Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms

The MsFLASH-03 study, Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR
for Treatment of Menopausal Symptoms, is a randomized, double-blind, placebo-controlled,
three arm clinical trial. The design includes: 3 weeks of daily recording of hot flashes
prior to drug treatment; 8 weeks of double-blind treatment with oral estradiol, venlafaxine,
or placebo; followed by 14 days of drug taper for those on venlafaxine and 14 days of
progesterone treatment for those on estradiol; followed by 2 weeks with no treatment for all
groups; and a telephone follow-up post-treatment.

Inclusion Criteria:

- Females aged 40-62 years

- Postmenopausal or perimenopausal

- Having bothersome hot flashes

- In general good health

- Signed informed consent

Exclusion Criteria:

- Recent use of systemic hormone therapy or hormonal contraceptives

- Recent use of any prescribed, over-the-counter or herbal therapies that are taken
specifically for hot flashes

- Recent use of selective estrogen receptor modulators (SERMS) or aromatase inhibitors

- Recent use of psychotropic medications, including SSRIs (selective serotonin reuptake
inhibitors), SNRIs (serotonin-norepinephrine reuptake inhibitors), MAOIs (monoamine
oxidase inhibitors), and other antidepressants and anxiolytics.

- Known hypersensitivity or contraindications (reasons not to take) to venlafaxine,
estrogen, or progestins

- Not using a medically approved method of birth control, if sexually active and not 12
or more months since last menstrual period

- Recent drug or alcohol abuse

- Lifetime diagnosis of psychosis or bipolar disorder

- Suicide attempt in the past 3 years or any current suicidal ideation

- Current major depression (assessed during screening)

- Pregnancy, intending pregnancy, or breast feeding

- History of:

- Pre-breast cancer or high-risk breast cancer condition

- Abnormal bleeding suggestive of endometrial pre-cancer or endometrial
hyperplasia

- Asthma, diabetes mellitus, epilepsy, and migraine disorders that are not stable
or under medical management

- Abnormal screening blood tests

- Current participation in another drug trial or intervention study

- Inability or unwillingness to complete the study procedures