4. Discussion
abdominal pain, menstrual pain, PMDD, headache, migraine
PMS, MENSTRUAL PAIN, CONTRACTIONS, DISORDERS, MIGRAINE, PATHOGENESES
We conducted a randomized, placebo-controlled, double-blind, parallel-group study involving healthy women experiencing subjective menstrual symptoms, with the test food being OLL2809. Analgesics are the most frequently used treatment for menstrual pain in Japan. Consequently, this study was meticulously structured to minimize the effect of analgesic use on the evaluation of menstrual symptoms. This was achieved by excluding individuals with a tendency to proactively take analgesics before the onset of menstrual pain and instructing participants not to use analgesics prophylactically before symptom onset. However, participants were not restricted from using analgesics when symptoms appeared. As a results, the use of analgesics was anticipated to be a significant confounding variable, and there were notable differences in the analgesic use scores between the groups at baseline (Although the pathogeneses of PMS and PMDD remain unclear, they have been reported to be linked to cyclic variations in estrogen and progesterone levels, accompanied by a decrease in serotonin secretion [In this study, the improvement effect of OLL2809 was primarily observed on psychological symptoms before menstruation, whereas there was a limited effect on physical symptoms before and during menstruation. The relationship between the physical and psychological symptoms associated with menstruation has been widely reported. Symptoms such as headache and migraine, resulting from neurovascular disorders due to estrogen withdrawal before menstruation, and lower abdominal pain, associated with uterine contractions induced by prostaglandins can affect psychological symptoms such as mood swings and irritation [The first limitation was the possibility of selection bias owing to the selection of participants with moderate MDQ total scores. Although external validity may be compromised, we believe that the study population is not extremely biased; therefore, it is possible to observe this effect in the study population. Secondly, the MDQ, SF-36, and VAS scores used as endpoints were subjective assessments. Given the absence of objective biomarkers for menstrual symptoms, the mechanism of action of OLL2809 remains unclear based on the current results. We speculate that this lack of clarity may be related to the stress response of the HPA axis. However, further investigation is necessary to elucidate how OLL2809 ingestion improves premenstrual psychological symptoms.