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维生素 D 与子宫肌瘤生长、发病和消退:一项前瞻性超声研究。

Vitamin D and uterine fibroid growth, incidence, and loss: a prospective ultrasound study.

机构信息

Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina.

Public Health and Epidemiology Practice at Westat, Durham, North Carolina.

出版信息

Fertil Steril. 2022 Dec;118(6):1127-1136. doi: 10.1016/j.fertnstert.2022.08.851. Epub 2022 Sep 21.

Abstract

OBJECTIVE

Fibroid treatments that have few side-effects and can preserve fertility are a clinical priority. We studied the association between serum vitamin D and uterine fibroid growth, incidence, and loss.

DESIGN

A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates.

SETTING

Detroit, Michigan area.

PATIENTS

Self-identified African American or Black women aged 23-35 at enrollment without previous clinical diagnosis of fibroids.

INTERVENTION(S): Serum 25(OH)D measured using immunoassay or liquid chromatography-tandem mass spectrometry.

MAIN OUTCOME MEASURE(S): The primary outcomes were fibroid growth, as measured by change in log volume per 18 months, and fibroid incidence (first detection of fibroid in previously fibroid-free uterus). Adjusted growth estimates from linear mixed models were converted to estimated difference in volume for high vs. low 25(OH)D. Incidence differences were estimated as hazard ratios from age-specific Cox regression. A secondary outcome fibroid loss (reduction in fibroid number between visits), was modeled using Poisson regression. Covariates (reproductive and hormonal variables, demographics, body mass index, current smoking) and 25(OH)D were modeled as time-varying factors.

RESULT(S): At enrollment among 1,610 participants with ≥1 follow-up ultrasound, mean age was 29.2 years, 73% had deficient vitamin D (<20ng/mL), and only 7% had sufficient vitamin D (≥30ng/mL). Serum 25(OH)D ≥20ng/mL compared with <20ng/mL was associated with an estimated 9.7% reduction in fibroid growth (95% confidence interval [CI]: -17.3%, -1.3%), similar to the minimally adjusted estimate -8.4% (95% CI: -16.4, 0.3). Serum 25(OH)D ≥30ng/mL compared with <30ng/mL was associated with an imprecise 22% reduction in incidence (adjusted hazard ratio=0.78; 95% CI: 0.47, 1.30), similar to the unadjusted estimate of 0.84 (95% CI: 0.51, 1.39). The >30ng/mL group also had a 32% increase in fibroid loss (adjusted risk ratio=1.32; 95% CI: 0.95, 1.83).

CONCLUSION(S): Our data support the hypothesis that high concentrations of vitamin D decrease fibroid development but are limited by the few participants with serum 25(OH)D ≥30ng/mL. Interventional trials that raise and maintain 25(OH)D concentrations >30ng/mL and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols.

摘要

目的

寻找副作用小且能保留生育能力的纤维瘤治疗方法是临床重点。我们研究了血清维生素 D 与子宫肌瘤生长、发病和消退之间的关系。

设计

一项前瞻性社区队列研究(2010-2012 年入组),5 年内进行 4 次研究访问,以进行标准化超声检查、测量 25-羟维生素 D(25(OH)D)并更新协变量。

地点

密歇根州底特律地区。

患者

自我认定的非洲裔美国或黑人女性,入组时年龄在 23-35 岁,无先前的子宫肌瘤临床诊断。

干预措施

使用免疫测定或液相色谱-串联质谱法测量血清 25(OH)D。

主要观察指标

主要结局是子宫肌瘤生长,以每 18 个月的对数体积变化衡量;子宫肌瘤发病(在先前无子宫肌瘤的子宫中首次发现子宫肌瘤)。线性混合模型中的调整生长估计值转换为高 25(OH)D 与低 25(OH)D 之间体积的估计差异。发病率差异通过年龄特异性 Cox 回归估计为风险比。次要结局为子宫肌瘤消退(两次就诊之间的子宫肌瘤数量减少),采用泊松回归模型进行建模。协变量(生殖和激素变量、人口统计学、体重指数、当前吸烟状况)和 25(OH)D 作为时变因素进行建模。

结果

在入组的 1610 名至少有一次随访超声检查的参与者中,平均年龄为 29.2 岁,73%的人维生素 D 缺乏(<20ng/mL),只有 7%的人维生素 D 充足(≥30ng/mL)。血清 25(OH)D≥20ng/mL 与<20ng/mL 相比,子宫肌瘤生长估计减少 9.7%(95%置信区间:-17.3%,-1.3%),与最小调整估计值-8.4%(95%置信区间:-16.4%,0.3%)相似。血清 25(OH)D≥30ng/mL 与<30ng/mL 相比,发病率估计降低 22%(调整后的危险比=0.78;95%置信区间:0.47,1.30),与未调整的估计值 0.84(95%置信区间:0.51,1.39)相似。>30ng/mL 组的子宫肌瘤消退率也增加了 32%(调整风险比=1.32;95%置信区间:0.95,1.83)。

结论

我们的数据支持高浓度维生素 D 可减少子宫肌瘤发生的假设,但由于血清 25(OH)D≥30ng/mL 的参与者较少,数据受到限制。需要进行提高和维持 25(OH)D 浓度>30ng/mL 的干预试验,并前瞻性监测子宫肌瘤的发展,以进一步评估补充维生素 D 的疗效并确定最佳治疗方案。

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