Which form of estrogen best improves bone strength in women with functional hypothalamic amenorrhea?

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

Adolescents and young adult females with functional hypothalamic amenorrhea will be randomly assigned to one of three estrogen regimens for 12 months: transdermal 17-beta estradiol patches with cyclic oral progesterone, oral 17-beta estradiol with cyclic oral progesterone, or a transdermal ethinyl estradiol-plus-levonorgestrel birth-control patch. All participants receive provided calcium and vitamin D supplements and attend four study visits over the year with bone density and strength measurements at baseline and follow-up. The trial directly compares natural estradiol delivered through the skin versus by mouth and versus a synthetic contraceptive patch to see which approach better preserves or improves skeletal health during the critical bone-accrual years.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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.

Exclusion Criteria:

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

  1. 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.
  2. 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's running

• University of Virginia Medical Center
  Charlottesville, Virginia, United States Recruiting
• University of Virginia
  Charlottesville, Virginia, United States Recruiting

Study contacts

• Principal investigator: Madhusmita Misra, MD, MPH — University of Virginia
• Study coordinator: Madhusmita Misra, MD, MPH
• Email: madhusmita.misra@uvahealth.org
• Phone: 434-924-9141

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.