Hormone Replacement Therapy in Adolescents With Premature Ovarian Insufficiency

* INCLUSION CRITERIA: Inclusion Criteria for POI Participants To be eligible to participate in this study, an individual must meet all the following criteria: 1. Individuals aged 11-19 years, inclusive, at the time of enrollment. 2. Diagnosis of premature ovarian insufficiency. 3. Documentation of one elevated serum FSH measurement greater than the testing laboratory's upper reference range (for age/Tanner stage). 4. Identify as female (i.e., sex assigned at birth) 5. Negative pregnancy test. Inclusion Criteria for Healthy Volunteers: 1. Individuals aged 11-19 years. 2. Identify as female (i.e., sex assigned at birth) 3. Negative pregnancy test. 4. Absence of known chronic disease EXCLUSION CRITERIA: Male participants are excluded from both study groups (POI and Healthy Volunteers) as POI affects only the female reproductive system, while pregnant participants are not eligible to have DXA or HRpQCT imaging for safety reasons. Exclusion Criteria for POI participants: An individual who meets any of the following criteria will be excluded from participation in this study: 1. POI in the setting of Turner syndrome. 2. Patients who screened positive for celiac disease. 3. Receipt of any medications including HRT determined by the investigator to affect bone metabolism 3 months prior to enrollment. 4. Any medical condition determined by the investigator to affect bone health will be excluded. 5. Presence of a medical, psychiatric, or social condition which, in the opinion of the investigator, would place undue burden on the subject, NIH resources, or increase risk of participation. 6. Report of sexual activity but refusal to use a copper intrauterine device or double barrier forms of contraception during the study. Exclusion Criteria for Healthy Volunteers: For healthy volunteers, all exclusion criteria will apply as for POI participants except for number 1.