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Obstetrics & Gynecology 2001;98:52-56
© 2001 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Bladder Neck Circulation by Doppler Ultrasonography in Postmenopausal Women With Urinary Stress Incontinence

Eing-Mei Tsai, MD, PhD, Cheng-Hui Yang, MD, Hung-Sheng Chen, MD, Ching-Hu Wu, MD and Jau-Nan Lee, MB, MD, PhD

From the Department of Obstetrics and Gynecology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.

Address reprint requests to: Jau-Nan Lee, MD, PhD, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, 100 Shih-Chuan First Road, San Ming District, Kaohsiung, Taiwan, Republic of China; E-mail: jaunanlee{at}hotmail.com


    ABSTRACT
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: To investigate the effect of hormone replacement therapy (HRT) on bladder neck circulation in postmenopausal women with genuine urinary stress incontinence (USI).

METHODS: A total of 227 women were enrolled in the study, including 114 postmenopausal women with USI (n = 57) or without USI (n = 57) and 113 premenopausal women with USI (n = 55) or without USI (n = 58). The bladder neck circulation was measured in 31 postmenopausal women with USI and in 12 without USI, all of whom received 0.625 mg conjugated equine estrogen plus 5 mg medroxyprogesterone acetate daily for 6 months. Bladder neck blood flow data detected by perineal color Doppler ultrasonography and weekly urinary diary data were collected before HRT and then 3 and 6 months after beginning HRT. Two-way analysis of variance and repeated measures of variance were used for statistical analysis. Power analysis was done by a two-sided test with a significance level at .05.

RESULTS: The pulsatility index (PI) was significantly higher in the postmenopausal than in the premenopausal women. The postmenopausal women with USI had the highest PI level. The presence of USI did not change the PI values in the premenopausal women. After 3 months of HRT, the PI levels decreased significantly (P < .001) in the postmenopausal women with USI. The subjective improvement of USI appeared after 3 months of HRT.

CONCLUSION: The blood flow around the bladder neck in women can be measured by perineal color Doppler ultrasonography. Hormone replacement therapy increases the blood flow around the bladder neck in postmenopausal women with USI. The clinical improvement of USI can be seen with HRT after 3 months.

The problems of urinary incontinence are common among postmenopausal women.1,2 The etiology is a combination of urethral sphincter dysfunction and poor structural support of the urethrovesical junction,3 including the mucosa, connective tissue, striated and smooth muscle, and vascular tissue. Furthermore, hormonal factors such as hypoestrogenism are also important.4 Estrogen affects the urinary tract at multiple levels of function. A sensitivity and responsiveness to estrogens are noted in epithelial, connective, muscular, and vascular tissues of the urethra and bladder.5,6

Animal studies have demonstrated improvement in the urodynamic parameters of bladder outlet function, specifically in the mean urethral pressure and urethral length, with estrogen therapy.7 In humans, it has also been documented that estrogen treatment could increase the maximum urethral closure pressure, abdominal pressure transmission to the proximal urethra, and functional urethral length.8 Thus, estrogen preparations have been used for many years in the management of urinary incontinence.9,10 Although few reports have delineated the subjective improvements of urinary stress incontinence (USI) after hormonal therapy,11 the objective efficacy of estrogen therapy remains controversial.

Any consideration of hormonal effect on the continence mechanism must take into account not only the direct steroid receptor levels, but also the hormonal interactions with other systems. For instance, the support of the bladder outlet, as well as the effect on neurologic control and vascular circulation, is important. Blood flow to the submucosal vascular "sponge" is an important component in intrinsic urethral function and therefore, represents a theoretical basis for the estrogen effect on the intrinsic continence mechanism.12 The purpose of this study was to examine the hypothesis that an analogous situation exists in the bladder neck. To clarify the role of hormone replacement therapy (HRT) on the continence mechanism further, we studied the effect of HRT on the bladder neck circulation by perineal color Doppler ultrasonography and by the clinical improvements of USI after HRT in postmenopausal women.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The study groups were recruited between January 1, 1997 and December 31, 1999. Patients consulting the urogynecologic clinic were asked to participate in the study. Patients with urethral cysts, urinary tract infection, or diverticulum were excluded. Genuine USI was defined as urinary leakage documented by direct visualization without the evidence of detrusor instability. The urodynamic evaluation consisted of subtracted provocative cystometry, passive and dynamic urethral profilometry, a direct visualization test, and uroflowmetry. Objective urinary loss was demonstrated by the cough stress test. The cough stress test was performed when the patient had a full bladder after screening cystometry. Detrusor instability was diagnosed when bladder contractions occurring during cystometry could not be voluntarily suppressed.

Menopausal subjects were defined as women who had experienced the natural cessation of menses for at least 1 year. Premenopausal women were aged 35–48 years, with regular menstrual periods. A total of 227 women who had not received HRT were recruited and classified into four groups: group A (n = 57) included postmenopausal women with USI, group B (n = 57) included postmenopausal women without USI, group C (n = 55) included premenopausal women with USI, and group D (n = 58) included premenopausal women without USI. All the women provided written informed consent.

Perineal color Doppler ultrasonography (Toshiba SAA-340A, Tokyo, Japan) was used to study the blood flow in the bladder neck. The pulsatility index (PI) was defined as (S - D)/A,13 where S was the peak systolic frequency shift, D the end-diastolic frequency, and A the mean frequency shift during one cardiac cycle. The PI reflected the impedance to the point of sampling. The bladder neck was identified without urethral catheterization. The bladder capacity was set at a self-comfortable full sensation level, about 150–250 mL. The patients were examined in the lithotomy position. Perineal ultrasonography was performed using a 3.5-MHz convex probe. The probe enclosed in a condom was positioned just adjacent to the perineum and between the labia majora. Color Doppler ultrasonography examinations were performed with a pulse repetition frequency of 4.5 kHz, wall filters at 70 Hz, and color and Doppler gains at 70–90%. The examinations included the bladder, urethra, and bladder neck. We measured the flow velocity waveform of the color signals nearest the bladder neck. At least three consecutive waveforms of adequate quality were obtained. The mean PI of each waveform was calculated. The mean PI of the three waveforms was recorded. For quality control, the PI measurements were calculated twice in 12 randomly selected normal women, at baseline and 72 hours later. The intercoefficient of variation was 2.5%.

All postmenopausal women (groups A and B) received HRT using a continuous combination regimen (0.625 mg conjugated equine estrogen and 5 mg medroxyprogesterone acetate daily) for 6 months. The episodes of urinary incontinence were recorded weekly using a standardized urinary diary,14 at 0 (before HRT) and 3 and 6 months after HRT. Perineal color Doppler ultrasound examinations were scheduled at 0 (before HRT) and 3 and 6 months after HRT. Forty-three postmenopausal women, including 31 (54.4%) in group A and 12 (21.1%) in group B completed the ultrasound studies. The PI values were reported as the mean ± standard deviation. The Student paired t test, Student t test, two-way analysis of variance, and repeated-measures analysis of variance with the Bonferroni t test were used for statistical analyses. P < .05 was considered significant. Power analysis with a two-sided test at significance level of .05 was performed.


    RESULTS
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Figure 1Go demonstrates the bladder neck blood flow detected by color Doppler ultrasonography. The average distance from the measuring point to the bladder neck was 0.61 ± 0.26 cm (range 0.25–1.25 cm). Table 1Go shows the demographics of the study group.



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Figure 1. Bladder neck circulation detected by perineal color Doppler ultrasonography. B = bladder; N = bladder neck; U = uterus.

Tsai. Bladder Neck Circulation. Obstet Gynecol 2001.

 

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Table 1. Demographics of Study Group
 
Table 2Go demonstrates that menopausal status and USI both have an effect on the PI level. In postmenopausal women, the PI values were significantly higher in women with USI (2.35 ± 0.61, group A) than in those without USI (1.56 ± 0.71, group B). However, the PI values did not show any statistically significant difference between the premenopausal women with USI (1.34 ± 0.58, group C) and those without (1.28 ± 0.43, group D). The PI values were significantly higher in the postmenopausal women than in the premenopausal ones, regardless of the presence of USI. Figure 2Go shows the changes in the PI value at 0 (pretreatment), 3, and 6 months after HRT in the postmenopausal women with USI (n = 31) and without USI (n = 12). By repeated-measures analysis of variance using the Bonferroni t test, the PI level significantly decreased in women with USI (P < .001). In postmenopausal women with USI, the PI values were 2.31 ± 0.52 before HRT, 1.54 ± 0.47 at 3 months after HRT, and 1.48 ± 0.58 at 6 months after HRT. Power analysis was adequate for more than 95%. However, in women without USI, the PI values were 2.27 ± 0.67 before HRT, 2.04 ± 0.41 at 3 months after HRT, and 2.01 ± 0.63 at 6 months after HRT. Because of the small number of cases, nonparametric analysis using the Wilcoxon signed-rank test was applied for statistical analysis. No significant changes in the PI values during the 6 months of HRT were noted in the group of women without USI.


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Table 2. Comparison of Pulsatility Index of Bladder Neck in Women With or Without Urinary Stress Incontinence
 


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Figure 2. Change of pulsatility index (PI) in patients with or without urinary stress incontinence (USI) after hormone replacement therapy (HRT). Repeated-measures analysis of variance using the Bonferroni t test: P < .001. Asterisks indicate significant decrease of PI level after HRT at 3 and 6 months compared with before treatment. Women without USI tested by the nonparametric Wilcoxon signed-rank test showed P > .05.

Tsai. Bladder Neck Circulation. Obstet Gynecol 2001.

 
In 31 postmenopausal women with USI receiving HRT, 14 women complained of having no obvious improvement in terms of USI episodes. The number of USI episodes per week was 13.4 ± 1.74 before HRT, 11.5 ± 1.87 at 3 months after HRT, and 11.14 ± 1.96 at 6 months after HRT. On the other hand, 17 women from this same group experienced clinical improvement in urinary incontinence, with USI episodes per week of 13.60 ± 1.37 before HRT, 7.80 ± 0.66 at 3 months after HRT, and 7.10 ± 1.09 at 6 months after HRT. Multiple comparisons in repeated analysis of variance using the Bonferroni t test showed that for subjects experiencing clinical improvement and for subjects who lacked improvement, the episodes decreased significantly after 3 months of HRT (P <.05). At either 3 or 6 months after HRT, the number of USI episodes was significantly lower (P < .05) in the clinical improvement group than in the nonimprovement group (Fig. 3Go). Using a two-sided test with a significance level at .05 for the power analysis revealed an accuracy of more than 75%.



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Figure 3. Improvement of weekly urinary stress incontinence (USI) episodes in postmenopausal women after hormone replacement therapy (HRT). Repeated-measures analysis of variance with the Bonferroni t test: P < .05. Asterisks indicate significant effect of HRT on USI episodes after 3 and 6 months compared with before treatment. The comparison between the improvement and nonimprovement groups revealed a significantly lower number of episodes in the improvement group. The power analysis was more than 75% by two-sided test with the significance level at .05.

Tsai. Bladder Neck Circulation. Obstet Gynecol 2001.

 

    DISCUSSION
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The study of USI in association with menopause and hypoestrogenic status is a challenging task. The reasons for the varying clinical responsiveness to estrogen remain unclear. Urinary stress incontinence results from multiple factors that may involve the mucosa, connective tissue, smooth muscle, and vascular tissues of the urogenital tract. A sufficient vascular supply is essential to support the normal connective tissues. More importantly, the blood supply from the pelvic vessels provides condensations of endopelvic fascia to reinforce the normal position of the pelvic organs. Anatomically, the blood supply to the remainder of the urethra and adjacent vagina is from the inferior vesical artery through the vaginal artery that runs along the superior lateral aspect of the vagina.15

The present investigation applied the convex probe to the perineum by color Doppler ultrasonography, which could confidently identify the blood flow around the peribladder neck region. Using this approach, we demonstrated the circulation of the bladder neck that should arise from the branches of the inferior vesical arteries. Reports are available concerning the assessment of the velocity of the urethral artery. Color Doppler ultrasonography has been used to locate the urethral artery in male patients with urethral stricture.16 Bamshad et al17 measured urethral blood flow by laser Doppler flowmetry in male patients during cardiopulmonary bypass. The simple technique presented here provides a useful and convenient model for assessing urethral blood flow in women.

Postmenopausal women have a higher PI of the vessels around the bladder neck than do premenopausal women. This fact may imply that hypoestrogenism induces higher vessel resistance and thus decreases the blood flow. Urinary stress incontinence itself and USI interacting with menopause can alter the PI. Therefore, in our study, women with both menopause and USI had the highest PI. However, the existence of USI in premenopausal women did not affect the PI level significantly. These data suggest that the bladder neck circulation has little impact on USI in premenopausal women. In contrast, the bladder neck blood supply seems to be involved in the etiology of USI in postmenopausal women.

Hormone replacement therapy in postmenopausal women has gained increasing popularity during the past decade. Hormone replacement therapy during peri- or postmenopause has numerous benefits for the quality of life, such as the relief of vasomotor symptoms and the prevention of osteoporosis and cardiovascular and cerebrovascular diseases.18–21 Several studies have reported that the PI as measured by Doppler ultrasonography in the internal carotid arteries and cerebral arteries demonstrated a direct estrogen effect on the blood vessels.22,23 Other studies presented evidence that HRT could reduce the PI of the uterine,24 brachial, dorsalis pedis, popliteal, and radial arteries.25 The present results also revealed that HRT could reduce the PI value even in small caliber vessels such as the urethral arteries.

Urinary stress incontinence is a common problem in older women. Obesity and hysterectomy may have the greatest impact on the prevalence of daily incontinence.26 Nevertheless, little is known about the relationship between HRT and USI. The urethral cytologic features could be changed by estrogen.11 Additionally, estrogen increases the intraluminal urethral pressure.7 However, controversy still remains about the impact of HRT on USI.27 In the present study, HRT relieved the subjective symptoms of USI in 17 (55%) of 31 patients after 3 months of therapy. Also, the blood flow around bladder neck increased after HRT in postmenopausal women with USI.


    Footnotes
 
PII S0029-7844(01)01379-5

Received October 30, 2000. Received in revised form February 12, 2001. Accepted February 22, 2001.


    REFERENCES
 TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
1. Diokno AC, Brock BM, Brown MB, Herzog AR. Prevalence of urinary incontinence and other urologic symptoms in the noninstitutionalized elderly. J Urol 1986;136: 1022–5.[Medline]

2. Thomas TM, Plymat KR, Blannin J, Meade TW. Prevalence of urinary incontinence. BMJ 1980;281:1243–5.

3. Fantl JA, Wyman JF, McClish DK, Bump RC. Urinary incontinence in the community-dwelling women: Clinical, urodynamic and severity characteristics. Am J Obstet Gynecol 1990;162:946–51.[Medline]

4. Fantl JA, Wyman JF, Anderson RL, Matt DW, Bump RC. Postmenopausal urinary incontinence: Comparison between non-estrogen-supplemented and estrogen-supplemented women. Obstet Gynecol 1988;71:823–8.[Medline]

5. Stumpf WE, Sar M, Joshi SG. Estrogen target cells in the skin. Experimentia 1974;30:196–8.[Medline]

6. Brincat M, Moniz CF, Studd JW, Darby AJ, Magos A, Cooper D. Sex hormones and skin collagen content in postmenopausal women. BMJ 1983;287:1337–8.

7. Bump RC, Friedman CI. Intraluminal urethral pressure measurements in the female baboon: Effects of hormonal manipulation. J Urol 1986;136:508–11.[Medline]

8. Klutke JJ, Bergman A. Hormonal influence on the urinary tract. Urol Clin North Am 1995;22:629–39.[Medline]

9. Salmon UJ, Walter RI, Geist SH. The use of estrogens in the treatment of dysuria and incontinence in postmenopausal women. Am J Obstet Gynecol 1941;42:845–7.

10. Youngblood VH, Tomlin EM, Davis JB. Senile urethritis in women. J Urol 1957;78:150–2.[Medline]

11. Bergman A, Karram MM, Bhatia NN. Changes in urethral cytology following estrogen administration. Gynecol Obstet Invest 1990;29:211–3.[Medline]

12. Zinner NR, Sterling AM, Ritter RC. Role of inner urethral softness in urinary continence. Urology 1980;16:115–7.[Medline]

13. Gangar KF, Vyas S, Whitehead M, Crook D, Meire H, Campbell S. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet 1991;338:839–42.[Medline]

14. Wyman JF, Choi SC, Harkins SW, Wilson MS, Fantl JA. The urinary diary in evaluation of incontinence women: A test-retest analysis. Obstet Gynecol 1988;71:812–7.[Medline]

15. The urogenital system. In: Goss CM, ed. Gray’s anatomy. Philadelphia: Lea & Febiger, 1980:1265–339.

16. Chiou RK, Donovan JM, Anderson JC, Matamoros A Jr, Wobig RK, Taylor RJ. Color Doppler ultrasound assessment of urethral artery location: Potential implication for technique of visual internal urethrotomy. J Urol 1998;159: 798–9.

17. Bamshad BR, Poon MW, Stewart SC. Effect of cardiopulmonary bypass on urethral blood flow as measured by laser Doppler flowmetry. J Urol 1998;160:2030–2.[Medline]

18. Lindsay R, Cosman F. The risk of osteoporosis in aging women. In: Sitruk-Ware R, Utian WH, eds. Menopause and hormonal replacement therapy. New York: Marcel Dekker, 1991:47–72.

19. Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 1985;313:1044–9.[Abstract]

20. Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987;75:1102–9.[Abstract/Free Full Text]

21. Paganini-Hill A, Ross RK, Henderson BE. Postmenopausal oestrogen treatment and stroke: Prospective study. BMJ 1988;297:519–22.

22. Gangar KF, Vyas S, Whitehead M, Crook D, Meire H, Campbell S. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet 1991;338:839–42.

23. Penotti M, Nencioni T, Gabrielli L, Farina M, Castiglioni E, Polvani F. Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy. Am J Obstet Gynecol 1993; 169:1226–32.[Medline]

24. Pirhonen JP, Vuento MH, Mäkinen JI, Salmi TA. Long-term effects of hormone replacement therapy on the uterus and on uterine circulation. Am J Obstet Gynecol 1993;168: 620–3.[Medline]

25. Lau TK, Wan D, Yim SF, Sanderson JE, Haines CJ. Prospective, randomized, controlled study of the effect of hormone replacement therapy on peripheral blood flow velocity in postmenopausal women. Fertil Steril 1998;70: 284–8.[Medline]

26. Brown JS, Seeley DG, Fong J, Black DM, Ensrud KE, Grady D. Urinary incontinence in older women: Who is at risk? Study of osteoporotic fractures. Obstet Gynecol 1996;87:715–21.[Abstract]

27. Fantl JA, Cardozo L, McClish DK. 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 1994;83: 12–8.[Abstract/Free Full Text]





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