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Vol. 47. Issue 6.
Pages 278-290 (January 2004)
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Vol. 47. Issue 6.
Pages 278-290 (January 2004)
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Tratamiento farmacológico de la incontinencia urinaria de esfuerzo
Pharmacological treatment of urinary stress incontinence
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17311
M. Espuña
Corresponding author
mespuna@medicina.ub.es

Correspondencia: ICGON. Hospital Clínic. Villarroel, 170. 08036 Barcelona. España
, M. Puig
Institut Clínic de Ginecologia, Obstetrícia i Neonatologia (ICGON). Hospital Clínic. Universidad de Barcelona. Barcelona. España
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Resumen

La incontinencia urinaria de esfuerzo (IUE) es la pérdida involuntaria de orina asociada a un esfuerzo físico que provoca un aumento de la presión abdominal (toser, reír, correr o incluso andar). Se estima que, en aproximadamente el 50% de las mujeres con incontinencia urinaria (IU), su síntoma principal es la IUE. La uretra en sí misma tiene un importante papel en el conjunto de los mecanismos de continencia, recibe inervación triple: simpática, parasimpática y somática. El estímulo somático llega a la uretra desde el núcleo de Onuf, situado en la médula sacra, a través del nervio pudendo, la estimulación de receptores nicotínicos, en el músculo estriado uretral provoca la contracción refleja y también la voluntaria del esfínter uretral. En estudios experimentales, se ha comprobado la implicación de la serotonina en el control central del aparato urinario inferior, aunque ha resultado difícil establecer el tipo de acción, la mayoría de estudios reconoce que la activación central dependiente de la serotonina produce una inhibición en los mecanismos sensoriales y la estimulación de la actividad somática motora del esfínter estriado uretral. Mediante técnicas inmunohistoquímicas, se ha podido observar que las neuronas del núcleo de Onuf que van al esfínter estriado uretral, están rodeadas de numerosos terminales adrenérgicos y serotoninérgicos y, por tanto, sensibles a los efectos de un inhibidor de la recaptación de serotonina (5-HT) y norepinefrina (NE). El incremento de serotonina y noradrenalina en la zona del núcleo de Onuf, provoca un aumento de actividad neural que trae como consecuencia un estímulo que favorece una contracción prolongada del esfínter uretral. Según esta observación, cualquier fármaco que actúe en el sistema nervioso central (SNC) y produzca un incremento en el aporte de serotonina y noradrenalina tiene un efecto que puede potenciar la continencia.

La duloxetina es un inhibidor combinado de la recaptación de 5-HT y NE. Los ensayos clínicos realizados en un total de 1.913 mujeres con IU de predominio de esfuerzo, con duloxetina frente a placebo y el metaanálisis de éstos, proporcionan datos consistentes y de peso que apoyan la seguridad y la eficacia de la duloxetina para el tratamiento de la IUE. Esta forma de tratamiento se podrá ofrecer como primera opción terapéutica, al igual que la reeducación muscular del suelo pélvico a mujeres con diagnóstico de IUE. Los estudios de extensión y el uso del fármaco en la práctica clínica, indicarán el lugar exacto que ocupará el tratamiento farmacológico de la IUE en el contexto de la atención a la IU en la mujer.

Palabras Clave:
Incontinencia urinaria
Mujer
Tratamiento farmacológico
Abstract

Urinary stress incontinence (USI) consists of involuntary urine loss associated with physical stress that increases abdominal pressure (coughing, laughing, running or even walking). In approximately 50% of women with urinary incontinence (UI), the main symptom is USI. In itself, the urethra plays an important role in the set of mechanisms of continence and receives innervation from 3 sources: sympathetic, parasympathetic and somatic. The somatic stimulus reaches the urethra from Onuf’s nucleus, situated in the ventral horn of the spinal cord at sacral 2 level, through the pudendal nerve, and stimulation of nicotinic receptors in the striated urethral muscle provokes reflex and voluntary contractions of the urethral sphincter. Experimental studies have demonstrated the involvement of serotonin in central control of the lower urinary apparatus. Although it has been difficult to establish the type of action, most studies recognize that central serotonin-dependent activation inhibits the sensory mechanisms and stimulation of somatic motor activity of striated urethral muscle. Immunohistochemical techniques have revealed that the neurons of Onuf’s nucleus that reach the striated urethral sphincter are surrounded by numerous adrenergic and serotoninergic terminals and are therefore sensitive to the effects of serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. The increase of serotonin and noradrenalin in the area of Onuf’s nucleus increases neural activity, which leads to a stimulus favoring prolonged contraction of the urethral sphincter. According to this observation, any drug that, acting on the central nervous system, increases the contribution of serotonin and noradrenalin, could increase continence.

Duloxetine is a combined 5-HT and NE reuptake inhibitor. Clinical trials of duloxetine versus placebo performed in 1913 women with UI, mainly USI, and meta-analysis of these drugs provide consistent and robust data supporting the safety and efficacy of duloxetine in the treatment of USI. This form of treatment will be offered as the first-line therapeutic option along with pelvic floor reeducation in women with a diagnosis of USI. Studies of the drug in clinical practice will indicate its precise role in the pharmacological treatment of USI in the context of female UI.

Key Words:
Urinary Incontinence
Woman
Pharmacological treatment
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Bibliografía
[1.]
P. Abrams, L. Cardozo, M. Fall, D. Griffiths, P. Rosier, U. Ulmsten, et al.
The standardisation of terminology in lower urinary tract function. Report from the Standardisation Sub-committee of the International Continence Society.
Neurourol and Urodyn, 21 (2002), pp. 167-178
[2.]
J. Wijma, A.E. Weis Potters, B.T. De Wolf, D.J. Tinga, J.G. Aarnoudse.
Anatomical and functional changes in the lower urinary tract during pregnancy.
Bjog, 108 (2001), pp. 726-732
[3.]
Clinical Practice Guideline No 2.
Depart Health. Public Health Service AHCPR Publication 96-0682. Rockville:,
[4.]
P. Abrams, L. Cardozo, S. Khoury, A. Wein.
Incontinence. Recommendations of International Scientific Committee. Evaluation and treatment of urinary incontinence, pelvic organ prolapse and faecal incontinence. Second International Consultation on Incontinence.
Edition 2002, pp. 1079-1117
[5.]
S. Hunskaar, E.P. Arnold, K. Burgio, A.C. Diokno, A.R. Herzog, V.T. Mallett.
Epidemiology and natural history of urinary incontinence.
Int Urogynecol J, 11 (2000), pp. 301
[6.]
C. Hampel, D. Wienhold, N. Benken, C. Eggersmann, J.W. Thuroff.
Prevalence and natural history of female incontinence.
Eur Urol, 32 (1997), pp. 3
[7.]
H. Sandvik, S. Hunskaar, A. Vanvik, H. Bratt, A. Seim, R. Hermstad.
Diagnostic classification of female urinary incontinence: an epidemiological survey corrected for validity.
J Clin Epidemiol, 48 (1995), pp. 339
[8.]
P.E. Petros, U. Ulmsten.
An integral theory of female urinary incontinence.
Acta Scand Gynecol, 69 (1990), pp. 1-79
[9.]
J.O.L. Delancey.
Structural aspects of the extrinsic continence mechanism.
Obstet Gynecol, 72 (1988), pp. 296-301
[10.]
K. Bo, T. Talseth.
Change in urethral pressure during voluntary pelvic floor muscle contraction and vaginal electrical stimulation.
Int Urogynecol J Pelvic Floor Dysfunct, 8 (1997), pp. 3-6
[11.]
J.O.L. De Lancey.
Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis.
Am J Obstet Gynecol, 170 (1994), pp. 1713-1723
[12.]
W.H. Umek, T. Laml, D. Stutterecker, A. Obermair, S. Leodolter, E. Hanzal.
The urethra during pelvic floor contraction: observations on three-dimensional ultrasound.
Obstet Gynecol, 100 (2002), pp. 796-800
[13.]
W.C. De Groat, M.O. Fraser, M. Yoshiyama, S. Smerin, C. Tai, M.B. Chancellor, et al.
Neural control of the urethra.
Scand J Urol Nephrol Suppl, (2001), pp. 35-43
[14.]
C. Suárez, S. Bustamente, L. Méndez.
Neurofisiología del tracto urinario inferior y suelo pélvico. Pag 17-30.
Tratado de Uroginecología. Incontinencia Urinaria,
[15.]
W.C. De Groat, N. Yoshimura.
Pharmacology of the lower urinary tract.
Annu Rev Pharmacol Toxicol, 41 (2001), pp. 691-721
[16.]
M.O. Fraser, M.B. Chancellor.
Neural control of the urethra and development of pharmacotherapy for stress urinary incontinence.
BJU Int, 91 (2003), pp. 743-748
[17.]
A.C. Diokno, M. Taub.
Ephedrine in treatment of urinary incontinence.
Urology, 5 (1975), pp. 624-625
[18.]
A. Ek, K.E. Andersson, B. Gullberg, U. Ulmsten.
The effects of long-term treatment with norephedrine on stress incontinence and urethral closure pressure profile.
Scand J Urol Nephrol, 12 (1978), pp. 105-110
[19.]
L. Collste, M. Lindskog.
Phenylpropanolamine in treatment of female stress urinary incontinence. Double-blind placebo controlled study in 24 patients.
Urology, 30 (1987), pp. 398-403
[20.]
W.N. Kernan, C.M. Viscoli, L.M. Brass, J.P. Broderick, T. Brott, E. Feldmann, et al.
Phenylpropanolamine and the risk of hemorrhagic stroke.
N Engl J Med, 343 (2000), pp. 1826-1832
[21.]
D.M. Gleason, R.J. Reilly, M.R. Bottaccini, M.J. Pierce.
The urethral continence zone and its relation to stress incontinence.
J Urol, 112 (1974), pp. 81-88
[22.]
A.V. Kaisary.
Beta adrenoceptor blockade in the treatment of female urinary stress incontinence.
J Urol, 90 (1984), pp. 351-353
[23.]
A.T. Cole, F.A. Fried.
Favorable experiences with imipramine in the treatment of neurogenic bladder.
J Urol, 107 (1972), pp. 44-45
[24.]
C.M. Castleden, C.F. George, A.G. Renwick, M.J. Asher.
Imipramine a possible alternative to current therapy for urinary incontinence in the elderly.
J Urol, 125 (1981), pp. 318-320
[25.]
I. Gilja, M. Radej, M. Kovacic, J. Parazajder.
Conservative treatment of female stress incontinence with imipramine.
J Urol, 132 (1984), pp. 909-911
[26.]
C.M. Castleden, H.M. Duffin, R.S. Gulati.
Double-blind study of imipramine and placebo for incontinence due to bladder instability.
Age Ageing, 15 (1986), pp. 299-303
[27.]
J.A. Fantl, L. Cardozo, D.K. McClish.
Estrogen therapy in the management of urinary incontinence in postmenopausal women: a meta-analysis. First report of the Hormones and Urogenital Therapy Committee.
Obstet Gynecol, 83 (1994), pp. 12-18
[28.]
C.J. Sultana, M.D. Walters.
Estrogen and urinary incontinence in women.
Maturitas, 20 (1994), pp. 129-138
[29.]
S. Jackson, A. Shepherd, S. Brookes, P. Abrams.
The effect of oestrogen supplementation on post-menopausal urinary stress incontinence: a double-blind placebo-controlled trial.
Br J Obstet Gynaecol, 106 (1999), pp. 711-718
[30.]
D. Grady, J.S. Brown, E. Vittinghoff, W. Applegate, E. Varner, T. Snyder, For the HERS Research Group.
Postmenopausal hormones and incontinence: the Heart and Estrogen/Progestin Replacement Study.
Obstet Gynecol, 97 (2001), pp. 116-120
[31.]
F. Grodstein, K. Lifford, N.M. Resnick, G.C. Curhan.
Postmenopausal hormone therapy and risk of developing urinary incontinence.
Obstet Gynecol, 103 (2004), pp. 254-260
[32.]
L. Cardozo, G. Bachmann, D. McClish, D. Fonda, L. Birgerson.
Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee.
Obstet Gynecol, 92 (1998), pp. 722-727
[33.]
H. Danuser, K.B. Thor.
Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat.
Br J Pharmacol, 118 (1996), pp. 150-154
[34.]
K.B. Thor, M.A. Katofiasc, H. Danuser, J. Springer, J.M. Schaus.
The role of 5-HT(1A) receptors in control of lower urinary tract function in cats.
Brain Res, 946 (2002), pp. 290-297
[35.]
W.C. De Groat.
Influence of central serotonergic mechanisms on lower urinary tract function.
Urology, 59 (2002), pp. 30-36
[36.]
K.B. Thor.
Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: implications for treating stress urinary incontinence.
Urology, 62 (2003), pp. 3-9
[37.]
K.B. Thor, M.A. Katofiasc.
Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose- anesthetized female cat.
J Pharmacol Exp Ther, 274 (1995), pp. 1014-1024
[38.]
P.A. Norton, N.R. Zinner, I. Yalcin, R.C. Bump, For the Duloxetine Urinary Incontinence Study Group.
Duloxetine versus placebo in the treatment of stress urinary incontinence.
Am J Obstet Gynecol, 187 (2002), pp. 40-48
[39.]
R.R. Dmochowski, J.R. Miklos, P.A. Norton, N.R. Zinner, I. Yalcin, R.C. Bump, For the Duloxetine Urinary Incontinence Study Group.
Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence.
[40.]
P. Van Kerrebroeck, P. Abrams, R. Lange, M. Slack, J.J. Wyndaele, I. Yalcin, For the Duloxetine Urinary Incontinence Study Group.
Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence.
Bjog, 111 (2004), pp. 249-257
[41.]
R.J. Millard, K. Moore, R. Rencken, I. Yalcin, R.C. Bump, For the Duloxetine UI Study Group.
Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial.
Bju Int, 93 (2004), pp. 311-318
[42.]
R. Bump, C. Hooper, S. Koke, I. Yalcin.
Worldwide efficacy of duloxetine after 12 weeks and 1 year in women with stress urinary incontinence (sui): a 4- study meta-analysis.
Neurourol Urodyn, 22 (2003), pp. 337
[43.]
L. Cardozo, H. Drutz, S. Baygani, R. Bump.
Duloxetine response and onset of action in women with severe stress urinary incontinence (SUI) awaiting continence surgery.
IUGA congress, Buenos Aires,
[44.]
N.A. Black, S.H. Downs.
The effectiveness of surgery for stress incontinence in women: a systematic review.
British Journal of Urolology, 78 (1996), pp. 497-510
[45.]
K.L. Ward, P. Hilton, for the UK and Ireland TVT Trial Group.
A prospective multicenter randomized trial of tension-free vaginal tape and colposuspension for primary urodynamic stress incontinence: two-year follow-up.
Am J Obstet Gynecol, 190 (2004), pp. 324-331
[46.]
E.J.C. Hay-Smith, K. Bø, L.C.M. Berghmans, H.J.M. Hendriks, R.A. De Bie, E.S.C. Van Waalwijk van Doorn.
Pelvic floor muscle training for urinary incontinence in women (Cochrane Review).
The Cochrane Library, issue 1, (2001),
[47.]
P.S. Goode, K.L. Burgio, J.L. Locher, D.L. Roth, M.G. Umlauf, H.E. Richter, et al.
Effect of behavioral training with or without pelvic floor electrical stimulation on stress incontinence in women: a randomized controlled trial.
Jama, 16 (2003), pp. 345-352
Copyright © 2004. Sociedad Española de Ginecología y Obstetricia
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