A TSEC for Symptom Management in Menopausal Women With Multiple Sclerosis

Inclusion Criteria: * Women aged 40-62 years. * Perimenopausal: 6 months of amenorrhea; women who had a bi-lateral oophorectomy; women without a uterus and who still have one or both ovaries, with FSH level \> 20 mIU/mL and estradiol ≤ 50 pg/mL; women with a uterus who have skipped 2 or more menstrual cycles with an amenorrhea interval; women who are using the Mirena IUD or who have had an endometrial ablation and who still have one or both ovaries, with FSH level \> 20 mIU/mL and estradiol ≤ 50 pg/mL * Bothersome MS symptoms: Mean of two or more hot flashes/night sweats per 24 hrs; Hot flashes/night sweats rated as bothersome ('moderately' to 'a lot') and/or severe ('moderate' to 'severe') on 4 or more 12 hour (day/night) blocks of times * In general good health (determined by medical history, blood pressure, and heart rate) * No history of endometrial, ovarian, or breast cancer; No abnormal mammogram in the last 2 years; Absence of any current severe or unstable medical illness MS considerations: * If using psychotropic medications: no change in the past 3 months * If on DMT, no change in past 6 months Normal vitamin D levels (20-50 ng/mL) Exclusion Criteria: * BMI \>35 kg/m2 as higher BMI may affect PK/PD * Use of hormone therapy or hormonal contraceptives 2 months prior to enrollment * Use of any prescribed therapy that is taken specifically for hot flashes in the past 1 month. * Use of any over-the-counter or herbal therapies that are taken specifically for hot flashes in the past 2 weeks. * Use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors during the 2 months before enrollment. * Known hypersensitivity or contraindications to estrogen. * Drug or alcohol abuse in the past 1 year * Depression: moderate or severe (HAD score \> 8) Other psychiatric disease meeting DSM-IV criteria * Lifetime diagnosis of psychosis or bipolar disorder. * Pregnancy, intending pregnancy, or breast feeding History of any of the following, as determined by clinician review of the potential participant's medical history: * Pre-breast cancer or high-risk breast cancer condition; * Abnormal bleeding suggestive of endometrial pre-cancer; * Endometrial hyperplasia; * Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable or under medical management; * Active or past history of venous or arterial thromboembolism * History of gallstones IF gallbladder intact * Known or suspected estrogen-dependent neoplasia * History of coronary artery disease * Hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients * Known hepatic impairment or disease * Thyroid dysfunction on thyroid medications * Known hypoparathyroidism * Blood test results indicating: * Liver function tests: AST \>2.5 times upper limit of normal; ALT \>2.5 times upper limit of normal; total bilirubin 1.5 times upper limit of normal; * Kidney test: creatinine \>1.5 mg/dL; * Blood count: hematocrit \<30%; * Hemoglobin \<8 g/dL. * Current participation in another drug trial or intervention study. * Inability or unwillingness to complete the study procedures. MS considerations: * Clinical relapse within the last three months (to ensure disease stability) * Steroid treatment in prior 1 month * Evidence of other structural brain disease (e.g. prior stroke) MRI considerations: * Metal implants * Prior head trauma * Claustrophobia requiring anxiolytic or sedation, or other contraindication to MRI.