|Year : 2019 | Volume
| Issue : 2 | Page : 57-62
Vitamin D status in women with pelvic floor disorders: A meta-analysis of observational studies
Zinat Ghanbari1, Maryam Karamali1, Naghmeh Mirhosseini2, Maryam Akbari3, Reza Tabrizi3, Kamran B Lankarani4, Tahereh Eftekhar1, Maryam Deldar Pesikhani1, Shokoofeh Borzabadi5, Zatollah Asemi6
1 Reproductive Health Research Center, Tehran University of Medical Science, Tehran, Iran
2 School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada
3 Health Policy Research Center, Institute of Health, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
4 Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5 Biology Department, Science and Research Branch, Islamic Azad University, Tehran, Iran
6 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
|Date of Web Publication||3-Jul-2019|
Dr. Zatollah Asemi
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan
Source of Support: None, Conflict of Interest: None
| Abstract|| |
The current evidence regarding the association between vitamin D status and pelvic floor disorder (PFD) are inconclusive. This meta-analysis was aimed to summarize existing data demonstrating the association between Vitamin D status and PFD using published observational studies. All national and international databases including Web of Science, PubMed, Google Scholar, and Scopus were searched up until January 30, 2018, and related published studies retrieved for meta-analysis. The effect sizes of Vitamin D status were presented as standardized mean difference (SMD) with 95% confidence interval (CI), using random-effect models and inverse variance method. The Cochran Q statistic and I2 tests were used to evaluate the heterogeneity across included studies. Seven studies with 3219 women were included our meta-analysis. There was heterogeneity existing among included studies (I2 = 96.4%, P < 0.001), so a random-effect model was used. The findings of this meta-analysis revealed that the mean serum Vitamin D levels in women with PFD were significantly lower than healthy women (SMD −0.60; 95% CI, −1.06, −0.13; P = 0.01). This meta-analysis demonstrates lower levels of serum Vitamin D in women with PFD rather than healthy women. Additional prospective studies regarding the association between Vitamin D status and PFD are required to confirm our findings.
Keywords: Meta-analysis, observational studies, pelvic floor disorder, Vitamin D levels
|How to cite this article:|
Ghanbari Z, Karamali M, Mirhosseini N, Akbari M, Tabrizi R, Lankarani KB, Eftekhar T, Pesikhani MD, Borzabadi S, Asemi Z. Vitamin D status in women with pelvic floor disorders: A meta-analysis of observational studies. J Mid-life Health 2019;10:57-62
|How to cite this URL:|
Ghanbari Z, Karamali M, Mirhosseini N, Akbari M, Tabrizi R, Lankarani KB, Eftekhar T, Pesikhani MD, Borzabadi S, Asemi Z. Vitamin D status in women with pelvic floor disorders: A meta-analysis of observational studies. J Mid-life Health [serial online] 2019 [cited 2022 Nov 27];10:57-62. Available from: https://www.jmidlifehealth.org/text.asp?2019/10/2/57/261982
| Introduction|| |
Pelvic floor disorder (PFD), the major clinical problem in postmenopausal women, includes pelvic organ prolapse (POP), urinary incontinence (UI), and fecal incontinence (FI). More than 24% of nonpregnant women suffer from PFD, which almost doubles by aging, with its prevalence being 36%–49% after the age of 60 years. PFD might be significantly associated with other morbidities and affect woman's quality of life. PFD poses economic burden on healthcare because of complex medical conditions and coincident morbidities which lead to subsequent diagnostic and therapeutic issues.,,
Vitamin D plays a critical role in bone growth and preserving bone mineral density. The current evidence has shown that less concentrations of serum 25-hydroxyvitamin D are correlated with reduced postural stability and increased risk of falls. The prevalence of low Vitamin D status among postmenopausal women worldwide is ranged from 1.6% to 86% depending on the regional location and seasonal variation. Earlier studies demonstrating the impact of Vitamin D on skeletal muscle strength and function are inconsistent., However, it is highly suggested that Vitamin D has a considerable effect on the function and efficiency of skeletal muscle. Recent literature has proposed the contribution of low Vitamin D status in the incidence of PFD. The weakness of pelvic floor muscle which is noticed in women suffering from PFD symptoms might probably be related to low Vitamin D status. Further, detrusor muscles in bladder wall have Vitamin D receptor (VDR); therefore, Vitamin D deficiency may impair the function of urinary bladder leading to paravaginal defect (PVD) symptoms. Navaneethan et al. have shown a high prevalence of low Vitamin D status and its significant association with PFD among postmenopausal women. In another study, increased FI symptoms were shown to be associated with hypovitaminosis D.
There are several studies that have confirmed the association between serum Vitamin D levels and PFD; however, we did not find any meta-analyses to summarize the findings of existing publications. Considering the disagreements among the current evidence regarding the association of serum Vitamin D levels and PFD, the aim of the study was to systematically review existing evidence and to summarize the available findings in a meta-analysis, if possible.
| Materials and Methods|| |
The related studies were detected by searching in the national and international online databases including Web of Science, PubMed, Google Scholar, and Scopus until January 30, 2018. Two independent authors (MA and RT) performed the search process. The search keywords were selected using MeSH terms and text words: exposure (“Vitamin D status” OR “Vitamin D levels” OR “Vitamin D concentrations”) and outcomes (“PFD” OR “POP” OR “UI” OR “FI” OR “stress urinary incontinency” OR “urge incontinency” OR “vaginal apex prolaps” OR “anterior vaginal wall prolaps” OR “posterior vaginal wall prolaps” OR “rectocele” OR “perineal defect” OR “anterior colporraphy” OR “custocele” OR “paravaginal defect (PVD)” OR “lower urinary tract dysfunction”). The reference list of the selected studies was hand searched to include the articles which were not captured in the primary electronic search. Further, authors contacted with appropriate research institutes, centers, experts, and researches for gray literatures and unpublished studies. Articles published in English were used in this meta-analysis.
Relevant studies were included in the meta-analysis, after screening for the title, abstract, and the full text of the articles and excluding irrelevant and duplicate papers. Studies were selected according to the following inclusion criteria: original observational studies with cross-sectional, case–control and cohort design, studies related to PFD among women diagnosed based on the national guidelines, however, women without PFD were considered as control group, and studies that reported the mean changes of serum Vitamin D (ng/mL), along with standard deviation (SD) for both case and control groups. Articles not reporting the mean differences and SD of Vitamin D, case reports or case series, the abstracts with no available full text, and articles with low score of quality assessment were excluded from the meta-analysis.
STROBE checklist, specified for observational studies, was applied to evaluate the quality of selected studies. This checklist examined different methodological aspects (with 12 questions) including total sample size, study design, sampling methods, study participants, the method and tool of data collection, the definitions of different variables, the assessment of samples, statistical analyses, the aims of study, the appropriate style to report findings based on the goals of the study. One score was devoted to each item, and the studies with at least 8 points were included in this meta-analysis.
Two independent authors (MA and RT) extracted data from observational studies using the standard Excel spreadsheets. The extracted data included;first author's name, country study conducted, publication date, study method, sample size in intervention and control groups, outcomes, and the mean and SD of serum Vitamin D (ng/mL) in both groups.
All statistical analyses were conducted using STATA version 12.0 (Stata Corp, College Station, TX, USA). The Cochrane's Q test and the I2 statistic were applied to assess the heterogeneity among included studies. On heterogeneous studies, random effect model was used to pool data in the meta-analysis. Cohen statistics and inverse variance method were applied to calculate standardized mean difference (SMD) and 95% confidence interval. Further, to evaluate the source of heterogeneity, subgroup analyses were conducted based on the potential confounders such as country (the USA vs. India vs. other), and outcome (PFD vs. other related conditions). Moreover, the sensitivity analysis was conducted to evaluate the contribution of each study in the pooled effect size (SMD) and Egger's test was used to examine the publication bias among the included studies.
| Results|| |
Overall, 321 articles were found through database search. After screening the title, abstract, and the full-text of the articles and removing non-relevant and duplicate studies, seven observational studies, with 3219 women included, were eligible to be included in our meta-analysis. Flowchart of step by step detailed study identification and selection are depicted in [Figure 1]. The study characteristics assessing the relationship between serum Vitamin D levels and PFD are indicated in [Table 1]. The study sample size ranged between 60 and 1674. These studies were published between 2012 and 2017. Out of seven included studies, two had cohort design and five case–controls.
The relationship between Vitamin D status and pelvic floor disorder
Seven studies assessed the association between Vitamin D levels and PFD among women. A random-effect model was used due to the heterogeneity among included studies (I2 = 96.4%, P < 0.001). The findings indicated that the mean of serum Vitamin D levels was significantly lower in cases with PFD rather than healthy women in control group (SMD − 0.60; 95% confidence interval (CI), −1.06, −0.13; P = 0.012) [Figure 2].
|Figure 2: The forest plot of the association between Vitamin D status and pelvic floor disorders by using the random effect model|
Click here to view
Because of existing heterogeneity among included studies, subgroup analyses were conducted based on the country and outcome to specify the relation between Vitamin D levels and PFD. We found a reduction of heterogeneity for some of the strata of these variables. Our finding revealed a significant association between Vitamin D levels and risk of PFD, using trials performed in India (SMD = −0.37, 95% CI: −0.67, −0.07; I2 = 0.0%) versus those in the United States (SMD = −0.29, 95% CI: −0.61, 0.04; I2 = 81.5%) or other locations (SMD = −1.29, 95% CI: −3.82, 1.23; I2 = 99.4%). Considering type of outcome, three studies conducted in women with PFD showed significant association between Vitamin D levels and disease (SMD = −0.43, 95% CI: −0.60, −0.25; I2 = 0.0%) when compared to other pelvic conditions SMD = −0.74, 95% CI: −1.49, −0.00; I2 = 98.1%).
The significant results demonstrating the association between Vitamin D status and risk of PFD remained unchanged after applying sensitivity analysis. However, the lower and upper pooled SMD for the relation between Vitamin D levels and risk of PFD in the sensitivity analysis were −0.70 (95% CI: −1.34, −0.06) after excluding Lee and Lee and −0.23 (95% CI: −0.42, −0.04) after removing Nseir et al. [Figure 3].
|Figure 3: Sensitivity analysis based on the contribution of each study on pooled standard mean difference|
Click here to view
Egger's regression tests were used to assess any significant evidence of publication bias, and we did not find any bias among included studies assessing the relationship between Vitamin D levels and risk of PFD (B = −5.97, P = 0.126).
| Discussion|| |
This systematic review and meta-analysis, to our best knowledge, is the first report demonstrating the relationship between serum Vitamin D levels and PFD. The current meta-analysis revealed that Vitamin D status is significantly compromised among women with PFD rather than healthy women.
Improved Vitamin D status has been shown to be significantly associated with muscle strength, better neuromuscular function, and postural stability., Muscle weakness, which is common among elderly people, is correlated with hypovitaminosis D, because the ability of skin to synthesize provitamin D (25-hydroxycholecalciferol) reduces with aging. Since pelvic floor muscle is composed of skeletal muscles with VDR, their function might be affected by the circulating concentrations of Vitamin D. There are a few retrospective and two epidemiological studies (including community-dwelling women) have shown the association between Vitamin D deficiency and PFD.,, The Leicestershire MRC Incontinence Study Group (a longitudinal cohort study) indicated that the consumption of higher doses of Vitamin D was significantly correlated with lower risk of overactive bladder. Further, UI symptoms, but not FI symptoms, were less common in Vitamin D sufficient group, even after controlling for demographic factors which might confound the link between PFD and Vitamin D concentrations. With increasing serum Vitamin D concentrations, the risk of PFD decreased significantly, irrespective of the age. Elderly women have shown to be more prone toward Vitamin D deficiency due to decreased outdoor activity and attenuated function of the skin to change 25-hydroxycholecalciferol into active form of Vitamin D. Hence, Vitamin D deficiency is a precipitating factor for PFD in postmenopausal women.
The suggested mechanisms involving Vitamin D in the effective function of musculoskeletal system include promoting calcium metabolism and absorption, protecting muscle cell against hyperinsulinemia, insulin resistance, and increased inflammation.,, VDRs play an important role in the function of smooth and skeletal muscles., Randomized studies have provided controversial evidence, however, many observational studies support the beneficial effects of Vitamin D on muscle function and efficacy., The advantages of Vitamin D have been proven in proper functioning of both skeletal and smooth muscles., Improved serum Vitamin D levels stimulate skeletal muscle proliferation and contribute to proper function of muscle cells via binding to VDR. Specifically, the levator ani and coccygeus muscles (intra-pelvic skeletal muscles) have been shown to be influenced by increased Vitamin D intake.
The weakness of pelvic floor musculature might contribute to the symptoms related to pelvic floor dysfunction including; urinary and FI. Pelvic floor muscles are composed of both smooth and skeletal muscles; therefore, the physiological function of pelvic floor can be modulated through improving Vitamin D status. The variation in geographical regions and subsequently different baseline levels of Vitamin D might complicate its impact on muscle function in these patients. Furthermore, study designs, sample size along with participants' characteristics might explain the discrepancies between different studies.
| Conclusions|| |
This meta-analysis revealed Vitamin D status is significantly compromised among women diagnosed with PFD, compared to healthy women. Additional prospective studies regarding the association between Vitamin D status and PFD are necessary.
The present study was supported by a grant from the Vice-chancellor for Research, SUMS, Shiraz, and Iran.
Financial support and sponsorship
The present study was founded by a grant from the Vice Chancellor for Research, Shiraz University of Medical Sciences, in Iran.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Greer WJ, Richter HE, Bartolucci AA, Burgio KL. Obesity and pelvic floor disorders: A systematic review. Obstet Gynecol 2008;112:341-9.
Nygaard I, Barber MD, Burgio KL, Kenton K, Meikle S, Schaffer J, et al.
Prevalence of symptomatic pelvic floor disorders in US women. JAMA 2008;300:1311-6.
Abed H, Rogers RG. Urinary incontinence and pelvic organ prolapse: Diagnosis and treatment for the primary care physician. Med Clin North Am 2008;92:1273-93, xii.
Doumouchtsis SK, Chrysanthopoulou EL. Urogenital consequences in ageing women. Best Pract Res Clin Obstet Gynaecol 2013;27:699-714.
Brown JS, Waetjen LE, Subak LL, Thom DH, Van den Eeden S, Vittinghoff E, et al.
Pelvic organ prolapse surgery in the United States, 1997. Am J Obstet Gynecol 2002;186:712-6.
Boyles SH, Weber AM, Meyn L. Procedures for pelvic organ prolapse in the United States, 1979-1997. Am J Obstet Gynecol 2003;188:108-15.
Ryan ZC, Craig TA, McGee-Lawrence M, Westendorf JJ, Kumar R. Alterations in Vitamin D metabolite, parathyroid hormone and fibroblast growth factor-23 concentrations in sclerostin-deficient mice permit the maintenance of a high bone mass. J Steroid Biochem Mol Biol 2015;148:225-31.
Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C, et al.
Effects of a short-term Vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000;15:1113-8.
Bischoff HA, Stähelin HB, Dick W, Akos R, Knecht M, Salis C, et al.
Effects of Vitamin D and calcium supplementation on falls: A randomized controlled trial. J Bone Miner Res 2003;18:343-51.
Gaugris S, Heaney RP, Boonen S, Kurth H, Bentkover JD, Sen SS, et al.
Vitamin D inadequacy among post-menopausal women: A systematic review. QJM 2005;98:667-76.
Lips P, Binkley N, Pfeifer M, Recker R, Samanta S, Cohn DA, et al.
Once-weekly dose of 8400 IU Vitamin D(3) compared with placebo: Effects on neuromuscular function and tolerability in older adults with Vitamin D insufficiency. Am J Clin Nutr 2010;91:985-91.
Dhesi JK, Jackson SH, Bearne LM, Moniz C, Hurley MV, Swift CG, et al.
Vitamin D supplementation improves neuromuscular function in older people who fall. Age Ageing 2004;33:589-95.
Crescioli C, Morelli A, Adorini L, Ferruzzi P, Luconi M, Vannelli GB, et al.
Human bladder as a novel target for Vitamin D receptor ligands. J Clin Endocrinol Metab 2005;90:962-72.
Navaneethan PR, Kekre A, Jacob KS, Varghese L. Vitamin D deficiency in postmenopausal women with pelvic floor disorders. J Midlife Health 2015;6:66-9.
Parker-Autry CY, Gleason JL, Griffin RL, Markland AD, Richter HE. Vitamin D deficiency is associated with increased fecal incontinence symptoms. Int Urogynecol J 2014;25:1483-9.
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al.
Strengthening the reporting of observational studies in epidemiology (STROBE): Explanation and elaboration. Ann Intern Med 2007;147:W163-94.
Akbari M, Moosazadeh M, Ghahramani S, Tabrizi R, Kolahdooz F, Asemi Z, et al.
High prevalence of hypertension among Iranian children and adolescents: A systematic review and meta-analysis. J Hypertens 2017;35:1155-63.
Parker-Autry CY, Markland AD, Ballard AC, Downs-Gunn D, Richter HE. Vitamin D status in women with pelvic floor disorder symptoms. Int Urogynecol J 2012;23:1699-705.
Lee HS, Lee JH. Vitamin D and urinary incontinence among Korean women: A propensity score-matched analysis from the 2008-2009 Korean national health and nutrition examination survey. J Korean Med Sci 2017;32:661-5.
Nseir W, Taha M, Nemarny H, Mograbi J. The association between serum levels of Vitamin D and recurrent urinary tract infections in premenopausal women. Int J Infect Dis 2013;17:e1121-4.
Sharma S, Goel N, Madhu S, Rajaram S, Sharma S. Serum elastin and 25 hydroxy Vitamin D levels in women with pelvic organ prolapse. Parameters 2013;1:3.
Parker-Autry C, Houston DK, Rushing J, Richter HE, Subak L, Kanaya AM, et al.
Characterizing the functional decline of older women with incident urinary incontinence. Obstet Gynecol 2017;130:1025-32.
Venning G. Recent developments in Vitamin D deficiency and muscle weakness among elderly people. BMJ 2005;330:524-6.
Ghose RR. Vitamin D deficiency and muscle weakness in the elderly. N
Z Med J 2005;118:U1582.
Semba RD, Garrett E, Johnson BA, Guralnik JM, Fried LP. Vitamin D deficiency among older women with and without disability. Am J Clin Nutr 2000;72:1529-34.
Badalian SS, Rosenbaum PF. Vitamin D and pelvic floor disorders in women: Results from the national health and nutrition examination survey. Obstet Gynecol 2010;115:795-803.
Dallosso HM, McGrother CW, Matthews RJ, Donaldson MM; Leicestershire MRC Incontinence Study Group. Nutrient composition of the diet and the development of overactive bladder: A longitudinal study in women. Neurourol Urodyn 2004;23:204-10.
Upreti V, Maitri V, Dhull P, Handa A, Prakash MS, Behl A, et al.
Effect of oral Vitamin D supplementation on glycemic control in patients with type 2 diabetes mellitus with coexisting hypovitaminosis D: A parellel group placebo controlled randomized controlled pilot study. Diabetes Metab Syndr 2018;12:509-12.
Salekzamani S, Bavil AS, Mehralizadeh H, Jafarabadi MA, Ghezel A, Gargari BP, et al.
The effects of Vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: A randomized double-blind placebo-controlled clinical trial. Endocrine 2017;57:51-9.
Bischoff-Ferrari HA, Borchers M, Gudat F, Dürmüller U, Stähelin HB, Dick W, et al.
Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 2004;19:265-9.
Martínez P, Moreno I, De Miguel F, Vila V, Esbrit P, Martínez ME, et al.
Changes in osteocalcin response to 1,25-dihydroxyvitamin D(3) stimulation and basal Vitamin D receptor expression in human osteoblastic cells according to donor age and skeletal origin. Bone 2001;29:35-41.
Parker-Autry CY, Burgio KL, Richter HE. Vitamin D status: A review with implications for the pelvic floor. Int Urogynecol J 2012;23:1517-26.
Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. J Pharmacol Pharmacother 2012;3:118-26.
] [Full text]
Zhu K, Austin N, Devine A, Bruce D, Prince RL. A randomized controlled trial of the effects of Vitamin D on muscle strength and mobility in older women with Vitamin D insufficiency. J Am Geriatr Soc 2010;58:2063-8.
Janssen HC, Samson MM, Verhaar HJ. Muscle strength and mobility in Vitamin D-insufficient female geriatric patients: A randomized controlled trial on Vitamin D and calcium supplementation. Aging Clin Exp Res 2010;22:78-84.
[Figure 1], [Figure 2], [Figure 3]
|This article has been cited by|
||Serum vitamin D levels in females with urinary incontinence: a meta-analysis of observational trials
| ||Chih-Chen Hsu, Yu-Chen Huang, Syuan-Hao Syu, Hung-Jen Shih, Yung-Wei Lin, Chi-Hao Hsiao, Ke-Hsun Lin, Liang-Ming Lee, Yu-Ching Wen |
| ||International Urogynecology Journal. 2021; |
|[Pubmed] | [DOI]|
||Effect of Vitamin D on Elastin and Collagen Expression: In Vitro Study of Pelvic Organ Prolapse Prevention
| ||. Rahajeng, Tatit Nurseta, Bambang Rahardjo, Yahya Irwanto, Daniel Alexander Suseno |
| ||European Journal of Medical and Health Sciences. 2021; 3(1): 37 |
|[Pubmed] | [DOI]|