Oral ethinyl estradiol treatment in women with cystic fibrosis is associated with lower bone mineral density

Abstract

Objective: The purpose of this study was to determine whether estrogen supplementation primarily from oral contraceptive pills compared to no estrogen supplementation is associated with differences in mean bone mineral density (BMD) measured by DXA in a cross-sectional study of women with cystic fibrosis (CF).

Methods: In this cross-sectional study of women with CF followed at a single center, we analyzed 49 women with CF ages 18-50 years with a documented DXA. BMD of women with CF taking estrogen supplementation was compared to BMD of women with CF not taking estrogen supplementation.

Results: Twelve women with CF were taking estrogen supplementation with mean dose of 23.3 mcg/day (SD 6.9 mcg/day) of ethinyl estradiol. There were no statistically significant differences between demographics of the 12 women with CF taking estrogen supplementation compared to the 37 women with CF not taking estrogen supplementation. Women taking estrogen had lower mean lumbar spine Z-score: -0.7 ± 0.7, compared to women not taking estrogen, Z-score: -0.04 ± 1.0 (p-value 0.046). Women taking estrogen had lower mean BMD at the lumbar spine: 0.952 ± 0.086 g/cm², compared to women not taking estrogen: 1.023 ± 0.105 g/cm² (p-value 0.038). Similar trends were seen at the total hip and femoral neck.

Conclusion: Low-dose estrogen supplementation in premenopausal women with CF was associated with lower BMD compared to no estrogen supplementation in a similar group of premenopausal young women with CF. Future studies are needed to investigate the optimal formulation, route of administration, and dose to accrue and preserve bone mass in premenopausal women with CF.

Keywords: BMD, Bone mineral density; BMI, Body mass index; CF, Cystic fibrosis; CFBD, Cystic fibrosis-related bone disease; CFTR, Cystic fibrosis transmembrane conductance regulator; Cystic fibrosis-related bone disease; DXA, Dual X-ray absorptiometry; Estrogen; Ethinyl estradiol; FEV1, Forced expiratory volume in 1 second; FVC, Forced vital capacity; Hypogonadism; Lumbar spine; Osteoporosis; POI, Primary ovarian insufficiency.

Fig. 1

Lumbar spine Z-score vs age by estrogen exposure: Bone mineral density Z-scores at the lumbar spine from each subject taking estrogen (red triangles) compared to each subject not taking estrogen (blue squares). The dashed line represents Z-score of 0. Only 2 (16.7%) women with CF taking estrogen had a Z-score > 0; whereas, 17 (45.9%) women with CF not taking estrogen had a Z-score > 0. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Femoral neck Z-score vs age by estrogen exposure: Bone mineral density Z-scores at the femoral neck from each subject taking estrogen (red triangles) compared to each subject not taking estrogen (blue squares). The dashed line represents Z-score of 0. Of the women with CF taking estrogen, 3 of 12 (25%) subjects had Z-score > 0; whereas, 20 of 36 (55.6%) subjects with CF not taking estrogen had Z-score > 0. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Total hip Z-score vs age by estrogen exposure: Bone mineral density Z-scores at the total hip from each subject taking estrogen (red triangles) compared to each subject not taking estrogen (blue squares). The dashed line represents Z-score of 0. Of the women with CF taking estrogen, 4 of 12 (33.3%) subjects had Z-score > 0; whereas, 19 of 36 (52.8%) subjects with CF not taking estrogen had Z-score > 0. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Box plots of BMD Z-score by estrogen exposure: Women exposed to estrogen compared to women not exposed to estrogen had lower BMD Z-score at lumbar spine (p-value 0.046), femoral neck (0.049), and total hip (>0.05).

Fig. 5

Lumbar spine BMD Z-score by ethinyl estradiol dose: The lumbar spine BMD Z-score of subjects exposed to estrogen (red triangles) are plotted against the average daily dose of ethinyl estradiol in their prescribed estrogen supplement. Subjects exposed to progesterone only without estrogen (purple circle) have been plotted adjacent to subjects exposed to neither estrogen not progesterone (blue square). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)