Department of Obstetrics and Gynecology, The University of Chicago Pritzker School of Medicine, Chicago, IL.
Department of Obstetrics and Gynecology, The University of Chicago Pritzker School of Medicine, Chicago, IL; Department of Obstetrics and Gynecology Northshore University HealthSystem, Evanston, IL.
Am J Obstet Gynecol. 2024 May;230(5):553.e1-553.e14. doi: 10.1016/j.ajog.2024.01.018. Epub 2024 Jan 29.
The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments.
To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions.
We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment.
During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s; P=.001; q=.002) and the endometrium (26.37±9.33 s; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s; P=.001; q=.002) and endometrium (75.50±2.57 s; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping.
Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.
导致月经痛的机制尚不清楚。然而，对月经痛患者进行动态、非侵入性的盆腔影像学检查，可以帮助确定治疗靶点，并测试新的治疗方法。
为了研究导致月经痛的机制，我们在多个条件下分析了痛经患者和无痛经对照者的超声和补充功能磁共振成像参数。
我们在月经期间和月经外对有痛经和无痛经的参与者进行了功能磁共振成像。为了阐明是否存在局部氧供应和灌注的变化，我们获得了子宫内膜和子宫肌层的功能磁共振成像 R2测量值。R2测量值是计算对氧合和去氧血红蛋白的顺磁特性敏感的核磁共振弛豫率。我们还比较了在服用萘普生钠的镇痛剂量前后的参数。此外，我们还使用多普勒超声进行了类似的测量，以实时识别在月经痉挛期间子宫动脉速度是否发生变化。混合模型统计用于解释条件之间的个体内效应。采用虚假发现率调整进行了多次比较的校正。
在月经期间，经历痛经的参与者的子宫肌层（β±标准误差均值，15.74±2.29 s；P=.001；q=.002）和子宫内膜（26.37±9.33 s；P=.005；q=.008）的 R2值明显增加，表明组织缺血。无痛经的对照组也观察到类似的增加，在子宫肌层（28.89±2.85 s；P=.001；q=.002）和子宫内膜（75.50±2.57 s；P=.001；q=.003）。事后分析显示，无痛经对照组的 R2值在月经期间明显更高（子宫肌层，P=.008；子宫内膜，P=.043）。虽然萘普生钠增加了痛经患者的子宫内膜 R2值（48.29±15.78 s；P=.005；q=.008），但它降低了无痛经对照组的子宫肌层 R2值。多普勒结果与功能磁共振成像结果一致（-8.62±3.25 s；P=.008；q=.011）。与月经外的测量值相比，月经期间的搏动指数（-0.42±0.14；P=.004；q=.004）和阻力指数（-0.042±0.012；P=.001；q=.001）降低，而萘普生钠则显著逆转了这些变化。萘普生钠在无痛经对照组中产生了相反的效果。在有症状的月经痉挛期间，搏动指数、阻力指数、收缩期峰值速度和最小舒张期速度没有明显的实时变化。
功能磁共振成像和多普勒指标表明，痛经患者的子宫灌注和氧供应比无痛经对照组更好。萘普生钠的治疗机制与子宫灌注和氧供应的相对减少有关。在无痛经对照组中观察到相反的药理作用。在月经痉挛期间，没有足够的证据表明周期性子宫灌注受损。因此，前列腺素可能对无痛经对照组具有保护性血管收缩作用，而对痛经患者则具有相反的作用。
