SUN-337 Low Dose Ethinyl Estradiol in Women with Cystic Fibrosis Does Not Preserve Bone Mass

BACKGROUND: Cystic fibrosis-related bone disease (CFBD) affects 26% of adults with cystic fibrosis (CF). CFBD increases the risk for fractures, which in turn limits patients’ ability to effectively perform daily therapies necessary to maintain health. Factors contributing to CFBD include nutritional deficiencies, inflammation, glucocorticoid use, CF-related diabetes and untreated hypogonadism. Hypogonadism in CF is thought to be functional, although the distribution of etiologies of female hypogonadism in the modern era of CF therapies is unknown. Estrogen supplementation is commonly prescribed in the form of oral contraceptives to women with low bone mineral density (BMD). At our CF center, the average dose of ethinyl estradiol prescribed to women is 20 mcg. Recent evidence suggests that oral estrogen is ineffective for restoring bone health in women with functional hypogonadism and specifically that doses < 30 mcg oral ethinyl estradiol are inadequate. It is unknown if estradiol supplementation will restore and/or maintain BMD in women with CFBD. METHODS: The purpose of this study was to examine the skeletal health of a cross-section of premenopausal women seen at a single CF center taking 20 mcg or less of ethinyl estradiol daily (low-dose estrogen) compared to women not taking estrogen supplement. As screening for an IRB-approved intervention study, we collected health information by chart review. RESULTS: In a 12-week period, 98 women were seen in CF clinic. Of women 18 - 50 years old with CF and a documented DXA, 37 women were not taking estrogen supplement (mean age 30.8 ± 5.9 years) and 6 women were taking low-dose estrogen (mean age 30.4 ± 7.1 years). There were not statistically significant differences in other baseline characteristics known to modify CFBD. Women not taking estrogen had higher lumbar spine z-score: -0.04 ± 1.0, compared to women taking low-dose estrogen, z-score: -0.7 ±, 0.5 (p-value 0.01). Women not taking estrogen had higher BMD at the lumbar spine: 1.02 ± 0.1 g/cm(2), compared to women taking low-dose estrogen: 0.95 ± 0.1 g/cm(2) (p-value 0.03). Similar trends were seen at the total hip and femoral neck (p-values > 0.05). DISCUSSION: In this retrospective single-center chart review, women not taking estrogen supplement compared to women taking low-dose estrogen supplement had higher BMD. This was statistically significant at the lumbar spine, the DXA site with mostly trabecular bone. Estrogen deficiency causes trabecular bone loss, which can be restored with estrogen supplementation. These findings raise concern that low-dose estrogen supplementation for women with CF is inadequate for optimal bone accrual and may be detrimental. The ideal route and dose of estrogen supplementation for skeletal health of premenopausal women with CF still needs to be clarified. REFERENCES: CFF Patient Registry 2017; Aris JCEM 2005; Ackerman JCEM 2019; Anabtawi J CF 2019; Hughan J CF 2019