Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women
Overview
- Phase
- Phase 2
- Intervention
- Placebo Pill
- Conditions
- Not specified
- Sponsor
- Cedars-Sinai Medical Center
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Rate of Change of Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to determine whether young women with functional hypothalamic amenorrhea (premenopausal HypoE) is associated with risk factors for pre-clinical cardiovascular disease (CVD).
For this study, the investigators will measuring vascular function and inflammatory markers on:
- young women with functional 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 (women with functional hypothalamic amenorrhea) will be randomized to use either an estrogen patch or a placebo patch (no active medicine) for 12 weeks, 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 inflammation.
Detailed Description
Study Aims: 1. To test the hypothesis premenopausal HypoE (women with FHA) is associated with pre-clinical CVD as determined by reductions in vascular endothelial function. 2. To test the hypothesis premenopausal HypoE (women with FHA) is associated with increased immune-mediated inflammation. 3. To test the hypothesis whether estrogen replacement can reduce inflammation and improve vascular endothelial function in premenopausal HypoE women (women with FHA). In a randomized, double-blind placebo-controlled trial in premenopausal HypoE women (women with FHA) 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 (for endometrial safety) on vascular endothelial function 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 to measures reactive hyperemic index (RHI) using peripheral arterial tonometry (PAT)
Investigators
Chrisandra Shufelt
Professor and Chair, Division of General Internal Medicine
Mayo Clinic
Eligibility Criteria
Inclusion Criteria
- •For premenopausal Hypo E and normal control women, inclusions include:
- •Premenopausal currently not on hormone therapy,
- •English speaking (for the purposes of complete psychosocial assessment)
- •able to give informed consent
- •a gynecological age (age since menarche) \> 10 and \< 25 years, and chronological age \> 18 years
- •Within 90-110% of ideal body weight as determined by the 1983 Metropolitan Height and weight table for women
- •All participants with hypothalamic amenorrhea will be diagnosed based on exclusion of other etiologies for their amenorrhea, including pregnancy, thyroid dysfunction, hyperprolactinemia, premature ovarian insufficiency, and polycystic ovary disease
- •For recently menopausal women inclusions include:
- •Follicle stimulating hormones (FSH) \>30 and 12 months of amenorrhea, within 3 years of final menstrual period with natural menopausal not on hormone therapy
- •English speaking
Exclusion Criteria
- •For premenopausal Hypo E and normal control women exclusions include:
- •Hypertension
- •Hyperlipidemia
- •Medications including psychotropic or illicit drugs, medical, neurological
- •Ophthalmologic disease except acuity problems
- •Major Axis I disorder other than depression
- •Pregnancy in the last 12 months and/or lactating in the last 6 months
- •Current use of hormone contraceptive or any estrogen or progestin therapy
- •For HypoE women, exclusion criteria include:
- •Allergy to adhesive or tape
Arms & Interventions
Transdermal Placebo Patch, Placebo Pill
Placebo Transdermal Patch, Placebo Pill
Intervention: Placebo Pill
17Beta Estradiol, Progesterone
17Beta Estradiol (0.1mg/day) , Progesterone (100mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 100mg is a peanut based product
Intervention: 17beta Estradiol
17Beta Estradiol, Progesterone
17Beta Estradiol (0.1mg/day) , Progesterone (100mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 100mg is a peanut based product
Intervention: Progesterone
Transdermal Placebo Patch, Placebo Pill
Placebo Transdermal Patch, Placebo Pill
Intervention: Transdermal placebo patch
Outcomes
Primary Outcomes
Rate of Change of Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry
Time Frame: Baseline, week 12 on trial
Change in PAT measured as reactive hyperemia index (RHI) from baseline to week 12 on treatment or placebo. Reactive hyperemia index (RHI) is the post-to-pre occlusion PAT signal ratio in the occluded arm, relative to the same ratio in the control arm, corrected for baseline vascular tone of the occluded arm calculated by taking the ratio of the pulse amplitude during the hyperemic phase (after a period of blood flow occlusion) to the baseline pulse amplitude. The values below \<1.67 are abnormal and suggest impaired endothelial function or endothelial dysfunction.
Secondary Outcomes
- Serum Inflammatory Markers(Change in serum hsCRP from baseline to week 12 on treatment or placebo)
- Serum Estradiol Levels(Serum estradiol levels after 12 week of treatment vs placebo)
- Quality of Life (Questionnaire)(Change in quality of life scores after 12 week of treatment vs placebo)
- Depression(Change in PHQ-9 Scores after 12 week of treatment vs placebo)
- Change in Insomnia Severity Index After 12 Week of Treatment vs Placebo(Insomnia score after 12 week of treatment vs placebo)
- Anxiety(Change in Anxiety Scores after 12 week of treatment vs placebo)
- Stress(Change in stress scores after 12 week of treatment vs placebo)
- Change in Serum Estradiol Levels(change in estradiol after 12 week of treatment vs placebo)