Phase 2
N=29
Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women
Estrogen Deficiency · Cardiovascular Disease (CVD) · Functional Hypothalamic Amenorrhea · Endothelial Dysfunction
Bottom Line
View on ClinicalTrials.gov: NCT03018366 ↗Enrolled (actual)
29
Serious AEs
0.0%
Results posted
Feb 2025
Primary outcome: Primary: Rate of Change of Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry — 0.20; 0.25 change of RHI
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- 17beta Estradiol (Drug); Transdermal placebo patch (Drug); Progesterone (Drug); Placebo Pill (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Cedars-Sinai Medical Center
- Primary completion
- Feb 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Change of Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry |
0.20; 0.25 | — |
| SECONDARY Serum Inflammatory Markers |
0.0857; 0.0322 | — |
| SECONDARY Serum Estradiol Levels |
108.0; 36.5 | — |
| SECONDARY Quality of Life (Questionnaire) |
2.14; -0.45; 1.83; 2.69 | — |
| SECONDARY Depression |
-0.67; -0.08 | — |
| SECONDARY Change in Insomnia Severity Index After 12 Week of Treatment vs Placebo |
8.0; 3.9 | — |
| SECONDARY Anxiety |
-0.31; -0.54 | — |
| SECONDARY Stress |
-0.49; -0.46 | — |
| SECONDARY Change in Serum Estradiol Levels |
84; -4.7 | — |
| SECONDARY Serum Inflammatory Markers |
0.0857; 0.0322 | — |
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.
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 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
- Able to give informed consent
- Within 90-110% of ideal body weight
Exclusion Criteria
For premenopausal Hypo E and normal control women exclusions include:
- Smoking
- Hypertension
- Hyperlipidemia
- Diabetes
- 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
For recently menopausal women exclusions also include:
- Previous or current use of hormone therapy, estrogen or progestin
- Surgical or chemotherapy induced menopause
- Premature ovarian failure
Data sourced from ClinicalTrials.gov (NCT03018366). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.