The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction

Murat Topcuoğlu

doi:10.4274/atfm.galenos.2022.09226

Research Article

Yüksek Homosistein Seviyelerinin Erektil Disfonksiyon Süresi ve Şiddeti Üzerine Etkileri

Year 2022, Volume: 75 Issue: 1, 124 - 129, 30.06.2022

Murat Topcuoğlu

Abstract

Amaç: Yüksek serum homosistein düzeyleri ile erektil disfonksiyon (ED) şiddeti, süresi ve aynı zamanda vasküler patoloji içeren diabetes mellitus
(DM), aterosklerotik kalp hastalığı (ASKH), metabolik sendrom, hipertansiyon gibi hastalıklarla olan ilişkisini klinik ve laboratuvar değerleri ile
göstermeyi amaçladık.

Gereç ve Yöntem: ED şikayeti ile başvuran 82 hasta, serum homosistein değerlerine göre, 15 μmol/L’den düşük hastalar (Grup 1) ve 15 μmol/L’den
yüksek hastalar (Grup 2) olarak iki gruba ayrıldı. Her iki grup yaş, ED süresi ve şiddeti, eşlik eden sistemik hastalıklar öyküsü DM, ASKH, hipertansiyon
ve laboratuvar [açlık kan şekeri, total kolesterol, yüksek yoğunluklu lipoprotein (HDL), düşük yoğunluklu lipoprotein (LDL), çok düşük yoğunluklu
lipoprotein (VLDL), trigliserit, total testosteron] değerleri açısından karşılaştırıldı. Hastaların ED şiddeti Uluslararası Erektil Fonksiyon İndeksi anketinin
kısa formu ile değerlendirildi.

Bulgular: Grup 2 hastalarda ED şiddeti ve süresi ortalaması, Grup 1 hastalara göre istatistiksel anlamlı olarak daha uzundu. Grup 2’de, DM ve ASKH
eşlik eden hasta oranı Grup 1’e göre anlamlı yüksek iken hipertansiyon oranı açısından gruplar benzerdi. Laboratuvar değerleri açısından, her iki
grup, serum total kolesterol ve HDL değerleri açısından benzerken, LDL, VLDL, trigliserit değerleri açısından izlenen fark istatistiksel açıdan Grup 1
lehine anlamlı idi.

Sonuç: ED’nin temel nedenlerinden biri olan endotelyal disfonksiyonun tanı ve takibi için biyokimyasal belirteçlerin rolü birçok çalışmada incelenmiştir.
Bu amaç doğrultusunda ilgi gören ve ED ile ilişkisi araştırılan parametrelerden bir tanesi de serum homosistein seviyeleridir. Homosistein, ED için
varsayılan bir risk faktörü olmaya devam etmektedir. Bulgular daha fazla olgu sayılı çalışmalarla desteklenirse, ED gelişiminin ve ilerlemesinin
önlenmesinde ve medikal tedavi yanıtının takibinde bir belirteç olarak katkı sağlayabilir.

Keywords

Homosistein, Erektil Disfonksiyon, Vasküler Patoloji

Ethical Statement

Etik Kurul Onayı: Araştırmanın etik kurul onayı hastanemizin klinik araştırmalar etik kurulundan 21/03 numarasıyla alındı. Hasta Onayı: Hasta onamı alındı. Hakem Değerlendirmesi: Editörler kurulunun içinden ve dışından olan kişiler tarafından değerlendirilmiştir.

Supporting Institution

Project Number

Thanks

References

1. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84:50-56.
2. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54-61.
3. Fung MM, Bettencourt R, Barrett-Connor E. Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. J Am Coll Cardiol. 2004;43:1405-1411.
4. Hsueh WA, Lyon CJ, Quiñones MJ. Insulin resistance and the endothelium. Am J Med. 2004;117:109-117.
5. Maas R, Schwedhelm E, Albsmeier J, et al. The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. Vasc Med. 2002;7:213-225.
6. Sullivan ME, Keoghane SR, Miller MA. Vascular risk factors and erectile dysfunction. BJU Int. 2001;87:838-845.
7. Bansal TC, Guay AT, Jacobson J, et al. Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. J Sex Med. 2005;2:96-103.
8. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89-95.
9. Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about? Swiss Med Wkly. 2006;136:745-756.
10. Zhang Z, Xu Z, Dai Y, et al. Elevated serum homocysteine level as an independent risk factor for erectile dysfunction: a prospective pilot casecontrol study. Andrologia. 2017;46.
11. Emsley AM, Jeremy JY, Gomes GN, et al. Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta. Br J Pharmacol. 1999;126:1034-1040.
12. Finkelstein JD, Martin JJ. Homocysteine. Int J Biochem Cell Biol. 2000;32:385-389.
13. Sanchez E, Pastuszak AW, Khera M. Erectile dysfunction, metabolic syndrome, and cardiovascular risks: facts and controversies. Transl Androl Urol. 2017;6:28-36.
14. Pickard RS, Powell PH, Zar MA. Nitric oxide and cyclic GMP formation following relaxant nerve stimulation in isolated human corpus cavernosum. Br J Urol. 1995;75:516-522.
15. Meigs JB, Hu FB, Rifai N, et al. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291:1978-1986.
16. Khan MA, Thompson CS, Emsley AM, et al. The interaction of homocysteine and copper markedly inhibits the relaxation of rabbit corpus cavernosum: new risk factors for angiopathic erectile dysfunction? BJU Int. 1999;84:720-724.
17. Jones RW, Jeremy JY, Koupparis A, et al. Cavernosal dysfunction in a rabbit model of hyperhomocysteinaemia. BJU Int. 2005 ;95:125-130.
18. Katsiki N, Perez-Martinez P, Mikhailidis DP. Homocysteine and Non-Cardiac Vascular Disease. Curr Pharm Des. 2017;23:3224-3232.
19. Jiang W, Xiong L, Bin Yang, et al. Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity. Sci Rep. 2016;6:26647.
20. Sreckovic B, Sreckovic VD, Soldatovic I, et al. Homocysteine is a marker for metabolic syndrome and atherosclerosis. Diabetes Metab Syndr. 2017;11:179-182.
21. Demir T, Comlekçi A, Demir O, et al. Hyperhomocysteinemia: a novel risk factor for erectile dysfunction. Metabolism. 2006;55:1564-1568.
22. Bots ML, Launer LJ, Lindemans J, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med. 1999;159:38-44.
23. Sansone M, Sansone A, Romano M, et al. Folate: a possible role in erectile dysfunction? Aging Male. 2018;21:116-120.
24. Wilcken DE, Wilcken B. The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest. 1976;57:1079-1082.
25. Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med. 1991;324:1149-1155.
26. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995;274:1049-1057.
27. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.
28. Shimbo D, Grahame-Clarke C, Miyake Y, et al. The association between endothelial dysfunction and cardiovascular outcomes in a populationbased multi-ethnic cohort. Atherosclerosis. 2007;192:197-203.
29. Giltay EJ, Hoogeveen EK, Elbers JM, et al. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. Atherosclerosis. 1998;139:197-198.
30. Godsland IF, Rosankiewicz JR, Proudler AJ, et al. Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men. J Clin Endocrinol Metab. 2001;86:719-723.
31. Hajer GR, van der Graaf Y, Olijhoek JK, et al. Levels of homocysteine are increased in metabolic syndrome patients but are not associated with an increased cardiovascular risk, in contrast to patients without the metabolic syndrome. Heart. 2007;93:216-220.
32. Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578-1588.
33. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567-1577.
34. Fonseca V, Dicker-Brown A, Ranganathan S, et al. Effects of a high-fatsucrose diet on enzymes in homocysteine metabolism in the rat. Metabolism. 2000;49:736-741.
35. Oron-Herman M, Rosenthal T, Sela BA. Hyperhomocysteinemia as a component of syndrome X. Metabolism. 2003;52:1491-1495.
36. Najib S, Sánchez-Margalet V. Homocysteine thiolactone inhibits insulinstimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol. 2005;34:119-126.
37. Daly C, Fitzgerald AP, O’Callaghan P, et al. Homocysteine increases the risk associated with hyperlipidaemia. Eur J Cardiovasc Prev Rehabil. 2009;16:150-155.
38. Foody JM, Milberg JA, Pearce GL, et al. Lipoprotein(a) associated with coronary artery disease in older women: age and gender analysis. Atherosclerosis. 2000;153:445-451.
39. Gao W, Jiang N, Meng Z, et al. Hyperhomocysteinemia and hyperlipidemia in coronary heart disease. Chin Med J (Engl). 1999;112:586-589.
40. Nakhai Pour HR, Grobbee DE, Muller M, et al. Serum sex hormone and plasma homocysteine levels in middle-aged and elderly men. Eur J Endocrinol. 2006;155:887-893.

The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction

Year 2022, Volume: 75 Issue: 1, 124 - 129, 30.06.2022

Murat Topcuoğlu

Abstract

Objectives: We aimed to demonstrate the relationship between high serum homocysteine levels and severity, duration of erectile dysfunction
(ED), also the diseases including vascular pathologies like diabetes mellitus (DM), atherosclerotic heart disease (ASHD), hypertension, and metabolic
syndrome with clinical and laboratory values.

Materials and Methods: Eighty-two patients admitted with ED were divided into two groups based on serum homocysteine values, as patients
with a homocysteine value of less than 15 μmol/L (Group 1) and patients with a homocysteine value of more than 15 μmol/L (Group 2). Both groups
were compared in terms of age, duration and severity of ED, history of concomitant systemic diseases like DM, ASHD, hypertension and laboratory
values [fasting blood sugar, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL),
triglyceride, total testosterone] values. The severity of ED in patients was evaluated with the short form of the International Index of Erectile
Function questionnaire.

Results: Severity and duration of ED were statistically more significant in the patients in Group 2 than in the patients in Group 1. While the ratio
of patients with DM and ASHD was significantly higher in Group 2 than in Group 1, the groups were similar for ratio of hypertension. In terms of
laboratory values, both groups were similar for serum total cholesterol and HDL while the difference observed for LDL, VLDL and triglyceride was
statistically significant in favor of Group 1.

Conclusion: The role of biochemical markers in the diagnosis and follow-up of endothelial dysfunction, which is one of the main causes of ED,
has been investigated in many studies. For this purpose, one of the parameters that has been investigated for its relationship with ED is serum
homocysteine level. Homocysteine remains as a putative risk factor for ED. If results are supported by studies with larger number of cases, it may
contribute as a marker in the prevention of ED development and progression and also in the follow-up of medical treatment response.

Keywords

Homocysteine, Erectile Dysfunction, Vascular Pathology

Supporting Institution

Project Number

Thanks

References

1. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84:50-56.
2. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151:54-61.
3. Fung MM, Bettencourt R, Barrett-Connor E. Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. J Am Coll Cardiol. 2004;43:1405-1411.
4. Hsueh WA, Lyon CJ, Quiñones MJ. Insulin resistance and the endothelium. Am J Med. 2004;117:109-117.
5. Maas R, Schwedhelm E, Albsmeier J, et al. The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. Vasc Med. 2002;7:213-225.
6. Sullivan ME, Keoghane SR, Miller MA. Vascular risk factors and erectile dysfunction. BJU Int. 2001;87:838-845.
7. Bansal TC, Guay AT, Jacobson J, et al. Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. J Sex Med. 2005;2:96-103.
8. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89-95.
9. Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about? Swiss Med Wkly. 2006;136:745-756.
10. Zhang Z, Xu Z, Dai Y, et al. Elevated serum homocysteine level as an independent risk factor for erectile dysfunction: a prospective pilot casecontrol study. Andrologia. 2017;46.
11. Emsley AM, Jeremy JY, Gomes GN, et al. Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta. Br J Pharmacol. 1999;126:1034-1040.
12. Finkelstein JD, Martin JJ. Homocysteine. Int J Biochem Cell Biol. 2000;32:385-389.
13. Sanchez E, Pastuszak AW, Khera M. Erectile dysfunction, metabolic syndrome, and cardiovascular risks: facts and controversies. Transl Androl Urol. 2017;6:28-36.
14. Pickard RS, Powell PH, Zar MA. Nitric oxide and cyclic GMP formation following relaxant nerve stimulation in isolated human corpus cavernosum. Br J Urol. 1995;75:516-522.
15. Meigs JB, Hu FB, Rifai N, et al. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291:1978-1986.
16. Khan MA, Thompson CS, Emsley AM, et al. The interaction of homocysteine and copper markedly inhibits the relaxation of rabbit corpus cavernosum: new risk factors for angiopathic erectile dysfunction? BJU Int. 1999;84:720-724.
17. Jones RW, Jeremy JY, Koupparis A, et al. Cavernosal dysfunction in a rabbit model of hyperhomocysteinaemia. BJU Int. 2005 ;95:125-130.
18. Katsiki N, Perez-Martinez P, Mikhailidis DP. Homocysteine and Non-Cardiac Vascular Disease. Curr Pharm Des. 2017;23:3224-3232.
19. Jiang W, Xiong L, Bin Yang, et al. Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity. Sci Rep. 2016;6:26647.
20. Sreckovic B, Sreckovic VD, Soldatovic I, et al. Homocysteine is a marker for metabolic syndrome and atherosclerosis. Diabetes Metab Syndr. 2017;11:179-182.
21. Demir T, Comlekçi A, Demir O, et al. Hyperhomocysteinemia: a novel risk factor for erectile dysfunction. Metabolism. 2006;55:1564-1568.
22. Bots ML, Launer LJ, Lindemans J, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med. 1999;159:38-44.
23. Sansone M, Sansone A, Romano M, et al. Folate: a possible role in erectile dysfunction? Aging Male. 2018;21:116-120.
24. Wilcken DE, Wilcken B. The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest. 1976;57:1079-1082.
25. Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med. 1991;324:1149-1155.
26. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 1995;274:1049-1057.
27. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.
28. Shimbo D, Grahame-Clarke C, Miyake Y, et al. The association between endothelial dysfunction and cardiovascular outcomes in a populationbased multi-ethnic cohort. Atherosclerosis. 2007;192:197-203.
29. Giltay EJ, Hoogeveen EK, Elbers JM, et al. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. Atherosclerosis. 1998;139:197-198.
30. Godsland IF, Rosankiewicz JR, Proudler AJ, et al. Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men. J Clin Endocrinol Metab. 2001;86:719-723.
31. Hajer GR, van der Graaf Y, Olijhoek JK, et al. Levels of homocysteine are increased in metabolic syndrome patients but are not associated with an increased cardiovascular risk, in contrast to patients without the metabolic syndrome. Heart. 2007;93:216-220.
32. Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578-1588.
33. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567-1577.
34. Fonseca V, Dicker-Brown A, Ranganathan S, et al. Effects of a high-fatsucrose diet on enzymes in homocysteine metabolism in the rat. Metabolism. 2000;49:736-741.
35. Oron-Herman M, Rosenthal T, Sela BA. Hyperhomocysteinemia as a component of syndrome X. Metabolism. 2003;52:1491-1495.
36. Najib S, Sánchez-Margalet V. Homocysteine thiolactone inhibits insulinstimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol. 2005;34:119-126.
37. Daly C, Fitzgerald AP, O’Callaghan P, et al. Homocysteine increases the risk associated with hyperlipidaemia. Eur J Cardiovasc Prev Rehabil. 2009;16:150-155.
38. Foody JM, Milberg JA, Pearce GL, et al. Lipoprotein(a) associated with coronary artery disease in older women: age and gender analysis. Atherosclerosis. 2000;153:445-451.
39. Gao W, Jiang N, Meng Z, et al. Hyperhomocysteinemia and hyperlipidemia in coronary heart disease. Chin Med J (Engl). 1999;112:586-589.
40. Nakhai Pour HR, Grobbee DE, Muller M, et al. Serum sex hormone and plasma homocysteine levels in middle-aged and elderly men. Eur J Endocrinol. 2006;155:887-893.

There are 40 citations in total.

Details

Primary Language	English
Subjects	Urology
Journal Section	Articles
Authors	Murat Topcuoğlu 0000-0003-2155-5171
Project Number	-
Publication Date	June 30, 2022
Published in Issue	Year 2022 Volume: 75 Issue: 1

Cite

APA	Topcuoğlu, M. (2022). The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 75(1), 124-129. https://doi.org/10.4274/atfm.galenos.2022.09226
AMA	Topcuoğlu M. The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası. June 2022;75(1):124-129. doi:10.4274/atfm.galenos.2022.09226
Chicago	Topcuoğlu, Murat. “The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 75, no. 1 (June 2022): 124-29. https://doi.org/10.4274/atfm.galenos.2022.09226.
EndNote	Topcuoğlu M (June 1, 2022) The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası 75 1 124–129.
IEEE	M. Topcuoğlu, “The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 75, no. 1, pp. 124–129, 2022, doi: 10.4274/atfm.galenos.2022.09226.
ISNAD	Topcuoğlu, Murat. “The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 75/1 (June 2022), 124-129. https://doi.org/10.4274/atfm.galenos.2022.09226.
JAMA	Topcuoğlu M. The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2022;75:124–129.
MLA	Topcuoğlu, Murat. “The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 75, no. 1, 2022, pp. 124-9, doi:10.4274/atfm.galenos.2022.09226.
Vancouver	Topcuoğlu M. The Effects of High Homocystein Levels on Duration and Severity of Erectile Dysfunction. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2022;75(1):124-9.

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