Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Valentyna Yasinska; Cristina Gómez; Johan Kolmert; Magnus Ericsson; Anton Pohanka; Anna James; Lars I Andersson; Maria Sparreman-Mikus; Ana R Sousa; John H Riley; Stewart Bates; Per S Bakke; Nazanin Zounemat Kermani; Massimo Caruso; Pascal Chanez; Stephen J Fowler; Thomas Geiser; Peter H Howarth; Ildikó Horváth; Norbert Krug; Paolo Montuschi; Marek Sanak; Annelie Behndig; Dominick E Shaw; Richard G Knowles; Barbro Dahlén; Anke-Hilse Maitland-van der Zee; Peter J Sterk; Ratko Djukanovic; Ian M Adcock; Kian Fan Chung; Craig E Wheelock; Sven-Erik Dahlén; Eva Wikström Jonsson; U-BIOPRED Study Group

doi:10.1183/23120541.00269-2023

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

ERJ Open Res. 2023 Oct 2;9(5):00269-2023. doi: 10.1183/23120541.00269-2023. eCollection 2023 Sep.

Authors

Valentyna Yasinska^{1

2

3}, Cristina Gómez^{2

3

4}, Johan Kolmert^{2

3

4}, Magnus Ericsson^{5

6

7}, Anton Pohanka^{5

6}, Anna James^{2

3

4}, Lars I Andersson^{1

2

3}, Maria Sparreman-Mikus^{1

2

3}, Ana R Sousa⁸, John H Riley⁸, Stewart Bates⁸, Per S Bakke⁹, Nazanin Zounemat Kermani¹⁰, Massimo Caruso¹¹, Pascal Chanez¹², Stephen J Fowler^{13

14}, Thomas Geiser¹⁵, Peter H Howarth^{16

17}, Ildikó Horváth^{18

19}, Norbert Krug²⁰, Paolo Montuschi^{10

21}, Marek Sanak²², Annelie Behndig²³, Dominick E Shaw²⁴, Richard G Knowles²⁵, Barbro Dahlén^{1

2

3}, Anke-Hilse Maitland-van der Zee²⁶, Peter J Sterk²⁶, Ratko Djukanovic^{16

17}, Ian M Adcock¹⁰, Kian Fan Chung¹⁰, Craig E Wheelock^{2

3

4}, Sven-Erik Dahlén^{1

2

3

4}, Eva Wikström Jonsson^{5

6}; U-BIOPRED Study Group

Affiliations

¹ Clinical Lung and Allergy Research, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
² Department of Respiratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
³ The Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
⁴ Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁶ Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
⁷ Laboratoire AntiDopage Français, Université Paris-Saclay, Châtenay-Malabry, France.
⁸ Respiratory and Speciality Group, GSK, Clinical Sciences, Stockley Park, UK.
⁹ Institute of Clinical Science, University of Bergen, Bergen, Norway.
¹⁰ National Heart and Lung Institute and Data Science Institute, Imperial College London, London, UK.
¹¹ Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
¹² Assistance Publique des Hôpitaux de Marseille, Clinique des Bronches, Allergies et Sommeil, Aix Marseille Université, Marseille, France.
¹³ Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK.
¹⁴ Manchester Academic Health Science Centre and NIHR Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
¹⁵ Department of Pulmonary Medicine, University Hospital, University of Bern, Bern, Switzerland.
¹⁶ Faculty of Medicine, Southampton University, Southampton, UK.
¹⁷ NIHR Southampton Respiratory Biomedical Research Center, University Hospital Southampton, Southampton, UK.
¹⁸ Department of Public Health, Semmelweis University, Budapest, Hungary.
¹⁹ National Koranyi Institute for Pulmonology, Budapest, Hungary.
²⁰ Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
²¹ Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
²² Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
²³ Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
²⁴ Nottingham NIHR Biomedical Research Centre, University of Nottingham, Nottingham, UK.
²⁵ Knowles Consulting, Stevenage Bioscience Catalyst, Stevenage, UK.
²⁶ Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Abstract

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.

Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.

Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months.

Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.