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Does Testosterone Have a Role in Erectile Function?

  • Nasser Mikhail
    Correspondence
    Requests for reprints should be addressed to Nasser Mikhail, MD, MSc, Endocrinology Division, Department of Medicine, Olive View-UCLA Medical Center, 14445 Olive View Drive, Sylmar, CA 91342
    Affiliations
    Endocrinology Division, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, Calif
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      Abstract

      Purpose

      Despite the well-established role of testosterone in enhancing libido, its exact contribution to erections in men remains unclear. The main objectives of this review are to clarify the role of testosterone in erectile function and evaluate its therapeutic value in men with erectile dysfunction (ED).

      Methods

      Review of the relevant literature (English, French, and Spanish) from 1939 to June 2005 was conducted using data sources from MEDLINE, endocrinology text books, and hand searching of cross-references from original articles and reviews. Clinical trials, animal studies, case reports, reviews, and guidelines of major associations were included.

      Results

      Animal and preliminary human studies suggest that testosterone may facilitate erection by acting as vasodilator of the penile arterioles and cavernous sinusoids. Following castration, most, but not all, men had partial or complete loss of erection. Hypogonadism is not a common finding in ED, occurring in about 5% of cases, and in general, there is lack of association between serum testosterone levels, when present in normal or moderately low levels, and erectile function. Most trials using testosterone for treatment of ED in hypogonadal men suffer from methodological problems and report inconsistent results, but overall, suggest that testosterone may be superior to placebo. Erectile function is more likely to improve with testosterone therapy in patients with severe degrees of hypogonadism. Testosterone treatment may ameliorate the response to the phosphodiesterase 5 (PDE5) inhibitors in hypogonadal men and men with low-normal serum testosterone. Repeated measurement of morning serum total testosterone is a fairly accurate and easy method to evaluate androgenecity, but measurement of free or bioavailable testosterone is recommended in conditions that alter the levels of sex-hormone-binding globulin (SHBG), such as in the elderly and in obesity.

      Conclusions

      Available data suggest that in most men circulating levels of testosterone, well below the normal range, are essential for normal erection and that higher levels of serum testosterone may not have major impact on erectile function. Screening for hypogonadism in all men with ED is necessary to identify cases of severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment.

      Keywords

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      References

      1. NIH Consensus Conference. Impotence.
        JAMA. 1993; 270: 83-90
        • Tomlinson J.M.
        • Wright D.
        Impact of erectile dysfunction and its subsequent treatment with sildenafil.
        BMJ. 2004; 328: 1037-1039
        • Feldman H.A.
        • Goldstein I.
        • Hatzichristou D.G.
        • Krane R.J.
        • McKinlay J.B.
        Impotence and its medical and psychological correlates.
        J Urol. 1994; 151: 54-61
        • Solomon H.
        • Man J.W.
        • Jackson G.
        Erectile dysfunction and the cardiovascular patient.
        Heart. 2003; 89: 251-254
        • Goldstein I.
        • Lue T.F.
        • Padma-Nathan H.
        • Rosen R.C.
        • Steers W.D.
        • Wicker P.A.
        • Sildenafil Study Group
        Oral sildenafil in the treatment of erectile dysfunction.
        N Engl J Med. 1998; 338: 1397-1404
      2. Viagra (sildenafil citrate). Prescribing information 2002.

      3. Levitra (vardenafil HCL). Prescribing information 2003.

      4. Cialis (tadalafil). Prescribing information 2003.

        • Skakkebaek N.E.
        • Bancroft J.
        • Davidson D.W.
        • Warner P.
        Androgen replacement with oral testosterone undecanoate in hypogonadal men.
        Clin Endocrinol. 1981; 14: 49-61
        • Kwan M.
        • Greenleaf W.J.
        • Mann J.
        • et al.
        The nature of androgen action on male sexuality.
        J Clin Endocrinol Metab. 1983; 57: 557-562
        • O’Carroll R.
        • Shapiro C.
        • Bancroft J.
        Androgen behaviour and nocturnal erection in hypogonadal men.
        Clin Endocrinol. 1985; 23: 527-538
        • Nankin H.R.
        • Lin T.
        • Osterman J.
        Chronic testosterone cypionate therapy in men with secondary impotence.
        Fertil Steril. 1986; 46: 300-307
        • Carani C.
        • Zini D.
        • Baldini A.
        • Della Casa L.
        • Ghizzani A.
        • Marrama P.
        Effects of androgen treatment in impotent men with normal and low levels of free testosterone.
        Arch Sex Behav. 1990; 19: 223-234
        • Bagatell C.J.
        • Heiman J.R.
        • Rivier J.E.
        • Bremner W.J.
        Effects of endogenous testosterone and estradiol on sexual behavior in normal young men.
        J Clin Endocrinol Metab. 1994; 78: 711-716
        • Haren M.T.
        • Morley J.E.
        • Chapman I.M.
        • et al.
        Defining ‘relative’ androgen deficiency in aging men.
        Climacteric. 2002; 5: 15-25
        • Kalinchenko S.Y.
        • Kozlov G.I.
        • Gontcharov N.P.
        • Katsiya G.V.
        Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone.
        Aging Male. 2003; 6: 94-99
        • Wang C.
        • Cunningham G.
        • Dobs A.
        • et al.
        Long-term testosterone gel (androgel) treatment maintains beneficial effects on sexual function and mood and fat mass, and bone mineral density in hypogonadal men.
        J Clin Endocrinol Metab. 2004; 89: 2085-2098
        • Matsumoto A.M.
        • Bremner W.J.
        Serum testosterone assays—accuracy matters.
        J Clin Endocrinol Metab. 2004; 89: 520-524
        • Wang C.
        • Catlin D.H.
        • Demers L.M.
        • et al.
        Measurement of total serum testosterone in adult men.
        J Clin Endocrinol Metab. 2004; 89: 534-543
        • Mohr B.A.
        • Guay A.T.
        • O’Donnell A.B.
        • McKinlay J.B.
        Normal, bound, and nonbound testosterone levels in normally ageing men.
        Clin Endocrinol. 2005; 62: 64-73
        • Barrett-Connor E.
        Male testosterone.
        Clin Endocrinol. 2005; 62: 263-264
        • Cohan P.
        • Korenman S.G.
        Erectile dysfunction.
        J Clin Endocrinol Metab. 2001; 86: 2391-2394
        • Chamness S.L.
        • Ricker D.D.
        • Crone J.K.
        • et al.
        The effect of androgen on nitric oxide synthase in the male reproductive tract of the rat.
        Fertil Steril. 1995; 63: 1101-1107
        • Chou T.M.
        • Sudhir K.
        • Hutchison S.J.
        • et al.
        Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo.
        Circulation. 1996; 94: 2614-2619
        • Anderson K.
        Erectile physiological and pathophysiological pathways involved in erectile dysfunction.
        J Urol. 2003; 170: S6-S14
        • Reilly C.M.
        • Stopper V.S.
        • Mills T.
        Androgens modulate the α-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum.
        J Androl. 1997; 18: 26-31
        • Mills T.M.
        • Lewis R.W.
        • Stopper V.S.
        Androgenic maintenance of inflow and venous occlusion during erection in the rat.
        Biol Reprod. 1998; 59: 1413-1418
        • Heaton J.P.W.
        • Varrin S.J.
        Effects of castration and exogenous testosterone supplementation in an animal model of penile erection.
        J Urol. 1994; 151: 797-800
        • Mitchell J.
        • Stewart J.
        Effects of castration, steroid replacement, and sexual experience on mesolimbic dopamine and sexual behaviors in the male rat.
        Brain Res. 1988; 491: 116-127
        • Edwards E.
        • Hamilton J.
        • Duntley S.
        Testosterone propionate as a therapeutic agent in patients with organic disease of peripheral vessels.
        N Engl J Med. 1939; 220: 865
        • Hamm L.
        Testosterone propionate in the treatment of angina pectoris.
        J Clin Endocrinol. 1942; 2: 325-328
        • Levine S.A.
        • Likoff W.B.
        The therapeutic value of testosterone propionate in angina pectoris.
        N Engl J Med. 1943; 229: 770-772
        • Lesser M.A.
        Testosterone propionate therapy in one hundred cases of angina pectoris.
        J Clin Endocrinol. 1946; 6: 549-557
        • Webb C.M.
        • McNeill J.G.
        • Hayward C.S.
        • de Zeigler D.
        • Collins P.
        Effects of testosterone on coronary vasomotor regulation in men with coronary artery disease.
        Circulation. 1999; 100: 1690-1696
        • Kang S.
        • Jang Y.
        • Kim Y.
        • et al.
        Effect of oral administration of testosterone on brachial artery vasoreactivity in men with coronary artery disease.
        Am J Cardiol. 2002; 89: 862-864
        • Worboys S.
        • Kotsopoulos D.
        • Teede H.
        • et al.
        Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodialation in postmenpopausal women already receiving estrogen.
        J Clin Endocrinol Metab. 2001; 86: 158-161
        • Aversa A.
        • Isidori A.M.
        • De Martino M.U.
        • et al.
        Androgens and penile erection.
        Clin Endocrinol (Oxf). 2000; 53: 517-522
        • Aversa A.
        • Isidori A.M.
        • Spera G.
        • Lenzi A.
        • Fabbri A.
        Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction.
        Clin Endocrinol. 2003; 58: 632-638
        • Becker A.J.
        • Uckert S.
        • Stief C.G.
        • et al.
        Cavernous and systemic testosterone plasma levels during different penile conditions in healthy males and patients with erectile dysfunction.
        Urology. 2001; 58: 435-440
        • Storelu S.
        • Gregoire M.
        • Gerard D.
        • et al.
        Neuroanatomical correlates of visually evoked sexual arousal in human males.
        Arch Sex Behav. 1999; 28: 1-21
        • Hatzichristou D.
        • Hatzimouratidis K.
        • Bekas M.
        • et al.
        Diagnostic steps in the evaluation of patients with erectile dysfunction.
        J Urol. 2002; 168: 615-620
        • Spark R.F.
        • White R.
        • Connolly P.B.
        Impotence is not always psychogenic. Newer insights into hypothalamic-pituitary-gonadal dysfunction.
        JAMA. 1980; 243: 750-755
        • Buvat J.
        • Lemaire A.
        Endocrine screening in 1,022 men with erectile dysfunction.
        J Urol. 1997; 158: 1764-1767
        • Earle C.M.
        • Stuckey B.G.A.
        Biochemical screening in the assessment of erectile dysfunction.
        Urology. 2003; 62: 727-731
        • Korenman S.G.
        • Morley J.E.
        • Mooradian A.D.
        • et al.
        Secondary hypogonadism in older men.
        J Clin Endocrinol Metab. 1990; 71: 963-969
        • Rhoden E.L.
        • Teloken C.
        • Sogari P.R.
        • Souto C.A.V.
        The relationship of serum testosterone to erectile function in normal aging men.
        J Urol. 2002; 167: 1745-1748
        • Christ-Crain M.
        • Mueller B.
        • Gasser T.C.
        • et al.
        Is there a clinical relevance of partial androgen deficiency in the aging male?.
        J Urol. 2004; 172: 624-627
        • Bhasin S.
        • Woodhouse L.
        • Casaburi R.
        • et al.
        Testosterone dose-response relationships in healthy young men.
        Am J Physiol. 2001; 281: E1172-E1181
        • Buena F.
        • Swerdloff R.S.
        • Steiner B.S.
        • et al.
        Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal range.
        Fertil Steril. 1993; 59: 1118-1123
        • Tsujimura A.
        • Matsumiya K.
        • Matsuoka Y.
        • et al.
        Bioavailable testosterone with age and erectile dysfunction.
        J Urol. 2003; 170: 2345-2347
        • Mantzoros C.S.
        • Georgiadis E.I.
        • Trichopoulos D.
        Contribution of dihydrotestosterone to male sexual behaviour.
        BMJ. 1995; 310: 1289-1291
        • McCullagh E.P.
        • Renshaw J.F.
        The effects of castration in the adult male.
        JAMA. 1934; 103: 1140-1143
        • Ellis W.J.
        • Grayhack J.T.
        Sexual function in aging males after orchiectomy and estrogen therapy.
        J Urol. 1963; 89: 895-899
        • Greenstein A.
        • Plymate S.R.
        • Katz P.G.
        Visually stimulated erection in castrated men.
        J Urol. 1995; 153: 650-652
        • Mills T.M.
        • Reilly C.M.
        • Lewis R.W.
        Androgens and penile erection.
        J Androl. 1996; 17: 633-637
        • Hirshkowitz M.
        • Moore C.A.
        • O’Connor S.
        • et al.
        Androgen and sleep-related erections.
        J Psychosom Res. 1997; 42: 541-546
        • Gray P.B.
        • Singh A.B.
        • Woodhouse L.J.
        • et al.
        Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men.
        J Clin Endocrinol Metab. 2005; 90: 3838-3846
        • Carani C.
        • Bancroft J.
        • Rio G.D.
        • Marrama P.
        Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men.
        Psychoneuroendocrinology. 1992; 17: 647-654
        • Anderson R.A.
        • Bancroft J.
        • Wu F.C.U.
        The effects of exogenous testosterone on sexuality and mood of normal men.
        J Clin Endocrinol Metab. 1992; 75: 1503-1507
        • Mulhall J.P.
        • Valenzuela R.
        • Aviv N.
        • Parker M.
        Effect of testosterone supplementation on sexual function in hypogonadal men with erectile dysfunction.
        Urology. 2004; 63: 348-352
        • Morales A.
        • Johnston B.
        • Heaton J.
        • Clark A.
        Oral androgens in the treatment of hypogonadal impotent men.
        J Urol. 1994; 152: 1115-1118
        • Foresta C.
        • Caretta N.
        • Rossato M.
        • et al.
        Role of androgens in erectile function.
        J Urol. 2004; 171: 2358-2362
        • Rakic Z.
        • Starcevic V.
        • Starcevic V.P.
        • Marinkovic J.
        Testosterone treatment in men with erectile disorder and low levels of total testosterone in serum.
        Arch Sex Behav. 1997; 26: 495-504
        • Monga M.
        • Kostelec M.
        • Kamarei M.
        Patient satisfaction with testosterone supplementation for the treatment of ererctile dysfunction.
        Arch Androl. 2002; 48: 433-442
        • Steidle C.
        • Schwartz S.
        • Jacoby K.
        • et al.
        AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function.
        J Clin Endocrinol Metab. 2003; 88: 2673-2681
        • Morales A.
        • Johnston B.
        • Heaton J.P.W.
        • Lundie M.
        Testosterone supplementation for hypogonadal impotence.
        J Urol. 1997; 157: 849-854
        • Jain P.
        • Rademaker A.W.
        • Mcvary K.T.
        Testosterone supplementation for erectile dysfunction.
        J Urol. 2000; 164: 371-375
        • Shabsigh R.
        • Kaufman J.M.
        • Steidle C.
        • Padma-Nathan H.
        Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.
        J Urol. 2004; 172: 658-663
        • Kalinchenko S.Y.
        • Kozlov G.I.
        • Gontcharov N.P.
        • Katsiya G.V.
        Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone.
        Aging Male. 2003; 6: 94-97
        • Chatterjee R.
        • Wood S.
        • McGarrigle H.H.
        • et al.
        A novel therapy with testosterone and sildenafil for erectile dysfunction in patients on renal dialysis or after renal transplantation.
        J Fam Plann Reprod Health Care. 2004; 30: 88-90
        • Chatterjee R.
        • Kottaridis P.D.
        • McGarrigle H.H.
        • Linch D.C.
        Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies.
        Bone Marrow Transplant. 2002; 29: 607-610
        • Carosa E.
        • Martini P.
        • Brandetti F.
        • et al.
        Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels.
        Clin Endocrinol. 2004; 61: 382-386
        • Morelli A.
        • Filippi S.
        • Mancina R.
        • et al.
        Androgens regulate phosphodiesterase type 5 expression and functional activity in the corpora cavernosa.
        Endocrinology. 2004; 145: 2253-2263
        • Rhoden E.L.
        • Morgentaler A.
        Risks of testosterone-replacement therapy and recommendations for monitoring.
        N Engl J Med. 2004; 350: 482-492
        • Allan C.A.
        • McLachlan R.I.
        Age-related changes in testosterone and the role of replacement therapy in older men.
        Clin Endocrinol. 2004; 60: 653-670
        • Guay A.T.
        • Perez J.B.
        • Jacobson J.
        • Newton R.A.
        Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated risk factors.
        J Androl. 2002; 22: 793-797
        • Park K.
        • Ku J.H.
        • Kim S.W.
        • Paick J.
        Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction.
        BJU Int. 2005; 95: 366-370
        • Lanfranco F.
        • Kamischke A.
        • Zitzmann M.
        • Nieschlag E.
        Klinefelter’s syndrome.
        Lancet. 2004; 364: 273-283
        • Ansong K.S.
        • Punwaney R.B.
        An assessment of the clinical relevance of serum testosterone level determination in the evaluation of men with low sexual drive.
        J Urol. 1999; 162: 719-721
        • Govier F.E.
        • McClure R.D.
        • Kramer-Levien D.
        Endocrine screening for sexual dysfunction using free testosterone determinations.
        J Urol. 1996; 156: 405-408
        • Citron J.T.
        • Ettinger B.
        • Rubinoff H.
        • et al.
        Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism.
        J Urol. 1996; 155: 529-533
        • Rhoden E.L.
        • Estrada C.
        • Levine L.
        • Morgentaler A.
        The value of pituitary magnetic resonance imaging in men with hypogonadism.
        J Urol. 2003; 170: 795-798
        • Elin R.J.
        • Winters S.J.
        Current controversies in testosterone testing.
        Clin Lab Med. 2004; 24: 119-139
        • Handelsman D.J.
        Androgen action and pharmacologic uses.
        in: Degroot L.J. Jameson J.L. Burger H. Endocrinology. 4th edn. W.B. Saunders Company, Philadelphia, PA2001: 2232-2242
        • Manni A.
        • Partidge W.M.
        • Cefalu W.
        • et al.
        Bioavailability of albumin bound testosterone.
        J Clin Endocrinol Metab. 1985; 61: 705-710
        • Morley J.E.
        • Patrick P.
        • Perry H.M.
        Evaluation of assays available to measure free testosterone.
        Metabolism. 2002; 51: 554-559
        • Synder P.J.
        Hypogonadism in elderly men—what to do until evidence comes.
        N Engl J Med. 2004; 350: 440-442
        • Vermeulen A.
        • Verdonck L.
        • Kaufman J.M.
        A critical evaluation of simple methods for the estimation of free testosterone.
        J Clin Endocrinol Metab. 1999; 84: 3666-3672
        • Taieb J.
        • Mathian B.
        • Millot F.
        • et al.
        Testosterone measured by 10 immuno-assays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children.
        Clin Chem. 2003; 49: 1381-1395
        • Marrama P.
        • Carani C.
        • Baraghini G.F.
        • et al.
        Circadian rhythm of testosterone and prolactin in the ageing.
        Maturitas. 1982; 4: 131-138
        • Plymate S.R.
        • Tenover J.S.
        • Bremmer W.J.
        Circadian variation in testosterone, sex hormone-bibding globulin and calculated non sex hormone binding globulin bound testosterone in healthy young and elderly men.
        J Androl. 1989; 10: 366-371
        • Gupta S.K.
        • Lindemulder E.A.
        • Sathyan G.
        Modeling of circadian testosterone in healthy men and hypogonadal men.
        J Clin Pharmacol. 2000; 40: 731-738
        • Diver M.J.
        • Imtiaz K.E.
        • Ahmad A.M.
        • et al.
        Diurnal rhythms of serum total, free, and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men.
        Clin Endocrinol. 2003; 58: 710-717
        • Winters S.J.
        Clinical disorders of the testis.
        in: Degroot L.J. Jameson J.L. Burger H. Endocrinology. 4th edn. W.B. Saunders Company, Philadelphia, PA2001: 2269-2290
        • Zumofff B.
        • Strain G.W.
        • Miller L.K.
        • et al.
        Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity.
        J Clin Endocrinol Metabol. 1990; 71: 929-931
        • Vermeulen A.
        • Kaufman J.M.
        • Deslypere J.P.
        • Thomas G.
        Attenuated luteinizing (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men.
        J Clin Endocrinol Metab. 1993; 76: 1140-1146
        • Giagulli V.A.
        • Kaufman J.M.
        • Vermeulen A.
        Pathogenesis of the decreased androgen levels in obese men.
        J Clin Endocrinol Metab. 1994; 79: 997-1000
        • Isidori A.M.
        • Caprio M.
        • Strollo F.
        Leptin and androgens in male obesity.
        J Clin Endocrinol Metab. 1999; 84: 3673-3680
        • Pitteloud N.
        • Hardin M.
        • Dwyer A.A.
        • et al.
        Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men.
        J Clin Endocrinol Metab. 2005; 90: 2636-2641
        • Marin P.
        • Holmang S.
        • Jonsson L.
        • et al.
        The effects of testosterone treatment on body composition and metabolism in middle-aged obese men.
        Int J Obes Relat Metab Disord. 1992; 16: 991-997
        • Marin P.
        • Krotkiewski M.
        • Bjorntorp P.
        Androgen treatment of middle-aged, obese men.
        Eur J Med. 1992; 1: 329-336
        • Liverman C.T.
        • Blazer D.G.
        Testosterone and Aging. Institute of Medicine, The National Academies Press, Washington, DC2004
        • Writing Group for the Women’s Health Initiative Investigators
        Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled trial.
        JAMA. 2002; 288: 321-333
        • Rosen R.C.
        • Riley A.
        • Wagner G.
        • et al.
        The International Index of Erectile Function (IIEF).
        Urology. 1997; 49: 822-830