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.