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†These authors contributed equally.
Background: The goal of this work was to compare the serum vitamin D
level in women with uterine leiomyoma to that of controls, and to examine its
association with the etiopathogenesis of this disease. Methods: This
case-control study included 110 premenopausal women referred to a university
hospital from January 2020 to December 2020. The study group consisted of 55
cases who underwent surgery for uterine fibroids, while the control group
was comprised of 55 subjects without uterine fibroids. The
number and volume of existing fibroids in each subject was assessed by
transvaginal ultrasonography. Serum vitamin D status was determined by
radioimmunoassay for 25-hydroxyvitamin D. Results: Average serum
25-hydroxyvitamin D levels in patients with uterine fibroids (20.52
Uterine leiomyoma develops primarily from uterine smooth muscle cells and is the most frequent benign tumor in the female reproductive system. Although most women with uterine leiomyomas have no symptoms, some present with a range of symptoms that may include abnormal uterine bleeding, changes in menstruation, anemia, infertility, obstetric complications, and gastric disorders such as bloating and constipation [1, 2]. Estimates of the prevalence of uterine leiomyomas range from as low as 5% to as high as 69% [3]. Their prevalence is around 70% by the age of 50 years, and up to 80% in African Americans [4, 5]. Symptomatic uterine leiomyomas generate enormous medical and economic burdens and are the major reason for hysterectomy in the USA [6]. Moreover, the financial burden of uterine leiomyoma in the USA is estimated to be 34 billion dollars annually. This includes direct costs associated with medications and surgery, and indirect costs due to absence from work, related gynecological visits, and diagnostic tests [7]. Risk factors for uterine fibroids are thought to be estrogen, progestogen and ethnicity. However, the full etiology of leiomyoma is not yet known [3, 8].
Vitamin D group members are fat-soluble steroid compounds consisting of two main groups of highly lipophilic substances: Calcitriol, also referred to as vitamin D3, and Ergocalciferol, which is also known as vitamin D2. Vitamin D undergoes metabolization in the liver and kidney where it is eventually converted to biologically active 1,25-dihydroxyvitamin D3 (1,25 (OH) 2D3). This binds to vitamin D receptor (VDR), which then activates vitamin D response elements in the promoter and regulatory regions of its target genes. The major physiological roles of vitamin D are regulation of calcium and phosphorus homeostasis in bone, intestine, parathyroid and kidney tissues [9]. Several recent studies reported that low serum levels of vitamin D correlated negatively with the presence of leiomyoma in various ethnic groups, indicating that vitamin D deficiency could be a risk factor for uterine leiomyomas [10, 11]. Another study found that fibroid tumor size was significantly reduced by 1,25-dihydroxyvitamin D3, suggesting that paricalcitol could be effective and safe for treating uterine fibroids [12]. Most of the studies published to date on vitamin D and uterine leiomyomas have been from western countries, and there are still no firm conclusions regarding the correlation between serum vitamin D levels and this tumor type.
We previously reported that VDR expression was significantly lower in uterine leiomyoma tissue compared to healthy uterine smooth muscle tissue [13]. Based on this observation, we speculated that reduced VDR expression may contribute to the pathogenesis of uterine leiomyoma. However, the serum level of vitamin D in Asian women with this disease is currently unknown. Therefore, in the current work we compared serum vitamin D levels between women with and without uterine fibroids in a Chinese population. We also explored whether a low vitamin D concentration is a risk factor for the etiopathogenesis of uterine leiomyoma.
Women participating in this case-control study were referred to our department from January 2020 to December 2020. The ethics committee from the first affiliated hospital, Nanchang University, granted approval (CDYFYYLK2021-9-022). Written informed consent was obtained from eligible participants before entering the study.
Female participants were of reproductive age, had symptomatic uterine
leiomyomas, and were scheduled to undergo laparoscopic hysterectomy or myomectomy
surgery. All underwent a transvaginal ultrasound scan. The study group was
defined as patients with more than one fibroid lesion of
The number and size of uterine leiomyomas was evaluated using transvaginal
ultrasound. Lesion volume was calculated using the formula (a
In a preliminary study, the average serum 25-hydroxyvitamin D
level was 20.23
Statistical analysis was performed using SPSS 22.0 software (IBM Corp., Armonk,
NY, USA). Differences in baseline characteristics and in the mean serum vitamin D
level between women with uterine leiomyomas and those without (controls) were
evaluated with the independent sample t-test or Fisher’s test,
respectively. The difference in 25-hydroxyvitamin D deficiency between the two
groups was analyzed using the Cochran-Mantel-Haenszel test. Correlations between
vitamin D level and total fibroid volume, fibroid number and fibroid location
were evaluated using the Pearson correlation test and analysis of variance.
Predictors of uterine fibroids were determined using a logistic regression model.
p
In total, 55 women with uterine leiomyomas and 55 without leiomyomas
participated in the study. All subjects were from the Han race. The mean patient
age in the leiomyoma group was 45.42
Parameter | Leiomyoma group (n = 55) | Control group (n = 55) | p value | |
Age (yrs) | 45.42 |
43.84 |
0.18 | |
BMI | 23.24 |
23.56 |
0.45 | |
Medical history | 1 | |||
Diabetes | 0 (0.00) | 1 (1.82) | ||
Hypertension | 4 (7.27) | 4 (7.27) | ||
None | 51 (92.73) | 50 (90.91) | ||
Data are shown as mean |
The serum 25-hydroxyvitamin D level of women with leiomyomas
was 20.52
Parameter | Leiomyoma (n = 55) | Controls (n = 55) | p value | |
Vitamin D mean |
20.52 |
24.18 |
0.004 | |
Vitamin D status | 0.001 | |||
Deficient | 28 (50.91) | 13 (23.64) | ||
Insufficient | 25 (45.45) | 34 (61.82) | ||
Sufficient | 2 (3.64) | 8 (14.55) | ||
Data are presented as the mean |
To further examine whether vitamin D correlates with uterine
leiomyoma, the factors of patient age, BMI, medical history and serum vitamin D
level were entered into a multiple logistic regression model. Vitamin D was the
only factor found to be significantly associated with uterine leiomyomas (Table 3). The model also showed that an increase of one unit in the vitamin D
concentration reduced the risk of uterine fibroids by 10% (OR (odds ratio) =
0.90, 95% CI (confidence interval) = 0.84–0.98). The total volume of leiomyomas
in women from the leiomyoma group ranged from 6.92 cm
Parameter | Estimate | Adjusted OR | 95% CI | p value |
---|---|---|---|---|
Age | 0.06 | 1.06 | (0.98, 1.15) | 0.13 |
BMI | –0.10 | 0.90 | (0.73, 1.11) | 0.33 |
Medical history (Yes vs. No) | –0.25 | 0.78 | (0.15, 4.16) | 0.77 |
Vitamin D | –0.10 | 0.90 | (0.84, 0.98) | 0.01 |
OR, Odds ratio; CI, Confidence interval. |
Vitamin D can inhibit cell proliferation and angiogenesis, as well as inducing
cell differentiation and apoptosis [18]. As reviewed recently [19], current data
suggests that vitamin D supplementation may reduce cancer incidence. Low serum
vitamin D levels have been reported in several gynecologic and obstetric
abnormalities, such as infertility, polycystic ovary syndrome and premature
delivery [20]. Low vitamin D levels may also be involved with the etiology of
leiomyoma [21, 22], since reports show that deficiency correlates with the
development of uterine leiomyoma [11, 23, 24, 25], whereas sufficiency correlate with
less risk of developing fibroids [26]. A 2013 Italian case-control study [11]
found that vitamin D levels were significantly lower in 128 cases with leiomyoma
compared to 256 controls (p = 0.010). Moreover, the percentage of cases
with a deficiency (
To date, there are no firm conclusions regarding possible correlations between
serum vitamin D and the volume and location of uterine leiomyomas. Among women
with three or more leiomyomas in the report by Paffoni et al. [11], 7
(37%) were 25-hydroxyvitamin D3 deficient and 21 (19%) were not (p =
0.08). Moreover, these workers found no associations between 25-hydroxyvitamin D3
deficiency and the dimension, location and number of leiomyomas. Several other
studies also reported no correlations between serum vitamin D concentrations and
location, size, volume and number of uterine leiomyomas [24, 25, 30]. One study
found a trend for lower serum vitamin D levels in patients with
An early study on vitamin D treatment of uterine fibroids reported that
Calcitriol showed dose-dependent inhibition of leiomyoma and myometrial cells
[31]. This work stimulated further research into the possible inhibitory effect
of vitamin D on leiomyomas [9]. Vitamin D can inhibit the proliferation of human
uterine leiomyoma cells by decreasing the expression of cell proliferation
nuclear antigen, Bcl-w, catechol-O-methyltransferase and cyclin-dependent kinase
1 [32]. It can also do this by inhibiting the Wnt/
There has been very little research on vitamin D and its possible association with uterine leiomyoma in the Chinese population. This study found that Chinese patients with uterine fibroids had significantly decreased serum 25-hydroxyvitamin D levels compared to those without. However, there were several limitations to this case-control study. First, it was an observational rather than prospective and randomized controlled study. Second, the study had a relatively sample size. Finally, the study was not completely representative of women with uterine leiomyomas because it was hospital-based. More large, prospective and population-based cohort studies are warranted to confirm the association between serum vitamin D levels and uterine leiomyomas.
In conclusion, the level of serum vitamin D was found to be lower in Chinese patients with uterine leiomyomas compared to those without, indicating that its deficiency may be a risk factor for this disease.
All data generated or analyzed during this study are included in this published article.
Conception and design—FL; Administrative support—FL, XC; Provision of study materials or patients—ZS, XT, JY; Collection and assembly of data—XC, FY, ZS, XT; Data analysis and interpretation—FY, FL; Manuscript writing—XC, FY, ZS, XT, JY, FL; Final approval of manuscript—XC, FY, ZS, XT, JY, FL.
The study was approved by institutional review board of the first affiliated hospital of Nanchang University (CDYFYYLK2021-9-022). Written informed consent was signed by eligible subjects before taking part in the study.
Not applicable.
This work was supported by the Science and Technology Research Project of Education Department of Jiangxi Province (Grant No. GJJ190040) and Science and Technology Project of Jiangxi Provincial Health Commission (Grant No. 20201016).
The authors declare no conflict of interest.
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