Timing Estrogen After MenoPaUSe
Condition: Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      The aim of the current study is to test whether the effect of estrogen on insulin metabolism
      depends on the timing of treatment relative to when a woman went through menopause. The
      investigators hypothesize that estrogen will improve insulin sensitivity in early
      postmenopausal women, but decrease insulin sensitivity in late postmenopausal women.
    

Detailed description: 
      Large clinical trials have shown a reduced incidence of type 2 diabetes in postmenopausal
      women randomized to estrogen-based hormone therapy compared to placebo. Moreover, studies
      suggest development of diabetes is reduced in postmenopausal women who used hormone therapy
      for a part of the postmenopausal period compared to women who never used hormone therapy.
      Consistent with this, our preliminary data suggest that the timing of estrogen treatment
      relative to the menopause may be an important determinant of whether there are favorable
      effects on insulin action. Our observations suggest that estrogen improves insulin
      sensitivity in early postmenopausal women, but may decrease insulin sensitivity in those more
      than 10 years past menopause. More and more studies suggest estrogens have divergent effects
      on cardiovascular risk when initiated close to the onset of menopause rather than distant
      from the menopause; we hypothesize this is also true for diabetes risk. The goal of this
      study is to determine whether the effects of estrogen on insulin metabolism are different in
      women who are early postmenopausal compared to late postmenopausal. To meet our goal, we
      propose to measure insulin sensitivity in women who are within 6 years of the onset of
      menopause or more than 10 years beyond the menopause and who have not used hormone therapy
      previously. All women will be studied on two separate occasions, one day with and one day
      without short-term (1 week) treatment with transdermal estradiol. We expect that estradiol
      will increase insulin sensitivity in early postmenopausal women and decrease insulin
      sensitivity in late postmenopausal women. We also expect that estrogen receptors in fat and
      muscle may change with increasing time after menopause. Thus, we will collect fat and muscle
      biopsies to compare changes in estrogen receptors between early and late postmenopausal women
      and in response to 1 week of estradiol treatment. We believe these studies will provide
      evidence for a benefit of estradiol on insulin sensitivity when administered early, but not
      late, after menopause; likely contributing to delayed onset of type 2 diabetes in
      postmenopausal women.
    

Intervention name(s): Estradiol
Intervention type(s): Drug
Intervention description(s): 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
Other intervention name(s): Climara
Intervention MeSH terms: Estradiol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Other
Keywords: menopause; estrogen; insulin sensitivity; estrogen receptors