Review
Pharmacotherapy for erectile dysfunction

https://doi.org/10.1016/S0165-6147(00)01587-XGet rights and content

Abstract

Erectile dysfunction (ED) is defined as the consistent inability to obtain or maintain an erection for satisfactory sexual relations. An estimated 20–30 million men suffer from some degree of sexual dysfunction. The past 20 years of research on erectile physiology have increased our understanding of the biochemical factors and intracellular mechanisms responsible for corpus cavernosal smooth muscle contraction and relaxation, and revealed that ED is predominantly a disease of vascular origin. Since the advent of sildenafil (Viagra®), there has been a resurgence of interest in ED, and an increase in patients presenting with this disease. A thorough knowledge of the physiology of erection is essential for future pharmacological innovations in the field of male ED.

Section snippets

Physiology of normal penile erection

The process of penile erection is dependent on an intact central and peripheral nervous system. To understand the etiologies of ED, it is essential to understand the neural and vascular pathways that function during penile erection. Normal erectile function involves three synergistic and simultaneous processes: (1) a neurologically mediated increase in penile arterial inflow; (2) relaxation of cavernosal smooth muscle; and (3) restriction of venous outflow from the penis. ED occurs as a result

Vasoactive intracavernous and transurethral injection therapy

In the early 1980s, Virag and Brindley were the first to report on the clinical efficacy of intracavernosal injections of pharmacological agents to induce penile erection 17., 18.. Since that time, intracavernosal injections of vasoactive agents have been the most reliable and effective therapy for male ED. However, intracavernosal injection can cause pain, hypotension and a local fibrotic reaction in the penis 19. Direct injection of vasoactive agents into corpora cavernosa bypasses the

Oral pharmacological therapies

There has been a profound change in the current strategies for the pharmacological treatment of ED with the advent of effective oral erectogenic drugs. In the past, the first-line therapies for men suffering from ED were intracavernous and intraurethral pharmacological regimens. However, these agents have now become second-line therapies behind the oral agents. In the past, fear of injections and concern about other adverse effects from intracavernous therapy prevented several patients from

Gene therapy for ED

Somatic gene therapy can be defined as the ability to introduce genetic material into an appropriate cell type in vivo, thus altering gene expression of that cell to produce a therapeutic effect. It has been suggested that the penis is an ideal organ for the use of gene therapy because of its external location, easy accessibility and the low turnover rate of vascular smooth muscle cells, thus allowing a desired gene to be expressed for long periods of time without affecting the systemic

Concluding remarks

The increased public awareness of male sexual dysfunction will undoubtedly advance our understanding of the physiological mechanisms of erectile function and promote the development of new, more effective oral and local agents for the treatment of ED. The recent use of effective oral agents as first-line therapy in most ED patients has been established. Although sildenafil can cause serious adverse reactions in some individuals, such as patients with coronary disease taking nitrates, it has

References (49)

  • A.L. Burnett

    Nitric oxide in the penis: physiology and pathology

    J. Urol.

    (1997)
  • C. Nathan et al.

    Nitric oxide synthases: roles, tolls, and controls

    Cell

    (1994)
  • C.G. Stief

    Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction

    J. Urol.

    (1992)
  • H. Porst

    Prostaglandin E1 and the nitric oxide donor linsidomine for erectile failure: a diagnostic comparative study of 40 patients

    J. Urol.

    (1993)
  • T.P. Dousa

    Cyclic-3′,5′-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney

    Kidney Int.

    (1999)
  • T.J. Bivalacqua

    Potentiation of erectile response and cAMP accumulation by combination of prostaglandin E1 and rolipram, a selective inhibitor of the type 4 phosphodiesterase (PDE 4)

    J. Urol.

    (1999)
  • P. Kunelius

    Is high-dose yohimbine hydrochloride effective in the treatment of mixed-type impotence? A prospective, randomized, controlled double-blind crossover study

    Urology

    (1997)
  • Impotence: NIH consensus development panel on impotence

    J. Am. Med. Assoc.

    (1993)
  • E.O. Laumann

    Sexual dysfunction in the United States: prevalence and predictors

    J. Am. Med. Assoc.

    (1999)
  • W.J. Hellstrom et al.

    Peyronie's disease: etiology, medical, and surgical therapies

    J. Androl.

    (2000)
  • S.R. Aboseif et al.

    Anatomy of the Penis

  • K.E. Andersson et al.

    Physiology of penile erection

    Physiol. Rev.

    (1995)
  • T.F. Lue

    Erectile dysfunction

    New Engl. J. Med.

    (2000)
  • A.L. Burnett

    Nitric oxide: a physiologic mediator of penile erection

    Science

    (1992)
  • Cited by (100)

    • Herbal slimming products and natural sexual enhancers

      2021, Aromatic Herbs in Food: Bioactive Compounds, Processing, and Applications
    • PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration

      2019, Journal of Sexual Medicine
      Citation Excerpt :

      ED is associated with chronic illnesses, such as depression and cardiovascular diseases.1 Penile erection depends on neural, vascular, and cavernosal tissue integrity.2,3 After sexual arousal, cavernous nerve terminals and smooth muscle endothelium release neurotransmitters.2,4

    • Male Sexual Behavior

      2017, Hormones, Brain and Behavior: Third Edition
    • Effects of chronic l-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum

      2016, Pharmacological Reports
      Citation Excerpt :

      At the level of the central nervous system (CNS), the hypothalamic and limbic systems are responsible for the psychological components of penile erection. Erectogenic signals are released from these central areas to facilitate the spinal cord pathways, which lead to erection of the penis via peripheral mechanisms [2]. Dopamine is a critical central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans [3,4].

    • Male Sexual Behavior

      2015, Knobil and Neill's Physiology of Reproduction: Two-Volume Set
    View all citing articles on Scopus
    View full text