Role of Estrogen on Skeletal Outcomes in FHA

Recruiting now · Phase 2

Conditions studied: Bone Strength, Bone Density, FHA (Functional Hypothalamic Amenorrhea)

In brief

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

Key facts

Study ID: NCT07010146
Run by: University of Virginia
People needed: 150
Starts: 2025-10-01
Expected to finish: 2030-05-31
Last updated by the study team: 2026-07-17

Who can join

Age: 14 and older, up to 30. Sex: female. Healthy volunteers: not accepted.

You 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 active. 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 may not qualify 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)

Where it is running

University of Virginia Medical Center — Charlottesville, Virginia, United States (enrolling)
University of Virginia — Charlottesville, Virginia, United States (enrolling)

Full record on ClinicalTrials.gov

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