Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma

Mark D DeBoer, Brenda R Phillips, David T Mauger, Joe Zein, Serpil C Erzurum, Anne M Fitzpatrick, Benjamin M Gaston, Ross Myers, Kristie R Ross, James Chmiel, Min Jie Lee, John V Fahy, Michael Peters, Ngoc P Ly, Sally E Wenzel, Merritt L Fajt, Fernando Holguin, Wendy C Moore, Stephen P Peters, Deborah Meyers, Eugene R Bleecker, Mario Castro, Andrea M Coverstone, Leonard B Bacharier, Nizar N Jarjour, Ronald L Sorkness, Sima Ramratnam, Anne-Marie Irani, Elliot Israel, Bruce Levy, Wanda Phipatanakul, Jonathan M Gaffin, W Gerald Teague, Mark D DeBoer, Brenda R Phillips, David T Mauger, Joe Zein, Serpil C Erzurum, Anne M Fitzpatrick, Benjamin M Gaston, Ross Myers, Kristie R Ross, James Chmiel, Min Jie Lee, John V Fahy, Michael Peters, Ngoc P Ly, Sally E Wenzel, Merritt L Fajt, Fernando Holguin, Wendy C Moore, Stephen P Peters, Deborah Meyers, Eugene R Bleecker, Mario Castro, Andrea M Coverstone, Leonard B Bacharier, Nizar N Jarjour, Ronald L Sorkness, Sima Ramratnam, Anne-Marie Irani, Elliot Israel, Bruce Levy, Wanda Phipatanakul, Jonathan M Gaffin, W Gerald Teague

Abstract

Background: Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch.

Methods: To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n = 68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression.

Results: From pre-/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV1% and FVC %.

Conclusions: These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty.

Trial registration: ClinicalTrials.gov registration number: NCT01748175 .

Keywords: Asthma; Estradiol; Lung function; Puberty; Sex hormones; Testosterone.

Conflict of interest statement

Ethics approval and consent to participate

Study procedures were approved by the IRB at each institution and an independent Data Safety Monitoring Board. All subjects provided written informed consent and/or assent. For participants under 16 years-old consent was provided by a parent or legal guardian.

Competing interests

There are no conflicts of interest with the study sponsors (NIH/NHLBI) or any commercial entity in the study design, the collection, analysis, and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. The authors submit they will declare potential conflicts of interests per BMC Pulmonary Medicine publication policies.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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