①更年期障害の各症状に対する漢方治療不応例の要因分析
2014年～2021年に更年期症状を主訴として慶應義塾大学病院漢方医学センター外来を受診し、研究参加について同意を得た、45歳～55歳の女性84名を対象とした。診療録および自動問診システムより患者背景情報、更年期症状の種類・重症度（VAS値）、漢方医学的診断結果、臨床検査値および処方歴を収集した。主訴となる更年期症状としては「疲れやすい・だるい・身体が重い」が32名（38.1%）と最も多く、次いで「のぼせや顔のほてり・汗をかきやすい」が27名（32.1%）、「身体の冷え」が12名（14.3%）であった。治療の効果判定は主訴のVAS値の変化および診療録の記載に基づき行い、初診から3ヵ月間に主訴のVAS値が初診時から7.2%以上低下あるいは診療録に改善と記載がある症例を治療有効例、VAS値の低下が7.2%未満あるいは診療録に改善が見られない旨が記載されている症例を治療不応例と定義した。有効例52名および不応例32名の患者背景を比較した結果、閉経後に治療を開始した患者において治療不応が多い傾向が見られた。次年度も引き続き不応例に見られる特徴と治療の適正化に向けた提案について検討を継続し、論文報告を行う予定である。
②更年期女性に対するエストロゲン受容体遺伝子解析
今年度はエストロゲン受容体遺伝子のプロモーター領域のDNAメチル化頻度解析の条件検討を行った。DNAメチル化解析はバイサルファイトシークエンス法で行うこととし、解析条件を決定した。メチル化頻度と更年期症状の重症度および治療効果との関連を検討し診断や治療に活用するための知見を得ることを目的として、慶應義塾大学病院漢方医学センター外来を受診し書面で同意を得た40歳～60歳の女性を対象にエストロゲン受容体遺伝子のDNAメチル化解析を行う予定である。次年度に患者検体の解析ができるよう、現在、研究実施計画を倫理委員会に申請する準備を行っている。
1. Factor analysis of the non-responders to Kampo treatment for menopausal symptoms
This study included 84 women aged 45-55 years with chief complaints of menopausal symptoms who made initial visits to the Kampo Clinic of Keio University Hospital between October 2014 and October 2021. All registered patients provided written informed consent. Patient background information, symptom severity (VAS values), traditional medicine pattern diagnosis, laboratory data, and prescription history were collected from medical records. The most common menopausal symptoms were "easily tired, feel sluggish and heavy" in 32 patients (38.1%), followed by "hot flashes and increased sweating" in 27 patients (32.1%), and "cold sensation (hie)" in 12 patients (14.3%). The efficacy of treatment was based on the change in the VAS value of the chief complaint of menopausal symptoms and on the medical record. Treatment responders were identified as those in whom the VAS value of the chief complaint decreased by 7.2% or more from the initial value, or for whom the medical record indicated improvement within three months of the first visit. Fifty-two patients responded to the treatment, and 32 were non-responders. Comparing patient backgrounds, treatment non-response tended to be more frequently observed in patients who started treatment during the postmenopausal period. In the next fiscal year, we will continue to study the characteristics observed in non-responders, propose new treatment ideas, and eventually publish the results.
2. Estrogen receptor gene analysis in menopausal women
We have developed a method for analyzing the frequency of DNA methylation in the promotor region of the estrogen receptor gene. DNA methylation analysis will be performed with the bisulfite sequencing method, and the analysis conditions were determined in this fiscal year. In order to obtain knowledge for diagnosis and treatment of menopausal symptoms, we are attempting to identify the association between methylation process and the severity of menopausal symptoms and treatment response. Women aged 40-60 years who visited the Kampo Clinic of Keio University Hospital and provided written informed consent will be included in this study. We are currently preparing to submit a research plan to the Ethics Committee so that patient samples can be analyzed in the next fiscal year.