What this study is
The purpose of this study is to assess whether the natural form of estrogen (17-beta estradiol) given as a patch so that it is absorbed through your skin, is better at improving bone strength over 1 year than natural estrogen (17-beta estradiol) taken by mouth, or a synthetic form oestrogen (ethinyl estradiol) given as a patch that also provides birth control.
Participants will:
1. Take estrogen for 1 year either (i) in its natural form as a patch twice a week (and progesterone by mouth for 12 days of each month), or (ii) in its natural form as a pill daily (and progesterone by mouth for 12 days of each month), or (iii) in a synthetic form as a birth control patch weekly for 3 weeks with 1 week off the patch. You will not be able to choose which form of estrogen you will receive as this will be assigned to you based on a pre-existing randomization sequence (like the flip of a coin) 2. Take provided calcium and vitamin D supplements 3. Attend 4 study visits over 12 months with two at the beginning and then every 6 months that include:
- History and Physical Exams
- Lab Work
- Imaging studies
- Questionnaires
- Dietary recalls
What's being tested
- transdermal 17β-E2 with cyclic progestin
Intervention · DRUG
100-mcg transdermal 17β-E2 patch (to be applied twice weekly) (continuous use), with 200 mg micronized progesterone given for 12 days of every month
- oral 17β-E2 with cyclic progestin
Intervention · DRUG
2 mg of oral 17β-E2 pills daily, with 200 mg micronized progesterone given for 12 days of every month
- transdermal EE+LNG
Intervention · DRUG
transdermal EE (30 mcg) + LNG (120 mcg) contraceptive patch (TWIRLA). Patch will be applied once a week for 3 consecutive weeks, with the 4th week off the patch (to be repeated after 4 weeks).
Study details
- Official title
- Role of Estrogen Formulation and Route of Delivery on Skeletal Outcomes in Functional Hypothalmic Amenorrhea
- Sponsor
- University of Virginia
- Conditions
- Bone Strength · Bone Density · FHA (Functional Hypothalamic Amenorrhea)
- Enrolling
- 150 people
- Starts
- 2025-10-01
- Est. completion
- 2030-05-31
- Design
- Open-label, randomized, parallel groups, Phase 2
- Record
- View on ClinicalTrials.gov ↗
Who can join
Age 14 Years – 30 YearsSex FEMALEHealthy volunteers Not acceptedYou may qualify if
- Females, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
- Women of reproductive age: use of an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no systemic skeletal effects) for study duration if sexually activeExcept: Note: Women who receive a progestin implant for contraception after study enrollment will be allowed to continue and will not be excluded from study.
- Biochemical criteria: negative βHCG (pregnancy test), TSH within 2x the upper limit of normal, prolactin <10 ng/mL above upper limit of normal, potassium between 3.0-5.0, ALT ≤3 times upper limit of normal, LDL ≤190 mg/dl.
- Patients with known hypothyroidism will be included if appropriately treated with levothyroxine and have a TSH within 2x the upper limit of normal for at least a month preceding the baseline study visit.
- Menstrual criteria: < 3 menses in the preceding 6 months.
You can't join if
- Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus; Primary thyroid dysfunction will be defined as a TSH level more than 2X the upper limit of normal per given reference range with unknown thyroid antibody status, or an abnormal TSH if known positive antibodies.; Patients with hypothyroidism will be excluded if not appropriately treated with levothyroxine and if they do not have a TSH level within 2X the upper limit of normal for at least a month preceding the baseline study visit, given possible effects on the reproductive axis and bone.
- Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation)
- Substance use disorder; current smoker (>10 cigarettes per day)
- Pregnant, planning to become pregnant within 12 months of the end of treatment and/or breastfeeding
- Hypertension or use of anti-hypertensive medications
- Other conditions causing oligo-amenorrhea such as PCOS, premature ovarian insufficiency
- Known sensitivity or absolute contraindication to any component of study medications (high risk thromboembolic disease, breast cancer or other estrogen- or progestin-sensitive cancer, liver tumors, acute viral hepatitis, decompensated cirrhosis, undiagnosed abnormal uterine bleeding
- BMI ≥ 25 kg/m2 (efficacy of the contraceptive patch being used in the study is lower at higher BMIs)
Sign in and we'll check these against your records.Full criteria on ClinicalTrials.gov ↗
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Study locations (2)
2 openContact for every open site
- Madhusmita Misra, MD, MPH · Contact434-924-9141madhusmita.misra@uvahealth.org
University of Virginia Medical Center
Charlottesville, Virginia, United States
- Contactcmb6w@virginia.edu
- Madhusmita Misra, MD, MPH · Principal investigator
- Christine Burt Solorzano, MD · Sub-investigator
RecruitingUniversity of Virginia
Charlottesville, Virginia, United States
Recruiting
Study team
Sponsor
University of Virginia
Study ID 302682
Principal investigator
Madhusmita Misra, MD, MPH
University of Virginia
Frequently asked questions
The sponsor hasn't published answers to common questions for this trial.