Prolapse and sexual function in women with benign joint hypermobility syndrome

Transcription

1 DOI: / Urogynaecology Prolapse and sexual function in women with benign joint hypermobility syndrome H Mastoroudes, a I Giarenis, a L Cardozo, a S Srikrishna, a M Vella, a D Robinson, b H Kazkaz, b R Grahame b a King s College Hospital NHS Foundation Trust, b University College Hospital NHS Foundation Trust, London, UK Correspondence: Dr Heleni Mastoroudes, Department of Urogynaecology, suite 8, 3rd floor Golden Jubilee Wing, King s College Hospital, Denmark Hill, London SE5 9RS, UK. heleni.mastoroudes@nhs.net Accepted 12 October Objective To determine whether pelvic organ prolapse (POP) and sexual dysfunction are more severe in women with benign joint hypermobility syndrome (BJHS) than in the normal population. Design Case control study. Setting King s College Hospital NHS Foundation Trust, London, UK and University College Hospital, London, UK. Population Women diagnosed with BJHS (n = 60) at University College Hospital. Control participants (n = 60) recruited from King s College Hospital NHS Foundation Trust. Methods Objective assessment of POP was undertaken using the Pelvic Organ Prolapse Quantification System (POP-Q). Both s were asked to complete the Prolapse quality of life (P-QOL) and pelvic organ prolapse/urinary incontinence sexual (PISQ-12) questionnaires. Results In all, 120 women (60 in Study, 60 in Control ) were recruited. All women in the study were matched with healthy control women according to age, parity and ethnicity. There was a statistically significant difference between points Aa, Ba, Ap, Bp and C in study and control s showing that prolapse is objectively more severe in those with BJHS. Significantly more women with BJHS felt that POP interfered with sex and defecation compared with the control. The impact of prolapse symptoms on quality of life was statistically different in almost all nine P-QOL domains. Conclusions A large number of women with BJHS have prolapse symptoms, which significantly affect their quality of life. POP is more severe in women with BJHS. Keywords Benign joint hypermobility syndrome, prolapse, sexual function. Main outcome measures Comparison of vaginal anatomy using POP-Q between the two s. Comparison of P-QOL and PISQ- 12 quality of life scores between the two s. Please cite this paper as: Mastoroudes H, Giarenis I, Cardozo L, Srikrishna S, Vella M, Robinson D, Kazkaz H, Grahame R. Prolapse and sexual function in women with benign joint hypermobility syndrome. BJOG 2013;120: Introduction Benign joint hypermobility syndrome (BJHS), also known as Ehlers Danlos III, is a hereditary connective tissue disorder causing hypermobility of joints. Kirk et al. 1 coined the term hypermobility syndrome in 1976 and this was defined as the occurrence of musculoskeletal symptoms in the presence of joint hypermobility in healthy individuals (in the absence of other rheumatic disease). This syndrome may present with joint dislocation and subluxation, arthralgia, arthritis, tendonitis, tenosynovitis, damaged ligaments and ligamentous attachments and fractures. There are associated symptoms such as joint pain and instability. BJHS can also involve other organ systems resulting in other collagen-related disorders. 2 Hypermobility is found more frequently in non-caucasian populations. 1 The prevalence in adults varies between 0.6 and 35%, 3,4 depending on age, sex, ethnicity and the scoring system used to make a diagnosis. It is more common in women and seems to decrease with age. Unfortunately, BJHS is under-recognised both by lay people and by the medical profession and therefore is poorly managed. 5 The basic pathophysiology of BJHS is an underlying abnormality in collagen. Up to 28 different types of collagen have been described, but collagens I V are the most common. Collagen type I is the most abundant in the human body and has a high tensile strength compared with collagen III, which is more elastic. It has been observed that the ratio of type III to type I collagen is increased in the ª 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2013 RCOG 187

2 Mastoroudes et al. hypermobile population. 6 This alteration in the ratio leads to a general decrease in tensile strength resulting in global tissue damage. 7,8 Patients with hypermobility have been shown to have an increased concentration of type III procollagen. 9 The high collagen content in the musculotendinous pelvic floor can result in pelvic floor problems in women with this condition, such as pelvic organ prolapse and urinary incontinence. Urogenital prolapse has a significant adverse impact on quality of life. Three large population studies have shown that the prevalence of stage three and four prolapse ranges from 2 to 11% Prolapse accounts for 20% of women on the waiting list for gynaecological surgery and there is an 11.1% lifetime risk of surgery for prolapse with a 29% reoperation rate. 13 Given the background abnormality of collagen in BJHS the aim of this case control study was to determine whether pelvic organ prolapse and sexual dysfunction is more severe in affected women than in the normal population. Methods All women who had been referred to the tertiary referral hypermobility clinic at University College Hospital, and diagnosed with BJHS were invited to participate in this study between October 2010 and August University College Hospital has a multinational catchment population and is also one of the three adult hypermobility clinics in the UK. Patients had been sent information leaflets regarding this study, together with their appointment letters. Sixty women with BJHS agreed to participate in this study. Inclusion criteria included: women aged between 18 and 60 years who understood English and who had BJHS. All women gave informed consent before participating. Women above the age of 60, who did not speak English and who had previous prolapse surgery were excluded. Ethical approval was obtained from the local ethics committee. A diagnosis of BJHS was made using the revised 1998 Brighton criteria for BJHS, which was published by the British Society of Rheumatology Special Interest Group on the Heritable Disorders of Connective Tissue. 12 These comprise sets of major and minor criteria (see Appendix S1). The criteria are met when either two major, or one major and two minor, or four minor are satisfied. The Brighton criteria have been shown to have excellent reproducibility. 13 The Beighton score, which may be used as an initial screen is no longer considered the gold standard for recognising hypermobility (see Appendix S2). 14 This test only samples five joints, and fails to identify degree of laxity. There is no universal agreement on the value needed to make a diagnosis for BJHS using the Beighton score but most researchers use a score of 4/9. In addition, 60 control participants were recruited from King s College Hospital NHS Trust medical personnel and other hospital staff who did not fulfil the Brighton criteria. The inclusion criteria were the same as for the study apart from the fact that they had no BJHS. All those who had previous prolapse surgery were excluded. They were matched to the study according to age, parity and ethnicity. All study and control participants were asked to complete the prolapse quality of life questionnaire (P-QOL) and the pelvic organ prolapse/urinary incontinence sexual questionnaires (PISQ-12) both of which have been validated 16,17. The P-QOL is a simple and reliable questionnaire that assesses the severity of symptoms caused by urogenital prolapse and their impact on the quality of life of affected women. The questionnaire comprises 20 questions representing nine quality of life domains and a measurement of symptom severity. A high total score indicates a greater impairment of quality of life. The scoring system has previously been reported and validated. 16 The PISQ-12 is a short form of a reliable, conditionspecific instrument to evaluate sexual function in heterosexual women with urogenital prolapse or urinary incontinence. There are 12 domains that are graded on a fivepoint Likert scale ranging from never to always. Of the 12 questions, nine are general sexual-function questions and three directly pertain to women with prolapse or incontinence. The scoring system has previously been reported and the questionnaire has been validated. 17 The scores were lower in those women with poorer sexual functioning and depressive symptoms. Objective assessment was undertaken using the Pelvic Organ Prolapse Quantification System (POP-Q). The POP- Q system, developed by the International Continence Society is a standardised, reliable and descriptive method that allows measurement of the support of nine specific points of the vagina in centimetres. 18 All nine points were measured using POPstix (a wooden measuring spatula with 1-cm markers) (POPstix, Endoventure, Auckland, New Zealand) for comparison. This was performed in the left lateral position at the participant s maximal Valsalva effort. The scores for P-QOL and PISQ-12 were compared between study and control s. We compared the nine POP-Q points and dichotomised our data into POP-Q 2 and POP-Q < 2 as we felt this was more clinically relevant. We also considered an association between anterior and posterior compartment prolapse in relation to symptoms of voiding dysfunction and obstructed defecation, respectively. Our target sample size was 60 cases and 60 controls. This was based on recruitment achieved in previous urogynaecology studies assessing urinary incontinence and pelvic organ prolapse in BJHS. Given the fact that the exact prevalence of prolapse in women with BJHS is not known, the power calculation was based on the prevalence of urinary 188 ª 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2013 RCOG

3 Prolapse and sexual function in women with benign joint hypermobility incontinence in women with BJHS in a study by Jha et al. 19 The prevalence of incontinence in this study was 60% in the BJHS, and it was calculated that having 60 women in each would result in a power of 80% to detect a difference of 30% at a 5% significance level. All analyses were performed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). Frequencies, percentages of different responses and the statistical difference were analysed using chi-square and Fischer s exact tests. Data analysis comparing the quality of life scores was performed with the Wilcoxon signed-rank test. Paired t test was used to compare the POP- Q measurements. Correlation analysis was performed using the Kendall s τ-b test. Results One hundred and twenty women were recruited during a 10- month period. All women with BJHS were matched with healthy volunteers according to age (P = 0.096), parity (P = 0.321) and ethnicity (P = 0.188). The women ranged in age from 18 to 60 years with a mean of 39.4 years. The median parity was 1 (range 0 3) and there was no statistical difference between vaginal deliveries and caesarean sections in both s. There was no significant difference between the feeling of a bulge/lump in the vagina between study and control s. Significantly more women with BJHS (27%, 16/60) felt that the bulge interfered with sex compared with the control (10%, 6/60) (P = 0.032). The presence of heaviness or dragging in the vagina or lower abdomen, vaginal discomfort, backache and lower backache were all statistically greater in the study (Table 1). Defecatory problems were also more common in the study. Significantly more women (23%, 14/60) in the study felt that the vaginal bulge interfered with them emptying their bowels, compared with (5%, 3/60) of the control (P = 0.007). The difference in women straining to open their bowels between study and control s was also statistically significant (P < 0.001). This was a problem for 61.7% (37/60) of the study. Sixty-three percent (38/60) of women in the study felt that they had not completely emptied their bowels (P < 0.001) and 33.3% felt the need to perform digitation to defecate (P = 0.001). The majority of women (71.7%;43/60) with BJHS were constipated and found it difficult to empty their bowels (P < 0.001). There was a significant correlation between those women with BJHS who had a posterior compartment prolapse and straining to open their bowels (P = 0.028), bowels being incompletely empty (P = 0.017) and women needing to digitate to empty their bowels (P = 0.014). The impact of prolapse symptoms on quality of life was statistically significant in seven out of nine domains of the Table 1. P-QOL vaginal bulge symptoms comparison between study and control s Heaviness or dragging feeling as the day goes on from the vagina or the lower abdomen Discomfort in the vagina which is worse when standing and relieved by lying down Backache which is worse on standing and better on lying down Lower backache worsens with vaginal discomfort Bold values are statistically significant. P-QOL (General Health Perception, Physical Limitation, Social Limitation, Personal Relationships, Emotions, Sleep/ Energy and Severity Measures; Figure 1). The PISQ-12 scores were significantly different between the two s (P = 0.002). The PISQ-12 Total score for the study was (standard deviation [SD] 8.1) and for the control 8.9 (SD 5.3). The comparison of the degree of prolapse in anterior, posterior and middle compartments between the study and control s can be seen in Table 2. There was a statistically significant difference between points Aa, Ba, Ap, Bp and C in study and control s, which shows that prolapse is more severe in those with BJHS (Table 2). The majority (73.3%;44/60) of the BJHS had a clinically significant prolapse (POP-Q ordinal stage 2) compared with only 35% (21/60) of the control (P < 0.001). Discussion Study Control P value 28.3% (17/60) 5.0% (3/60) % (15/60) 5.0% (3/60) % (36/60) 23.3% (14/60) < % (22/60) 5.0% (3/60) <0.001 The findings of our study confirm that the prevalence of a clinically significant prolapse was more common in women with BJHS than in the normal population, which is consistent with our hypothesis. This is evident not only from the ordinal stage of the prolapse but also from individual POP-Q points in all compartments. Our study is the first case control study attempting to establish the association between worsening objective evidence of prolapse in those with BJHS and its effect on quality of life. Previous studies have shown a higher ª 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2013 RCOG 189

4 Mastoroudes et al. Figure 1. Comparison of P-QOL domain scores between study and control s. GHP, general health perception; PI, prolapse impact; RL, role limitations; PL, physical limitations; SL, social limitations; PR, personal relations; E, emotions; SE, sleep energy; SM, severity measures. *P > Table 2. Results of POP-Q POP-Q Points Study (median) Control (median) IQR study IQR control P value Aa to0 3 to+1 <0.05 Ba to0 3 to Ap to0 3 to Bp to0 3 to C to 6 8 to D to 8 9 to Genital hiatus (cm) Perineal <0.001 body (cm) Total vaginal length (cm) IQR, interquartile range. Bold values are statistically significant. incidence of BJHS in women with known pelvic organ prolapse. 20,21 Others have previously reported high prevalence of more severe prolapse (36 66%) in those with BJHS. 22,23 Our study also showed a high prevalence at 73.3% when including those with a prolapse, at stage 2 or greater. Despite objective evidence of prolapse, an insignificant proportion of women were troubled by this; although on direct questioning regarding specific prolapse symptoms, the symptoms were found to be significantly higher in women in the study than in control women. The impact of prolapse on quality of life in the study was not significantly affected compared with the General Health Perception. This is likely to be explained by the other health-related issues from their underlying BJHS. Another possible explanation is the fact that prolapse may have been present over a long period of time, so they may have become accustomed to the symptoms. Some women with extensive objective evidence of prolapse are often not symptomatic. The literature has demonstrated a strong association between BJHS and obstructed defecation 24,25 and the findings of our study support this. A significant proportion of the study population had difficulty in emptying their bowels completely, which was often associated with the need to use assistance in the form of digitation to relieve the problem. This concurs with results of previous studies. 24 We hypothesise that different pathophysiological mechanisms may be contributory. Hypermobility may contribute to this by cause a generalised increase in pelvic floor descent during straining. Equally the presence of a posterior wall prolapse might also be a contributory factor. Our study shows that there is a significantly higher incidence of prolapse in the posterior compartment of the study population compared with the controls. It is not known whether this is the result of chronic straining to open their bowels or whether the prolapse has resulted in chronic straining problems. We recognise that there are some limitations to our study. Most of the women were Caucasian rather than fromethnic minorities; therefore our results may not be representative of the overall population with BJHS. Although the symptoms section of the P-QOL is validated, our results might have been more robust had we used a validated bowel symptom questionnaire, such as the International Consultation on Incontinence Questionnaire Bowels, 26 although we were apprehensive regarding the possibility of causing questionnaire fatigue, which might have affected compliance. We also recognise that their bowel symptoms may also be the result of other conditions that were not excluded, such as slow transit constipation, intussusception and impaired rectal sensation. This study took place in a specialist rheumatology clinic, which makes it more likely that these women have comorbidities compared with the general population. We only included women with BJHS, which represents the worst end of the hypermobility disease spectrum, making it difficult to estimate the prevalence of prolapse in those with pure joint hypermobility. 190 ª 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2013 RCOG

5 Prolapse and sexual function in women with benign joint hypermobility This cross-sectional study can prove a correlation between the two s but to infer anything about causation, a longitudinal study would be required. Conclusion To the best of our knowledge this is the largest case control study looking at the relationship between BJHS and prolapse and sexual function to date. Our study suggests that although these women do not find their prolapse bothersome, it does have an impact on their life in the form of bowel evacuation symptoms and also sexual dysfunction. The incidence of prolapse and all the symptoms related to it is significant; much of this may still go unnoticed. We hope that the findings of this study may provide knowledge about the pathophysiology of prolapse and obstructed defecation. Disclosures of interest HM, IG, MV, SS, RG, and HK have no interests to disclose. LC is a consultant for Allergan, Astellas, Ethicon, Merck, Pfizer and Teva; has received speaker honoraria from Astellas and Pfizer; and participated in trials with Astellas and Pfizer. DR has acted as Consultant for Astellas, Ferring, Gynaecare, Uroplasty, Pfizer, Recordati and Novo-Nordisc; has received speaker honoraria from Astellas, Ferring, Gynaecare, Uroplasty, Pfizer and Recordati; and participated in trials with Astellas, Pfizer and Boston Scientific. Contribution to authorship HM was responsible for acquisition, analysis and interpretation of the data, and for drafting and revision of the manuscript. IG and MV analysed and interpreted the data and drafted the article. SS analysed the data and drafted the manuscript. HK acquired data and revised the manuscript. DR, RG and LC were responsible for the concept and design of the study and for revision for important intellectual content. All authors gave final approval before submission for potential publication. Details of ethics approval Ethical approval was obtained from the Research and Ethics committee: South East London REC 3. Reference: 10/H0808/ 18. Date of approval 1 April Funding Funding was provided by the King s College Hospital Trust- Funded R&D Grants for Supporting Information Additional Supporting Information may be found in the online version of this article: Appendix S1. The Brighton criteria. Appendix S2. The nine-point Beighton hypermobility score. & References 1 Kirk JA, Ansell BM, Bywaters EG. The hypermobility syndrome. Musculoskeletal complaints associated with generalized joint hypermobility. Ann Rheum Dis 1967;26: Lammers K, Lince SL, Spath MA, Van Kempen LC, Hendriks JC, Vierhout ME, et al. Pelvic organ prolapse and collagen associated disorders. Int Urogynecol J 2012;23: Beighton P, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis 1973;32: Verhoeven JJ, Tuinman M, Van Dongen PW. 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