JAGS 38~326-328,1990
Role of Estrogens in the Treatment of Female Urinary Incoiitinence Linda Cardozo, MD, MRCOG
mbryologically the female genital and urinary systems develop in close proximity, both arising from the primitive urogenital sinus. Animal and 1 human studies have shown that the urethra is estrogen sensitive, and estrogen receptors have been identified in the human female urethra. Thus there is good reason to suppose that changes in estrogen levels influence the lower urinary tract in women. Continence exists when the maximum urethral pressure exceeds the intravesical pressure at all times except during micturition. This positive closure pressure is produced by the four functional layers of the urethra: namely, the epithelium, connective tissue, vascular tissue, and muscle, all of which are affected by estrogen status.'-' At the time of menopause, circulating estrogen levels fall, causing urogenital atrophy. An increase in the incidence of lower urinary tract symptoms occurs, but it is still not certain whether this is due to the menopause itself or just part of the aging process. Thomas et a15 noted an increase in' the prevalence of urinary incontinence around the age of 35 years, but there did not seem to be a further large increase following the menopause, although the prevalence of urinary incontinence did show an increase with age. However, in a Swedish study, Iosif and Bekassf found that 70% of incontinent elderly women related the onset of their incontinence to their last menstrual period, but this was retrospective data. Bungay et a17 showed that there was a relatively high incidence of the symptoms of frequency and urgency of micturition in women at all ages, but that this was not particularly related to the menopause.
F
From King's College Hospital, London, United Kingdom. Prepared for the National Institutesof Health ConsensusDevelopment Conference on Urinary Incontinence in Adults, Bethesda, Maryland, October 3-5,1988. Address correspondence and reprint requests to Linda Cardozo, MD, MRCOG, 8 Devonshire Place, London WIN IPB, United Kingdom.
0 1990 by the American Geriatrics Society
The use of estrogen therapy for postmenopausal urinary incontinence remains controversial. Early studies were purely subjective, lacked controls, and were performed before the advent of urodynamic studieswhich enable an accurate diagnosis to be made. However, they did provide evidence of symptomatic improvement. In the first report by Salmon et a1,8 16 women with dysuria, frequency, urgency, and incontinence were treated with intramuscular estrogen therapy. After four weeks, 12 were symptomatically improved. The authors then discontinued therapy and when symptoms returned, repeated the c o m e of treatment. They showed that once again there was subjective improvement and concluded that the estrogen must be responsible. Musiani9 treated a series of 110 stress-incontinent women with quinestradoland reported 36 cured and 43 improved. Using estradiol implants SchleyerSaunders'O showed that 70 of 100 postmenopausal women with undiagnosed urinary incontinence were significantly improved, and thus the need for surgery was reduced. With the advent of pressure transducers, the effect of estrogens on the urethral pressure profile underwent scrutiny. Caine and Raz" reported increased maximum urethral pressures together with symptomatic improvement in 26 of 40 women with stress incontinence who underwent treatment with conjugated oral estrogens. Also studying stress-incontinent women, Faber and HeidenreichI2showed a significant rise in the urethral pressure profile in 39 of 41 undergoing treatment with estriol (a weak estrogen that is thought to have a specific effect on the urogenital tissues). Interestingly, although they reported clinical improvement, none of the women was cured. In Norway, RudI3 treated 24 stress-incontinent women with a combination of high-dose estradiol and estriol. He showed a significant increase in transmission of intraabdominal pressure to the urethra as well as an 0002-8614/90/53.50
IAGS-MARCH 1990-VOL 38, NO.3
increase in the maximum urethral pressure and urethral length at rest. Symptomatic improvement occurred in 70% of his subjects. Similar findings were reported by Hilton and Stanton," who used intravaginal estradiol cream to treat ten women with urodynamically proven genuine stress incontinence. They showed a significant increase in the stress maximum urethral-closure pressure because of improved pressure transmission in the mid-urethra. There was also significant subjective improvement in the symptoms of stress incontinence, urgency, and frequency. There have been very few properly placebo-controlled studies of estrogen therapy in the management of urinary incontinence. Those that have appeared in the literature are described below. Twenty years ago Judge15recruited 20 long-stay female geriatric patients into a double-blind placebo-controlled trial of quinestradol. The active preparation significantly reduced the frequency of incontinenceduring the fifth week of treatment. No placebo effect was noted. Estriol was used to treat 34 women aged 75 years in a double-blind placebo-controlled cross-over study.16 The women received 3 mg oral estriol (or equivalent placebo) daily for three months. There was no objective assessment and the women were divided into three groups on the basis of symptoms alone -stress incontinence, urge incontinence, or mixed incontinence. The authors noted that estriol was more effective than placebo in improving women with urge incontinence or mixed incontinence, but there was no difference between estriol and placebo in those women with stress incontinence. However, only 11 women had stress incontinence alone, all with minimal atrophy, and the short "washout" period in this study may have obscured potential differences. Walter and colleagues" looked at the problem of sensory-urge incontinence.They administered either estradiol with estriol or placebo for four months of cyclical therapy to 29 postmenopausal women who had urodynamically proven stable bladders. They showed significant improvement in urgency and urge incontinence in seven of 15 women treated with estrogen, which was significantly more than with placebo. However, they reported no improvement in any of the eight women with stress incontinence in either group and could not detect any change in the urethral pressure profile. The most recently reported placebo-controlled study using subjective and objective parameters is by Wilson et a1,18 in which 36 women participated in a doubleblind study of cyclical oral estrone for three months. Although there was symptomaticimprovement, the authors were unable to find any sigxuficant difference in subjective response, urethral pressure profiles, or Urilos test (an objective quantification test of urine loss). They concluded that the risks of estrogen therapy may out-
ESTROGENS AND FEMALE URINARY INCONTINENCE
327
weigh the benefit in the management of genuine stress incontinence. Our own preliminary data from King's College and Dulwich Hospitals yield similar results. Forty-six women with urodynamically (videocystourethrography with pressure and flow studies) proven genuine stress incontinence were randomly allocated to a 50 mg estradiol implant (24)or placebo implant (22). All the women completed a medically supervised symptom questionnaire and a visual analogue symptom score. They all underwent urethral pressure profilometry as described by Hilton and Stanton19and a pad weighmg test.*OAfter three months they were reassessed using the same parameters. There was no significant subjective improvement in either group. However, there was sigruficant objective improvement in bladder base descent as seen on the videocystourethrogram.This is interesting: it has long been speculated that estrogen replacement is beneficial in cases of prolapse, but there has, as yet, been no reported evidence of this. Side effects and complicationswith estrogen therapy would appear to be few. In Hilton and Stanton's study," one of the 11 women who started treatment with intravaginal cream was withdrawn because of breast tenderness and enlargement. Samsioeet all6reported that four of 34 elderly women treated with estriol stopped therapy because of mastodynia or metorrhagia. In the study by Wilson et all8two of the 16 women treated with oral estrone discontinued treatment; one had palpitations, and the other had a myocardial infarct that was probably unrelated to the treatment. There have been no other reported problems despite the use, in some cases, of high doses of estrogen. The potential adverse effects of estrogens include their effect on lipid metabolism and an increased incidence of endometrial carcinoma when long-term unopposed estrogens are prescribed to a woman with an intact uterus. However, all the studies reported have been short term: the longest duration of treatment was four months. Recent studies have shown that women receiving hormone replacement therapy (with natural estrogens) are less likely to suffer from cerebrovascular accidents and ischaemic heart disease,21,22 and the benefits in terms of the reduced risk of osteoporosis are well known. Recently the effect of estrogen supplementation has been studied. Fantl et a123assessed 72 postmenopausal women clinically and urodynamically. Twenty-three of these women were already taking estrogen replacement for other indications, and the remaining 49 were nonestrogen supplemented. The only sigxuficant difference that these authors reported was a decreased incidenceof nocturia in the estrogen-supplementedgroup. They hypothesized that hypoestrogenism may affect the sensory threshold of the lower urinary tract. Unfortunately, the effect of estrogen in combination with other drugs has not been widely studied. Ek et al"
328 CARDOZO
JAGS-MARCH 1990-VOL 38. NO. 3
treated 13 postmenopausal stress-incontinent women with oral estradiol for one month and then with estradiol plus norephedrin or placebo for another month. They showed that estradiol alone had no effect on symptoms or urethral pressure profile but that estradiol plus norephedrin sigdcantly improved symptomsand increased the urethral pressure profile. Beisland et alu combined 80mg estriol intramuscularly every four weeks with oral phenylpropanolamine 50 mg twice daily and found that eight of 13 stress-incontinent women became dry; this work was, however, uncontrolled. The same authorsz6later performed a controlled cross-over trial of phenylpropanolamine (50 mg twice daily orally) and estriol(1 mg vaginal suppository daily) separately and in combination, in 20 postmenopausal women with genuine stress incontinence. Urodynamic investigations were carried out before and after each period of treatment. Both phenylpropanolamine and estriol increased maximum urethral closure pressure, but only estriol increased functional urethral length. Phenylpropanolamine was clinically more effective than estriol but did not cause complete continence. However, with the combined treatment eight patients became dry and nine were considerably improved. Two women withdrew because of side effects (vaginalbleeding in one). As yet this work has not been reproduced. Thus, the conclusions drawn from the published data are: (1) There have been very few appropriate placebocontrolled studies using subjective and objective parameters for assessment-so more are urgently needed. (2) Estrogen replacement apparently alleviates urgency, urge incontinence, frequency, noduria, and dysuria. (3) There is no conclusive evidence that estrogen even improves (let along cures) stress incontinence.
However, estrogen supplementation definitely improves the quality of life of many pen- and postmenopausal women. It can be administered orally, vaginally, percutaneously, or in implants, but, for a woman with a uterus, progestogensmust be taken cyclicallyto prevent the development of endometrial hyperplasia or caranoma. Perhaps the role of estrogen in the management of postmenopausal urinary incontinenceis as an adjunctto other methods of treatmentsuch as surgery, physiotherapy, or drugs. This is certainly a hypothesis worth testing and should be included in future research in this field. REFERENCES 1. Tapp AJS, Cardozo LD The postmenopausal bladder. Br J Hosp Med 3520-23,1986 2. Versi E, Cardom LD, Studd JWW, et ak Intemal urinary
3.
4. 5. 6. 7. 8.
9. 10. 11.
12. 13. 14. 15. 16. 17.
18. 19.
20.
21. 22.
23.
24. 25.
26.
sphincter in maintenance of female continence. Br Med J 292166-167,1986 Tapp AJS, Cardom LD, Versi E, Studd JWW:The prevalence of variation of resting urethral pressure in women and its association with lower urinary tract function. Br J Urol 61:314-317, 1988 Versi E, Cardozo LD, Brincat M, et al. Correlation of urethral physiology and skin collagen in postmenopausal women. Br J Obstet Gynaecol95:147-152,1988 Thomas TM, Plymat KR, Blannin J, Meade Tw:Prevalence of urinary incontinence. Br Med J 281:1243-1245,1980 Iosif CS, Bekassy Z Prevalence of genito-urinary symptoms in the later menopause. Acta Obstet Gynecol Scand 63957-260, 1984 Bungay CT, Vessey MP, McPherson CK Study of symptoms in middle life with special reference to the menopause. Br Med J 281:181-183,1980 Salmon UL, Walter RI, Cast S H The use of estrogens in the treatment of dysuria and incontinence in postmenopausal women. Am J Obstet Gynecol42:845-847,1941 Musiani U A partially successfulattempt at medical treatment of urinary stress incontinence in women. Urol Int 27:405-410, 1972 Schleyer-Saundm E Hormone implantsfor urinarydisordersin postmenopausal women. J Am Geriatr Soc 24337-339,1976 Caine M, Raz S The role of female hormones in stress incontinence. Proceedings of the 16th congress of the International society of Urology, Amsterdam, 1973 Faber P, Heidenreich J: Treatment of stress incontinence with estrogen in postmenopausal women. Urol Int 32221 -223,1971 Rud T The effects of oestrogens and gestagens on the urethral pressure profile in urinary continent and stress incontinent women. Acta Obstet Gynecol Scand 59:265-270,1980 Hilton P, Stanton SL The use of intra-vaginaloestrogen mam in genuine stress incontinence. Br J Obstet Gynaecol90940-944, 1983 JudgeTG: The use of quinestradol in elderly incontinentwomen: a preliminary report. Gerontol Clin 11:159-164.1969 Samsioe G,Jansson I, Mellstrom D, Svanborg A Occurrence, nature and treatment of urinary incontinence in a 70-year-old female population. Maturitas 7335-342,1985 Walter S, Wolf H, Barlebo H, Jensen H. Urinary continence in postmenopausal women treated with oestrogens:a double-blind clinical trial. Urol Int 33~135-143,1978 Wilson PD, Faragher B, Butler B, et ak Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. Br J Obstet Cynaecol94568-574,1987 Hilton P, Stanton SL Urethral pressure measurements by microtransducer: the results in symptom-free women and in those with genuine stress incontinence. Br J Obstet Gynaecol90919933,1983 Versi E, Cardom LD. Perineal pad weighing versusvideographic analysis in genuine stress incontinence. Br J Obstet Gynaecol 93:364-366,1986 Paganini-Hill A, Ross RK, Hendezson B E Postmenopausal oestrogen treatment and stroke: a prospective study. Br Med J 297519-523,1988 Stampfer MJ, Willett WC, Colditz GA, et al.A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 313:1044-1049,1985. Fantl JA, Wyman JF,Anderson RL, et al. Poetmenopausal urinary incontinence: comparison between non-estrogen supplemented and estrogen-supplemented women. Obstet Gynecol 71:823-826,1988 Ek A, Anderason KE, GallbergB, UlmstenU Effects of oestradiol and combined norephedrin and oestradiol treatment on female stress incontinence. Zentralbl Gynakol102839-844,1980 Beisland HO, Fossberg E, Sander S On incompetent urethral closure mechanism: treatment with esbiol and phenylpropanolamine. Scand J Urol Nephrol (Suppl) 60:67-69,1981 Beisland HO, F O S S ~ E, WM ~ m A, Sander S Urethral sphincteric insdiaency in postmenopausal females: treatment with phenylpropanolamineand esbiol separately and in combmation. Urol Int 39911-216,1984
Role of Estrogens in the Treatment of Female Urinary Incoiitinence Linda Cardozo, MD, MRCOG
mbryologically the female genital and urinary systems develop in close proximity, both arising from the primitive urogenital sinus. Animal and 1 human studies have shown that the urethra is estrogen sensitive, and estrogen receptors have been identified in the human female urethra. Thus there is good reason to suppose that changes in estrogen levels influence the lower urinary tract in women. Continence exists when the maximum urethral pressure exceeds the intravesical pressure at all times except during micturition. This positive closure pressure is produced by the four functional layers of the urethra: namely, the epithelium, connective tissue, vascular tissue, and muscle, all of which are affected by estrogen status.'-' At the time of menopause, circulating estrogen levels fall, causing urogenital atrophy. An increase in the incidence of lower urinary tract symptoms occurs, but it is still not certain whether this is due to the menopause itself or just part of the aging process. Thomas et a15 noted an increase in' the prevalence of urinary incontinence around the age of 35 years, but there did not seem to be a further large increase following the menopause, although the prevalence of urinary incontinence did show an increase with age. However, in a Swedish study, Iosif and Bekassf found that 70% of incontinent elderly women related the onset of their incontinence to their last menstrual period, but this was retrospective data. Bungay et a17 showed that there was a relatively high incidence of the symptoms of frequency and urgency of micturition in women at all ages, but that this was not particularly related to the menopause.
F
From King's College Hospital, London, United Kingdom. Prepared for the National Institutesof Health ConsensusDevelopment Conference on Urinary Incontinence in Adults, Bethesda, Maryland, October 3-5,1988. Address correspondence and reprint requests to Linda Cardozo, MD, MRCOG, 8 Devonshire Place, London WIN IPB, United Kingdom.
0 1990 by the American Geriatrics Society
The use of estrogen therapy for postmenopausal urinary incontinence remains controversial. Early studies were purely subjective, lacked controls, and were performed before the advent of urodynamic studieswhich enable an accurate diagnosis to be made. However, they did provide evidence of symptomatic improvement. In the first report by Salmon et a1,8 16 women with dysuria, frequency, urgency, and incontinence were treated with intramuscular estrogen therapy. After four weeks, 12 were symptomatically improved. The authors then discontinued therapy and when symptoms returned, repeated the c o m e of treatment. They showed that once again there was subjective improvement and concluded that the estrogen must be responsible. Musiani9 treated a series of 110 stress-incontinent women with quinestradoland reported 36 cured and 43 improved. Using estradiol implants SchleyerSaunders'O showed that 70 of 100 postmenopausal women with undiagnosed urinary incontinence were significantly improved, and thus the need for surgery was reduced. With the advent of pressure transducers, the effect of estrogens on the urethral pressure profile underwent scrutiny. Caine and Raz" reported increased maximum urethral pressures together with symptomatic improvement in 26 of 40 women with stress incontinence who underwent treatment with conjugated oral estrogens. Also studying stress-incontinent women, Faber and HeidenreichI2showed a significant rise in the urethral pressure profile in 39 of 41 undergoing treatment with estriol (a weak estrogen that is thought to have a specific effect on the urogenital tissues). Interestingly, although they reported clinical improvement, none of the women was cured. In Norway, RudI3 treated 24 stress-incontinent women with a combination of high-dose estradiol and estriol. He showed a significant increase in transmission of intraabdominal pressure to the urethra as well as an 0002-8614/90/53.50
IAGS-MARCH 1990-VOL 38, NO.3
increase in the maximum urethral pressure and urethral length at rest. Symptomatic improvement occurred in 70% of his subjects. Similar findings were reported by Hilton and Stanton," who used intravaginal estradiol cream to treat ten women with urodynamically proven genuine stress incontinence. They showed a significant increase in the stress maximum urethral-closure pressure because of improved pressure transmission in the mid-urethra. There was also significant subjective improvement in the symptoms of stress incontinence, urgency, and frequency. There have been very few properly placebo-controlled studies of estrogen therapy in the management of urinary incontinence. Those that have appeared in the literature are described below. Twenty years ago Judge15recruited 20 long-stay female geriatric patients into a double-blind placebo-controlled trial of quinestradol. The active preparation significantly reduced the frequency of incontinenceduring the fifth week of treatment. No placebo effect was noted. Estriol was used to treat 34 women aged 75 years in a double-blind placebo-controlled cross-over study.16 The women received 3 mg oral estriol (or equivalent placebo) daily for three months. There was no objective assessment and the women were divided into three groups on the basis of symptoms alone -stress incontinence, urge incontinence, or mixed incontinence. The authors noted that estriol was more effective than placebo in improving women with urge incontinence or mixed incontinence, but there was no difference between estriol and placebo in those women with stress incontinence. However, only 11 women had stress incontinence alone, all with minimal atrophy, and the short "washout" period in this study may have obscured potential differences. Walter and colleagues" looked at the problem of sensory-urge incontinence.They administered either estradiol with estriol or placebo for four months of cyclical therapy to 29 postmenopausal women who had urodynamically proven stable bladders. They showed significant improvement in urgency and urge incontinence in seven of 15 women treated with estrogen, which was significantly more than with placebo. However, they reported no improvement in any of the eight women with stress incontinence in either group and could not detect any change in the urethral pressure profile. The most recently reported placebo-controlled study using subjective and objective parameters is by Wilson et a1,18 in which 36 women participated in a doubleblind study of cyclical oral estrone for three months. Although there was symptomaticimprovement, the authors were unable to find any sigxuficant difference in subjective response, urethral pressure profiles, or Urilos test (an objective quantification test of urine loss). They concluded that the risks of estrogen therapy may out-
ESTROGENS AND FEMALE URINARY INCONTINENCE
327
weigh the benefit in the management of genuine stress incontinence. Our own preliminary data from King's College and Dulwich Hospitals yield similar results. Forty-six women with urodynamically (videocystourethrography with pressure and flow studies) proven genuine stress incontinence were randomly allocated to a 50 mg estradiol implant (24)or placebo implant (22). All the women completed a medically supervised symptom questionnaire and a visual analogue symptom score. They all underwent urethral pressure profilometry as described by Hilton and Stanton19and a pad weighmg test.*OAfter three months they were reassessed using the same parameters. There was no significant subjective improvement in either group. However, there was sigruficant objective improvement in bladder base descent as seen on the videocystourethrogram.This is interesting: it has long been speculated that estrogen replacement is beneficial in cases of prolapse, but there has, as yet, been no reported evidence of this. Side effects and complicationswith estrogen therapy would appear to be few. In Hilton and Stanton's study," one of the 11 women who started treatment with intravaginal cream was withdrawn because of breast tenderness and enlargement. Samsioeet all6reported that four of 34 elderly women treated with estriol stopped therapy because of mastodynia or metorrhagia. In the study by Wilson et all8two of the 16 women treated with oral estrone discontinued treatment; one had palpitations, and the other had a myocardial infarct that was probably unrelated to the treatment. There have been no other reported problems despite the use, in some cases, of high doses of estrogen. The potential adverse effects of estrogens include their effect on lipid metabolism and an increased incidence of endometrial carcinoma when long-term unopposed estrogens are prescribed to a woman with an intact uterus. However, all the studies reported have been short term: the longest duration of treatment was four months. Recent studies have shown that women receiving hormone replacement therapy (with natural estrogens) are less likely to suffer from cerebrovascular accidents and ischaemic heart disease,21,22 and the benefits in terms of the reduced risk of osteoporosis are well known. Recently the effect of estrogen supplementation has been studied. Fantl et a123assessed 72 postmenopausal women clinically and urodynamically. Twenty-three of these women were already taking estrogen replacement for other indications, and the remaining 49 were nonestrogen supplemented. The only sigxuficant difference that these authors reported was a decreased incidenceof nocturia in the estrogen-supplementedgroup. They hypothesized that hypoestrogenism may affect the sensory threshold of the lower urinary tract. Unfortunately, the effect of estrogen in combination with other drugs has not been widely studied. Ek et al"
328 CARDOZO
JAGS-MARCH 1990-VOL 38. NO. 3
treated 13 postmenopausal stress-incontinent women with oral estradiol for one month and then with estradiol plus norephedrin or placebo for another month. They showed that estradiol alone had no effect on symptoms or urethral pressure profile but that estradiol plus norephedrin sigdcantly improved symptomsand increased the urethral pressure profile. Beisland et alu combined 80mg estriol intramuscularly every four weeks with oral phenylpropanolamine 50 mg twice daily and found that eight of 13 stress-incontinent women became dry; this work was, however, uncontrolled. The same authorsz6later performed a controlled cross-over trial of phenylpropanolamine (50 mg twice daily orally) and estriol(1 mg vaginal suppository daily) separately and in combination, in 20 postmenopausal women with genuine stress incontinence. Urodynamic investigations were carried out before and after each period of treatment. Both phenylpropanolamine and estriol increased maximum urethral closure pressure, but only estriol increased functional urethral length. Phenylpropanolamine was clinically more effective than estriol but did not cause complete continence. However, with the combined treatment eight patients became dry and nine were considerably improved. Two women withdrew because of side effects (vaginalbleeding in one). As yet this work has not been reproduced. Thus, the conclusions drawn from the published data are: (1) There have been very few appropriate placebocontrolled studies using subjective and objective parameters for assessment-so more are urgently needed. (2) Estrogen replacement apparently alleviates urgency, urge incontinence, frequency, noduria, and dysuria. (3) There is no conclusive evidence that estrogen even improves (let along cures) stress incontinence.
However, estrogen supplementation definitely improves the quality of life of many pen- and postmenopausal women. It can be administered orally, vaginally, percutaneously, or in implants, but, for a woman with a uterus, progestogensmust be taken cyclicallyto prevent the development of endometrial hyperplasia or caranoma. Perhaps the role of estrogen in the management of postmenopausal urinary incontinenceis as an adjunctto other methods of treatmentsuch as surgery, physiotherapy, or drugs. This is certainly a hypothesis worth testing and should be included in future research in this field. REFERENCES 1. Tapp AJS, Cardozo LD The postmenopausal bladder. Br J Hosp Med 3520-23,1986 2. Versi E, Cardom LD, Studd JWW, et ak Intemal urinary
3.
4. 5. 6. 7. 8.
9. 10. 11.
12. 13. 14. 15. 16. 17.
18. 19.
20.
21. 22.
23.
24. 25.
26.
sphincter in maintenance of female continence. Br Med J 292166-167,1986 Tapp AJS, Cardom LD, Versi E, Studd JWW:The prevalence of variation of resting urethral pressure in women and its association with lower urinary tract function. Br J Urol 61:314-317, 1988 Versi E, Cardozo LD, Brincat M, et al. Correlation of urethral physiology and skin collagen in postmenopausal women. Br J Obstet Gynaecol95:147-152,1988 Thomas TM, Plymat KR, Blannin J, Meade Tw:Prevalence of urinary incontinence. Br Med J 281:1243-1245,1980 Iosif CS, Bekassy Z Prevalence of genito-urinary symptoms in the later menopause. Acta Obstet Gynecol Scand 63957-260, 1984 Bungay CT, Vessey MP, McPherson CK Study of symptoms in middle life with special reference to the menopause. Br Med J 281:181-183,1980 Salmon UL, Walter RI, Cast S H The use of estrogens in the treatment of dysuria and incontinence in postmenopausal women. Am J Obstet Gynecol42:845-847,1941 Musiani U A partially successfulattempt at medical treatment of urinary stress incontinence in women. Urol Int 27:405-410, 1972 Schleyer-Saundm E Hormone implantsfor urinarydisordersin postmenopausal women. J Am Geriatr Soc 24337-339,1976 Caine M, Raz S The role of female hormones in stress incontinence. Proceedings of the 16th congress of the International society of Urology, Amsterdam, 1973 Faber P, Heidenreich J: Treatment of stress incontinence with estrogen in postmenopausal women. Urol Int 32221 -223,1971 Rud T The effects of oestrogens and gestagens on the urethral pressure profile in urinary continent and stress incontinent women. Acta Obstet Gynecol Scand 59:265-270,1980 Hilton P, Stanton SL The use of intra-vaginaloestrogen mam in genuine stress incontinence. Br J Obstet Gynaecol90940-944, 1983 JudgeTG: The use of quinestradol in elderly incontinentwomen: a preliminary report. Gerontol Clin 11:159-164.1969 Samsioe G,Jansson I, Mellstrom D, Svanborg A Occurrence, nature and treatment of urinary incontinence in a 70-year-old female population. Maturitas 7335-342,1985 Walter S, Wolf H, Barlebo H, Jensen H. Urinary continence in postmenopausal women treated with oestrogens:a double-blind clinical trial. Urol Int 33~135-143,1978 Wilson PD, Faragher B, Butler B, et ak Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. Br J Obstet Cynaecol94568-574,1987 Hilton P, Stanton SL Urethral pressure measurements by microtransducer: the results in symptom-free women and in those with genuine stress incontinence. Br J Obstet Gynaecol90919933,1983 Versi E, Cardom LD. Perineal pad weighing versusvideographic analysis in genuine stress incontinence. Br J Obstet Gynaecol 93:364-366,1986 Paganini-Hill A, Ross RK, Hendezson B E Postmenopausal oestrogen treatment and stroke: a prospective study. Br Med J 297519-523,1988 Stampfer MJ, Willett WC, Colditz GA, et al.A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 313:1044-1049,1985. Fantl JA, Wyman JF,Anderson RL, et al. Poetmenopausal urinary incontinence: comparison between non-estrogen supplemented and estrogen-supplemented women. Obstet Gynecol 71:823-826,1988 Ek A, Anderason KE, GallbergB, UlmstenU Effects of oestradiol and combined norephedrin and oestradiol treatment on female stress incontinence. Zentralbl Gynakol102839-844,1980 Beisland HO, Fossberg E, Sander S On incompetent urethral closure mechanism: treatment with esbiol and phenylpropanolamine. Scand J Urol Nephrol (Suppl) 60:67-69,1981 Beisland HO, F O S S ~ E, WM ~ m A, Sander S Urethral sphincteric insdiaency in postmenopausal females: treatment with phenylpropanolamineand esbiol separately and in combmation. Urol Int 39911-216,1984
![[Urethrocystography in female urinary incontinence].](/assets/img/hold.png)
