Abstract
Background:
Pelvic organ descent is a common gynecological disorder called pelvic organ prolapse (POP). Conservative care and surgical repair are women’s primary treatments for pelvic organ prolapse. Modifying risk factors is a crucial keystone to reducing its prevalence.
Methods:
This unmatched case-control study was conducted at a Tehran referral hospital (June 15 to September 10, 2020) and involved 287 participants (139 cases, 148 controls). Structured questionnaires gathered socio-demographic, obstetric, health, and lifestyle data. Analyses encompassed univariate and multivariate logistic regression.
Results:
Among cases, 69 (49.6%) had anterior prolapse, 46 (33.1%) had posterior prolapse, and 24 (17.3%) experienced complete prolapse. The mean age of participants with POP was 62.7 ± 10.7 years compared to 44.5 ± 12.7 years for controls. Risk factors significantly associated with POP included higher BMI (28.01 ± 4.7 vs 26.18 ± 4.6; p = 0.002), gravidity (4.49 ± 2.89 vs 2.18 ± 1.63; p < 0.001), vaginal deliveries (3.60 ± 2.07 vs 1.03 ± 1.57; p < 0.001), prolonged labor (12.2% vs 2.7%; OR: 4.91, 95% CI: 1.61–14.99), and comorbidities such as diabetes mellitus (30.2% vs 8.8%; OR: 4.49, 95% CI: 2.29–8.83) and hypertension (34.5% vs 6.8%; OR: 7.28, 95% CI: 3.50–15.12). Protective factors included higher education levels and a history of cesarean delivery (mean cesarean count: 0.31 ± 0.72 vs 0.78 ± 0.88; p < 0.001).
Conclusions:
This study highlights key risk factors for POP among Iranian women, emphasizing the need for targeted preventive strategies. Public health interventions addressing these factors may reduce the burden of POP in developing regions.
Introduction
Pelvic organ prolapse (POP) is the descent or herniation of one or more pelvic organs from their anatomical location. 1 POP results from a combined series of long-term failures involving pelvic floor muscles, connective tissue, and the pubococcygeal portion of the levator ani muscle, which are responsible for supporting the pelvic organs. 2 POP is a prevalent condition affecting 40% to 60% of women who experienced delivery, and it has been reported in approximately 42% of Iranian females. 3
POP can influence various aspects of life, including social interactions and psychological and sexual functioning.4,5 Conservative treatment, such as Kegel exercise and modifying risk factors, is recommended for mild to moderate prolapse, while surgery is an option for severe POP. 6 According to the high prevalence of POP, the frequent need for reoperation, and the high-cost burden to both the individual and governments, evaluation of risk factors for the occurrence of POP is of crucial significance. 7 Although the risk factors for symptomatic POP have been studied in developed countries, sufficient data from developing countries are lacking. 8
This study aims to identify the risk factors in emerging POP. Increased awareness helps healthcare providers to implement preventive measures, ultimately reducing the incidence of POP and alleviating the associated healthcare costs and burdens on affected individuals.
Materials and methods
Study design and population
This was an unmatched case-control study designed to identify the determinants of pelvic organ prolapse. The study population comprised all women who visited the urology clinic at a referral hospital in Tehran, Iran, from June 15 to September 10, 2020. The study included all female patients with symptomatic pelvic organ prolapse involving at least one pelvic floor compartment (anterior., middle, posterior part). Women aged 18 and above with stages three or higher were enrolled. The controls included women who presented for upper tract (mainly kidney stones) urologic problems during the same period without any evidence of POP. Demographic data were gathered. Ethical approval was received from the Institutional Review Committee of the Labbafinejad hospital (IR.SBMU.MSP.REC.1401.614). Written informed consent was obtained from all eligible participants.
We obtained the required sample size of 132 by determining the prevalence of POP among Iranian females according to the previous study and applying the formula for sample size determination for a case-control study (n ⩾ 2 (Z_α + Z_β)2 σ2)/(μ_1 − μ_2)2). The formula state that alpha is type one error (Z_α = 1.96), beta is type two error (Z_β = 1.28), and a medium effect size ((μ_1 − μ_2)⁄σ = 0.4).
Data collection tools and procedure
An interviewer-administered structured questionnaire designed from similar studies was used to gather study participants’ socio-demographic, obstetric, urologic, and medical information. The questionnaire was translated into Persian and then translated into English to ensure consistency. A reliability assessment was conducted, and the Cronbach’s alpha value of the tools was 0.88. A data collector took measurements of weight and height. The simplified Pelvic Organ Prolapse Quantification System (S-POPQ) was used to classify the prolapse stage.
Study variables
The dependent variable was POP. The independent variables were socio-demographic characteristics (age, education, occupation (type), workload, place of residence), health status (smoking, alcohol consumption, constipation, chronic cough, diarrhea, diabetes mellitus, body mass index (BMI), Family history of POP and obstetric and gynecological conditions (gravidity, parity, age at first birth and marriage, delivery method, delivery site, instrumental delivery, episiotomy, perineal damage/tear in previous births, induced labor, fundal pressure, history of abortion, birth spacing, duration of labor, birth weight, menstrual status). The BMI was defined as underweight if less than 18.5 kg/m2, standard if 18.5–24.9 kg/m2, and overweight if more than 25 kg/m2. A heavy workload was defined as activities that require lifting heavy objects or performing extensive physical labor that strains the pelvic organs, such as farming, herding, timber collection, and fetching water. An alcohol consumption history was recorded if the patient had consumed two or more drinks per day (more than moderate consumption; CDC Dietary Guidelines for Alcohol 2020–2025). A smoking history was recorded if the patient had smoked in the past 12 months. Chronic constipation was defined as having fewer than three weekly stools lasting at least 3 months. Chronic cough was defined as a cough lasting more than 8 weeks. Labor lasting more than 16–24 h was considered prolonged labor.
Statistical analysis
Statistical analysis was performed using SPSS version 26.0 (IBM, Armonk, NY, USA). The subjects were divided into two groups, which were cases and controls. All potential risk factors were initially analyzed using univariate analysis. The selection of variables was informed by a thorough review of the existing literature and guided by clinical relevance to ensure a robust and meaningful analysis. Student’s t-tests were performed on continuous variables, and chi-square or Fisher’s exact tests were performed on categorical variables. A multivariate direct binary logistic regression analysis was carried out on all variables that had statistical significance on univariate analysis to determine independent risk factors for POP. The P-value of <0.05 determined statistical significance.
Results
Among 287 participants who met inclusion criteria, 139 (48.5%) were enrolled as patients and 148 (51.5%) as controls. The mean age was 53.33 ± 14.86 (range; 24–86) years. Among the patients, 69 (49.6%) participants experienced anterior compartment prolapse, 46 (33.1%) had posterior prolapse, and 24 (17.3%) individuals suffered from middle compartment prolapse. Demographic characteristics are summarized in Table 1. Among various demographic factors, there was a statistically significant association between our groups in case of age, BMI, marital status (OR: 20.18, CI: 2.66–152.90), and presence of menopause (OR: 9.90, CI: 5.61–17.49). Marital age was negatively associated with POP development (t: −6.78, p < 0.001). However, the residence area did not show any significant relationship. Regarding socio-economic factors, women with higher education showed a lower incidence rate. The mean age at the first and last pregnancy was lower (t: −5.91, p < 0.001) and higher (t: 2.16, p = 0.032), respectively, in the patient’s group. On the other hand, age at first pregnancy was lower among the case group. Although smoking (OR: 0.387, CI: 0.134–1.12, p = 0.071) and alcohol consumption (OR: 0.345, CI: 0.069–1.74, p = 0.180) were negatively associated with the development of POP, they did not reach statistical significance. Moreover, the number of abortions was higher in the case group, though without statistical significance.
Demographic characteristics.
Among gynecologic-related factors, there was a positive correlation between-, the number of pregnancies (t: 7.96), the number of vaginal deliveries (t: 11.25), prolonged labor (OR: 4.91, CI: 1.61–14.99), and POP. Obstetrics-related factors are summarized in Table 2. The presence of a family history of POP also was not significantly associated with the probability of developing this disorder in their relatives (p = 0.744). Performing a Cesarean section was shown to be a protective factor against POP (t: −4.70, p < 0.001). The birth weights of the first and second babies had a significant effect on the occurrence of POP, but there was no more significant effect on the subsequent offspring.
Obstetric and gynecologic characteristics.
Comorbidities including diabetes mellitus type 2 (OR: 4.49, CI: 2.29–8.83), hypertension (OR: 7.28, CI: 3.50–15.12), and hypothyroidism (OR: 2.016, CI: 1.05–3.86) were also showed to be more prevalent in the case group. Dyspareunia, lower urinary tract symptoms, and incontinence were common chief complaints mentioned (summarized in Table 3). Women with a history of previous surgery or obstetric/gynecologic (summarized in Table 2) manipulation, including performing episiotomy (OR: 4.34, CI: 2.40–7.83), perineal damage (OR: 6.04, CI: 2.97–12.29), previous pelvic surgery (OR: 4.44, CI: 2.53–7.80), and instrumental assisted delivery (OR: 4.47, CI: 1.23–16.20) had significantly more incidence of developing POP. Some medical risk factors were also significantly associated with the incidence of POP. There was a tendency in symptomatic cases with constipation (OR: 2.56, CI: 1.44–4.57) than women without developing POP. However, our results showed that chronic cough did not affect the incidence of POP. History of Fundal pressure to aid the vaginal delivery was significantly higher among patients (OR: 2.76, CI: 1.47–5.18).
Medical history and comorbidities.
Further analysis regarding the grade of cystocele, we found that married patients (p < 0.001), marriage age (p < 0.001), elevated ages at first and last pregnancy (p < 0.001), repeated pregnancies and NVDs (p < 0.001), higher birth weight (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.001), hypothyroidism (p = 0.017), chronic constipation (p < 0.001), menopause (p < 0.001), and those with history of perineal damage (p < 0.001) and pelvic manipulations were associated with statistically significant higher grades. However, patients with higher levels of education (p < 0.001) and shorter labor time (p < 0.001) experienced lower grades. Nevertheless, number of abortions (p = 0.766), smoking (p = 0.086), alcohol consumption (p = 0.128), familial history of POP (p = 0.304), chronic cough (p = 0.077), and workload (p = 0.266) did not show any correlation.
Discussion
Our study aimed to identify key risk factors for pelvic organ prolapse (POP) in a cohort of Iranian women, providing insights that contribute to both regional and global understanding of POP. The findings of this study emphasize the significant influence of various socio-demographic, obstetric, and medical factors on the development of POP, some of which align with existing literature, while others reveal regional-specific factors that require further investigation. Unlike many studies conducted in Western populations, this research highlights region-specific variables, such as early marriage, differing obstetric practices, and cultural norms, which significantly impact POP prevalence. These findings are essential for tailoring preventive measures and resource allocation in developing countries.
Our study further validates that advancing age is a prominent risk factor for POP, consistent with the established global trend. 9 Improved health indicators and increased life expectancy have contributed to a significant rise in the prevalence of POP among women older than 60. St Martin et al. have reported that the estimated annual national cost of pelvic organ prolapse surgery in the United States was 1.523 billion dollars. 9 Apart from various physical impacts related to POP, adverse psychological effects on patients cause embarrassment, decreased self-confidence, and social isolation.4,5 Besides, most studies and reviews published regarding the risk factors have been performed explicitly on patients in Western countries. 9 Thus, this study aimed to investigate the risk factors for POP in a tertiary hospital in a developing country.
POP risk factors can be categorized as modifiable and non-modifiable factors; all seem to be associated with different stages of weakness of the pelvic floor fascia. 2 Non-modifiable risk factors include age, ethnicity, sex, and genetic factors. 10 Our findings indicate that women over the age of 60 are at a higher risk for developing POP, supporting findings from both developed and developing nations that show a clear age-related trend in POP prevalence. It has been shown that women aged 60–69 sought medical treatment for POP at a rate eight times higher than women aged 30–39, highlighting the growing healthcare demand for older populations. 11
Nevertheless, despite some studies introducing age as a confirmed risk factor, Elbiss et al. found no correlation among Emirati women. 12 Genetic factors are also shown to predispose the development of POP, affecting collagen and soft tissue structure and culminating in the weakness of pelvic fascia. Collagen type 3 alpha one has been identified in a meta-analysis as an essential factor in POP, providing strength and rehabilitation potential following damages. 13 Comparison of vaginal tissue among women with and without POP supported the increased levels of collagen type 3 and Matrix Metallopeptidase 9 among women with POP.2,14 Moreover, according to a review by Guler and Roovers, increased collagen type 3 among POP patients was introduced as a “cause” rather than a “result.” 2 In the present study, the education level is significantly associated with POP in such a way that women with higher degrees experienced a lower prevalence of POP. This finding is consistent with those established by Elbiss et al., confirming that the higher the level of education, the healthier the lifestyle. 12 Although several studies highlight heavy workloads as a predisposing factor, our study did not find a significant association between workload and POP. Similarly, rural residency was not identified as a significant risk factor in our study, which contrasts with the findings of some global studies. This discrepancy may stem from cultural differences and daily life practices within our study population.15,16
Another significant finding in our study was the association between vaginal delivery and an increased risk of POP, a result consistent with previous research that underscores the damaging effects of childbirth on the pelvic floor. Gravidity and associated factors are also crucial in developing POP, serving as the most potent predisposing factor. 8 Although a study showed no correlation between the frequency of gravidity and POP, 17 our findings were congruent to other studies and Western countries, supporting the positive correlation between gravidity and POP. Moreover, we showed that women married at younger ages were more at risk of subsequent POP. Despite our results, some studies showed that short intervals between pregnancies are also associated with a higher risk of POP.15,18 The findings above are probably due to nerve and fascial damage during pregnancy, specifically multiple pregnancies with short intervals.
Interestingly, we found that performing a cesarean section appeared to serve as a protective factor against POP. This finding corroborates the results of studies suggesting that cesarean deliveries reduce the mechanical stress on the pelvic floor, although it is important to note that cesarean delivery is not without its own risks, and the potential for POP to develop in women with a history of cesarean deliveries cannot be excluded. 19
The present study revealed that the number of abortions was not influential. Furthermore, we also showed that the birth weight of children can significantly increase the probability of further POP. Our results also support the idea that pelvic floor damage is more severe after the first two pregnancies, emphasizing the need for early interventions in women with larger babies or those experiencing difficult deliveries. 20
Among modifiable risk factors, obstetrics and gynecologic-related factors are easily preventable by education and compliance with simple rules during and after pregnancy. 15 Our findings showed that instrumental assisted delivery caused a 9.68-fold increase in developing POP. Besides, fundal pressure was significantly less frequent in healthy individuals than in women with symptomatic POP. Moreover, women with prolonged labor were 10 times more at risk of POP. Therefore, strict criteria are needed for obstetricians regarding the indication of inducing labor with instruments and using fundal pressure. History of previous pelvic surgeries is also a potential risk factor for POP, according to the high possibility of iatrogenic damage on nerves, ligaments, and vascular components. 12 Performing episiotomy revealed a direct association with POP that was consistent with the findings of Memon and Handa. 21
According to recent literature, some comorbidities have also been shown as potential risk factors. 22 Hormonal changes, including decreased blood levels of Estrogen and its receptor expression among postmenopausal women, have also been associated with altered collagen structures, weakening the strength and composition of collagens. Estrogen affects extracellular matrix composition and growth factors, leading to collagen synthesis, metabolism, and morphology alteration. 23 Lang’s findings also supported the data mentioned above by investigating fewer estrogen receptors in the pelvic ligaments of women with POP compared to healthy individuals, establishing menopause as a risk factor. 24 Our findings also supported that postmenopausal women were almost 10 times more likely to develop POP. Similar to our findings, BMI is also known as a potential risk factor 10 ; however, the primary pathophysiology is under debate. Some studies support the hypothesis of increased abdominal pressure directed toward pelvic components. 25 Surprisingly, according to a study performed by Tan et al. among Australian women, there was no association between BMI and intra-abdominal pressure. 26
Nevertheless, it seems that metabolic syndrome and altered amounts of triglyceride among obese patients may play a crucial role in developing POP. 27 While our findings confirmed the issues mentioned above, we showed a direct correlation between hypothyroidism, diabetes mellitus type 2, and hypertension alone with POP. However, Bohoussou et al. found no significant association between diabetes and POP. 28 Isık et al. did not show any association between diabetes alone and hypertension alone but showed a correlation between POP and the concomitant presence of diabetes and hypertension. 22 The possible pathophysiology may be due to the neuropathy, vascular damage, and further reduction of tissue rehabilitation potential in diabetic patients. A review study has recently revealed a positive correlation between the amount of reactive oxygen species and POP, culminating in altered collagen metabolism and composition. 29 Therefore, one hypothetical mechanism regarding the association between DM and the development of POP may be through the induction of oxidative stress. Considering the relationship between the reactive oxygen species, there may be a similar mechanism following hypertension 30 and hypothyroidism. 31 The current study also explored the association between POP and medical conditions. Although there was found to be a direct correlation between constipation and POP, unlike previous studies, 8 the presence of chronic cough did not reach statistical significance. However, Hatice Isık depicted no correlation between chronic cough and POP. We also showed that smoking might be a preventive factor, consistent with recent studies.8,15 Moreover, to our knowledge, this study is among the first to conclude a negative relationship between alcohol consumption and further probability of POP development. Besides, we showed that stage 4 pelvic organ prolapse was less prevalent among smokers and alcohol users; however, it did not reach statistical significance.
The control group comprised women presenting with unrelated urological complaints without clinical evidence of POP. While this approach reduces confounding, it may introduce selection bias, which we acknowledge as a limitation of this study design. Also, this study includes the single-center, single-city evaluation. However, since our center is a tertiary center in the capital of Iran, the results provided are separate, and we may generalize our findings to other populations in our country. Future studies may adopt matched-pair designs to strengthen the validity of findings.
In the current study, we found a direct association between POP and pelvic floor manipulations, including instrumental assisted labor, induced fundal pressure, prolonged delivery, episiotomy, and pelvic floor surgeries, necessitating the enforcement of strict criteria for obstetricians and healthcare providers. We also showed that advanced age, early marriage, parity, vaginal delivery, menopause, and lower education may increase the risk of further POP development. Moreover, women with concomitant comorbidities, including diabetes mellitus type 2, hypertension, and hypothyroidism, are at more risk of developing POP. The birth weight of only first and second children was significantly correlated with POP. Therefore, by increasing public awareness of the risk factors, the incidence of POP and the burden of costs imposed on the healthcare system may be effectively reduced.
Footnotes
Acknowledgements
None
Authors’ contributions
FS: project administration, critical review, supervision
BN: critical review, conception, Data analysis and interpretation
HH: conception, data curation, Data analysis and interpretation
MD: drafting, critical review, Methodology
NR: data curation, conception, Investigation
MA: conception, data curation, Methodology
HR: drafting, data curation, Investigation
HM: drafting, conception, Investigation
PT: data curation, drafting, Data analysis and interpretation
NR: drafting, conception, Methodology
SS: data curation, drafting, Data analysis and interpretation
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics approval and consent to participate
Institutional Review Committee of the Labbafinejad Hospital (IR.SBMU.MSP.REC.1401.614). Written informed consent was obtained from all eligible participants.
Consent for publication
Not applicable.
Availability of data and materials
The data supporting this study’s findings are available from the corresponding author upon reasonable request.
