The goal of this study is to learn about the role of estrogen and other hormones in bone development in adolescent and young adult women with cystic fibrosis (CF). The study has two main components, an observational study and a feasibility sub-study. The main questions it aims to answer are:

• How do different forms of hormonal contraception (e.g. birth control pill or other progesterone only methods) impact bone health?
• Is a study of transdermal estradiol (estrogen skin patches) feasible in this group?
• How does transdermal estradiol impact bone health and quality of life?

Participants in the observational study will have three study visits (baseline, 6 months, and 12 months). At all visits, participants will have blood drawn and will complete questionnaires. At the baseline and 12 month visits, participants will additionally have x-rays and DXAs (bone density assessment). Between visits, participants will complete brief questionnaires. Researchers will compare various measurements over time to assess the impact of different forms of hormonal contraception.

Participants in the feasibility sub-study will apply transdermal estradiol patches once weekly for 12 months, fill out brief quality-of-life surveys in between study visits, and complete blood draws and questionnaires at four study visits (baseline, 3 months, 6 months, and 12 months). The participants will also have x-rays and DXAs performed at the baseline and 12 month visits. Researchers will examine changes in various measurements to determine the impact of transdermal estradiol.

Observational Study:

Inclusion Criteria:

• CF Diagnosis
• Females who have had at least 1 menstrual cycle
• Planning to use same formulation of estrogen supplementation (or none) for duration of study

Exclusion Criteria:

• Use of anti-osteoporosis therapy including anti-resorptives such as bisphosphonates or anabolic agents such as teriparatide or denosumab
• Conditions in which bone loss is known to be present or expected to occur, such as lactation
• Pregnant or planning to become pregnant
• In the opinion of the CF care team or study investigators participant should not participate in the study
• Inability to provide informed consent/assent

Feasibility Sub-Study:

Inclusion Criteria:

• All of above and
• <35 years old
• At least 2 years after first menstrual cycle
• Symptoms of low estrogen and/or low serum estradiol levels (< 50 pg/mL)

Exclusion Criteria:

• All of above and
• Contraindications to transdermal estradiol
• Current use of systemic estrogen (such as estrogen-containing oral contraceptive pill)
• Previous lung or liver transplant
• Use of chronic systemic glucocorticoids
• Severe vitamin D deficiency (serum 25(OH)D < 6 ng/mL)
• Conditions increasing risk of clot: history of previous deep vein thrombus or pulmonary embolism, current immobility, current peripherally inserted central catheter or mediport, known hypercoagulable condition
• Baseline study visit falls between 1 and 8 weeks after initiation of CF transmembrane receptor (CFTR) modulator
• Currently in pulmonary exacerbation
• Recent antibiotic use within the past 4 weeks for an acute pulmonary exacerbation
• Unwilling or unable to use a non-estrogen containing method of contraception such as barrier, abstinence, or progesterone-only method