Clinical Drug Investigation

, Volume 25, Issue 6, pp 409–416 | Cite as

A Randomised Comparison of the Effects of Nebivolol and Atenolol with and without Chlorthalidone on the Sexual Function of Hypertensive Men

  • Bahar Boydak
  • Sanem Nalbantgil
  • Francesco Fici
  • Istemi Nalbantgil
  • Mehdi Zoghi
  • Filiz Ozerkan
  • Istemihan Tengiz
  • Erturul Ercan
  • Hasan Yilmaz
  • Umit Yoket
  • Remzi Onder
Original Research Article


Background and objective: Erectile dysfunction, which is common in men with hypertension, has been reported as a common adverse effect of many antihypertensive drug classes, including β-blockers and diuretics. Atenolol and nebivolol are both β1-selective blockers, but nebivolol is a new-generation compound with nitric oxide-mediated vasodilating activity. The aim of the study was to compare the effects of nebivolol and atenolol ± chlorthalidone on the sexual function of hypertensive men.

Methods: A total of 131 male patients (mean age 47.3 ± 4.6 years) with newly diagnosed hypertension were included in the study. All the patients were married and had not previously experienced any erectile dysfunction. After a 4-week placebo run-in period, patients were randomised to receive 12 weeks’ therapy with nebivolol 5 mg/day (n = 43), atenolol 50 mg/day (n = 44), or atenolol 50 mg/ day + chlorthalidone 12.5 mg/day (n = 44), according to a double-blind design. After 4 weeks of treatment, drug dosage could be doubled in patients not responding to therapy. Erectile function (instances of successful intercourse/month) was assessed by means of a questionnaire at the end of the placebo run-in period (baseline) and at the end of double-blind treatment. Blood pressure was also assessed at these times.

Result: At the end of the 12-week, double-blind treatment period, the mean number of episodes of satisfactory sexual intercourse per month was significantly decreased from baseline in the groups receiving atenolol (from 7.0 to 3.7; p < 0.01) and atenolol + chlorthalidone (from 6.4 to 2.8; p < 0.01). In contrast, the mean number of episodes of satisfactory sexual intercourse per month remained constant in the group of patients receiving nebivolol (6.4 during the baseline assessment and 6.0 during the last month of treatment). Blood pressure and heart rate were significantly decreased from baseline in all treatment groups.

Conclusion: Increased release of nitric oxide associated with nebivolol may counteract the detrimental effect of β-blockade on penile erection, thereby allowing maintenance of sexual activity in previously untreated hypertensive men compared with a significant decrease observed in the sexual activity of men receiving atenolol-based treatment.


Nitric Oxide Sexual Activity Erectile Dysfunction Atenolol Sexual Function 
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This article received no outside funding, and the authors have no potential conflicts of interest that are directly relevant to its contents.


  1. 1.
    Della Chiesa A, Pfiffner D, Meier B, et al. Sexual activity in hypertensive men. J Hum Hypertens 2003; 17(8): 515–21PubMedCrossRefGoogle Scholar
  2. 2.
    Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: results from the health professionals’ follow-up study. Ann Intern Med 2003; 139(3): 161–8PubMedGoogle Scholar
  3. 3.
    Burchardt M, Burchardt T, Baer L, et al. Hypertension is associated with severe erectile dysfunction. J Urol 2000; 164(4): 1188–91PubMedCrossRefGoogle Scholar
  4. 4.
    Jensen J, Lendorf A, Stimpel H, et al. The prevalence and etiology of impotence in 101 male hypertensive outpatients. Am J Hypertens 1999; 12(3): 271–5PubMedCrossRefGoogle Scholar
  5. 5.
    Johannes CB, Araujo AB, Feldman HA, et al. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol 2000; 163(2): 460–3PubMedCrossRefGoogle Scholar
  6. 6.
    Lue TF. Erectile dysfunction. N Engl J Med 2000; 342(24): 1802–13PubMedCrossRefGoogle Scholar
  7. 7.
    Ko DT, Hebert PR, Coffey CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 2002; 288(3): 351–7PubMedCrossRefGoogle Scholar
  8. 8.
    Fogari R, Preti P, Derosa G, et al. Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. Eur J Clin Pharmacol 2002; 58(3): 177–80PubMedCrossRefGoogle Scholar
  9. 9.
    Fogari R, Zoppi A, Corradi L, et al. Sexual function in hypertensive males treated with lisinopril or atenolol: a cross-over study. Am J Hypertens 1998; 11(10): 1244–7PubMedCrossRefGoogle Scholar
  10. 10.
    Chang SW, Fine R, Siegel D, et al. The impact of diuretic therapy on reported sexual function. Arch Intern Med 1991; 151(12): 2402–8PubMedCrossRefGoogle Scholar
  11. 11.
    Wassertheil-Smoller S, Blaufox MD, Oberman A, et al. Effect of antihypertensives on sexual function and quality of life: the TAIM Study. Ann Intern Med 1991; 114(8): 613–20PubMedGoogle Scholar
  12. 12.
    Opie LH. Diuretic downsides: but in low doses they still seem among the best authenticated antihypertensives. Cardiovasc Drugs Ther 2000; 14(4): 407–9PubMedCrossRefGoogle Scholar
  13. 13.
    Grimm Jr RH, Grandits GA, Prineas RJ, et al. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS). Hypertension 1997; 29 (1 Pt 1): 8–14PubMedCrossRefGoogle Scholar
  14. 14.
    Anonymous. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21(6): 1011–53CrossRefGoogle Scholar
  15. 15.
    Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42(6): 1206–52PubMedCrossRefGoogle Scholar
  16. 16.
    Lopez-Sendon J, Swedberg K, McMurray J, et al. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 2004; 25(15): 1341–62PubMedCrossRefGoogle Scholar
  17. 17.
    Barksdale JD, Gardner SF. The impact of first-line antihypertensive drugs on erectile dysfunction. Pharmacotherapy 1999; 19(5): 573–81PubMedCrossRefGoogle Scholar
  18. 18.
    Fogari R, Zoppi A. Effect of antihypertensive agents on quality of life in the elderly. Drugs Aging 2004; 21(6): 377–93PubMedCrossRefGoogle Scholar
  19. 19.
    Bansal S. Sexual dysfunction in hypertensive men: a critical review of the literature. Hypertension 1988; 12(1): 1–10PubMedCrossRefGoogle Scholar
  20. 20.
    Rosen RC. Sexual dysfunction as an obstacle to compliance with antihypertensive therapy. Blood Press Suppl 1997; 1: 47–51PubMedGoogle Scholar
  21. 21.
    Rajfer J, Aronson WJ, Bush PA, et al. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 1992; 326(2): 90–4PubMedCrossRefGoogle Scholar
  22. 22.
    Andersson KE. Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol 2003; 170 (2 Pt 2): S6–13PubMedCrossRefGoogle Scholar
  23. 23.
    Tzemos N, Lim PO, MacDonald TM. Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study. Circulation 2001; 104(5): 511–4PubMedCrossRefGoogle Scholar
  24. 24.
    Ignarro LJ, Byrns RE, Trinh K, et al. Nebivolol: a selective beta (1)-adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide- and cyclic GMP-dependent mechanisms. Nitric Oxide 2002; 7(2): 75–82PubMedCrossRefGoogle Scholar
  25. 25.
    Cockcroft JR, Chowienczyk PJ, Brett SE, et al. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther 1995; 274(3): 1067–71PubMedGoogle Scholar
  26. 26.
    Toda N. Vasodilating beta-adrenoceptor blockers as cardiovascular therapeutics. Pharmacol Ther 2003; 100(3): 215–34PubMedCrossRefGoogle Scholar
  27. 27.
    Bulpitt CJ, Fletcher AE. The measurement of quality of life in hypertensive patients: a practical approach. Br J Clin Pharmacol 1990; 30(3): 353–64PubMedCrossRefGoogle Scholar
  28. 28.
    Fogari R, Zoppi A, Poletti L, et al. Sexual activity in hypertensive men treated with valsartan or carvedilol: a crossover study. Am J Hypertens 2001; 14(1): 27–31PubMedCrossRefGoogle Scholar
  29. 29.
    Williams GH. Assessing patient wellness: new perspectives on quality of life and compliance. Am J Hypertens 1998; 11 (11 Pt 2): 186S–91SPubMedCrossRefGoogle Scholar
  30. 30.
    McNeely W, Goa KL. Nebivolol in the management of essential hypertension: a review. Drugs 1999; 57(4): 633–51PubMedCrossRefGoogle Scholar
  31. 31.
    Grassi G, Trevano FQ, Facchini A, et al. Efficacy and tolerability profile of nebivolol vs atenolol in mild-to-moderate essential hypertension: results of a double-blind randomized multicentre trial. Blood Press Suppl 2003; 2: 35–40PubMedCrossRefGoogle Scholar
  32. 32.
    Fogari R, Zoppi A, Lazzari P, et al. Comparative effects of nebivolol and atenolol on blood pressure and insulin sensitivity in hypertensive subjects with type II diabetes. J Hum Hypertens 1997; 11(11): 753–7PubMedCrossRefGoogle Scholar
  33. 33.
    Van Nueten L, Taylor FR, Robertson JI. Nebivolol vs atenolol and placebo in essential hypertension: a double-blind randomised trial. J Hum Hypertens 1998; 12(2): 135–40PubMedCrossRefGoogle Scholar
  34. 34.
    Makolkin VI, Akhmedova OO, Buval’tsev VI, et al. Clinical and metabolic effects of cardioselective beta-adrenoblockers nebivolol and metoprolol in patients with hypertension and ischemic heart disease associated with type 2 diabetes. Kardiologiia 2003; 43(2): 40–3PubMedGoogle Scholar
  35. 35.
    Van Nueten L, Dupont AG, Vertommen C, et al. A dose-response trial of nebivolol in essential hypertension. J Hum Hypertens 1997; 11(2): 139–44PubMedCrossRefGoogle Scholar
  36. 36.
    Silvestri A, Galetta P, Cerquetani E, et al. Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo. Eur Heart J 2003; 24(21): 1928–32PubMedCrossRefGoogle Scholar
  37. 37.
    Panza JA, Quyyumi AA, Brush Jr JE, et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990; 323(1): 22–7PubMedCrossRefGoogle Scholar
  38. 38.
    Panza JA, Casino PR, Kilcoyne CM, et al. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 1993; 87(5): 1468–74PubMedCrossRefGoogle Scholar
  39. 39.
    Forte P, Copland M, Smith LM, et al. Basal nitric oxide synthesis in essential hypertension. Lancet 1997; 349(9055): 837–42PubMedCrossRefGoogle Scholar
  40. 40.
    Levy BI, Ambrosio G, Pries AR, et al. Microcirculation in hypertension: a new target for treatment? Circulation 2001; 104(6): 735–40PubMedCrossRefGoogle Scholar
  41. 41.
    Vicaut E. Hypertension and the microcirculation. Arch Mal Coeur Vaiss 2003; 96(9): 893–903PubMedGoogle Scholar
  42. 42.
    deGroat WC, Booth AM. Physiology of male sexual function. Ann Intern Med 1980; 92 (2 Pt 2): 329–31Google Scholar
  43. 43.
    Mangrella M, Rossi F, Fici F. Pharmacology of nebivolol. Pharmacol Res 1998; 38(6): 419–31PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Bahar Boydak
    • 1
  • Sanem Nalbantgil
    • 1
  • Francesco Fici
    • 2
  • Istemi Nalbantgil
    • 1
  • Mehdi Zoghi
    • 1
  • Filiz Ozerkan
    • 1
  • Istemihan Tengiz
    • 3
  • Erturul Ercan
    • 3
  • Hasan Yilmaz
    • 4
  • Umit Yoket
    • 5
  • Remzi Onder
    • 1
  1. 1.Cardiology DepartmentEge University Medical SchoolIzmirTurkey
  2. 2.Department of Experimental Medicine, Excellence Research Center on Cardiovascular DiseasesSecond University of NaplesNaplesItaly
  3. 3.Central Hospital Cardiology DepartmentIzmirTurkey
  4. 4.Sifa Medical Center Cardiology DepartmentIzmirTurkey
  5. 5.SSK Egitim Hospital, BozyakaIzmirTurkey

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