PhytoSERM for Menopausal Hot Flashes and Sustained Brain Health

Inclusion Criteria:

• Peri- or postmenopausal women, defined by any of the following:

1. Last menstrual period (LMP) completed ≥ 60 days and ≤ 8 years, per the Stages ofReproductive Aging Workshop (STRAW) criteria.
2. Post-hysterectomy or endometrial ablation ≥ 3 months and supported by FSH levels.

• Age 45-60 years.
• Presence of hot flashes ≥ 7 per day.
• Clinical laboratory values must be within normal limits or, if abnormal, must bejudged to be not clinically significant by the investigator.
• Mammogram within normal limits in the past 2 years: Breast Imaging Reporting and DataSystem (BI-RADS) category 1-2 or 3 with findings stable for 3 years.
• No medical contraindications to study participation.
• Stable medications for 4 weeks prior to the baseline visits.
• Ability to take oral medication and be willing to adhere to the PhytoSERM regimen.
• For females of reproductive potential: Negative pregnancy test and use of highlyeffective contraception by male partner for at least 1 month prior to screening andagreement to use such a method during study participation.

Exclusion Criteria:

• Use of isoflavone containing supplements.
• Known allergies to isoflavones or soy-based products.
• Montreal Cognitive Assessment total score < 22.
• Pregnancy
• Use of estrogen or progestin compounds within 8 weeks of baseline.
• Use of investigational agent within 12 weeks of baseline.
• Concurrent neurologic, systemic, or psychiatric disease that would influence cognitionor ability to provide informed consent and to participate.
• Known or suspected estrogen-dependent neoplasia (breast, ovarian and uterine cancers),active neoplastic disease, history of breast cancer, and endometrial hyperplasia.
• History within the last 5 years of any other primary or recurrent malignant disease,with the exception of resected cutaneous squamous cell carcinoma in situ, and basalcell carcinoma.
• History of epilepsy, focal brain lesion, head injury with loss of consciousness or DSMIV criteria for any major psychiatric disorder including psychosis, major depression,bipolar disorder, alcohol, or substance abuse.
• Thrombophlebitis, thrombosis, thromboembolic disorders, myocardial infarction,ischemic heart disease, cerebrovascular accident, stroke, TIA.
• Current use of tobacco or a history of alcohol abuse.
• Use of anticoagulants.
• Chronic use of most benzodiazepines
• Use of drugs, herbs, or dietary supplements to treat menopausal or cognitive symptomsless than 8 weeks prior to baseline (e.g., SSRIs, rhubarb, red clover, licorice,kudzu, black cohosh, ginseng or other similar roots, etc.)
• Evidence of any significant clinical disorder or laboratory finding, includingclinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary,gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratoryabnormality.
• Known allergy to soy-derived products/ proteins or branded over the counter products;hypersensitivity to estrogens or progestins.