Abstract
ABSTRACT: Adenomyosis is an estrogen-dependent disease featuring chronic inflammation. This study was undertaken to investigate whether vagal tone is reduced in patients with adenomyosis compared with healthy women. We recruited 75 patients with adenomyosis, as diagnosed by a combination of ultrasound and gynecological examination, and 75 healthy women without adenomyosis, endometriosis, or other uterine disorders per ultrasound examination. All recruited subjects received an electrocardiogram evaluation, and their heart rate variability was assessed. In addition, lesional stiffness for patients with adenomyosis and myometrial stiffness for healthy controls were measured by ultrasound elastography. Severity of dysmenorrhea and the amount of menstrual blood loss were also evaluated. Patients with adenomyosis exhibited statistically significant sympatho-vagal imbalance, featuring domination of the sympathetic branch of the autonomic nervous system over the parasympathetic branch, as evidenced by reduced vagal tone and increased sympathetic activity. In addition, lesional stiffness, a proxy for the extent of lesional fibrosis, was found to be negatively associated with vagal tone. Patients with adenomyosis have reduced vagal tone. In addition, reduced vagal tone is likely attributable to increased lesional stiffness, a proxy for the extent of lesional fibrosis, which correlated with the severity of dysmenorrhea and the amount of menstrual blood loss. This raises the prospect of employing vagus nerve stimulation as a possible therapeutics approach. Future human studies are needed to determine whether vagus nerve stimulation can have any therapeutic effects. LAY SUMMARY: Adenomyosis is a condition in which the inner lining of the uterus is found in the muscular wall of the uterus (called the myometrium). It is a common gynecological disease affecting mostly women of reproductive age. We found that patients with adenomyosis exhibited significant imbalance between the 'flight-or-fight' system and the 'rest-and-digest' system (sympatho-vagal imbalance), featuring reduced vagal tone (dampened calm-down system) and increased sympathetic activity (more anxiety and restlessness). In addition, we found that the stiffness of adenomyotic lesions, which can be viewed as a proxy for the 'age' of the lesions, was negatively associated with vagal tone. This reduced vagal tone may suggest that perhaps some vagal stimulating procedures, which are safe and non-invasive, can be used to boost vagal tone to achieve therapeutic purposes.