- Email: [email protected]
Integration of treatments for male erectile dysfunction
COMMENTARY
treated. Environmental control must be sought and compliance issues need to be addressed. When a diagnosis of steroid resistance is established, unproved therapies can be tried, most appropriately within a controlled clinical trial. The National Institutes of Health are supporting cooperative trials of alternative asthma therapies. Perhaps then the value of non-steroidal antiinflammatory agents will be clarified.
Arthur S Banner Veterans Affairs Medical Center, Manchester, NH 03104, USA; and Harvard Medical School, Cambridge, Massachusetts 1
Barnes PJ. Anti-inflammatory therapy for asthma. Annu Rev Med 1993; 44: 229–42. 2 Spahn JD, Leung DYM. The role of glucocorticoids in the management of asthma. Allergy Asthma Proc 1996; 17: 341–50. 3 Spahn JD, Leung DYM, Szefler SJ. New insights into the pathogenesis and management of steroid-resistant asthma. J Asthma 1997; 34: 177–94. 4 Spahn JD, Leung YM, Surs W, et al. Reduced glucorticoid binding affinity in asthma is related to ongoing allergic inflammation. Am J Respir Crit Care Med 1995; 151: 1709–14. 5 Kane GC, Peters SP, Fish JE. Alternative anti-inflammatory drugs in the treatment of bronchial asthma. Clin Pulm Med 1994; 1: 69–77. 6 Alexander AG, Barnes NC, Kay AB. Trial of cyclosporin in corticosteroid-dependent chronic severe asthma. Lancet 1992; 339: 324–28. 7 Mazer B, Gelfand EW. An open-label study of high dose intravenous immunoglobulin in severe childhood asthma. J Allergy Clin Immunol 1991; 87: 976–83. 8 Fish JE, Peters SP, Chambers CV, et al. An evaluation of colchicine as an alternative to inhaled corticosteroids in moderate asthma. Am J Respir Care Med 1997; 156: 1165º71. 9 Erzurum C, Leff JA, Cochran JE, et al. Lack of benefit of methotrexate in severe steroid dependent asthma. Ann Intern Med 1991; 114: 353–60. 10 Hill MR, Szefler SJ, Ball BD, et al. Monitoring glucocorticoid therapy: a pharmacokinetic approach. Clin Pharmacol 1990; 48: 390–98.
Integration of treatments for male erectile dysfunction Erectile dysfunction is common, increases in prevalence with age, and is a source of much emotional stress for sufferers and their partners. It is caused by a wide range of organic, psychological, psychiatric, interpersonal, and pharmacological factors.1 The treatment options have increased steadily in recent years, relatively effective physical means of treatment having gradually been added to earlier psychotherapeutic approaches, for which there is reasonable evidence of both short-term and longerterm efficacy. The main psychotherapeutic treatment is sex therapy, which consists of a graduated programme of homework assignments combined with education and psychological work to help overcome barriers to progress.2 Such treatment has been reserved largely for couples, on the basis that only by treating the patient with his partner can important interpersonal factors contributing to the erectile problem be overcome. Psychological treatments for men without partners have received little attention and clinicians have therefore tended to turn to physical treatments for this population. Recently a group working in Montreal3 reported a randomised controlled trial of group treatment of men without partners who had a range of sexual dysfunctions (erectile dysfunction, premature ejaculation, and inhibition of orgasm). They found that treatment focused on problems in interpersonal functioning, or one focusing on both interpersonal problems and sexual dysfunction,
THE LANCET • Vol 351 • January 3, 1998
was more effective after 12 months of follow- up than treatment aimed primarily at directly improving the sexual dysfunction. These results were especially evident in terms of the proportion of patients who no longer had sexual dysfunction and who had established a stable relationship with a partner. An obvious conclusion from this study is that interpersonal concerns can be extremely important in the genesis of sexual dysfunction. Such issues are also usually an important target for therapy in couples. A critical issue, therefore, concerns the implications of this fact in the light of the growing emphasis on physical treatments for erectile dysfunction, with their focus primarily on mechanical performance rather than interpersonal issues. Many men who seek help for sexual dysfunction are looking for a quick fix, and are usually reluctant to engage in psychological therapy. Physical treatments are therefore viewed as attractive. The first major development in physical treatments for male sexual dysfunction was the introduction of intracavernosal injections of vasoactive drugs such as papaverine and prostaglandin E1. A recent successful refinement of this approach is the administration of prostaglandin by gel inserted into the urethra.4 A further development was the introduction of vacuum constriction devices, by means of which blood is drawn into penile cavernous bodies by an externally created vacuum and retained in the penis by a constriction ring. The licensing of sildenafil, an entirely new type of medication for this problem, is now awaited. Sildenafil is an oral drug that enhances relaxation of smooth muscle in the corpus cavernosum through inhibition of the cyclic guanosine monophosphate phosphodiesterase (cGMP) enzyme, thus enhancing cGMP activity and thereby nitric oxide function in smooth-muscle relaxation.5 Preliminary studies suggest that sildenafil is substantially more effective than placebo in the treatment of erectile dysfunction6 and, unlike intracavernosal injections, functions mainly in response to physical stimulation and has few side-effects. The introduction of sildenafil, and no doubt other similar preparations in due course, is likely to result in a huge increase in demand for treatment. Leaving aside the cost concerns for purchasers, which are inevitably going to result in hard choices, there will be important challenges for clinical services and individual clinics in terms of how they deliver new physical treatments. Although these treatments, of which sildenafil is likely to become the flagship, have considerable appeal they will never be the total answer to erectile problems. Follow-up studies have shown that a surprisingly high proportion of patients do not persist with use of vacuum devices or intracavernosal injections,7 despite good initial response, mainly because of ineffectiveness, side-effects, lack of spontaneity, and partner dislike. Discontinuation of use is likely to be due partly to failure of some clinicians to engage the patient’s partner in the treatment. The results of the study from Montreal highlight the well-recognised importance of interpersonal factors in maintenance of male sexual dysfunction. Evidence of considerable partner sexual dysfunction in cases of psychogenic erectile dysfunction, often predating the onset of the sexual problem,8 further underlines the complex multifactorial nature of sexual difficulties. 7
COMMENTARY
There is a need for integrated approaches to male sexual dysfunction whereby patients can be assessed in clinics staffed by urologists, psychologists, or psychiatrists, and others specialised in sexual medicine. Through such an approach it should be possible for patients, and their partners where available, to be offered the most suitable treatment, whether it be physical treatment plus couple counselling, individual psychological therapy, conjoint sex therapy, or a combination of these therapies. Such a multidisciplinary approach will allow patients to receive the most effective care, including maximising the benefits of the new physical treatments.
Keith Hawton University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK 1 2 3
4
5
6 7
8
Bancroft J. Human sexuality and its problems. Edinburgh: Churchill Livingstone, 1989. Hawton K. Treatment of sexual dysfunctions by sex therapy and other approaches. Br J Psychiatry 1995, 167: 307–14. Stravynski A, Gaudette G, LesageA, et al. The treatment of sexually dysfunctional men without partners: a controlled study of three behavioural group approaches. Br J Psychiatry 1997; 170: 338–44. Padma-Nathan H, Hellstrom WJ, Kaiser FE, et al. Treatment of men with erectile dysfunction with transurethal alprostadil. N Engl J Med 1997; 336: 309–12. Jeremy JY, Ballard SA, Naylor AM, et al. Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 1997; 79: 958–63. Boolell M, Gepi-Attee S, Gingell JC, et al. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 1996; 78: 257–61. Althof SE, Turner LA, Levine SB, et al. Why do so many people drop out from auto-injection therapy for impotence? J Sex Marital Ther 1989; 15: 121–29. Speckens AEM, HengevedMW, Lycklam à Nijeholt GAB, et al. Psychosexual functioning of partners of men with presumed nonorganic erectile dysfunction: cause or consequence of the disorder? Arch Sex Behav 1995; 24: 157–72.
of pregnancy or to compel her to live a lifestyle that promotes the health of the baby. However, the threat of compensatory damages caused by breaches of personalservice terms might encourage compliance if the contract were enforceable. As soon as it draws breath at birth the baby gains independent legal status and its best interest becomes the paramount consideration for the courts. A key question for the legal review body is whether surrogacy arrangements should remain contrary to public policy and thus outside the law. Another must be what constitutes “reasonable” expenses and whether these should be permitted. But most urgently in need of reform is the designation of legal parenthood to the surrogate (and her husband if the pregnancy was created by medical intervention using in-vitro fertilisation or artificial insemination from donor pursuant to a surrogacy arrangement). The law should be changed to distinguish between the legal status of a surrogate who is also the genetic mother of a child and one who is neither genetically nor socially connected. Unless the surrogate is shown to be unfit to be a mother, the odds of custody and control are heavily stacked in her favour; she has not only prime legal status but also “possession” of the baby and thus the opportunity to “bond” with the baby, a factor that will strengthen her claim. Reform of the law relating to surrogacy is urgently needed also because of the desire for posthumous conception. In such cases surrogacy is usually arranged by the surviving partner but, as happened in California a month ago, it was arranged by the parents of an unmarried deceased woman.3 Another complication is the use of one surrogate to bear unrelated “twins” conceived by simultaneous artificial insemination on behalf of two unrelated couples.4 Had the Italian women who gave birth to these twins charged a fee, would there have been allegations of “baby farming ”?
Designating parents in surrogate pregnancies
Diana Brahams
Surrogacy contracts are outwith the law in the UK, whereas they can be legally binding in the USA. In the 1980s these contracts were held by the courts to be against public policy,1 and the Surrogacy Arrangements Act 1985 rushed through Parliament after the UK’s first commercial surrogate birth criminalises commercial surrogacy (though not the surrogate herself, or services performed without a fee or for “reasonable” expenses) and all advertising. The Human Fertilisation and Embryology Act 1990 confirmed the common law position that all surrogacy arrangements are unenforceable but acknowledged them with its provision for speedy adoption where this is consensual and appropriate. A judicial review led by Prof Margaret Brazier is under way. It was prompted by a highly publicised dispute between a 31-year-old married surrogate and a Dutch couple who had paid her £12 000 3 days after she became pregnant with the man’s sperm.2 The relationship soured, the surrogate claimed, falsely, that she had terminated the pregnancy, and later she decided to keep the baby, who is now the subject of a custody battle. Since in the UK a contract for personal services cannot be enforced by an order for specific performance, there is no power to stop a surrogate seeking a lawful termination
1 2 3
8
Old Square Chambers, London WC1R 5LQ, UK
4
Re C (A Minor) [1985] FLR 846. The Lancet. The baby market. Lancet 1997; 349: 1487. Connor S, Norton C. Parents create dead daughter’s child Sunday Times, Nov 30, 1997. Simini B. Italian surrogate “twins”. Lancet 1997; 350: 1307.
Duet for many See page 47 For a statistical approach that aims to settle debates, meta-analysis has generated a fair amount of controversy. Critics point to the hazards associated with combination of data from studies with differences in the degree of bias, the effects of heterogeneity between studies, and the problem of publication bias against trials with negative results. We hope that the pair of articles forming our Meta-analysis Duet will help to assuage these fears. Janice Pogue and Salim Yusuf (page 47) describe standards for the conduct, analysis, and interpretation of meta-analyses. Joseph Lau and colleagues (next week) argue that the strengths of meta-analysis outweigh the weaknesses. Both papers recommend a more prospective approach. Can they win over the scepticx? Rosalind Osmond The Lancet, London WC1B 3SL, UK
THE LANCET • Vol 351 • January 3, 1998
treated. Environmental control must be sought and compliance issues need to be addressed. When a diagnosis of steroid resistance is established, unproved therapies can be tried, most appropriately within a controlled clinical trial. The National Institutes of Health are supporting cooperative trials of alternative asthma therapies. Perhaps then the value of non-steroidal antiinflammatory agents will be clarified.
Arthur S Banner Veterans Affairs Medical Center, Manchester, NH 03104, USA; and Harvard Medical School, Cambridge, Massachusetts 1
Barnes PJ. Anti-inflammatory therapy for asthma. Annu Rev Med 1993; 44: 229–42. 2 Spahn JD, Leung DYM. The role of glucocorticoids in the management of asthma. Allergy Asthma Proc 1996; 17: 341–50. 3 Spahn JD, Leung DYM, Szefler SJ. New insights into the pathogenesis and management of steroid-resistant asthma. J Asthma 1997; 34: 177–94. 4 Spahn JD, Leung YM, Surs W, et al. Reduced glucorticoid binding affinity in asthma is related to ongoing allergic inflammation. Am J Respir Crit Care Med 1995; 151: 1709–14. 5 Kane GC, Peters SP, Fish JE. Alternative anti-inflammatory drugs in the treatment of bronchial asthma. Clin Pulm Med 1994; 1: 69–77. 6 Alexander AG, Barnes NC, Kay AB. Trial of cyclosporin in corticosteroid-dependent chronic severe asthma. Lancet 1992; 339: 324–28. 7 Mazer B, Gelfand EW. An open-label study of high dose intravenous immunoglobulin in severe childhood asthma. J Allergy Clin Immunol 1991; 87: 976–83. 8 Fish JE, Peters SP, Chambers CV, et al. An evaluation of colchicine as an alternative to inhaled corticosteroids in moderate asthma. Am J Respir Care Med 1997; 156: 1165º71. 9 Erzurum C, Leff JA, Cochran JE, et al. Lack of benefit of methotrexate in severe steroid dependent asthma. Ann Intern Med 1991; 114: 353–60. 10 Hill MR, Szefler SJ, Ball BD, et al. Monitoring glucocorticoid therapy: a pharmacokinetic approach. Clin Pharmacol 1990; 48: 390–98.
Integration of treatments for male erectile dysfunction Erectile dysfunction is common, increases in prevalence with age, and is a source of much emotional stress for sufferers and their partners. It is caused by a wide range of organic, psychological, psychiatric, interpersonal, and pharmacological factors.1 The treatment options have increased steadily in recent years, relatively effective physical means of treatment having gradually been added to earlier psychotherapeutic approaches, for which there is reasonable evidence of both short-term and longerterm efficacy. The main psychotherapeutic treatment is sex therapy, which consists of a graduated programme of homework assignments combined with education and psychological work to help overcome barriers to progress.2 Such treatment has been reserved largely for couples, on the basis that only by treating the patient with his partner can important interpersonal factors contributing to the erectile problem be overcome. Psychological treatments for men without partners have received little attention and clinicians have therefore tended to turn to physical treatments for this population. Recently a group working in Montreal3 reported a randomised controlled trial of group treatment of men without partners who had a range of sexual dysfunctions (erectile dysfunction, premature ejaculation, and inhibition of orgasm). They found that treatment focused on problems in interpersonal functioning, or one focusing on both interpersonal problems and sexual dysfunction,
THE LANCET • Vol 351 • January 3, 1998
was more effective after 12 months of follow- up than treatment aimed primarily at directly improving the sexual dysfunction. These results were especially evident in terms of the proportion of patients who no longer had sexual dysfunction and who had established a stable relationship with a partner. An obvious conclusion from this study is that interpersonal concerns can be extremely important in the genesis of sexual dysfunction. Such issues are also usually an important target for therapy in couples. A critical issue, therefore, concerns the implications of this fact in the light of the growing emphasis on physical treatments for erectile dysfunction, with their focus primarily on mechanical performance rather than interpersonal issues. Many men who seek help for sexual dysfunction are looking for a quick fix, and are usually reluctant to engage in psychological therapy. Physical treatments are therefore viewed as attractive. The first major development in physical treatments for male sexual dysfunction was the introduction of intracavernosal injections of vasoactive drugs such as papaverine and prostaglandin E1. A recent successful refinement of this approach is the administration of prostaglandin by gel inserted into the urethra.4 A further development was the introduction of vacuum constriction devices, by means of which blood is drawn into penile cavernous bodies by an externally created vacuum and retained in the penis by a constriction ring. The licensing of sildenafil, an entirely new type of medication for this problem, is now awaited. Sildenafil is an oral drug that enhances relaxation of smooth muscle in the corpus cavernosum through inhibition of the cyclic guanosine monophosphate phosphodiesterase (cGMP) enzyme, thus enhancing cGMP activity and thereby nitric oxide function in smooth-muscle relaxation.5 Preliminary studies suggest that sildenafil is substantially more effective than placebo in the treatment of erectile dysfunction6 and, unlike intracavernosal injections, functions mainly in response to physical stimulation and has few side-effects. The introduction of sildenafil, and no doubt other similar preparations in due course, is likely to result in a huge increase in demand for treatment. Leaving aside the cost concerns for purchasers, which are inevitably going to result in hard choices, there will be important challenges for clinical services and individual clinics in terms of how they deliver new physical treatments. Although these treatments, of which sildenafil is likely to become the flagship, have considerable appeal they will never be the total answer to erectile problems. Follow-up studies have shown that a surprisingly high proportion of patients do not persist with use of vacuum devices or intracavernosal injections,7 despite good initial response, mainly because of ineffectiveness, side-effects, lack of spontaneity, and partner dislike. Discontinuation of use is likely to be due partly to failure of some clinicians to engage the patient’s partner in the treatment. The results of the study from Montreal highlight the well-recognised importance of interpersonal factors in maintenance of male sexual dysfunction. Evidence of considerable partner sexual dysfunction in cases of psychogenic erectile dysfunction, often predating the onset of the sexual problem,8 further underlines the complex multifactorial nature of sexual difficulties. 7
COMMENTARY
There is a need for integrated approaches to male sexual dysfunction whereby patients can be assessed in clinics staffed by urologists, psychologists, or psychiatrists, and others specialised in sexual medicine. Through such an approach it should be possible for patients, and their partners where available, to be offered the most suitable treatment, whether it be physical treatment plus couple counselling, individual psychological therapy, conjoint sex therapy, or a combination of these therapies. Such a multidisciplinary approach will allow patients to receive the most effective care, including maximising the benefits of the new physical treatments.
Keith Hawton University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK 1 2 3
4
5
6 7
8
Bancroft J. Human sexuality and its problems. Edinburgh: Churchill Livingstone, 1989. Hawton K. Treatment of sexual dysfunctions by sex therapy and other approaches. Br J Psychiatry 1995, 167: 307–14. Stravynski A, Gaudette G, LesageA, et al. The treatment of sexually dysfunctional men without partners: a controlled study of three behavioural group approaches. Br J Psychiatry 1997; 170: 338–44. Padma-Nathan H, Hellstrom WJ, Kaiser FE, et al. Treatment of men with erectile dysfunction with transurethal alprostadil. N Engl J Med 1997; 336: 309–12. Jeremy JY, Ballard SA, Naylor AM, et al. Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 1997; 79: 958–63. Boolell M, Gepi-Attee S, Gingell JC, et al. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 1996; 78: 257–61. Althof SE, Turner LA, Levine SB, et al. Why do so many people drop out from auto-injection therapy for impotence? J Sex Marital Ther 1989; 15: 121–29. Speckens AEM, HengevedMW, Lycklam à Nijeholt GAB, et al. Psychosexual functioning of partners of men with presumed nonorganic erectile dysfunction: cause or consequence of the disorder? Arch Sex Behav 1995; 24: 157–72.
of pregnancy or to compel her to live a lifestyle that promotes the health of the baby. However, the threat of compensatory damages caused by breaches of personalservice terms might encourage compliance if the contract were enforceable. As soon as it draws breath at birth the baby gains independent legal status and its best interest becomes the paramount consideration for the courts. A key question for the legal review body is whether surrogacy arrangements should remain contrary to public policy and thus outside the law. Another must be what constitutes “reasonable” expenses and whether these should be permitted. But most urgently in need of reform is the designation of legal parenthood to the surrogate (and her husband if the pregnancy was created by medical intervention using in-vitro fertilisation or artificial insemination from donor pursuant to a surrogacy arrangement). The law should be changed to distinguish between the legal status of a surrogate who is also the genetic mother of a child and one who is neither genetically nor socially connected. Unless the surrogate is shown to be unfit to be a mother, the odds of custody and control are heavily stacked in her favour; she has not only prime legal status but also “possession” of the baby and thus the opportunity to “bond” with the baby, a factor that will strengthen her claim. Reform of the law relating to surrogacy is urgently needed also because of the desire for posthumous conception. In such cases surrogacy is usually arranged by the surviving partner but, as happened in California a month ago, it was arranged by the parents of an unmarried deceased woman.3 Another complication is the use of one surrogate to bear unrelated “twins” conceived by simultaneous artificial insemination on behalf of two unrelated couples.4 Had the Italian women who gave birth to these twins charged a fee, would there have been allegations of “baby farming ”?
Designating parents in surrogate pregnancies
Diana Brahams
Surrogacy contracts are outwith the law in the UK, whereas they can be legally binding in the USA. In the 1980s these contracts were held by the courts to be against public policy,1 and the Surrogacy Arrangements Act 1985 rushed through Parliament after the UK’s first commercial surrogate birth criminalises commercial surrogacy (though not the surrogate herself, or services performed without a fee or for “reasonable” expenses) and all advertising. The Human Fertilisation and Embryology Act 1990 confirmed the common law position that all surrogacy arrangements are unenforceable but acknowledged them with its provision for speedy adoption where this is consensual and appropriate. A judicial review led by Prof Margaret Brazier is under way. It was prompted by a highly publicised dispute between a 31-year-old married surrogate and a Dutch couple who had paid her £12 000 3 days after she became pregnant with the man’s sperm.2 The relationship soured, the surrogate claimed, falsely, that she had terminated the pregnancy, and later she decided to keep the baby, who is now the subject of a custody battle. Since in the UK a contract for personal services cannot be enforced by an order for specific performance, there is no power to stop a surrogate seeking a lawful termination
1 2 3
8
Old Square Chambers, London WC1R 5LQ, UK
4
Re C (A Minor) [1985] FLR 846. The Lancet. The baby market. Lancet 1997; 349: 1487. Connor S, Norton C. Parents create dead daughter’s child Sunday Times, Nov 30, 1997. Simini B. Italian surrogate “twins”. Lancet 1997; 350: 1307.
Duet for many See page 47 For a statistical approach that aims to settle debates, meta-analysis has generated a fair amount of controversy. Critics point to the hazards associated with combination of data from studies with differences in the degree of bias, the effects of heterogeneity between studies, and the problem of publication bias against trials with negative results. We hope that the pair of articles forming our Meta-analysis Duet will help to assuage these fears. Janice Pogue and Salim Yusuf (page 47) describe standards for the conduct, analysis, and interpretation of meta-analyses. Joseph Lau and colleagues (next week) argue that the strengths of meta-analysis outweigh the weaknesses. Both papers recommend a more prospective approach. Can they win over the scepticx? Rosalind Osmond The Lancet, London WC1B 3SL, UK
THE LANCET • Vol 351 • January 3, 1998