:422–426
Macut D, Damjanovic S, Panidis D et al (2006) Oxidised low-density lipoprotein concentration—early marker of an altered lipid metabolism in young women with PCOS. Eur J Endocrinol 155:131–136
Bentley-Lewis R, Seely E, Dunaif A (2011) Ovarian hypertension: polycystic ovary syndrome. Endocrinol Metab Clin North Am 40:433–449 (ix–x)
de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FM (2011) PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reprod Update 17:495–500
Mani H, Levy MJ, Davies MJ et al (2013) Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study. Clin Endocrinol (Oxf) 78:926–934
Wild RA, Carmina E, Diamanti-Kandarakis E et al (2010) Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 95:2038–2049
Macut D, Micic D, Cvijovic G et al (2001) Cardiovascular risk in adolescent and young adult obese females with polycystic ovary syndrome (PCOS). J Pediatr Endocrinol Metab 14(suppl 5):1353–1359 (discussion 1365)
Carmina E (2013) Oral contraceptives and cardiovascular risk in women with polycystic ovary syndrome. J Endocrinol Invest 36:358–363
Macut D, Simic T, Lissounov A et al (2011) Insulin resistance in non-obese women with polycystic ovary syndrome: relation to byproducts of oxidative stress. Exp Clin Endocrinol Diabetes 119:451–455
Repaci A, Gambineri A, Pasquali R (2010) The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 335:30–41
Diamanti-Kandarakis E, Katsikis I, Piperi C et al (2008) Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 69:634–641
Guven S, Karahan SC, Bayram C, Ucar U, Ozeren M (2009) Elevated concentrations of serum ischaemia-modified albumin in PCOS, a novel ischaemia marker of coronary artery disease. Reprod Biomed Online 19:493–500
Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS (2004) Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab 89:5454–5461
Shroff R, Kerchner A, Maifeld M, Van Beek EJ, Jagasia D, Dokras A (2007) Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab 92:4609–4614
Kravariti M, Naka KK, Kalantaridou SN et al (2005) Predictors of endothelial dysfunction in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:5088–5095
Ciccone MM, Favale S, Bhuva A et al (2009) Anteroposterior diameter of the infrarenal abdominal aorta is higher in women with polycystic ovary syndrome. Vasc Health Risk Manag 5:561–566
Wang ET, Ku IA, Shah SJ et al (2012) Polycystic ovary syndrome is associated with higher left ventricular mass index: the CARDIA women’s study. J Clin Endocrinol Metab 97:4656–4662
Cakir E, Dogan M, Topaloglu O et al (2013) Subclinical atherosclerosis and hyperandrogenemia are independent risk factors for increased epicardial fat thickness in patients with PCOS and idiopathic hirsutism. Atherosclerosis 226:291–295
Charmandari E, Weise M, Bornstein SR et al (2002) Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. J Clin Endocrinol Metab 87:2114–2120
Arlt W, Willis DS, Wild SH et al (2010) Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab 95:5110–5121
Mancini T, Kola B, Mantero F, Boscaro M, Arnaldi G (2004) High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin Endocrinol (Oxf) 61:768–777
Volkl TM, Simm D, Dotsch J, Rascher W, Dorr HG (2006) Altered 24-hour blood pressure profiles in children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 91:4888–4895
Amr NH, Ahmed AY, Ibrahim YA (2014) Carotid intima media thickness and other cardiovascular risk factors in children with congenital adrenal hyperplasia. J Endocrinol Invest 37:1001–1008
Botero D, Arango A, Danon M, Lifshitz F (2000) Lipid profile in congenital adrenal hyperplasia. Metabolism 49:790–793
Zimmermann A, Grigorescu-Sido P, AlKhzouz C et al (2010) Alterations in lipid and carbohydrate metabolism in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res Paediatr 74:41–49
Falhammar H, Filipsson H, Holmdahl G et al (2007) Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 92:110–116
Harrington J, Pena AS, Gent R, Hirte C, Couper J (2012) Adolescents with congenital adrenal hyperplasia because of 21-hydroxylase deficiency have vascular dysfunction. Clin Endocrinol (Oxf) 76:837–842
Unluhizarci K, Kaltsas G, Kelestimur F (2012) Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism. Eur J Clin Invest 42:86–94
Talaei A, Adgi Z, Mohamadi Kelishadi M (2013) Idiopathic hirsutism and insulin resistance. Int J Endocrinol 2013:593197
Erkan M, Albayrak M, Karatas A et al (2014) Are insulin resistance and serum resistin levels increased in women with idiopathic hirsutism? Eur Rev Med Pharmacol Sci 18:1889–1895
Young RH, Scully RE (2001) Differential diagnosis of ovarian tumors based primarily on their patterns and cell types. Semin Diagn Pathol 18:161–235
Pelusi C, Forlani G, Zanotti L, Gambineri A, Pasquali R (2013) No metabolic impact of surgical normalization of hyperandrogenism in postmenopausal women with ovarian androgen-secreting tumours. Clin Endocrinol (Oxf) 78:533–538
Diamanti-Kandarakis E, Mitrakou A, Raptis S, Tolis G, Duleba AJ (1998) The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. J Clin Endocrinol Metab 83:2699–2705
Studen KB, Sebestjen M, Pfeifer M, Prezelj J (2011) Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome. Eur J Endocrinol 164:389–395
Naka KK, Kalantaridou SN, Bechlioulis A et al (2011) Effect of ethinylestradiol/cyproterone acetate on endothelial function in young non-obese women with polycystic ovary syndrome: a pilot study. Gynecol Endocrinol 27:615–621
Tfayli H, Ulnach JW, Lee S, Sutton-Tyrrell K, Arslanian S (2011) Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors. J Clin Endocrinol Metab 96:1311–1319
Vieira CS, Martins WP, Fernandes JB et al (2012) The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome. Contraception 86:268–275
Mastorakos G, Koliopoulos C, Creatsas G (2002) Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril 77:919–927
Cinar N, Harmanci A, Bayraktar M, Yildiz BO (2013) Ethinyl estradiol-drospirenone vs ethinyl estradiol-drospirenone plus metformin in the treatment of lean women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 78:379–384
Merz CN, Johnson BD, Berga S, Braunstein G, Reis SE, Bittner V (2006) Past oral contraceptive use and angiographic coronary artery disease in postmenopausal women: data from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation. Fertil Steril 85:1425–1431
Bird ST, Hartzema AG, Brophy JM, Etminan M, Delaney JA (2013) Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. CMAJ 185:E115–E120
Conflict of interest
The authors of the manuscript declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Macut, D., Antić, I.B. & Bjekić-Macut, J. Cardiovascular risk factors and events in women with androgen excess. J Endocrinol Invest 38, 295–301 (2015). https://doi.org/10.1007/s40618-014-0215-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-014-0215-1