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.

子宫平滑肌瘤（肌瘤）是美国子宫切除术的主要指标。尽管与肌瘤相关的发病率和高昂的医疗费用，但在美国，这种情况几乎没有流行病学研究。子宫平滑肌瘤在组织学上可识别为良性平滑肌肿瘤，并具有不同量相关的纤维组织。许多女性具有多个子宫平滑肌瘤，但每个女性似乎都在克隆上截然不同。在肿瘤组织中已经发现了几种特定的细胞遗传学变化，但大多数没有染色体异常。这些良性肿瘤依赖于激素。他们在青春期后发展并在更年期后退缩。雌激素和孕激素都被认为是重要的兴奋剂，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。第一个是一项大型流行病学研究，即Nieh子宫肌瘤研究，设计为1）估计黑人和白人女性平滑肌瘤的特定年龄特异性累积发生率，35-49岁，35-49，2）疾病的危险因素，3）鉴定肿瘤中的肌脉冲因素与肌分型的相关因素，并在肌分型中匹配的肌分流率，并在肌分流中匹配，并在肌分型中匹配的时间，并在肌分流中匹配。症状包括骨盆疼痛和子宫出血。第二项研究（肌瘤生长研究，Shyamal Peddada，pi）是一项临床研究，旨在描述肌瘤生长并比较成长中与非肿瘤的增长肿瘤中的中间因素。第三项研究是子宫产后回归，随着妊娠和产后子宫回归监测肌瘤的变化。 第四项研究是一项针对肌瘤发生率的前瞻性研究，目前正在开发中。 在这项研究中，我们将在妇女患有肌瘤之前入学，并跟随她5年以上的肌瘤发生率。 在估计黑人和白人妇女子宫肌瘤的年龄特异性发生率后，我们开始检查子宫肌瘤的危险因素。怀孕是保护性的，尽管不是二十多岁之前发生的怀孕。酒精似乎增加了风险。在两种情况下，我们从肌瘤的动物模型中复制了发现。我们发现肌瘤的位置对于帕斯和非偶然的女性有所不同，并且产前暴露于DES与肌瘤的发育增加有关。 LH的增加与肿瘤患病率的增加有关，尽管LH可能没有直接增殖作用，正如我们假设的那样。我们发现没有证据表明使用口服避孕药或月经周期长度变化的肌瘤风险增加。我们还探索了有关体内脂肪和运动的数据。我们发现随着BMI的增加（类似于其他研究），风险的增加很小，我们还发现运动具有保护性。与最近的队列分析一样，吸烟与我们的数据中的风险无关。我们还收集了调查表数据，以进行有关早期暴露和几种环境/职业暴露的探索性分析。尽管很少有因素表现出与肌瘤发育的关联，但我们确实发现了驱虫剂与肌瘤的使用相关性。鉴于驱虫剂与乳腺癌之间的可能联系，这可能值得进一步研究。我们测量了从参与者收集的血液标本中的禁食胰岛素和IGF-1，假设两者都是肌瘤的危险因素。令人惊讶的是，两者都倾向于保护性，而糖尿病患者实际上具有肌瘤的可能性明显较小。 我们检查了与羟基化维生素D的生物标志物以及在外面的时间时与问卷数据有关的肌瘤患病率的维生素D状态。 通过两种方法，维生素D状态低的女性肌瘤患病率较高，黑人和白人的发现是一致的。 我们开始研究可能与肌瘤有关的饮食因素。 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。 已经分析了肌瘤生长研究数据，我们得出结论：1）肌瘤的自发回归发生，2）来自同一妇女的肌瘤以不同的速度生长，尽管激素环境均匀，3）肌瘤的大小并未预测生长速度，而4）在黑人之间造成黑人构成构成型构成黑人构成型构成黑人构成的差异。 我们目前正在研究肌瘤生长的短期变化。 在我们的研究中监测怀孕期间肌瘤变化和/或子宫产后回归期间的变化，我们发现在怀孕/产后期间，有36％的孤立肌瘤丢失了。 仍然倾向于失去体积的肿瘤。 现在，我们正在分析数据，以确定影响肌瘤减少程度的因素。 我们开始入学，参加2010年10月的肌瘤发病率的前瞻性研究。