DOI: 10.3724/SP.J.1263.2011.00035

Journal of Geriatric Cardiology 2011/8:1 PP.35-43

Andropause and the development of cardiovascular disease presentation-more than an epi-phenomenon

Andropause refers to a generalized decline of male hormones, including testosterone and dehydroepiandrosterone in middle-aged and aging men. This decline in hormones has been associated with changes such as depression, loss of libido, sexual dysfunction, and changes in body composition. Aging has been associated with an abundance of concomitant diseases, in particular cardiovascular diseases, and although andropause is correlated to aging, a causal relationship between reduction of androgens and the development of chronic diseases such as atherosclerosis and heart failure has not been convincingly established yet. On the other hand, increasing data has emerged that revealed the effects of low levels of androgens on cardiovascular disease progression. As an example, low levels of testosterone have been linked to a higher incidence of coronary artery disease. Whether hormone replacement therapy that is used for andropausal men to alleviate symptoms of “male menopause” can halt progression of cardiovascular disease, remains controversially discussed, primarily due to the lack of well-designed, randomized controlled trials. At least for symptom improvement, the use of androgen replacement therapy in andropausal men may be clinically indicated, and with the appropriate supervision and follow up may prove to be beneficial with regard to preservation of the integrity of cardiovascular health at higher ages.

Key words:andropause,age,androgen,testosterone,heart disease,heart failure,hormone therapy

ReleaseDate:2014-07-21 15:39:57

1 Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37: 614-636.

2 Hayflick L. Aging is not a disease. Aging 1998; 10: 146.

3 Hayflick L. "Anti-aging" is an oxymoron. J Gerontol A Biol Sci Med Sci. 2004; 59(6): B573-578.

4 Idler EL. Discussion: gender differences in self-rated health, in mortality, and in the relationship between the two. Gerontologist 2003; 43: 372-375.

5 Deeg DJH, Bath PA. Self-rated health, gender, and mortality in older persons: introduction to a special section. Gerontologist 2003; 43: 369-371.

6 Benyamini Y, Blumstein T, Lusky A, et al. Gender differences in the self-rated health-mortality association: is it poor self-rated health that predicts mortality or excellent self-rated health that predicts survival? Gerontologist 2003; 43: 396-405.

7 Paganelli R, Di Iorio A, Cherubini A, et al. Frailty of older age: the role of the endocrine--immune interaction. Curr Pharm Des 2006; 12: 3147-3159.

8 Schwarz ER. Heart failure in the elderly-some aspects in pathophysiology, diagnosis and therapy that require special attention. J Geriatr Cardiol 2007; 4: 44-49.

9 Walker EM Jr, Nillas MS, Mangiarua EI, et al. Age-associated changes in hearts of male Fischer 344/brown norway f1 rats. Ann Clin Lab Sci 2006; 36: 427-438.

10 Pandya K, Kim HS, Smithies O. Fibrosis, not cell size, delineates beta-myosinheavy chain reexpression during cardiac hypertrophy and normal aging in vivo. Proc Natl Acad Sci USA 2006; 103: 16864-16869.

11 Paternostro G, Vignola C, Bartsch DU, et al. Age-associated cardiac dysfunction in Drosophila melanogaster. Circ Res 2001; 88: 1053-1058.

12 Ocorr K, Akasaka T, Bodmer R. Age-related cardiac disease model of Drosophila. Mech Ageing Dev 2007; 128: 112-116.

13 Golubnitschaja O. Cell cycle checkpoints: the role and evaluation for early diagnosis of senescence, cardiovascular, cancer, and neurodegenerative diseases. Amino Acids 2007; 32: 359-371.

14 Fülöp N, Mason MM, Dutta K, et al. The impact of Type-2 diabetes and aging on cardiomyocyte function and O-Linked N-acetylglucosamine levels in the heart. Am J Physiol Cell Physiol 2007; 292: C1370-1378.

15 Kayo T, Allison DB, Weindruch R, et al. Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc Natl Acad Sci USA 2001; 98:5093-5098.

16 Zhang X, Azhar G, Furr MC, et al. Model of functional cardiac aging: young adult mice with mild overexpression of serum response factor. Am J Physiol Regul Integr Comp Physiol 2003; 285: R552-560.

17 Azhar G, Zhang X, Wang S, et al. Maintaining serum response factor activity in the older heart equal to that of the young adult is associated with better cardiac response to isoproterenol stress. Basic Res Cardiol 2007; 102: 233-244.

18 Marin-Garcia J, Pi Y, Goldenthal MJ. Mitochondrial-nuclear Cross-talk in the Aging and Failing Heart. Cardiovasc Drugs Ther 2006; 20: 477-491.

19 Torraco A, Diaz F, Vempati UD, et al. Mouse models of oxidative phosphorylation defects: Powerful tools to study the pathobiology of mitochondrial diseases. Biochim Biophys Acta 2009; 1793:171-180.

20 Trifunovic A, Hansson A, Wredenberg A, et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 2005; 102: 17993-17998.

21 Nguyen TV, Jayaraman A, Quaglino A, et al. Androgens selectively protect against apoptosis in hippocampal neurones. J Neuroendocrinol 2010; 22(9):1013-1022.

22 Ikeda Y, Aihara K, Akaike M, et al. Androgen receptor counteracts Doxorubicin-induced cardiotoxicity in male mice. Mol Endocrinol 2010; 24:1338-1348.

23 Vicencio JM, Ibarra C, Estrada M, et al. Testosterone induces an intracellular calcium increase by a nongenomic mechanism in cultured rat cardiac myocytes. Endocrinology 2006; 147: 1386-1395.

24 Zaugg M, Jamali NZ, Lucchinetti E, et al. Anabolic-androgenic steroids induce apoptotic cell death in adult rat ventricular myocytes. J Cell Physiol 2001; 187: 90-95.

25 Ahlgrim C, Guglin M. Anabolics and cardiomyopathy in a bodybuilder: case report and literature review. J Card Fail 2009; 15: 496-500.

26 Kindermann W. Cardiovascular side effects of anabolic- androgenic steroids. Herz 2006; 31: 566-573.

27 Nieminen MS, Rämö MP, Viitasalo M, et al. Serious cardiovascular side effects of large doses of anabolic steroids in weight lifters. Eur Heart J 1996; 17: 1576-1583.

28 Blümel JE, Chedraui P, Gili SA, et al. Is the Androgen Deficiency of Aging Men (ADAM) questionnaire useful for the screening of partial androgenic deficiency of aging men? Maturitas 2009; 63: 365-368.

29 Mäkinen JI, Perheentupa A, Irjala K, et al. Endogenous testosterone and serum lipids in middle-aged men. Atherosclerosis 2008; 197: 688-693.

30 Kaushik M, Sontineni SP, Hunter C. Cardiovascular disease and androgens: a review. Int J Cardiol 2010; 142: 8-14.

31 Schuler-Luttmann S, Monnig G, Enbergs A, et al. Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis. Arterioscler Thromb Vasc Biol 2000; 20: E10-15.

32 Mäkinen J, Järvisalo MJ, Pöllänen P, et al. Increased carotid atherosclerosis in andropausal middle-aged men. J Am Coll Cardiol 2005; 45: 1603-1608.

33 Javeshghani D, Sairam MR, Schiffrin EL, et al. Increased blood pressure, vascular inflammation, and endothelial dysfunction in androgen-deficient follitropin receptor knockout male mice. J Am Soc Hypertens 2007; 1: 353-361.

34 Haren MT, Kim MJ, Tariq SH, et al. Andropause: a quality-of-life issue in older males. Med Clin North Am 2006; 90: 1005-1023.

35 Denti L. The PADAM syndrome and its clinical manifestations: the muscle mass. J Endocrinol Invest 2005; 28(11 suppl): 43-45.

36 Wiltink J, Beutel ME, Brähler E, et al. Hypogonadism- related symptoms: development and evaluation of an empirically derived self-rating instrument (HRS 'Hypogonadism Related Symptom Scale'). Andrologia 2009; 41: 297-304.

37 Mitsiades N, Correa D, Gross CP, et al. Cognitive effects of hormonal therapy in older adults. Semin Oncol 2008; 35: 569-581.

38 Komiya A, Watanabe A, Fuse H. Bone and Men’s Health. Late-onset hypogonadism in males and male menopause (andropause). Clin Calcium 2010; 20: 234-244.

39 Schreiber G, Ziemer M. The aging male--diagnosis and therapy of late-onset hypogonadism. J Dtsch Dermatol Ges 2008; 6: 273-279.

40 Fuller SJ, Tan RS, Martins RN. Androgens in the etiology of Alzheimer's disease in aging men and possible therapeutic interventions. J Alzheimers Dis 2007; 12: 129-142.

41 Morley JE. Andropause, testosterone therapy, and quality of life in aging men. Cleve Clin J Med 2000; 67: 880-882.

42 Watkins ES. The medicalisation of male menopause in America. Soc Hist Med 2007; 20: 369-388.

43 Travison TG, Shackelton R, Araujo AB, et al. The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission. J Am Geriatr Soc 2008; 56: 831-839.

44 Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363:109-122.

45 Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrin Metabol 2007; 93: 68-75.

46 Haring R, Völzke H, Steveling A, et al. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79. Eur Heart J 2010; 31: 1494-1501.

47 Testosterone for ‘late-onset hypogonadism’ in men? Drug Ther Bull 2010; 48: 69-72.