Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea

Exclusion Criteria

• •For FHA and controls
• •Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
• •Use of bisphosphonates in the past year
• •Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation).
• •Current use of systemic corticosteroids
• •Migraine with aura as classified in IHS Classification ICHD-3.
• •Personal history of or first-degree relative with unprovoked thromboembolism (unless the subject has been tested and ruled out for a hypercoagulable state).
• •Active substance use disorder; currently smokes or vapes
• •History of malignancy or Paget disease of bone
• •Pregnant, planning to become pregnant within 12 months after the end of treatment and/or breastfeeding
• •Cardiovascular: History of myocardial infarction or stroke; history of hypertension or use of anti-hypertensive medications
• •Immunodeficiency or taking immunosuppressive therapy
• •Other conditions that can cause oligo-amenorrhea such as PCOS, primary ovarian insufficiency. A participant with PCOS may be included if a study clinician determines that missed menstrual periods are more likely a consequence of FHA.
• •Dental: Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (tooth extraction, dental implants, oral surgery in the past 3 months), poor oral hygiene, periodontal and/or pre-existing dental disease
• •Planned invasive dental procedure or other planned major surgery for 18 months after the baseline visit
• •Known sensitivity or absolute contraindication to any of the products or components of the medications to be administered (romosozumab, zoledronic acid, transdermal estradiol, micronized progesterone, calcium or vitamin D supplements)
• •BMD Z-score \<-2.5 (who we will refer for evaluation)