Possible Impacts of Vitamin-D Supplements on Uterine Fibroid

___________________________________________________ Background: Uterine fibroids, which are non-cancerous tumors found in the pelvic region, are prevalent among women of reproductive age. The incidence of uterine fibroids varies between 5.4% and 77%. These tumors develop within the muscular walls of the uterus in women who have not yet reached menopause. Symptomless or causing abnormal bleeding, pelvic pressure symptoms, infertility


Introduction
Depending on the patient's age, the purpose for treatment, the patient's concern for fertility preservation, and the patient's preference, a variety of treatments, including medication, surgery, and embolization or ablation of the uterine artery, may be recommended [1].Some women prefer to preserve their uterus and fertility rather than undergo the more common surgical methods of treating symptomatic fibroids (hysterectomy or myomectomy).Therefore, it appears that the potential downside of less risky treatments and intervention needs to be taken into account.Vitamin D has garnered significant attention in recent times due to its potential anti-carcinogenic properties, with particular attention given to colorectal cancer, breast cancer and skin cancers.
for colorectal cancer: vitamin D can be an economical and secure way of reducing the https://ejmr.journals.ekb.eg/incidence and improving prognosis in colorectal cancer, doses of vitamin D3 between 1,000 and 2,000 IU per day could reduce the incidence of colorectal cancer, as In order to ensure that the serum level remains above 33 ng/mL, it was observed that there is a 50% reduced risk of colorectal cancer when the serum 25(OH)D level is equal to or greater than 33 ng/mL, as compared to when it is equal to or less than 12 ng/mL [4].

Patients and Methods
This research was a randomized controlled trial (RCT) conducted in a tertiary care setting at a Beni-Suef University-affiliated hospital.
Between the months of January 2022 and June 2022, the research was done and carried on a total of 100 women in childbearing period diagnosed with uterine fibroid who had vitamin-D deficiency.

Sample size:
The  Also, vitamin-D level was measured every month.

Outcome:
Patients with vitamin D insufficiency saw a reduction in uterine fibroid size following 6 months of vitamin D administration.

Statistical Analysis:
The data was collected and entered to an Excel sheet.1).Most of the studied patients were less than or equal to 35 years old.The majority were overweight and parity 2 or more (Table 2).The group who receives Vit D supplementation showed sufficient level of Vit D while all studied patients in the control group showed Vit D deficiency (Table 3).Both the mean and the mean difference of vitamin D levels at 6 months were significantly different between the vitamin D group and the control group (Table 4).There is no significant difference in the size of the fibroid between Vit.D group and control group over the first three months while at the fourth visit, the Vit.D group had much smaller fibroids, fifth month and sixth months (Table 5).In every month, the Vit.D Group had a smaller mean difference than the other groups.
All females show improvement in the level of Vit D after 6 months regardless of their age, or https://ejmr.journals.ekb.eg/parity (Table 6).The size of the tumor decreased significantly over the six months in the group of Vit D supplementation there is almost no change in the size of fibroid over the 6 months and In the control group, fibroid size did not significantly decrease during the course of the study's 6-month follow-up (Table 7).This table shows that there was no significant improvement in the size of the fibroid over the 6 months.

The limitations of the study:
It's important to note that the study has some substantial drawbacks, such as a limited sample size and the fact that the trial was conducted in only one institution rather than being a multicentric study.Another drawback is that it is not a placebo-controlled, doubleblind study.Despite the study's shortcomings, a well-designed trial of vitamin D preparations in uterine fibroids was made possible by the findings.We hypothesized that the therapy we tested would be more effective, safer, and less expensive than current methods of preventing and treating uterine fibroids.

Conclusion and Recommendations: Conclusion:
As evident from the current study, Taking a vitamin D pill is a low-risk method of stabilizing Some research has focused on the connection between poor nutrition and the development of leiomyoma.High fruit consumption may minimize the risk of leiomyoma in black women, while consumption of dairy products, omega-3 fatty acids, soybean milk, food additives, and sweets all raise the risk [2].Vitamin-D (also referred to as "calciferol"): is a fat-soluble vitamin that is naturally present in a few foods, added to others, and available as a dietary supplement.It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin-D synthesis.1,25-dihydroxyvitamin D, often known as calcitriol, is the active form of vitamin D" [3].

For
breast cancer: vitamin-D affects the cell cycle, apoptosis, hormone receptors, angiogenesis, and hypoxia, all of which are related to breast cancer growth, progression and metastasis, Further studies have found that There has been a decrease in the occurrence of breast cancer of forty-five percent from the highest to the lowest quintile of circulating plasma levels of active 25 hydroxy-vitamin D3 in 25 studies [5].For skin cancers: It is recommended that increased exposure to sunlight is overall beneficial and that Elevated amounts of vitamin D may potentially enhance the prognosis of melanomas [6].As a result, the assumption was plausible, this could have a function in the pathophysiology of uterine fibroids.Although calcidiol serum levels were found to be insufficient in fibroidafflicted females, administration of the medicine resulted in smaller tumors.It just took 0.5 g/kg/d to get these outcomes.MMP-2 and MMP-9 appeared to be two of the enzymes affected.and it decreases catechol-o methyltransferase (COMT), MMPs affect many stages of tumor development, facilitating its growth through encouraging tumor growth, invasion, migration, angiogenesis, and suppression of apoptosis, it is possible to sustain tumor growth [7].This research supports the initiation of clinical trials to determine whether vitamin-D may be used as a long-term medicinal therapy for the treatment of fibroids [7].


Celiac disease, chronic renal illness, and liver disease are just a few examples of conditions that interfere with vitamin D metabolism.Methodology 100 Patients with uterine fibroids and vitamin-D deficiency were enrolled in single blinded randomized controlled study (block randomization) in which patients were divided into10 blocks of size 10, each block was randomized such that 5 patients are allocated to group A and 5 to group B. Patients are overweight with BMI more than 25 and less than 30 BMI=weight per kg ÷(height per m)×2 Group A: 50 patients received 50, 000 IU of vitamin-D3(ossofortin 50, 000IU) every week till reaching level of (30 ng/ml), then a maintenance dose of 2000 IU is given daily.Group B: 50 patients receiving regular treatment of uterine fibroid.https://ejmr.journals.ekb.eg/Then the size of fibroid was measured by abdominal ultrasound every month in both groups after treatment.

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fibroids (UFs) are a type of smooth muscle cell tumor that affects women at an alarming rate.The incidence of leiomyomas among reproductive-aged women varies widely, from 5.4% to 77%, depending on the diagnostic procedure used and the population studied in various epidemiological studies [8].Vitamin D is a crucial component of human nutrition.Vitamin D has recently been investigated for its potential role in UF formation [9].Angiogenesis, extracellular matrix synthesis, and immunological response are just few of the biological processes that are affected by vitamin D's functional effects, which also include inhibited cell proliferation and increased apoptosis and enhanced differentiation.It has been proposed that a positive feedback loop between extracellular matrix formation and cell proliferation is involved in the pathophysiology of fibroids, and that vitamin D may help to prevent this loop [10].Consequently, this study was conducted recruited patients with vitamin D insufficiency and set out to assess the impact of vitamin D supplementation on the growth of uterine fibroids.This research was a randomized controlled experiment with one-way blinding conducted at a Beni-Suef University-affiliated tertiary care center.The study was conducted over a period of six months, from January 2022 to https://ejmr.journals.ekb.eg/women in childbearing period diagnosed with uterine fibroid who had vitamin-D deficiency.All told, 122 potential trial participants were screened, and 100 (50 in each group) were ultimately included.Fourteen patients met eligibility but were not included in the trial because they did not meet one of the inclusion criteria, and eight patients declined to participate.The analysis relied on the data provided by 100 women in child bearing period diagnosed with uterine fibroid who had vitamin-D deficiency separated into halves: Group (A) which included 50 females who received Vit D supplementation.Group (B), the control group which included 50 females who received symptomatic treatment.The current investigation found no appreciable variations in either set of demographics.(age, BMI, parity, age at menarche, sun exposure) (p values = 0.352, 0.274, 0.375, 0.120) respectively and clinical characteristics (Vit D level at the beginning of the study and size of the fibroid) (p values = 0.417, 0.878) respectively.After Vitamin D supplementation for 6 months, the current study results revealed that the group who receive Vit D supplementation showed a sufficient level of Vit D while all studied patients in the control group showed Vit D deficiency with a large disparity between mean and average vitamin D levels at 6 months between the Vit.D group and control group (p value=0.001).As regards the fibroid size after Vitamin D supplementation for 6 monthsIn the present study, the researchers found that the Vit.D group and the control group did not differ significantly in fibroid size throughout the first three months while the size of the fibroid was significantly lower in the Vit.D group at the fourth, fifth month and sixth months.Consequently, the size of the tumor decreased significantly over the six months in the group of Vit D supplementation (p value>0.001) with no significant improvement in the size of the fibroid over the 6 months in the control group.Recent studies have shown that vitamin D can inhibit the proliferation of uterine fibroid cells, suggesting it may have anticancer effects and reducing the size of fibroid lesions.[2, 12, 13, 14].Recent research has found that Vitamin D deficiency increases a woman's risk of developing uterine fibroids.Vitamin D administration reduces uterine fibroid cell proliferation, according to research by Al-Hendy and Badr [15].Women who had enough vitamin D were found to have a lower risk of UFs by Baird et al. [16].Consistent with prior research, our results are.The efficacy of vitamin D supplementation in women with hypovitaminosis D and uterine fibroids was studied by Ciavattini et al. [17] in prospective research that included 108 women with uterine fibroids and concurrent hypovitaminosis D indicated the presence of a negative association between the initial concentration of 25-hydroxy-cholecalciferol https://ejmr.journals.ekb.eg/(25-OH-D3) and both the volume of the largest fibroid (r = -0.18,P = 0.01) as well as the overall volume of fibroids (r = -0.19,P = 0.01).After 12 months of supplementation, the 25-hydroxyvitamin D3 (25-OH-D3) serum level significantly increased among the women in the "study group," and it was stated that the rate of surgical or medicinal therapy due to "progression to extensive disease" was reduced (13.2%vs 30.9%,P=0.05).Consequently, it appears that vitamin D supplementation slows the spread of disease, reducing the need for invasive medical procedures [In agreement with our results, Vahdat et al. (2011) conducted a randomized, double-blind, placebo-controlled research with a cohort of 109 women who had previously undergone hysteroscopic myomectomy and were found to have vitamin D insufficiency whose participants were given either a daily 1000 IU pill of vitamin D (n = 55) or a placebo (n = 54) for a period of 12 months in order to examine the impact of vitamin D supplementation on the recurrence of uterine fibroids.The average age of the participants was 37.9 ± 6.5 years.In terms of demographics and health prior to the intervention, there were no notable differences between the two groups.Supplementation with vitamin D for a year cut UF recurrence rates in half.Recurrent UF was smaller in the vitamin D intervention group than in the control group (7.7 mm), a statistically significant difference (p < 0.001) Researchers Halder et al. [18] discovered in 2012 that inhibiting cell growth and proliferation-related genes, antiapoptotic genes, and estrogen and receptors with 1,25-OH-D3 dramatically reduced fibroid tumor size in Eker rats.These findings have important clinical implications since vitamin D may offer a safe, non-invasive treatment option for uterine fibroids.Paffoni et al. [19] undertook a case-control study with 128 breast cancer patients and healthy controls.Similar findings were found in another crosssectional investigation by Rosen et al. 52 women with uterine fibroids confirmed by MRI or ultrasound were found to have vitamin D levels below 30 ng/ml, as described in.Our findings were verified by a research showing that 85 percent of women with diagnosed uterine fibroids also had vitamin D deficiency.A second prospective cross-sectional study of Turkish premenopausal women found that wearing traditional dress, staying at home, and having a low level of education were all factors in an increased risk of vitamin D insufficiency.In addition, the study found that vit D deficiency was more common in women with leiomyoma than In the cases not having the tumor [21].In addition, According to the results of their examination of the National Health and Nutrition Examination Survey data, Mitro and Zota [22] discovered no link between vitamin D and the development of uterine fibroids, https://ejmr.journals.ekb.eg/ which included 3,590 women with uterine leiomyomata.Inadequate serum vitamin D was linked to considerably greater risks of uterine fibroids in white women, but not in black patients, according to a subgroup analysis of the same data.Geographical location, latitude, season, weather, clothing, and the usage of sunscreens all play a role in the amount of vitamin D produced in the body in response to sun exposure (in vivo).Fibroids are more common in black housewives because of their dark skin and their tendency to spend time indoors [12, 23].The strength points of this study: The randomized clinical trial design, stringent exclusion and inclusion criteria, and the absence of patients lost to follow-up during the research period are all strengths of this investigation.This is the first study to examine the impact of vitamin-D supplementation on the size of Uterine fibroid in patients with vitamin-D insufficiency, suggesting that doing so may slow the disease's growth and delay the need for more invasive forms of treatment.
fibroids and preventing them from growing into more serious leiomyomas, both of which can cause significant discomfort.Vitamin D appears to inhibit the development of fibroids.However, properly designed randomized controlled trials (RCTs) are required to determine whether or whether vitamin D supplementation is effective in preventing or stabilizing the growth of uterine fibroids, as well as the appropriate dosage and duration of such a therapy.Recommendations: Serum vitamin D level should be done as routine investigation in diagnosed women with fibroids in the uterus and corrected in case of deficiency which It might prevent the disease from becoming so advanced that standard medical or surgical treatment is required.Future prospective studies with larger sample sizes are recommended to verify if vitamin D administration is beneficial in preventing or reducing the progression of uterine fibroids.

Table ( 1
): Characteristics at baseline of the female participants investigated This table showed that Six months into the study, statistically speaking, a difference could be seen between the vitamin D group and the control group in terms of both the mean and the mean Comparison of fibroid growth in the control and vitamin D groups 6 months after intervention.This table showed that over the course of the first three months, there was no statistically significant difference in fibroid size between the Vit.D group and the control group while Four, five, and six month fibroid size was considerably less in the vitamin D group.Also, The Vitamin D Group had a consistently reduced mean difference throughout all months.Mean size of the fibroid over the 6 months in the control group (Group 50) This table shows that both groups were matched at the start of the analysis.In terms of demographics, neither group differed significantly from the other (age, , parity, BMI, age at menarche, sun exposure) and clinical characteristics (Vit D level at the beginning of the study and size of the fibroid).Table (2): Vitamin D levels in the control and vitamin D groups six months after intervention.difference of vitamin D levels.https://ejmr.journals.ekb.eg/Table(4): Table (5): Mean size of the fibroid over the 6 months in the VIT D group (Group 50) group.https://ejmr.journals.ekb.eg/Table(6):a.The correlation and t cannot be computed because the standard error of the difference is 0.