Higher serum testosterone and dihydrotestosterone, but not oestradiol, are independently associated with favourable indices of lung function in community‐dwelling men

Mohan, Shalini S.; Knuiman, Matthew; Divitini, Mark; James, Alan; Musk, Arthur W.; Handelsman, David J.; Beilin, Jonathan; Hunter, Michael; Yeap, Bu B.

doi:10.1111/cen.12738

Cited by 55 publications

(61 citation statements)

References 38 publications

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“…Of note, asthmatic men with low total testosterone levels had lower lung function than asthmatic men with normal testosterone levels-consistent with studies in non-asthmatic populations [18,19]-and total testosterone values in men with severe asthma were lower than those in men with non-severe asthma. These data also suggest a protective effect of androgens on lung function.…”

Section: Background and Significance Regarding Androgens For Patientssupporting

confidence: 81%

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

et al. 2019

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Introduction: Among individuals with severe asthma, FEV 1 is low in individuals with low dehydroepiandrosterone (DHEA) sulfate (DHEAS) levels. In the Severe Asthma Research Program (SARP), no women with DHEAS [ 200 lg/dL had an FEV 1 \ 60% predicted. DHEA has benefited patients with COPD and pulmonary hypertension in small trials. Therefore, we hypothesized that DHEA supplementation may improve FEV 1 in asthmatic women with low DHEAS. Methods: Premenopausal, nonsmoking, otherwise healthy women, 18-50 years old, with mild or moderate asthma and baseline FEV 1 [ 60% predicted received 100 mg DHEA orally every 12 h for 2 weeks. Spirometry and DHEAS were measured at the initial visit and 2 weeks later, after completion of DHEA treatment. Based on our previous work, the primary outcome variable for this pilot study was post-albuterol spirometry in the low-DHEAS group. Subjects also continued their other routine asthma management. Results: Serum DHEAS increased with DHEA treatment in women with starting DHEAS \ 200 lg/dL: this increase was from 71 ± 23 to 725 ± 295 lg/dL (n = 10; p = 0.0001). The increase in the high-DHEAS group was smaller. Post-albuterol FEV 1 increased by 51 mL, from 3.026 ± 0.5 to 3.077 ± 0.49 L (n = 10; p = 0.034 by paired t test, significant after Bonferroni), in women with low DHEAS. In the high-DHEAS group (baseline DHEAS C 200 lg/dl), post-albuterol FEV 1 did not change significantly (n = 3, p = NS). Three subjects were excluded: one had comorbid COPD, one could not perform spirometry, and one did not take the DHEA. There were no adverse effects of DHEA treatment in this trial. Conclusions: Endocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma. Their use has improved asthma outcomes. Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically for asthma treatment. Our results suggest that the over-thecounter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS \ 200 ug/dL. Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9939215. Key Summary PointsEndocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma.Their use has improved asthma outcomes.Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically.Our results suggest that the over-thecounter steroid DHEA may also improve lung function in asthma outcomes among women with DHEAS \ 200 ug/dL.

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Section: Background and Significance Regarding Androgens For Patientssupporting

confidence: 81%

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

et al. 2019

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“…20 Recent studies in men also shown that testosterone levels in smokers was higher than non-smokers. 36 These results are also consistent with studies showing the variation of FT levels in healthy adult males. 37 The average levels of SHBG in this study 34.01±1.53 nmol/L.…”

Section: Parwanto Mle Int J Res Med Sci 2017 Aug;5(8):3431-3437supporting

confidence: 91%

The negative correlation between testosterone levels and age in healthy Indonesian men residing in the special capital province of Jakarta, Indonesia

Parwanto¹

2017

Int J Res Med Sci

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Background: Testosterone levels in the circulation determined by production and secretion by Leydig cell in the testes. The action mechanism of testosterone to target cells mediated by sex hormone binding globulin (SHBG). The levels of testosterone and SHBG in circulation determine men's health. The objective in this study to know the relationship between testosterone, SHBG and insulin with age in healthy Indonesian men residing in the special capital province of Jakarta, Indonesia.Methods: This study is a cross-sectional study involving 250 healthy Indonesian men residing in the special capital province of Jakarta, Indonesia. Consecutive sampling was done in this study. Testosterone, SHBG and insulin in the serum were measured by immunoradiometric assay (IRMA). Glucose, triglycerides and albumin were measured using a spectrophotometer. Regression analysis was done to know the correlation between testosterone, SHBG and insulin with age.Results: The levels of TT, free testosterone (FT), SHBG and percentage of free testosterone (%FT) in healthy Indonesian men were negatively correlated with age (p<0.05). Free testosterone index (FTI) and insulin are not correlated with age (p>0.05). The levels of SHBG, FT, %FT and FTI were correlated positively with TT (p<0.05), but insulin did not correlate with TT (p>0.05). The %FT and FTI were positively correlated with FT (p<0.05), but SHBG and insulin levels did not correlate with FT (p>0.05). SHBG levels are not correlated with insulin (p>0.05). The rate of decline in TT levels in this study 9.8% per decade, while in SHBG levels 8.19% per decade.Conclusions: The levels of TT, FT, % FT and SHBG in this study were negatively correlated with age, but the FTI and insulin did not correlate with age. The rate of decline in TT levels in this study 9.8% per decade, while in SHBG levels 8.19% per decade.

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“…Testosterone is associated with decreased Th2 and Th1 inflammation in animal models of asthma (8,9). Epidemiologically, androgens are associated with better lung function in large healthy cohorts (10,11) and in disease (12). Increasing circulating levels of adrenal and gonadal androgens in males and females during adolescence are believed to be associated with improving asthma during adolescence (12), and gonadal androgens in particular may be associated with gender-based differences in asthma incidence and severity in adulthood (12,(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

“…Androgens inhibit human airway smooth muscle and fibroblast proliferation (4-6), promote airway smooth muscle relaxation (7), and inhibit both Th2 and Th1 inflammation in animal models of asthma (8,9). Androgens are associated with better lung function in large healthy cohorts (10,11) and in asthma (12). Increasing circulating…”

mentioning

confidence: 99%

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Zein

Gaston

Bazeley

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is 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%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention.

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Higher serum testosterone and dihydrotestosterone, but not oestradiol, are independently associated with favourable indices of lung function in community‐dwelling men

Cited by 55 publications

References 38 publications

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study

The negative correlation between testosterone levels and age in healthy Indonesian men residing in the special capital province of Jakarta, Indonesia

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

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