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