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Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers-Danlos syndrome
Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers-Danlos syndrome Michael E. Carley, MD, and Joseph Schaffer, MD Dallas, Texas OBJECTIVE: This study was undertaken to determine the prevalence of urinary incontinence and pelvic organ prolapse in a cohort of women with either Marfan syndrome or Ehlers-Danlos syndrome. STUDY DESIGN: Female patients with either Marfan syndrome or Ehlers-Danlos syndrome were identified through a medical records search at two urban hospitals. Each patient’s medical record was reviewed, and the history of pelvic organ prolapse and urinary incontinence was obtained through telephone interview. RESULTS: Twelve women with Marfan syndrome were identified. Among these women 5 (42%) reported a history of urinary incontinence and 4 (33%) reported a history of pelvic organ prolapse. Eight women with Ehlers-Danlos syndrome were identified. Among these women 4 (50%) reported a history of urinary incontinence and 6 (75%) reported a history of pelvic organ prolapse. CONCLUSIONS: Women with Marfan or Ehlers-Danlos syndrome have high rates of urinary incontinence and pelvic organ prolapse. This finding supports the hypothesized etiologic role of connective tissue disorders as a factor in the pathogenesis of these conditions. (Am J Obstet Gynecol 2000;182:1021-3.)
Key words: Ehlers-Danlos syndrome, incontinence, Marfan syndrome, prolapse
Urinary incontinence and pelvic organ prolapse have been attributed to numerous etiologic factors, including parity, age, ethnicity, increased intra-abdominal pressure, estrogen deficiency, smoking, neurologic injury, and hysterectomy.1 It has also been suggested that genetic or intrinsic differences in connective tissues may predispose individuals toward urinary incontinence or pelvic organ prolapse.2 However, literature examining the prevalence of these conditions among women with connective tissue disorders is sparse. Marfan syndrome is an autosomal dominant connective tissue disorder linked to a defect in the fibrillin 1 gene on chromosome 15 that has an approximate prevalence of 1:10,000.3, 4 Common clinical manifestations of the disorder include skeletal abnormalities, cardiovascular complications, and ocular abnormalities. Although several investigators have examined obstetric risks,5 gynecologic complications of women with Marfan syndrome have not been well described. Ehlers-Danlos syndrome represents a heterogeneous group of connective tissue disorders composed of ≥10 subtypes involving collagen gene defects. The prevalence has been estimated to be 1:5000.6 Clinical findings include hyperdistensibility of skin, hypermobility of joints, From the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center. Reprint requests: Michael E. Carley, MD, Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Graduate School of Medicine, 200 First St SW, Rochester, MN 55905. Copyright © 2000 by Mosby, Inc. 0002-9378/2000 $12.00 + 0 6/1/105410 doi:10.1067/mob.2000.105410
abnormal tissue fragility, and easy bruising.6 Potential gynecologic and urologic complications include endometriosis, dyspareunia, incontinence, pelvic organ prolapse, and bladder diverticula. This study was undertaken to examine the prevalence of urinary incontinence and pelvic organ prolapse in a cohort women with either Marfan syndrome or EhlersDanlos syndrome. Material and methods A medical records search of all women 18 years of age or greater with an International Classification of Diseases, Ninth Revision diagnosis code of either Marfan syndrome or Ehlers-Danlos syndrome was performed at an urban university-associated medical center and at an urban community-based teaching hospital. Through telephone interview each patient answered a series of items that included demographic information and gynecologic, urologic, obstetric, medical, surgical, and social histories. Each patient’s medical record was reviewed. Because many patients lived far from these medical centers, physical examination by the investigators was not practical. To determine the severity of urinary incontinence patients were asked multiple questions dealing with urinary symptoms. Patients with incontinence were categorized into 3 groups: women who reported one or more episodes of urinary incontinence per week, women who reported at least one episode of involuntary urine loss per day and considered the urinary incontinence to be lifestyle-altering, and women who had undergone a surgical procedure for urinary incontinence. In addition, pa1021
1022 Carley and Schaffer
May 2000 Am J Obstet Gynecol
Table I. Demographic and obstetric characteristics of women with Marfan and Ehlers-Danlos syndromes Parameter Age (y, mean ± SD) Race (No.) White Black Hispanic Height (cm, mean ± SD) Weight (kg, mean ± SD) Body mass index (kg/m2, mean ± SD) Smoker (No.) Gravidity Mean ± SD Median Parity Mean ± SD Median Nulliparous (No.) History of ≥1 cesarean delivery (No.)
Marfan syndrome Ehlers-Danlos (n = 12) syndrome (n = 8) 49 ± 12
46 ± 20
8 (67%) 3 (25%) 1 (8%)0 179 ± 7 77 ± 24 24 ± 5
7 (88%) 1 (13%) 0 (0%)0 163 ± 8 60 ± 8 22 ± 4
7 (58%)
2 (25%)
1.3 ± 2.3 0.5
3.0 ± 2.0 3
0.4 ± 0.7 0 8 (67%) 0 (0%)0
2.1 ± 1.2 2 1 (13%) 2 (25%)
tients with incontinence were asked a series of items to categorize the condition as stress, urge, or mixed urinary incontinence. Pelvic organ prolapse was similarly categorized on the basis of the patient’s report: pelvic organ prolapse symptoms only (reported pelvic pressure associated with a protrusion or bulge from the vagina), reported diagnosis by a physician of pelvic organ prolapse, and reported surgical repair of pelvic organ prolapse. Patients were also asked whether rectal prolapse had been diagnosed or treated. Descriptive statistics were used to summarize the demographic and obstetric characteristics. The prevalences of pelvic organ prolapse and urinary incontinence were calculated for women with Marfan syndrome and women with Ehlers-Danlos syndrome. Results The medical records search by International Classification of Diseases, Ninth Revision diagnosis codes identified 19 women with Marfan syndrome and 10 women with Ehlers-Danlos syndrome. Among those with Marfan syndrome, 5 were dead and 2 were not available for interview. Two of the 10 women with Ehlers-Danlos syndrome were not available for interview. The remaining 12 patients with Marfan syndrome and 8 patients with EhlersDanlos syndrome were used for statistical analysis. Demographic and general obstetric characteristics of the women with Marfan and Ehlers-Danlos syndromes are depicted in Table I. The prevalences of urinary incontinence, pelvic organ prolapse, and rectal prolapse among patients with Marfan syndrome and EhlersDanlos syndrome in this study population are listed in Table II. Among the 12 women with Marfan syndrome
Table II. Prevalences of urinary incontinence and pelvic organ prolapse diagnoses among women with Marfan and Ehlers-Danlos syndromes Marfan syndrome (n = 12) Diagnosis Urinary incontinence Any ≥1 episode/wk ≥1 episode/d Surgically treated incontinence Stress incontinence symptoms Mixed incontinence symptoms Pelvic organ prolapse Any Prolapse symptoms Physician-diagnosed prolapse Surgically treated prolapse Rectal prolapse
Ehlers-Danlos syndrome (n = 8)
No.
%
No.
%
5 3 2 0
42 25 17 00
4 1 1 2
50 13 13 25
5
42
4
50
1
08
1
08
4 1 2
33 08 17
6 1 2
75 13 25
1
08
3
38
0
00
2
25
5 (42%) reported a history of urinary incontinence and 4 (33%) reported a history of pelvic organ prolapse. Among the 8 women with Ehlers-Danlos syndrome, 4 (50%) reported a history of urinary incontinence and 6 (75%) reported a history of pelvic organ prolapse. Comment Although several case reports and small series have described potential obstetric risks among patients with Marfan syndrome and Ehlers-Danlos syndrome, little information regarding gynecologic and urologic complications exists. In this series we found high rates of both urinary incontinence and pelvic organ prolapse among women with either Marfan syndrome or Ehlers-Danlos syndrome. These findings are notable in light of the young mean age and relatively low median parity of both groups. It is interesting that all women with incontinence described symptoms of stress or mixed incontinence. In this cohort of patients, women with Ehlers-Danlos syndrome had a higher prevalence of pelvic organ prolapse than did those with Marfan syndrome. Although this difference may be related in part to the greater parity of the women with Ehlers-Danlos syndrome, it may also be related to differences in the roles collagen and fibrillin play in the support of the pelvic floor. Reported historical prevalence rates of both pelvic organ prolapse and urinary incontinence differ widely as a result of differences in patient populations studied and differences in categorization of urinary incontinence and pelvic organ prolapse. One study found that 58% of healthy middle-aged women reported loss of urine at
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some time. However, of these, only 10.5% reported one or more episodes of urinary incontinence per week.7 Although the prevalence of pelvic organ prolapse is less well defined, one study found that 14% of white women seen in a urogynecologic clinic had symptoms of prolapse.8 Although patients’ reports of stress or urge incontinence symptoms do not always correspond to diagnoses made through urodynamic evaluation,9 the finding that none of the patients who reported urinary incontinence described urge symptoms alone is meaningful. Stress incontinence may represent an anatomic defect and is often associated with pelvic relaxation, whereas urge incontinence is often the result of detrusor instability. Investigators examined collagen content in skin and round ligaments and found 40% reductions in those of women with stress urinary incontinence when compared with those of continent women.10 Theoretically, qualitative defects in collagen or fibrin may also result in pelvic floor weakening. We recognize several limitations of this investigation. First, this cohort of patients was identified through International Classification of Diseases, Ninth Revision diagnosis codes and may not be representative of all women with Marfan or Ehlers-Danlos syndrome. Second, the study relied on historical reports by the subjects rather than direct physical or urodynamic evaluation. Finally, the study is descriptive in nature and is limited by the absence of a control group. Larger, controlled, multicenter studies are needed to examine the prevalence of prolapse and incontinence among patients with Marfan and
Ehlers-Danlos syndromes through direct physical examination and urodynamic evaluation. High rates of pelvic organ prolapse and incontinence were found in both groups of patients, however, supporting the hypothesized etiologic role of connective tissue disorders as a potential factor in the occurrence of pelvic organ prolapse and urinary incontinence. REFERENCES
1. Carley ME, Turner RJ, Scott DE, Alexander JM. Obstetric history in women with surgically corrected adult urinary incontinence or pelvic organ prolapse. J Am Assoc Gynecol Laparosc 1999; 6:85-9. 2. Stoddard FJ, Meyers RE. Connective tissues disorders in obstetrics and gynecology. Am J Obstet Gynecol 1968;102:240-3. 3. Peltonen L, Kainulainen K. Elucidation of the gene defect in Marfan syndrome. FEBS Lett 1992;307:116-21. 4. Pyeritz RE. The Marfan syndrome. Am Fam Physician 1986; 34:83-94. 5. Simpson LL, Athanassious AM, D’Alton ME. Marfan syndrome in pregnancy. Curr Opin Obstet Gynecol 1997;9:337-41. 6. Steinmann B, Royce PM, Superti-Furga A. The Ehlers-Danlos syndrome. In: Royce PM, Steinmann B, editors. Connective tissue and its heritable disorders: molecular genetic and medical aspects. New York: John Wiley; 1993. p. 351-407. 7. Burgio KL, Matthews KA, Engel BT. Prevalence, incidence and correlates of urinary incontinence in healthy, middle-aged women. J Urol 1991;146:1255-9. 8. Mattox TF, Bhatia NN. The prevalence of urinary incontinence or prolapse among white and Hispanic women. Am J Obstet Gynecol 1996;174:646-8. 9. Cundiff GW, Harris RL, Coates KW, Bump RC. Clinical predictors of urinary incontinence in women. Am J Obstet Gynecol 1997;177:262-6. 10. Ulmsten U, Ekman G, Giertz G, Malmström A. Different biochemical composition of connective tissue in continent and stress incontinent women. Acta Obstet Gynecol Scand 1987; 66:455-7.
Key words: Ehlers-Danlos syndrome, incontinence, Marfan syndrome, prolapse
Urinary incontinence and pelvic organ prolapse have been attributed to numerous etiologic factors, including parity, age, ethnicity, increased intra-abdominal pressure, estrogen deficiency, smoking, neurologic injury, and hysterectomy.1 It has also been suggested that genetic or intrinsic differences in connective tissues may predispose individuals toward urinary incontinence or pelvic organ prolapse.2 However, literature examining the prevalence of these conditions among women with connective tissue disorders is sparse. Marfan syndrome is an autosomal dominant connective tissue disorder linked to a defect in the fibrillin 1 gene on chromosome 15 that has an approximate prevalence of 1:10,000.3, 4 Common clinical manifestations of the disorder include skeletal abnormalities, cardiovascular complications, and ocular abnormalities. Although several investigators have examined obstetric risks,5 gynecologic complications of women with Marfan syndrome have not been well described. Ehlers-Danlos syndrome represents a heterogeneous group of connective tissue disorders composed of ≥10 subtypes involving collagen gene defects. The prevalence has been estimated to be 1:5000.6 Clinical findings include hyperdistensibility of skin, hypermobility of joints, From the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center. Reprint requests: Michael E. Carley, MD, Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Graduate School of Medicine, 200 First St SW, Rochester, MN 55905. Copyright © 2000 by Mosby, Inc. 0002-9378/2000 $12.00 + 0 6/1/105410 doi:10.1067/mob.2000.105410
abnormal tissue fragility, and easy bruising.6 Potential gynecologic and urologic complications include endometriosis, dyspareunia, incontinence, pelvic organ prolapse, and bladder diverticula. This study was undertaken to examine the prevalence of urinary incontinence and pelvic organ prolapse in a cohort women with either Marfan syndrome or EhlersDanlos syndrome. Material and methods A medical records search of all women 18 years of age or greater with an International Classification of Diseases, Ninth Revision diagnosis code of either Marfan syndrome or Ehlers-Danlos syndrome was performed at an urban university-associated medical center and at an urban community-based teaching hospital. Through telephone interview each patient answered a series of items that included demographic information and gynecologic, urologic, obstetric, medical, surgical, and social histories. Each patient’s medical record was reviewed. Because many patients lived far from these medical centers, physical examination by the investigators was not practical. To determine the severity of urinary incontinence patients were asked multiple questions dealing with urinary symptoms. Patients with incontinence were categorized into 3 groups: women who reported one or more episodes of urinary incontinence per week, women who reported at least one episode of involuntary urine loss per day and considered the urinary incontinence to be lifestyle-altering, and women who had undergone a surgical procedure for urinary incontinence. In addition, pa1021
1022 Carley and Schaffer
May 2000 Am J Obstet Gynecol
Table I. Demographic and obstetric characteristics of women with Marfan and Ehlers-Danlos syndromes Parameter Age (y, mean ± SD) Race (No.) White Black Hispanic Height (cm, mean ± SD) Weight (kg, mean ± SD) Body mass index (kg/m2, mean ± SD) Smoker (No.) Gravidity Mean ± SD Median Parity Mean ± SD Median Nulliparous (No.) History of ≥1 cesarean delivery (No.)
Marfan syndrome Ehlers-Danlos (n = 12) syndrome (n = 8) 49 ± 12
46 ± 20
8 (67%) 3 (25%) 1 (8%)0 179 ± 7 77 ± 24 24 ± 5
7 (88%) 1 (13%) 0 (0%)0 163 ± 8 60 ± 8 22 ± 4
7 (58%)
2 (25%)
1.3 ± 2.3 0.5
3.0 ± 2.0 3
0.4 ± 0.7 0 8 (67%) 0 (0%)0
2.1 ± 1.2 2 1 (13%) 2 (25%)
tients with incontinence were asked a series of items to categorize the condition as stress, urge, or mixed urinary incontinence. Pelvic organ prolapse was similarly categorized on the basis of the patient’s report: pelvic organ prolapse symptoms only (reported pelvic pressure associated with a protrusion or bulge from the vagina), reported diagnosis by a physician of pelvic organ prolapse, and reported surgical repair of pelvic organ prolapse. Patients were also asked whether rectal prolapse had been diagnosed or treated. Descriptive statistics were used to summarize the demographic and obstetric characteristics. The prevalences of pelvic organ prolapse and urinary incontinence were calculated for women with Marfan syndrome and women with Ehlers-Danlos syndrome. Results The medical records search by International Classification of Diseases, Ninth Revision diagnosis codes identified 19 women with Marfan syndrome and 10 women with Ehlers-Danlos syndrome. Among those with Marfan syndrome, 5 were dead and 2 were not available for interview. Two of the 10 women with Ehlers-Danlos syndrome were not available for interview. The remaining 12 patients with Marfan syndrome and 8 patients with EhlersDanlos syndrome were used for statistical analysis. Demographic and general obstetric characteristics of the women with Marfan and Ehlers-Danlos syndromes are depicted in Table I. The prevalences of urinary incontinence, pelvic organ prolapse, and rectal prolapse among patients with Marfan syndrome and EhlersDanlos syndrome in this study population are listed in Table II. Among the 12 women with Marfan syndrome
Table II. Prevalences of urinary incontinence and pelvic organ prolapse diagnoses among women with Marfan and Ehlers-Danlos syndromes Marfan syndrome (n = 12) Diagnosis Urinary incontinence Any ≥1 episode/wk ≥1 episode/d Surgically treated incontinence Stress incontinence symptoms Mixed incontinence symptoms Pelvic organ prolapse Any Prolapse symptoms Physician-diagnosed prolapse Surgically treated prolapse Rectal prolapse
Ehlers-Danlos syndrome (n = 8)
No.
%
No.
%
5 3 2 0
42 25 17 00
4 1 1 2
50 13 13 25
5
42
4
50
1
08
1
08
4 1 2
33 08 17
6 1 2
75 13 25
1
08
3
38
0
00
2
25
5 (42%) reported a history of urinary incontinence and 4 (33%) reported a history of pelvic organ prolapse. Among the 8 women with Ehlers-Danlos syndrome, 4 (50%) reported a history of urinary incontinence and 6 (75%) reported a history of pelvic organ prolapse. Comment Although several case reports and small series have described potential obstetric risks among patients with Marfan syndrome and Ehlers-Danlos syndrome, little information regarding gynecologic and urologic complications exists. In this series we found high rates of both urinary incontinence and pelvic organ prolapse among women with either Marfan syndrome or Ehlers-Danlos syndrome. These findings are notable in light of the young mean age and relatively low median parity of both groups. It is interesting that all women with incontinence described symptoms of stress or mixed incontinence. In this cohort of patients, women with Ehlers-Danlos syndrome had a higher prevalence of pelvic organ prolapse than did those with Marfan syndrome. Although this difference may be related in part to the greater parity of the women with Ehlers-Danlos syndrome, it may also be related to differences in the roles collagen and fibrillin play in the support of the pelvic floor. Reported historical prevalence rates of both pelvic organ prolapse and urinary incontinence differ widely as a result of differences in patient populations studied and differences in categorization of urinary incontinence and pelvic organ prolapse. One study found that 58% of healthy middle-aged women reported loss of urine at
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Volume 182, Number 5 Am J Obstet Gynecol
some time. However, of these, only 10.5% reported one or more episodes of urinary incontinence per week.7 Although the prevalence of pelvic organ prolapse is less well defined, one study found that 14% of white women seen in a urogynecologic clinic had symptoms of prolapse.8 Although patients’ reports of stress or urge incontinence symptoms do not always correspond to diagnoses made through urodynamic evaluation,9 the finding that none of the patients who reported urinary incontinence described urge symptoms alone is meaningful. Stress incontinence may represent an anatomic defect and is often associated with pelvic relaxation, whereas urge incontinence is often the result of detrusor instability. Investigators examined collagen content in skin and round ligaments and found 40% reductions in those of women with stress urinary incontinence when compared with those of continent women.10 Theoretically, qualitative defects in collagen or fibrin may also result in pelvic floor weakening. We recognize several limitations of this investigation. First, this cohort of patients was identified through International Classification of Diseases, Ninth Revision diagnosis codes and may not be representative of all women with Marfan or Ehlers-Danlos syndrome. Second, the study relied on historical reports by the subjects rather than direct physical or urodynamic evaluation. Finally, the study is descriptive in nature and is limited by the absence of a control group. Larger, controlled, multicenter studies are needed to examine the prevalence of prolapse and incontinence among patients with Marfan and
Ehlers-Danlos syndromes through direct physical examination and urodynamic evaluation. High rates of pelvic organ prolapse and incontinence were found in both groups of patients, however, supporting the hypothesized etiologic role of connective tissue disorders as a potential factor in the occurrence of pelvic organ prolapse and urinary incontinence. REFERENCES
1. Carley ME, Turner RJ, Scott DE, Alexander JM. Obstetric history in women with surgically corrected adult urinary incontinence or pelvic organ prolapse. J Am Assoc Gynecol Laparosc 1999; 6:85-9. 2. Stoddard FJ, Meyers RE. Connective tissues disorders in obstetrics and gynecology. Am J Obstet Gynecol 1968;102:240-3. 3. Peltonen L, Kainulainen K. Elucidation of the gene defect in Marfan syndrome. FEBS Lett 1992;307:116-21. 4. Pyeritz RE. The Marfan syndrome. Am Fam Physician 1986; 34:83-94. 5. Simpson LL, Athanassious AM, D’Alton ME. Marfan syndrome in pregnancy. Curr Opin Obstet Gynecol 1997;9:337-41. 6. Steinmann B, Royce PM, Superti-Furga A. The Ehlers-Danlos syndrome. In: Royce PM, Steinmann B, editors. Connective tissue and its heritable disorders: molecular genetic and medical aspects. New York: John Wiley; 1993. p. 351-407. 7. Burgio KL, Matthews KA, Engel BT. Prevalence, incidence and correlates of urinary incontinence in healthy, middle-aged women. J Urol 1991;146:1255-9. 8. Mattox TF, Bhatia NN. The prevalence of urinary incontinence or prolapse among white and Hispanic women. Am J Obstet Gynecol 1996;174:646-8. 9. Cundiff GW, Harris RL, Coates KW, Bump RC. Clinical predictors of urinary incontinence in women. Am J Obstet Gynecol 1997;177:262-6. 10. Ulmsten U, Ekman G, Giertz G, Malmström A. Different biochemical composition of connective tissue in continent and stress incontinent women. Acta Obstet Gynecol Scand 1987; 66:455-7.