Uterine Leiomyomas

子宫肌瘤

• 批准号: 8149017
• 负责人: DONNA D. BAIRD
• 金额: $ 46.02万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149017
• 关键词: Address; Affect; Age; Alcohols; Benign; Blood specimen; Body fat; Childhood; Cytogenetics; Data; Data Analyses; Data Collection; Development; Dietary Factors; Enrollment; Environmental and Occupational Exposure; Epidemiologic Studies; Estrogens; Exercise; Exposure to; Fasting; Fibroid Tumor; Goals; Growth; Hemorrhage; High Prevalence; Histologic; Hormones; Hysterectomy; Incidence; Insect Repellents; Insulin; Insulin-Like Growth Factor I; Length; Link; Magnetic Resonance Imaging; Medical; Menopause; Menstrual cycle; Methods; Monitor; Morbidity - disease rate; National Institute of Environmental Health Sciences; Necrosis; Onset of illness; Pelvic Pain; Pregnancy; Progesterone; Prospective Studies; Puberty; Questionnaires; Research; Research Design; Risk; Risk Factors; Smoking; Smooth Muscle Tumor; Specimen; Symptoms; Time; Tissues; Transforming Growth Factors; Ultrasonography; United States; Urinary Incontinence; Urine; Uterine Fibroids; diabetic

Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. Uterine leiomyomas are histologically identifiable as benign smooth muscle tumors with varying amounts of associated fibrous tissue. Many women have more than one uterine leiomyoma, but each appears to be clonally distinct. Several specific cytogenetic changes have been identified in tumor tissue, but most show no chromosomal abnormalities. These benign tumors are hormone-dependent. They develop after puberty and regress after menopause. Both estrogen and progesterone are considered important stimulants, or at least permissive factors for tumor growth. To address the research needs in this field we have designed four studies. The first is a large epidemiologic study, the NIEHS Uterine Fibroid Study, designed to 1) estimate the age-specific cumulative incidence of leiomyomas in black and white women, aged 35-49, 2) identify risk factors for the condition, 3) compare growth mediating factors in tumor and matching myometrial tissues collected at time of hysterectomy, and 4) to identify factors associated with development of fibroid symptoms including pelvic pain and uterine bleeding. The second study (Fibroid Growth Study, Shyamal Peddada, PI) is a clinical study of fibroids designed to describe fibroid growth and compare the growth-mediating factors in growing vs nongrowing tumors. The third study, Postpartum Uterine Regression, monitors fibroid change with pregnancy and postpartum uterine regression. The fourth study, a prospective study of fibroid incidence, is currently under development. In this study we will enroll women before they have fibroids and follow them over 5 years for fibroid incidence. After estimating the age-specific incidence of uterine fibroids for black and white women, we began to examine risk factors for uterine fibroids. Pregnancy is protective, though not those that occur before the mid twenties. Alcohol appears to increase risk. In two cases we have replicated findings from animal models of fibroids. We find that the location of fibroids is somewhat different for parous and nonpauous women, and that prenatal exposure to DES is associated with increased development of fibroids. Increasing LH is associated with increased prevalence of the tumors, though LH may not be having direct proliferative effects, as we had hypothesized. We find no evidence for increased risk of fibroids with oral contraceptive use or with variability in menstrual-cycle length. We also explored our data on body fat and exercise. We find a small increase in risk with increased BMI (similar to other studies), and we also find that exercise is protective. As in the recent cohort analyses, smoking was not associated with risk in our data. We also collected questionnaire data for exploratory analyses on early-life exposures and several environmental/occupational exposures. While few factors showed associations with fibroid development, we did find an association of childhood use of insect repellent with fibroids. This may merit further investigation given the possible link between insect repellents and breast cancer. We measured fasting insulin and IGF-I in blood specimens collected from participants, hypothesizing both would be risk factors for fibroids. Surprisingly both tended to be protective, and diabetics were actually significantly less likely to have fibroids. We examined vitamin D status in relation to prevalence of fibroids both with the biomarker of hydroxylated vitamin D and with questionnaire data on time outside. With both methods, women with low vitamin D status had higher fibroid prevalence, and the findings were consistent for blacks and whites. We are beginning to examine dietary factors that may be related to fibroids. Regardiing fibroid symptoms, we found that urinary incontinence was significantly associated with fibroid size. We are currently examining the relationship between fibroid size and/or location and menstrual bleeding. The Fibroid Growth Study data have been analyzed and we conclude that: 1) spontaneous regression of fibroids occurs, 2) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu, 3) fibroid size does not predict growth rate, and 4) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women. We are currently examining short-term changes in growth of fibroids. In our study that monitored fibroid change during pregnancy and/or postpartum uterine regression we found that 36% of solitary fibroids were lost during the pregnancy/postpartum. Tumors that remained tended to have lost volume. We are now analyzing data to identify factors affecting the extent of fibroids reduction. We starting enrollment for the prospective study of fibroid incidence in October of 2010.

子宫肌瘤（纤维瘤）是美国子宫切除术的主要适应症。尽管与肌瘤相关的发病率和高昂的医疗费用，在美国却很少有关于这种情况的流行病学研究。子宫肌瘤在组织学上可识别为良性平滑肌肿瘤，具有不同数量的相关纤维组织。许多女性患有不止一种子宫肌瘤，但每一种似乎都具有克隆特征。在肿瘤组织中已经发现了几种特定的细胞遗传学变化，但大多数没有表现出染色体异常。这些良性肿瘤具有激素依赖性。它们在青春期后发展，并在更年期后消退。雌激素和孕激素都被认为是重要的刺激物，或者至少是肿瘤生长的允许因素。 为了满足该领域的研究需求，我们设计了四项研究。第一项是一项大型流行病学研究，即 NIEHS 子宫肌瘤研究，旨在 1) 估计 35-49 岁黑人和白人女性中肌瘤的特定年龄累积发病率，2) 确定该病的危险因素，3) 比较肿瘤中的生长介导因素和子宫切除时收集的匹配子宫肌组织，以及 4) 确定与肌瘤发展相关的因素 症状包括盆腔疼痛和子宫出血。第二项研究（肌瘤生长研究，Shyamal Peddada，PI）是一项肌瘤临床研究，旨在描述肌瘤生长并比较生长与非生长肿瘤的生长介导因素。第三项研究“产后子宫退化”监测子宫肌瘤随妊娠的变化和产后子宫退化。 第四项研究是肌瘤发病率的前瞻性研究，目前正在开发中。 在这项研究中，我们将在患有肌瘤之前招募女性，并跟踪她们 5 年以上的肌瘤发病率。 在估计了黑人和白人女性子宫肌瘤的特定年龄发病率后，我们开始检查子宫肌瘤的危险因素。怀孕具有保护作用，但二十多岁之前的怀孕则不然。酒精似乎会增加风险。在两个案例中，我们复制了肌瘤动物模型的研究结果。我们发现，经产和未经产女性的肌瘤位置有所不同，并且产前暴露于 DES 与肌瘤的发展增加有关。 LH 的增加与肿瘤患病率的增加有关，尽管 LH 可能不会像我们假设的那样具有直接的增殖作用。我们没有发现证据表明使用口服避孕药或月经周期长度的变化会增加肌瘤的风险。我们还探索了有关身体脂肪和运动的数据。我们发现，随着体重指数的增加，风险略有增加（与其他研究类似），而且我们还发现运动具有保护作用。正如最近的队列分析一样，我们的数据显示吸烟与风险无关。我们还收集了问卷数据，用于对生命早期暴露和几种环境/职业暴露进行探索性分析。虽然很少有因素显示与子宫肌瘤的发展有关，但我们确实发现儿童时期使用驱虫剂与子宫肌瘤存在关联。鉴于驱虫剂与乳腺癌之间可能存在联系，这可能值得进一步研究。我们测量了参与者血液样本中的空腹胰岛素和 IGF-I，假设两者都是肌瘤的危险因素。令人惊讶的是，两者都具有保护作用，而且糖尿病患者患肌瘤的可能性实际上要小得多。 我们通过羟基化维生素 D 生物标志物和户外时间问卷数据检查了维生素 D 状态与肌瘤患病率的关系。 通过这两种方法，维生素 D 水平较低的女性的肌瘤患病率较高，而且黑人和白人的研究结果是一致的。 我们开始研究可能与肌瘤相关的饮食因素。 关于肌瘤症状，我们发现尿失禁与肌瘤大小显着相关。 我们目前正在研究肌瘤大小和/或位置与月经出血之间的关系。 对肌瘤生长研究数据进行了分析，我们得出结论：1）肌瘤会自发消退，2）尽管荷尔蒙环境一致，但同一女性的肌瘤生长速度不同，3）肌瘤大小并不能预测生长速度，4）黑人和白人之间肌瘤生长的年龄相关差异可能导致黑人女性的症状负担较高。 我们目前正在检查肌瘤生长的短期变化。 在我们监测怀孕期间和/或产后子宫退化的研究中，我们发现 36% 的孤立性肌瘤在怀孕/产后消失。 留下的肿瘤往往体积缩小。 我们现在正在分析数据以确定影响肌瘤减少程度的因素。 我们于 2010 年 10 月开始招募肌瘤发病率前瞻性研究。