Vitamin D and uterine fibroid growth, incidence, and loss: a prospective ultrasound study.
Vitamin D and uterine fibroid growth, incidence, and loss: a prospective ultrasound study.
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DOI：
10.1016/j.fertnstert.2022.08.851
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发表时间：
2022-12
影响因子：
6.7
通讯作者：
Baird, Donna D.
中科院分区：
文献类型：
--
作者：
Harmon, Quaker E.;Patchel, Stacy A.;Denslow, Sheri;LaPorte, Frankie;Cooper, Tracy;Wise, Lauren A.;Wegienka, Ganesa;Baird, Donna D.
副作用少且能保持生育能力的子宫肌瘤治疗是临床优先考虑的问题。我们研究了血清维生素D与子宫肌瘤生长、发病率和损失之间的关系。一项前瞻性社区队列研究（2010-2012年入组），在五年内进行四次研究访视，进行标准化超声检查，测量25-羟基维生素D（25（OH）D），并更新协变量。自认为年龄在23-35岁的非裔美国人或黑人女性，在密歇根州底特律地区入组时既往未被临床诊断为肌瘤。使用免疫测定或液相色谱串联质谱法测定血清25（OH）D。主要结局是肌瘤生长（通过每18个月的对数体积变化测量）和肌瘤发生率（在先前无肌瘤的子宫中首次检测到肌瘤）。将线性混合模型的校正生长估计值转换为高与低25（OH）D的体积估计差异。根据年龄特异性考克斯回归，将发病率差异估计为风险比（HR）。使用泊松回归对次要结局，肌瘤丢失（访视之间肌瘤数量减少）进行建模。将协变量（生殖和激素变量、人口统计学、体重指数、当前吸烟）和25（OH）D建模为随时间变化的因素。在1610名参与者中，至少有一次随访超声，平均年龄为29.2岁，73%的人缺乏维生素D（<20 ng/ml），只有7%的人有足够的维生素D（≥ 30 ng/ml）。血清25（OH）D ≥ 20 ng/ml与<20 ng/ml相比，估计肌瘤生长减少9.7%（95%置信区间（CI）：− 17.3%，−1.3%），与最小调整估计值−8.4%（95%CI：−16.4，0.3）相似。血清25（OH）D ≥ 30 ng/ml与<30 ng/ml相比，发生率降低22%（不精确）[校正HR=0.78（95%CI：0.47，1.30）]，与未校正估计值0.84（95%CI：0.51，1.39）相似。> 30 ng/ml组的肌瘤丢失率也增加了32%（校正风险比1.32，95% CI：0.95，1.83）。我们的数据支持较高浓度的维生素D可减少纤维瘤发展的假设，但受血清25（OH）D ≥ 30 ng/ml的少数参与者的限制。需要进行干预性试验，将25（OH）D浓度提高并维持在30 ng/ml以上，然后前瞻性监测子宫肌瘤的发展，以进一步评估补充维生素D的功效并确定最佳治疗方案。
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. A prospective community cohort study (enrollment 2010–2012) with four study visits over five years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates. Self-identified African American or Black women aged 23–35 at enrollment without previous clinical diagnosis of fibroids from the Detroit, Michigan area. Serum 25(OH)D measured using immunoassay or liquid chromatography tandem mass-spectrometry. 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 (HR) 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. At enrollment among 1610 participants with at least one 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 to <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 to <30ng/ml was associated with an imprecise 22% reduction in incidence [adjusted HR=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). Our data support the hypothesis that higher 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 above 30ng/ml and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols.
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