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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 28  |  Issue : 3  |  Page : 181-186

Low plasma vitamin D as a predictor of uterine fibroids in a nigerian population


1 Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University/Usmanu Danfodiyo University Teaching Hospital, Sokoto, Sokoto State, Nigeria
2 Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Sokoto State, Nigeria
3 Department of Obstetrics and Gynaecology, Federal Medical Centre, Birnin Kebbi, Kebbi State, Nigeria
4 Department of Chemical Pathology, Usmanu Danfodiyo University/Usmanu Danfodiyo University Teaching Hospital, Sokoto, Sokoto State, Nigeria
5 Department of Chemical Pathology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Sokoto State, Nigeria

Date of Submission15-Mar-2021
Date of Decision13-Jul-2021
Date of Acceptance22-Jul-2021
Date of Web Publication22-Oct-2021

Correspondence Address:
Prof. Karima Abubakar Tunau
Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University/Usmanu Danfodiyo University Teaching Hospital, Sokoto, Sokoto State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/npmj.npmj_495_21

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  Abstract 


Background: Uterine fibroid is the most common benign tumour of the uterus and the exact cause is unknown. Vitamin D has been found to inhibit cell proliferation and enhance apoptosis in vitro. Aim: The aim of this study is to compare the plasma level of Vitamin D among women with uterine fibroids and those without uterine fibroids. Materials and Methods: This was an analytical cross-sectional study conducted among women with uterine fibroids and those without uterine fibroids. An interviewer-administered questionnaire was used to obtain relevant information. Five millilitres of venous blood was obtained for plasma Vitamin D assay. Data analysis was performed using the SPSS version 22. Level of significance was set at P < 0.05. Results: There were 100 participants recruited for the study. The mean age of the participants with uterine fibroid was 35.06 ± 6.6 years and that of controls was 33.28 ± 7 years. The mean plasma level of Vitamin D for all the participants was 12.47 ± 7.53 ng/ml. The mean plasma level of Vitamin D in those with uterine fibroids was significantly lower than in those without uterine fibroid (10.16 ± 7.78 vs. 14.35 ± 6.8; t = 2.517, P = 0.014). It also shows that 1 unit increase in Vitamin D level will reduce the risk of developing uterine fibroids by 8% (odds ratio = 0.92, 95% confidence interval = 0.86–0.99). Conclusion: The predictors of uterine fibroids were fewer hours spent outdoors, middle social class and low Vitamin D levels.

Keywords: Predictor, uterine fibroids, Vitamin D


How to cite this article:
Tunau KA, Garba JA, Panti AA, Shehu CE, Adamu AN, AbdulRahman MB, Ahmad MK. Low plasma vitamin D as a predictor of uterine fibroids in a nigerian population. Niger Postgrad Med J 2021;28:181-6

How to cite this URL:
Tunau KA, Garba JA, Panti AA, Shehu CE, Adamu AN, AbdulRahman MB, Ahmad MK. Low plasma vitamin D as a predictor of uterine fibroids in a nigerian population. Niger Postgrad Med J [serial online] 2021 [cited 2021 Nov 28];28:181-6. Available from: https://www.npmj.org/text.asp?2021/28/3/181/328769




  Introduction Top


Uterine fibroid is a benign tumour of the uterus that affects about 70%–80% of women.[1] Fibroids are more common in black women and present at an earlier age in them.[1] Some of the symptoms of uterine fibroids include dysmenorrhoea, menorrhagia and pressure symptoms. In addition, fibroids also impact on the quality of life of women.[2] Fibroid leads to morbidity in those who are affected and it has been reported that about one-third of employed participants reported missing work due to symptoms of fibroid and 24% felt that the symptoms hindered them from achieving their career potential.[2] The majority (79%) of women in a previous study have expressed desire for treatments of uterine fibroids that do not involve invasive surgery.[2] The exact cause of uterine fibroids is unknown and the actual reason for higher risk in African–American women is unknown.[3]

The active form of Vitamin D (1,25-dihydroxyvitamin D3) has a central role in bone mineralisation and the maintenance of extracellular calcium levels.[4],[5] In addition, it also has modulatory effect on cell growth and differentiation in many cell types.[5] Bioactive Vitamin D is antiproliferative and inhibits the cell cycle at G1 and S phase.[4],[6] It blocks the mitogenic signalling of oestrogen, epidermal growth factor, insulin-like growth factor-1 and decrease the effect of transforming growth factor-beta which is involved in fibrosis.[5],[7] It also stimulates Vitamin D receptor-mediated apoptosis.[5] Vitamin D receptors have been demonstrated in myometrium, endometrium and fibroid tissue.[6] It is overexpressed in the centre of the fibroid and has been proposed to have a role in the aetiology and growth of fibroid.[6]

It has been found that both fibroid and myometrial tissues are sensitive organs for Vitamin D and that their proliferation was effectively blocked by physiologic Vitamin D concentrations in vitro.[4] Previous studies on animal and human studies have found that Vitamin D inhibits fibroid cell proliferation in vitro and decreases the size of uterine fibroid in vivo animal models.[7],[8],[9] These findings have supported the possibility of the use of Vitamin D in the non-surgical management of uterine fibroid and suggested further research to fully understand the role of Vitamin D as an option of treatment of fibroid.[7],[8],[9]

Fibroid is three times more likely to occur in black women and there is still no possible explanation to this burden of disease.[10] There is paucity of published studies conducted to find the answer to higher burden of uterine fibroids among black women. Several studies in Western countries have found low Vitamin D among women with uterine fibroids and there is need to assess the Vitamin D status among women in tropical countries where there is ample exposure to sunlight.[11],[12],[13]

Studying other factors would help in identifying some modifiable contributors in the growth of uterine fibroids. Preventing uterine fibroid or slowing the growth of uterine fibroids would be more cost-effective than offering surgical treatment for uterine fibroid. Vitamin D deficiency can be tackled easily through supplementation if found to be associated with increased risk of uterine fibroids. Hence, the aim of this study was to compare the plasma level of Vitamin D among women with uterine fibroids and those without uterine fibroids; and determine if low Vitamin D is a predictor of uterine fibroids.


  Materials and Methods Top


Ethics

This study was conducted in line with the Helsinki Declaration of 1975 and in accordance with the ethical standards of the University Teaching Hospital Health Research and Ethics Committee, Sokoto, Sokoto State. Ethical approval was obtained from Health Research and Ethics Committee on 9 October 2019 with reference number HREC/2019/No. 870. Written informed consent was also obtained from the participants before data collection. The data were collected from 9 November 2019 to 31 January 2020.

Study design

This was an analytical cross-sectional study conducted among women presenting to the gynaecological clinic. The cases were women with symptomatic or asymptomatic uterine fibroids. The controls were women without uterine fibroids. They were matched for age and parity.

Both verbal and written consent was obtained from the participants before data collection. Participants within the reproductive age group (15–49 years) were recruited consecutively. Those that had an ultrasound diagnosis of uterine fibroids of any size were recruited as cases and matched controls with ultrasound that did not reveal uterine fibroids were recruited. Those excluded were pregnant women, those that are on any multivitamin or calcium supplementation and those with chronic liver disease.

Sample size was calculated using the formula for two group comparison.[14]



n =2 (Z1−α/2 + Z1−β) 2

1− μ2) 2

Where n = sample size,

ϭ = Estimated standard deviation = 8.13

Z1−α/2 = Z statistic for level of confidence of 95% =1.96

Z1−β = Z statistic for 80% power = 0.842

μ1 = Estimated mean (large) =29.53[12]

μ2 = Estimated mean (small) =24.45[12]







n = 40.2 ~ 41

Minimum sample size = 41

Adding 10% attrition = 41 + 5 = 46

The sample size was rounded up to 50 to improve the power of the study. Hence, 50 participants with uterine fibroids and 50 controls without uterine fibroids were recruited.

The cases that had an ultrasound scan that revealed uterine fibroid of any size were recruited. Matched controls had a transvaginal scan to confirm the absence of uterine fibroid before recruitment. Those that were incidentally found to have uterine fibroid during the transvaginal scan were recruited as cases.

An interviewer-administered questionnaire was filled to obtain relevant information. Height and weight were measured and 5 ml of venous blood was taken for analysis of Vitamin D. It was transported to the laboratory immediately for separation and analysis. Plasma Vitamin D was assayed by quantitative measurement of 25-OH Vitamin D using a kit of enzyme-linked immunoassay - ELISA (Accubind ELISA) microwells, product code: 7725-300. The cut off value from the kit used for the analysis was used to categorise the Vitamin D status of the participants. Value <10 ng/ml was taken as deficient, 10–29 ng/mL as insufficient and values ≥30 ng/ml were categorised as sufficient.[15]

Data analysis was performed with the Statistical Package for the Social Sciences version 22 (IBM SPSS statistics for windows version 22.0. Armonk, NY, USA: IBM Corp.). Independent sample t-test was used to compare the mean plasma Vitamin D between those with uterine fibroid and those without uterine fibroid. The Chi-square test was used to determine the association between categorical variables.

Variables found to have significant association were entered into the logistic regression model to determine the predictors of uterine fibroid. Simple logistic regression was used to determine the crude odd ratio and variables with P < 0.25 were entered into the multiple logistic regression to determine the adjusted odds ratio. Both backward and forward methods were done and the results were compared. Level of significance was set at P < 0.05.


  Results Top


There were 100 participants recruited for the study; 50 with uterine fibroid and 50 controls without uterine fibroids. Three blood samples (1 case and 2 controls) were lost and were not included in the statistical analysis for Vitamin D. This is shown in the Flow Chart [Figure 1] below:
Figure 1: Flow chart showing distribution of participants

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The mean age of the participants with uterine fibroid was 35.06 ± 6.6 years and that of controls was 33.28 ± 7 years. The youngest was 19 years while the eldest was 47 years. Most of the participants in both groups were between the age group of 30–39 years. There was no significant difference in most of the sociodemographic characteristics of the participants. This is shown in [Table 1].
Table 1: Socio-demographic characteristics of the participants

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The mean plasma level of Vitamin D for all the study participants was 12.47 ± 7.53 ng/ml. Thirty-three per cent (33%) had Vitamin D deficiency and only 1% had sufficient Vitamin D. This is shown in [Figure 2]. The mean plasma level of Vitamin D in those with uterine fibroids was 10.16 ± 7.78 ng/ml while that of controls was 14.35 ± 6.8 ng/ml. There was significant difference in the mean plasma Vitamin D level between cases and controls (t = 2.517, P = 0.014).
Figure 2: Vitamin D status among the participants

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Among those with uterine fibroids, 72% of them spent fewer (0–7) h outdoor compared to 46% among the controls. There was significant association between hours spent outdoor and uterine fibroid. In addition, 44.9% of the participants with uterine fibroid have Vitamin D deficiency compared to 20.8% of the controls and there was significant association between Vitamin D status and uterine fibroid. This is shown in [Table 2].
Table 2: Factors associated with uterine fibroid

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The factors that were found to be associated with uterine fibroid from the bivariate analysis were subjected to logistic regression. The factors that were significant are social class, number of hours outdoor and Vitamin D level. All the three factors were entered into the multiple logistic regression model. [Table 3] shows the final logistic regression model. The odds of developing uterine fibroids was 13.6 times higher in those in the middle class than in low social class (odds ratio [OR] =13.63, 95% confidence interval [CI] =2.6–71.3). The odds of developing uterine fibroids was 2.8 times higher in those who spent 7 h or less outdoor compared to those who spent 8–15 h outdoor (OR = 2.78, 95%CI = 1.32–6.93). It also shows that 1 unit increase in Vitamin D level will reduce the risk of developing uterine fibroids by 8% (OR = 0.92, 95% CI = 0.86–0.99).
Table 3: Multiple logistic regression final model showing adjusted odd ratio of predictors of uterine fibroids

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  Discussion Top


The main finding of this study was the high prevalence of Vitamin D deficiency among the participants. The predictors of uterine fibroids were social class, number of hours outdoor and Vitamin D level.

The mean plasma level of Vitamin D among the whole study participants was within the range of Vitamin D insufficiency and only 1% had sufficient Vitamin D levels. This may reflect the Vitamin D status of the population in the study area. These insufficient levels of Vitamin D have been observed among Fulani women in northern Nigeria[16] and other parts of Africa like Egypt[17] and Congo.[18] Even in studies conducted in the United States of America[11] and India,[19] the mean serum levels of Vitamin D was insufficient (10.4 ng/dl) in the black participants compared to their white counterparts (20.7 ng/dl). It has been suggested that at least 76% of black women of reproductive age may be suffering from Vitamin D deficiency.[16],[19],[20] This indicates that the Vitamin D deficiency is high despite abundant sunlight in the study area. It is thought that Melanin abundant on the black skin absorbs ultraviolet rays which may decrease the synthesis of Vitamin D by up to 99%.[11],[21] In addition, high temperatures experienced during the daytime may actually compromise adequate exposure to sunlight. Some other factors such as gender, level of sun exposure, high burden of infectious diseases, low calcium intake may cause increased utilization and turnover of Vitamin D.[22] High body mass index and high parity may probably have contributed to the Vitamin D deficiency.[23] There is a significant heritable component in Vitamin D levels and genetics have been suggested to have a role in the aetiology of Vitamin D insufficiency.[24]

The mean plasma level of Vitamin D in those with uterine fibroids was 10.16 ± 7.78 ng/ml while that of controls was 14.35 ± 6.8 ng/ml and this difference was statistically significant. This is consistent with findings in Egypt,[17] Italy,[12] Poland[13] and the United States[11] which have all suggested an inverse relationship between low levels of Vitamin D and the development of uterine fibroids. This appeared to be regardless of the method of testing used as some studies used ELISA like in the index study[13] while others used radioimmunoassay[11],[17] and chemiluscence assays.[12] The exact mechanism via which this occurs is still not fully understood, but there is increasing evidence that the lower level of Vitamin D in those with uterine fibroids could be due to the functions of Vitamin D on the cell growth. The active form of Vitamin D controls many genes like genes which are responsible for cell differentiation, angiogenesis, proliferation and apoptosis.[21] In addition, in vitro studies have demonstrated that 1,25 dihydroxy Vitamin D3 inhibits the growth of human fibroids.[7],[25] it is postulated that chronic low Vitamin D levels may promote chronic oestrogen and progesterone signalling in the myometrium which in the presence of other trigger factors may result to initiation and progression of fibroids.[17],[26],[27]

The significant risk factors for uterine fibroids identified in this study were number of hours spent outdoor, social class and Vitamin D status. The number of hours outdoor reflects an indirect assessment of sun exposure and Vitamin D synthesis. Those with a shorter duration of hours spent outdoor were more likely to develop uterine fibroid probably due to less sun exposure and lower Vitamin D. It is thought that a 30 min exposure of sunlight over the arms and face without a sunscreen at 10 am to 2 pm may be considered adequate.[19],[20],[28] It is difficult to explain the role of the middle social class and the development of fibroids, but there may be a relationship as this category of patients may spend fewer hours outdoors compared to their other counterparts. The finding of the middle class as predictor of uterine fibroid could just be because most of the participants were from the middle class and this does not reflect the true picture in the society. Other non-modifiable risk factors such as age and parity were controlled to remove the confounding effect on Vitamin D status. Family history and body mass index were not found to be associated with uterine fibroids in this study. This differs from what has been reported that the risk of fibroids is 2.5 times higher in those whose first-degree family relatives have uterine fibroids.[18],[29]

This study has identified that 1 unit increase in Vitamin D reduces the risk of developing uterine fibroids by 8%. Similar variable reduction in risks of uterine fibroids with higher Vitamin D levels have been shown by other studies.[11],[13],[17],[28] Baird et al.[11] has shown that a 10 ng increase in Vitamin D lowers the odds of developing fibroids by up to 20% while Ciebiera et al.[13] found a 1 unit increase in Vitamin D reduces the risk of fibroids by 4%. These findings suggest a possible role for Vitamin D in the prevention and perhaps treatment of uterine fibroids.[11],[12],[13],[17],[18],[24],[28],[30] If these findings are proven to be true then a cheap, cost-effective and non-invasive means of managing fibroids may have been discovered.

Some of the strengths of this study include the selection of controls after a transvaginal ultrasound scan to confirm that they do not have uterine fibroids. Matching for age was done to remove the effect of age as a possible confounder since Vitamin D level has been shown to decrease with age. In addition, this study did not just determine the association of uterine fibroids with Vitamin D, but logistic regression was used to determine the predictors after controlling for possible confounders.

One of the limitations of the study is that the premorbid Vitamin D status among women with uterine fibroids is not known. Number of hours outdoor was just an estimate and may not actually give us exact hours of sun exposure. Dietary intake of the participants was not assessed. Obtaining family history of asymptomatic uterine fibroids could be difficult and maybe a limitation in this study.


  Conclusion Top


The mean plasma level of Vitamin D in both cases and controls was within the range of Vitamin D insufficiency. However, the Vitamin D level in those with fibroids was significantly lower than in those without fibroids. The risk factors for uterine fibroids in this study were fewer hours spent outdoors, middle social class and low Vitamin D levels.

Recommendations

We recommend a community-based study to identify the baseline Vitamin D status of the population and also randomised control trials to find out the true effect of Vitamin D on fibroids. Perhaps Vitamin D supplementation may help in reducing the risk of developing uterine fibroids and other related health conditions; therefore, an interventional study by giving supplemental Vitamin D for those with fibroids is recommended to affirm the findings from this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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