Pilot E2 for Hypogonadal Women With CFBD

Cystic fibrosis (CF) is the most common fatal heritable disease in non-Hispanic whites; CF
results in frequent lung infections, chronic inflammation and progressive lung failure. With
advancements in medical care, patients with CF are living longer. The median survival of
women with CF born and diagnosed in 2010 is projected to be 37 years. Patients with CF are
now living long enough to develop comorbidities like Cystic Fibrosis related Bone Disease
(CFBD), hypogonadism manifesting as pubertal delay, premature ovarian insufficiency or
hypothalamic hypogonadism. These comorbidities in women without CF can be improved by
estrogen supplementation.

It is well established that treating hypogonadal (low estrogen levels) women with estrogen
can improve their bone health, slow the rate of bone loss and decrease bone turnover markers.
Supplemental estrogen given to hypogonadal women can improve sexual and reproductive health
including reduction of perimenopausal symptoms and improvement in sexual function which can
improve quality of life. There is very little research investigating the effects of estrogen
treatment for hypogonadal women with CF. The purpose of this study is to test the hypothesis
that daily oral estrogen supplements given to hypogonadal women with CFBD will improve their
bone health, sexual and reproductive health, and quality of life and modify markers of
inflammation and lung function.

Inclusion Criteria:

- Adult and adolescent female CF patients (age ≥ 18 years),

- presenting to the CF clinic for routine follow up of cystic fibrosis,

- hypogonadal women defined as E2 level < 25,

- dual energy X-ray absorptiometry (DEXA) scan within 2 years of enrollment with T- or
Z-score < -1,

- able to tolerate oral medications.

Exclusion Criteria:

- Inability to obtain or declined informed consent from the subject and/or legally
authorized representative,

- Pregnancy,

- Too ill to participate in study based on investigator's or study team's opinion,

- Current use of systemic estrogen,

- History of thromboembolic event within the previous 2 years,

- History of migraines with aura,

- Hypercoagulability including previous diagnosis of Factor V Leiden or Protein C or S
deficiency,

- Current smoker,

- History of diagnosis with breast or uterine cancer,

- Current significant liver disease with cholelithiasis or cirrhosis,

- Status post lung or liver transplantation,

- Current use of systemic steroids