RecruitingPhase 2NCT07010146

Role of Estrogen on Skeletal Outcomes in FHA

Role of Estrogen Formulation and Route of Delivery on Skeletal Outcomes in Functional Hypothalmic Amenorrhea

Sponsor

University of Virginia

Enrollment

150 participants

Start Date

Jul 1, 2025

Study Type

INTERVENTIONAL

Conditions

Bone Density FHA (Functional Hypothalamic Amenorrhea)Bone Strength

Summary

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: 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) Take provided calcium and vitamin D supplements 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

Eligibility

Sex: FEMALEMin Age: 14 YearsMax Age: 25 Years

Inclusion Criteria4

Females, age 14-25 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
Biochemical criteria: negative βHCG (pregnancy test), normal TSH, prolactin, potassium, ALT ≤3 times upper limit of normal, LDL ≤190 mg/dl
Menstrual criteria: \< 3 menses in the preceding 6 months.

Exclusion Criteria8

Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
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)

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Interventions

DRUGtransdermal 17β-E2 with cyclic progestin

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

DRUGoral 17β-E2 with cyclic progestin

2 mg of oral 17β-E2 pills daily, with 200 mg micronized progesterone given for 12 days of every month

DRUGtransdermal EE+LNG

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).