Mitro Susanna D, Waetjen L Elaine, Lee Catherine, Wise Lauren A, Zaritsky Eve, Harlow Siobán D, El Khoudary Samar R, Santoro Nanette, Solomon Daniel H, Thurston Rebecca C, Hedderson Monique M
Division of Research, Kaiser Permanente Northern California, Pleasanton, CA 94588, USA.
Department of Obstetrics and Gynecology, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
J Clin Endocrinol Metab. 2025 May 19;110(6):e1934-e1942. doi: 10.1210/clinem/dgae625.
Fibroids are noncancerous uterine tumors potentially associated with cardiovascular risk factors.
We aimed to examine prospectively associations of glucose, insulin, sex hormone-binding globulin (SHBG), and diabetes with incidence of fibroid diagnoses in midlife.
Participants in the Study of Women's Health Across the Nation (SWAN) cohort (n = 2570) reported fibroid diagnoses at enrollment (1996-1997) and 13 follow-up visits (1996-2013). At all visits, we measured glucose, insulin, and SHBG in fasting blood samples and calculated homeostatic model assessment for insulin resistance (HOMA-IR). Diabetes was defined using glucose levels, self-reported diabetes, or diabetes medication use. We used discrete-time survival models to estimate hazard ratios (HR) and 95% CI for associations of time-varying biomarkers and diabetes with incident fibroid diagnoses, adjusted for demographics and health care utilization. We also evaluated effect modification by menopausal status.
At baseline, 2.7% of participants (n = 70) were using diabetes medication. Time-varying glucose, insulin, HOMA-IR, and SHBG were not associated with fibroid diagnosis. However, diabetes was associated with a 28% lower incidence of fibroid diagnosis (adjusted HR 0.72, 95% CI 0.44, 1.17), driven by participants using metformin (adjusted HR 0.49, 95% CI 0.21, 1.12), though precision was limited. After stratification by menopausal status, higher HOMA-IR and insulin were associated with greater incidence of fibroid diagnosis during premenopause but not perimenopause, while the inverse association between diabetes and fibroids was strongest during perimenopause.
The effect of diabetes and biomarkers on fibroids may vary by menopausal status. Fibroid risk may increase with insulin resistance and decrease with diabetes treatment.
子宫肌瘤是一种非癌性子宫肿瘤，可能与心血管危险因素相关。
我们旨在前瞻性地研究血糖、胰岛素、性激素结合球蛋白（SHBG）和糖尿病与中年女性子宫肌瘤诊断发生率之间的关联。
全国女性健康研究（SWAN）队列中的参与者（n = 2570）在入组时（1996 - 1997年）及13次随访（1996 - 2013年）时报告子宫肌瘤诊断情况。在每次随访时，我们测量空腹血样中的血糖、胰岛素和SHBG，并计算胰岛素抵抗的稳态模型评估（HOMA-IR）。糖尿病通过血糖水平、自我报告的糖尿病或糖尿病药物使用情况来定义。我们使用离散时间生存模型来估计随时间变化的生物标志物和糖尿病与子宫肌瘤诊断事件之间关联的风险比（HR）和95%置信区间（CI），并对人口统计学和医疗保健利用情况进行了调整。我们还评估了绝经状态的效应修饰作用。
在基线时，2.7%的参与者（n = 70）正在使用糖尿病药物。随时间变化的血糖、胰岛素、HOMA-IR和SHBG与子宫肌瘤诊断无关。然而，糖尿病与子宫肌瘤诊断发生率降低28%相关（调整后HR 0.72，95% CI 0.44，1.17），这主要由使用二甲双胍的参与者驱动（调整后HR 0.49，95% CI 0.21，1.12），尽管精度有限。按绝经状态分层后，较高的HOMA-IR和胰岛素与绝经前子宫肌瘤诊断发生率较高相关，但与围绝经期无关，而糖尿病与子宫肌瘤之间的负相关在围绝经期最强。
糖尿病和生物标志物对子宫肌瘤的影响可能因绝经状态而异。子宫肌瘤风险可能随胰岛素抵抗增加而增加，随糖尿病治疗而降低。
