Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
Authors: Yasinska Valentyna , Gómez Cristina , Kolmert Johan , Ericsson Magnus , Pohanka Anton , James Anna , Andersson Lars I. , Sparreman-Mikus Maria , Sousa Ana R. , Riley John H. , Bates Stewart , Bakke Per S. , Zounemat Kermani Nazanin , Caruso Massimo , Chanez Pascal , Fowler Stephen J. , Geiser Thomas , Howarth Peter H. , Horváth Ildikó , Krug Norbert , Montuschi Paolo , Sanak Marek , Behndig Annelie , Shaw Dominick E. , Knowles Richard G. , Dahlén Barbro , Maitland-van der Zee Anke-Hilse , Sterk Peter J. , Djukanovic Ratko , Adcock Ian M. , Chung Kian Fan , Wheelock Craig E. , Dahlén Sven-Erik , Wikström Jonsson Eva ,   U-BIOPRED Study Group, Ahmed H. , Auffray C. , Bansal A.T. , Baribaud F. , Bel E.H. , Bigler J. , Billing B. , Bisgaard H. , Boedigheimer M.J. , Bønnelykke K. , Brandsma J. , Brinkman P. , Bucchioni E. , Burg D. , Bush A. , Campagna D. , Chaiboonchoe A. , Chalekis R. , Cheka T. , Compton C.H. , Corfield J. , Cunoosamy D. , D'Amico A. , De Meulder B. , Emma R. , Erpenbeck V.J. , Erzen D. , Fichtner K. , Fitch N. , Fleming L.J. , Formaggio R. , Frey U. , Gahlemann M. , Goss V. , Guo Y. , Hashimoto S. , Haughney J. , Hedlin G. , Hekking P.W. , Higenbottam T. , Hohlfeld J.M. , Knox A.J. , Konradson J. , Lazarinis N. , Lefaudeux D. , Li C-X. , Loza M.J. , Lutter R. , Manta A. , Masefield S. , Matthews J.G. , Mazein A. , Meiser A. , Middelveld R.J.M. , Miralpeix M. , Mores N. , Murray C.S. , Musial J. , Myles D. , Nordlund B. , Olsson H. , Östling J. , Pahus L. , Pavlidis S. , Postle A. , Powel P. , Praticò G. , Puig Valls M. , Rao R. , Reinke S. , Roberts A. , Roberts G. , Rowe A. , Sandström T. , Schofield J.P.R. , Seibold W. , Selby A. , Sigmund R. , Singer F. , Skipp P.J. , Smicker M. , Ström M. , Sun K. , Thornton B. , Uddin M. , van Aalderen W.M. , van Geest M. , Vestbo J. , Vissing N.H. , Wagener A.H. , Wagers S.S. , Weiszhart Z. , Wheelock Å. , Wilson S.J. 
Published: August 2023

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.