Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease
Abstract Background Advancements in therapies for patients with cystic fibrosis (CF) have decreased mortality, leading to increased prevalence of chronic complications including bone disease. CF-related bone disease (CFBD) is characterized by low bone mineral density (BMD) and fragility fractures. E...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Pilot and Feasibility Studies |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40814-021-00897-x |
| _version_ | 1818721998255161344 |
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| author | Malinda Wu Rabindra Tirouvanziam Neha Arora Vin Tangpricha |
| author_facet | Malinda Wu Rabindra Tirouvanziam Neha Arora Vin Tangpricha |
| author_sort | Malinda Wu |
| collection | DOAJ |
| description | Abstract Background Advancements in therapies for patients with cystic fibrosis (CF) have decreased mortality, leading to increased prevalence of chronic complications including bone disease. CF-related bone disease (CFBD) is characterized by low bone mineral density (BMD) and fragility fractures. Estrogen deficiency increases bone resorption, resulting in decreased BMD that can be restored with estrogen replacement. Current CF guidelines recommend treating female hypogonadal patients with CFBD with estrogen replacement, but no prospective study has investigated the effects of estrogen supplementation on CFBD. Estrogen is known to modulate inflammatory markers and autoimmune diseases. We proposed to test the hypothesis that estrogen status plays a critical role in optimizing bone health, modulating inflammation, preserving lung function, and maximizing quality of life in premenopausal women with CF. Methods We planned a randomized, placebo-controlled, investigator- and patient-blinded, pilot trial with two parallel arms. Eligible subjects were women with CF 18–50 years old with hypogonadism and low BMD who were not taking systemic glucocorticoids, had not had a prior transplant, and did not have contraindications to oral estradiol. Subjects would be block randomized to receive oral estradiol or placebo for 6 months. The primary outcome was feasibility metrics. Secondary outcomes included relative changes in estradiol, bone turnover markers, lung function, inflammatory markers, and quality of life metrics. The study was funded through departmental funds. Results Of 233 subjects screened, 86 subjects were women with CF 18–50 years old and none were eligible for participation. Most subjects were excluded due to absent DXA report (24%), normal BMD (22%), or use of systemic estrogen (16%). Due to difficulty recruiting the planned 52 subjects, the trial was closed for recruitment and no subjects were randomized. Conclusion This study was designed to investigate the feasibility of a safety and efficacy trial of estrogen therapy for women with CF. Unfortunately, due to eligibility criteria, the study was unable to recruit subjects. This feasibility study highlights the need for improved BMD screening in young women with CF. Future study designs may require the incorporation of a screening DXA as part of subject recruitment. Trial registration The study was registered on ClinicalTrials.gov ( NCT03724955 ). |
| first_indexed | 2024-12-17T20:47:38Z |
| format | Article |
| id | doaj.art-8aed41732b7b4136852d99d4cefc246b |
| institution | Directory Open Access Journal |
| issn | 2055-5784 |
| language | English |
| last_indexed | 2024-12-17T20:47:38Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Pilot and Feasibility Studies |
| spelling | doaj.art-8aed41732b7b4136852d99d4cefc246b2022-12-21T21:33:07ZengBMCPilot and Feasibility Studies2055-57842021-08-01711810.1186/s40814-021-00897-xFindings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone diseaseMalinda Wu0Rabindra Tirouvanziam1Neha Arora2Vin Tangpricha3Division of Endocrinology, Department of Pediatrics, Emory University School of MedicineDivision of Pulmonology, Allergy, Cystic Fibrosis and Sleep, Department of Pediatrics, Center for CF and Airways Disease Research, Emory University School of MedicineEmory University College of Arts and SciencesDivision of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of MedicineAbstract Background Advancements in therapies for patients with cystic fibrosis (CF) have decreased mortality, leading to increased prevalence of chronic complications including bone disease. CF-related bone disease (CFBD) is characterized by low bone mineral density (BMD) and fragility fractures. Estrogen deficiency increases bone resorption, resulting in decreased BMD that can be restored with estrogen replacement. Current CF guidelines recommend treating female hypogonadal patients with CFBD with estrogen replacement, but no prospective study has investigated the effects of estrogen supplementation on CFBD. Estrogen is known to modulate inflammatory markers and autoimmune diseases. We proposed to test the hypothesis that estrogen status plays a critical role in optimizing bone health, modulating inflammation, preserving lung function, and maximizing quality of life in premenopausal women with CF. Methods We planned a randomized, placebo-controlled, investigator- and patient-blinded, pilot trial with two parallel arms. Eligible subjects were women with CF 18–50 years old with hypogonadism and low BMD who were not taking systemic glucocorticoids, had not had a prior transplant, and did not have contraindications to oral estradiol. Subjects would be block randomized to receive oral estradiol or placebo for 6 months. The primary outcome was feasibility metrics. Secondary outcomes included relative changes in estradiol, bone turnover markers, lung function, inflammatory markers, and quality of life metrics. The study was funded through departmental funds. Results Of 233 subjects screened, 86 subjects were women with CF 18–50 years old and none were eligible for participation. Most subjects were excluded due to absent DXA report (24%), normal BMD (22%), or use of systemic estrogen (16%). Due to difficulty recruiting the planned 52 subjects, the trial was closed for recruitment and no subjects were randomized. Conclusion This study was designed to investigate the feasibility of a safety and efficacy trial of estrogen therapy for women with CF. Unfortunately, due to eligibility criteria, the study was unable to recruit subjects. This feasibility study highlights the need for improved BMD screening in young women with CF. Future study designs may require the incorporation of a screening DXA as part of subject recruitment. Trial registration The study was registered on ClinicalTrials.gov ( NCT03724955 ).https://doi.org/10.1186/s40814-021-00897-xCystic fibrosisOsteoporosisCystic fibrosis-related bone diseaseEstrogenEstradiolHypogonadism |
| spellingShingle | Malinda Wu Rabindra Tirouvanziam Neha Arora Vin Tangpricha Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease Pilot and Feasibility Studies Cystic fibrosis Osteoporosis Cystic fibrosis-related bone disease Estrogen Estradiol Hypogonadism |
| title | Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease |
| title_full | Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease |
| title_fullStr | Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease |
| title_full_unstemmed | Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease |
| title_short | Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease |
| title_sort | findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis related bone disease |
| topic | Cystic fibrosis Osteoporosis Cystic fibrosis-related bone disease Estrogen Estradiol Hypogonadism |
| url | https://doi.org/10.1186/s40814-021-00897-x |
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