Research Investigation of Soy and Estrogen
Condition: Menopause; Hot Flashes
MeSH terms: Hot Flashes
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the effects of oral estradiol and soy
      phytoestrogens on anxiety, stress responsivity and cognition in perimenopausal women.
    

Detailed description: 
      Anxiety is a common, but understudied complaint in midlife women, and increases during the
      menopausal transition. Changes in estrogen are dramatic during the menopausal transition, and
      indirect data suggest a potential role for estrogen, particularly estrogen receptor beta, in
      mediating anxiety. Two subtypes of the estrogen receptor, alpha and beta (ER-alpha and
      ER-beta), appear to be critically involved in the expression of anxiety in females. Compounds
      that preferentially target ER-beta, including plant-derived estrogens (phytoestrogens), lower
      both anxiety behaviors and responsivity to discrete stressors, including social stress, in
      laboratory animals. The primary aim of this proposal is to carry out the first study to
      translate these preclinical studies to humans by comparing and contrasting of the effects of
      phytoestrogens, estradiol, and placebo on daily anxiety and responses to moderate
      psychosocial stress in the laboratory. As second focus is emotional and non-emotional
      cognition. This focus stems from evidence that estrogen can protect against the negative
      impact of glucocorticoids on memory. These aims will be accomplished in a 12-week randomized
      placebo-controlled, clinical trial comparing three treatments: 1) a phytoestrogen supplement
      (Novasoy® 400, 55 mg tablet twice daily); 2) oral estradiol (1 mg/daily; plus 10 mg
      medroxyprogesterone acetate at study end 10 for 10 days); and 3) placebo (identical appearing
      tablets twice daily). The enrollment target is 120 healthy women in the menopausal transition
      (40 per group). To measure anxiety, women will complete the State-Trait Anxiety Inventory
      (STAI). To measure responsivity to psychosocial stress, parallel forms of the Trier Social
      Stress Test, a widely used laboratory induction that involves unanticipated public speaking
      and social evaluative fear, will be used to induce moderate psychosocial stress before and
      after treatment. At both laboratory sessions, measures of subjective stress (STAI), cortisol,
      and emotional memory performance will be obtained at multiple points during a control
      condition and during the psychosocial stress condition. Lastly, we will measure treatment
      effects on measures of verbal memory.
    

Intervention name(s): Soy Phytoestrogen; Estradiol; Medroxyprogesterone Acetate (MPA); Soy Placebo; MPA Placebo
Intervention type(s): Dietary Supplement; Drug; Drug; Drug; Drug
Intervention description(s): Novasoy® pill (55 mg); Estradiol pill (1 mg); medroxyprogesterone acetate (MPA) (10mg); oral placebo pill (0mg Soy Phytoestrogen); oral placebo pill (0mg MPA)
Other intervention name(s): NovaSoy 400; estrogen, estradiol acetate; MPA; sugar pill; sugar pill
Intervention MeSH terms: Medroxyprogesterone Acetate; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Medroxyprogesterone; Estradiol; Polyestradiol phosphate; Estrogens; Phytoestrogens
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: menopause; hot flashes; soy; estrogen; anxiety