Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Adolescents and Young Adults With Functional Hypothalamic Amenorrhea
The goal of this study is to determine whether romosozumab will improve bone density in girls and women with functional hypothalamic amenorrhea (cessation of the menstrual period due to intense exercise, stress, or an eating disorder) who have low bone density. Participants will be randomly assigned to receive romosozumab or placebo for 6 months. All participants will receive one IV infusion of zoledronate at the 6 month visit. All participants will also receive transdermal estradiol and cyclic progesterone. We will investigate whether participants who receive active romosozumab will demonstrate greater improvements in bone density at one year than those who receive placebo. We will also compare bone density over a year with healthy controls (girls and women of similar age who have regular menstrual periods).
⁃ For FHA and controls:
• Female, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
• For women of reproductive age, agree to use an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no evidence of systemic skeletal effects) for the study duration
• Biochemical criteria:
• Negative βHCG (pregnancy test)
• TSH within twice the upper limit of normal; potassium, magnesium within the normal range; prolactin \<10 ng/mL above the upper limit of normal; FSH not elevated.
• Serum ALT ≤ 3 times upper limit of normal, LDL ≤ 190 mg/dl
• eGFR ≥ 30ml/minute
• If the diagnosis of FHA is unclear, we may check additional labs (e.g., testosterone and sex hormone binding globulin if there is a suspicion of PCOS based on clinical hyperandrogenism).
⁃ Additional inclusion criteria for FHA:
• Less than 3 menses in the preceding 6 months
• BMD Z-score ≤ -1.0 at ≥ 1 skeletal site (for subjects \<18 years old, we will use the height Z-score-adjusted BMD Z-score using the pediatric bone density calculator developed by the National Institutes of Health and currently maintained by the Children's Hospital of Philadelphia)
• Dental check-up within the past year
• If the menstrual status of the subject is unclear due to the presence of a progestin-releasing IUD, serum estradiol levels will be checked twice, at least one week apart. Both estradiol levels must be \< 50 pg/mL.