MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms

MsFLASH-03: Comparative Efficacy of Low-Dose Estradiol and the SNRI Venlafaxine XR for Treatment of Menopausal Symptoms

The primary objective of this study is to determine the efficacy of both low-dose oral (by mouth) 17-ß-estradiol and the non-hormonal drug venlafaxine XR compared to placebo in reducing hot flashes. Included in this objective is the intention to compare venlafaxine XR to estradiol therapy, to provide evidence of the relative efficacy of venlafaxine to what is currently considered the most established but also a controversial therapy. 17-ß-estradiol is a type of estrogen. Venlafaxine XR is the extended release (XR) version of venlafaxine. Venlafaxine XR is an serotonin-norepinephrine reuptake inhibitor (SNRI). A placebo is a substance containing no medication.

The MsFLASH-03 study (Menopausal Strategies: Finding Lasting Answers for Symptoms and Health - 03), 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), serotonin-norepinephrine reuptake inhibitors (SNRIs), 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