Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women
Condition: Estrogen Deficiency; Cardiovascular Disease (CVD); Hypothalamic Amenorrhea
MeSH terms: Cardiovascular Diseases; Atherosclerosis; Inflammation; Amenorrhea
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether low estrogen levels in young women with
      hypothalamic amenorrhea (premenopausal HypoE) is associated with risk factors for
      cardiovascular disease.

      For this study, the investigators will measuring vascular function and immune markers on:

        -  young women with hypothalamic amenorrhea (>3 months of no menstrual cycle due to low
           estrogen)

        -  young women with regular menstrual cycles not on hormone therapy.

        -  recently menopausal women (<3 years from final menstrual period) not on hormone therapy.

      Premenopausal HypoE participants will then be randomized to use either an estrogen patch or a
      placebo patch (no active medicine) for 3 months, followed by estrogen or placebo patch plus
      progesterone or placebo pills for 2 additional weeks. The investigators are looking to see if
      estrogen improves vascular and immune function.
    

Detailed description: 
      Study Aims:

        1. To test the hypothesis premenopausal HypoE is associated with pre-clinical CVD as
           determined by reductions in vascular endothelial function and increased central arterial
           stiffness.

        2. To test the hypothesis premenopausal HypoE is associated with increased immune-mediated
           inflammation.

        3. To test the hypothesis estrogens can reduce inflammation, improve vascular endothelial
           function and central arterial stiffness in premenopausal HypoE women.

      In a randomized, double-blind placebo-controlled trial in premenopausal HypoE women the
      investigators will test 12 weeks of transdermal estradiol 0.1 mg/day patch or placebo
      followed by 2 weeks of estradiol plus progesterone 200mg on vascular endothelial function,
      arterial stiffness and immune-mediated inflammation versus placebo. Patches will be applied
      by the participant to the lower abdomen twice weekly, alternating sides.

      The investigators will be using non-invasive tests to measure vascular function including:

        -  Peripheral arterial tonometry (PAT)

        -  SphygmoCor measurements of central blood pressure

        -  Carotid intima-media thickness (CIMT)
    

Intervention name(s): 17beta Estradiol; Transdermal placebo patch; Progesterone; Placebo Pill
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Participants will use a dose of transdermal estradiol 0.1 mg/day patch for 12 weeks +/- 1week. PAT index vascular measures and serum immune markers will be measured after 6 and 12 weeks +/- 1week on estrogen patches. Patches will be applied by the participant to the lower abdomen twice weekly, alternating sides.; Participants will use a dose of placebo patches for 12 weeks +/- 1 week. Placebos will be applied by the participant to the lower abdomen twice weekly, alternating sides.; After 12 weeks +/- 1week of transdermal estradiol patch, participants will use estrogen patch plus progesterone for 2 additional weeks +/- 3 days. Progesterone is a peanut based product and for patients with a peanut allergy we will replace this with a synthetic progestin at an equivalent dose, medroxyprogesterone 10mg.; After 12 weeks +/- 1week of transdermal placebo patch, participants will use placebo patch plus placebo pill for 2 additional weeks +/- 3 days.
Other intervention name(s): Estradiol Transdermal Patch; Vivelle-Dot; Prometrium; Placebo Oral Pill
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Progesterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: estrogen; premenopause; menopause; amenorrhea