RESUMO
Context: Arthralgia affects menopausal patients. Aim: Here, we report a retrospective observational study evaluating the therapeutic efficacy of a combination of unkeito and boiogito for menopausal arthralgia. Settings and Design: Patients treated with a combination of unkeito and boiogito for menopausal arthralgia between April 2020 and October 2022 at three Japanese Kampo outpatient clinics were retrospectively examined. Treatment effectiveness was determined based on the patient's description of pain. Adverse events associated with this treatment regimen were also recorded. The study design was approved by the Tokai University Ethics Committee (Approval number: 22R196). Methods and Material: This study was conducted by retrospectively analysing the medical records of patients who attended the three medical facilities. All patients received Kampo medicines based on traditional medical diagnoses. Outpatients with a diagnosis of menopausal arthralgia were selected, and information on those who were treated with a combination of unkeito and boiogito was collected. Statistical Analysis: The age, height, and weight of all patients are represented as the mean ± standard deviation. Statistical analyses were not performed in this study as there was no comparison group. Results: During the study period, nine patients with menopausal arthralgia received the unkeito and boiogito combination. Four patients showed a "significant" response to the combination treatment, four showed an "effective" response, and one patient showed an "ineffective" response. One patient reported headache as an adverse event. Conclusion: The combination of unkeito and boiogito may be effective in the treatment of menopausal arthralgia.
RESUMO
Background: Polycystic ovary syndrome (PCOS) is a common disorder resulting in irregular menstruation and infertility due to improper follicular development and ovulation. PCOS pathogenesis is mediated by downregulated follicle-stimulating hormone receptor (FSHR) expression in granulosa cells (GCs); however, the underlying mechanism remains elusive. Unkeito (UKT) is a traditional Japanese medicine used to treat irregular menstruation in patients with PCOS. In this study, we aimed to confirm the effectiveness of UKT in PCOS by focusing on follicle-stimulating hormone (FSH) responsiveness. Methods: A rat model of PCOS was generated by prenatal treatment with 5α-dihydrotestosterone. Female offspring (3-week-old) rats were fed a UKT mixed diet or a normal diet daily. To compare the PCOS phenotype in rats, the estrous cycle, hormone profiles, and ovarian morphology were evaluated. To further examine the role of FSH, molecular, genetic, and immunohistological analyses were performed using ovarian tissues and primary cultured GCs from normal and PCOS model rats. Results: UKT increased the number of antral and preovulatory follicles and restored the irregular estrous cycle in PCOS rats. The gene expression levels of FSHR and bone morphogenetic protein (BMP)-2 and BMP-6 were significantly decreased in the ovarian GCs of PCOS rats compared to those in normal rats. UKT treatment increased FSHR staining in the small antral follicles and upregulated Fshr and Bmps expression in the ovary and GCs of PCOS rats. There was no change in serum gonadotropin levels. In primary cultured GCs stimulated by FSH, UKT enhanced estradiol production, accompanied by increased intracellular cyclic adenosine monophosphate levels, and upregulated the expression of genes encoding the enzymes involved in local estradiol synthesis, namely Cyp19a1 and Hsd17b. Furthermore, UKT elevated the expression of Star and Cyp11a1, involved in progesterone production in cultured GCs in the presence of FSH. Conclusions: UKT stimulates ovarian follicle development by potentiating FSH responsiveness by upregulating BMP-2 and BMP-6 expression, resulting in the recovery of estrous cycle abnormalities in PCOS rats. Restoring the FSHR dysfunction in the small antral follicles may alleviate the PCOS phenotype.