Effect of Menopause Hormone Therapy In Postmenopausal Women With CSVD And MCI (MIRACLE)

Inclusion Criteria: 40 ≤ age < 60 years Female; 1 year ≤ Natural menopause≤ 6 years; FSH ≥ 35 miu/ml and E2 ≤ 25 pg/ml; Head MRI shows CSVD-related image changes, meet one of the following: Parventricular or deep brain white matter hyperintense, Fazekas ≥ 2； Parventricular or deep brain white matter hyperintense, Fazekas = 1, with more than 2 vascular risk factors (hypertension, hyperlipidemia, type 2 diabetes, obesity, current smoking); Parventricular or deep brain white matter hyperintense, Fazekas = 1, with more than 1 vascular-derived lacunae; Recent small subcortical infarction within the last 3 months Mild cognitive dysfunction (18 ≤ MoCA <26); Independent in daily life (mRS ≤ 1） Sign informed consent. Note: Natural menopause: The self-reported last menstrual date of the subject CSVD related image changes: evaluated according to the STRIVE2 standard issued in 2023; Fazekas score: The total score is 6 , which is the sum of Fazekas scores for subcortical and periventricular white matter lesions; Recent subcortical small infarcts: lesions with a diameter of<20mm in the subcortical, basal ganglia, or brainstem regions that exhibit high signal intensity (ADC diffusion limitation) on DWI imaging, with or without corresponding clinical symptoms; With new clinical symptoms, FLAIR hyperintense lesions (<20mm in diameter) in subcortical, basal ganglia or corresponding parts of pons can be seen in FLAIR sequence of head MRI. MoCA: Montreal Cognitive Assessment; If the subject's education period ≤ 12 years, then increase by 1 point, with a maximum score of 30 points; mRS: Modified Rankin Scale Exclusion Criteria: Inheritable CSVD, such as CADASIL, CARASIL, etc. Confirmed neurodegenerative diseases, such as AD and PD; Clear non-vascular white matter lesions, such as multiple sclerosis, adult brain white matter dysplasia, metabolic encephalopathy, etc. History of intracranial hemorrhagic disease within the recent 6 months, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural / extradural hematoma, etc., as well as untreated aneurysms (diameter> 3mm) and cerebrovascular malformations. Cardiovascular and cerebrovascular events within the past 6 months, such as myocardial infarction, unstable angina pectoris, cerebral infarction, etc. Previously received or initiated menopausal hormone therapy. Previous Hysterectomy Vaginal bleeding of unknown origin Intra- and extra- cranial Atherosclerosis large artery stenosis (50-99%) or occlusion. Active venous or arterial thromboembolic diseases, such as Deep vein thrombosis, Pulmonary embolism, myocardial infarction, angina pectoris or congestive heart failure, in the last 6 months. Used drugs and Phytoestrogen supplements that affect estrogen levels in the past 3 months, such as soybean concentrate or extract, Kuntai capsule, Dingkundan, Lifumin, etc. Endometrial hyperplasia, vaginal ultrasound indicates endometrial ≥ 5mm (note: those confirmed as benign lesions by pathology can be included). Severe liver and kidney dysfunction: severe liver dysfunction refers to Alanine transaminase>3 times the upper limit of normal value or cereal grass Transaminase>3 times the upper limit of normal value; Severe renal insufficiency refers to blood creatinine>3.0 mg/dl (265.2 μmol/L) or glomerular filtration rate<30 ml/min/1.73m^2; Hypertension is still difficult to control after standardized treatment (blood pressure>160/100mmHg); Type 2 diabetes is still difficult to control after standard treatment (Glycated hemoglobin ≥ 8%). Known or suspected to have sex hormone dependent malignant tumors, such as breast cancer, endometrial cancer, cervical adenocarcinoma, ovarian cancer, and meningioma. Suffering from severe organic diseases with an expected survival time of<5 years. Other situations that are not suitable for menopausal hormone treatment, such as porphyria, otosclerosis, etc. Mental disorders diagnosed according to DSM-5 diagnostic criteria, or previous mental system diseases that cannot be fully communicated. Allergies to the active ingredients or any of the excipients of the research drug. Contraindications to MRI examination, such as Claustrophobia, metal implants in the body, etc. Unable to cooperate in completing follow-up due to geographical or other reasons. Situations deemed unsuitable by other researchers to participate in the study. Participating in other interventional clinical trials. -