Higher Dihydrotestosterone Is Associated with the Incidence of Lung Cancer in Older Men

Abstract

Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06-1.60; p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08-1.54; p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms.

Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels

“…Overall, these studies of men treated with supraphysiologic doses of DHT do not support the hypothesis that modest elevations of DHT and DHT/T ratios observed with commonly used TRT preparations (including injectable T esters, transdermal T, and oral TU) will yield deleterious effects in men, particularly in androgen-sensitive tissues like prostate. Consistent with this conclusion are recent data from a longitudinal, observational cohort study of 3638 men in which circulating DHT (measured by LC-MS/MS) was not associated with incident prostate cancer (56).…”

Pharmacoepidemiology of testosterone: Curbing off-label prescribing

“…The impact of exogenous testosterone on cardiovascular risk remains controversial with multiple meta‐analyses showing a consistent but nonsignificant increased odds ratio, suggesting increased cardiovascular risk but which remains underestimated by so‐far underpowered analyses which also overlook transient temporal effects . Similarly, although endogenous testosterone levels appears unrelated to future development of prostate cancer, the impact of exogenous testosterone treatment that modestly increases serum PSA is less well established with meta‐analysis showing minimal short‐term risk but larger and longer‐term studies are lacking.…”

Androgen Receptor(AR) and Estrogen Receptor α (ERα) Affect Cell Growth and Metastasis of Non-Small Cell Lung Cancer Through EGFR/PI3K/AKT Axis.

“…Cell migration and invasion assays showed that 10μM T and 10μM E 2 promoted cells migration and invasion, and 50μM T and 50μM E 2 inhibited cells migration and invasion, when T and E2 concentrations were increased to 100μM, cells migration and invasion were promoted again( Fig.4 A,B). A recent study reported higher T predict increased incidence of lung cancer over the next decade in older men (Chan et al , 2017). Marsaud V reported that the effect of E 2 on ERα expression in lung cancer was also related to intervention time (Marsaud et al , 2003).…”