Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production; androgens have potential benefits in asthma. A new study published in Proceedings of the National Academy of Sciences of the United States of America aimed to determine the association between dehydroepi and rosterone (DHEA)-sulfate and percentage predicted forced expiratory volume in 1s (FEV1PP). This study included the Severe Asthma Research Program (SARP) III cohort (n = 318), where in HSD3B1(1245) genotypes were assessed and the association between adrenal restrictive and adrenal permissive alleles and FEV₁PP in patients with glucocorticoid treatment (GC) and without daily oral glucocorticoid treatment (noGC) was investigated. Validation was performed in a second cohort (SARP Iⅈ n = 184). The results revealed that DHEA-sulfate was associated with FEV₁PP and is suppressed with GC treatment. GC patients—homozygous for the adrenal restrictive genotype—have lower FEV₁PP compared with noGC patients (54.3% vs. 75.1%). In patients with the homozygous adrenal permissive genotype, there was no significant FEV₁PP difference among GC versusnoGC patients. The results were independently confirmed – FEV₁PP for homozygous adrenal restrictive genotype in GC versusnoGC was 49.8 versus 63.4, and for homozygous adrenal permissive genotype, it was 66.7 versus 67.7. Hence, it was concluded that adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. It was stated that the findings throw light on opportunities for the prediction of GC resistance and pharmacologic intervention.