AFTER: Altering Fat Through Estrogen and Raloxifene
Condition: Postmenopause
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether estrogens specifically promote a reduction
      in fat from abdominal regions during weight loss and/or prevent the accumulation of abdominal
      fat during weight gain.
    

Detailed description: 
      The general aim of this study is to determine whether estrogen-based hormone therapy (HT) in
      postmenopausal women reduces the accumulation of abdominal visceral fat and whether this is a
      contributing factor to the effects of estrogens on cardiovascular risk factors. An additional
      aim is to determine whether raloxifene, a selective estrogen receptor modulator (SERM) that
      is suggested to be a safer alternative to estrogen for the prevention of osteoporosis, exerts
      similar effects as estrogen on fat distribution. Mechanisms for possible regional differences
      in the regulation of fat metabolism in estrogen-sufficient vs estrogen-deficient states will
      be investigated, as will the extent to which estrogen status and changes in visceral
      adiposity are associated with changes in risk for coronary artery disease (CAD) and Type 2
      diabetes mellitus (DM).

      The hypotheses being tested include 1) reductions in total fat mass and total abdominal and
      visceral fat will be significantly greater in women treated with HT or raloxifene than in
      those receiving placebo treatment, 2) the accumulation of total fat mass and total abdominal
      and visceral fat during the 12-month follow-up period will be significantly less in women on
      HT or raloxifene than in those receiving placebo treatment, 3) a reduction in visceral fat
      mass will be associated with increased sensitivity to insulin in the breakdown of fat in the
      whole body, and there will be an independent enhancing effect of HT and raloxifene on insulin
      action, and 4) changes in risk factors for CAD and Type 2 DM will be more closely associated
      with changes in visceral adiposity than with changes in total fat mass or other measures of
      regional adiposity, independent of and in addition to the effects of HT and raloxifene on
      risk factors.

      To meet these aims, a reduction in visceral fat will be induced in 108 postmenopausal women
      through a 6-month program of supervised exercise training plus mild caloric restriction.
      Participants will be randomized to receive HT, raloxifene, or placebo. The drug treatment
      will continue, but the fat reduction program will cease, during a 12-month follow-up period.
      Risk factors for CAD and Type 2 DM and insulin sensitivity in terms of the breakdown of fat
      on total body and regional adipose tissue will be evaluated before and after treatment and
      after the follow-up period (risk factors only). For the purpose of this application, HT
      refers to a regimen involving daily conjugated estrogens and, in women with a uterus,
      tri-monthly progestin treatment.
    

Intervention name(s): conjugated estrogens; Raloxifene; exercise plus mild caloric restriction for weight loss
Intervention type(s): Drug; Drug; Behavioral
Intervention MeSH terms: Raloxifene Hydrochloride; Estrogens; Estrogens, Conjugated (USP)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: metabolic syndrome; hormone therapy; abdominal adiposity; lipolysis