{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:32:32Z","timestamp":1768980752705,"version":"3.49.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Systemic inflammation and male hypogonadism are 2 increasingly recognized \u201cnonconventional\u201d risk factors for long\u2010QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate\u2013corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10\u00a0years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C\u2010reactive protein and interleukin\u20106 levels. Reduction of testosterone levels, which also inversely correlated with 17\u2010\u03b2 estradiol over time, significantly contributed to inflammation\u2010induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C\u2010reactive protein, testosterone, and 17\u2010\u03b2 estradiol levels; in these patients, increased C\u2010reactive protein and reduced testosterone were associated with a worse short\u2010term outcome of the arrhythmia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">During systemic inflammatory activation, interleukin\u20106 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen\u2010to\u2010estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long\u2010QT syndrome\/TdP risk in men.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.023371","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T11:54:20Z","timestamp":1640174060000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Transient Hypogonadism Is Associated With Heart Rate\u2013Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-1214","authenticated-orcid":false,"given":"Pietro Enea","family":"Lazzerini","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Surgery and Neurosciences University of Siena 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