Testosterone and cardiovascular disease

The cardiovascular actions of androgens (“male” sex steroids, e.g. testosterone, mainly acting via the androgen receptor) are poorly defined. Prostate cancer, the second most common cancer in men, is often efficiently treated with androgen deprivation therapy (ADT) that lower androgen levels or inhibit androgen action. However, severe cardiac side effects, including heart failure, are associated with ADT use. There are still critical knowledge gaps regarding mechanisms underlying the adverse cardiovascular effects of ADT. Our overall aim is to provide novel insights into the mechanisms by which ADT causes heart failure. We hope that our translational research will pave the way for tailored hormonal therapies with minimized cardiovascular side effects

Key publications

Olivius C, Landin-Wilhelmsen K, Ohlsson C, Poutanen M, Trimpou P, Olsson DS, Johannsson G, Tivesten Å.   Sex steroid levels in women with hypopituitarism: a case-controlled observational study.  Journal of Clinical Endocrinology and Metabolism. 2024 Apr 4:dgae197. doi: 10.1210/clinem/dgae197.    

Yeap BB, Marriott RJ, Dwivedi G, Adams RJ, Antonio L, Ballantyne CM, Bauer DC, Bhasin S, Biggs ML, Cawthon PM, Couper DJ, Dobs AS, Flicker L, Handelsman DJ, Hankey GJ, Hannemann A, Haring R, Hsu B, Karlsson M, Martin SA, Matsumoto AM, Mellström D, Ohlsson C, O'Neill TW, Orwoll ES, Quartagno M, Shores MM, Steveling A, Tivesten Å, Travison TG, Vanderschueren D, Wittert GA, Wu FCW, Murray K.   Testosterone and mortality risk in men.  Annals of Internal Medicine. 2024 Jun;177(6):768-781.    

Esposito D, Tivesten Å, Olivius C, Ragnarsson O, Johannsson G. Androgen deficiency in hypopituitary women: its consequences and management.  Rev Endocr Metab Disord. 2024 Jun;25(3):479-488.    

Ohlsson C, Nethander M, Norlén AK, Poutanen M, Freyr Gudmundsson E, Aspelund T, Sigurdsson S, Ryberg H, Gudnason V, Tivesten Å.    Serum DHEA and Testosterone Levels Associate Inversely with Coronary Artery Calcification in Elderly Men   Journal of Clinical Endocrinology and Metabolism. 2023 Nov 17;108(12):3272-3279    

Marriott RJ, Murray K, Adams RJ, Antonio L, Ballantyne CM, Bauer DC, Bhasin S, Biggs ML, Cawthon PM, Couper DJ, Dobs AS, Flicker L, Handelsman DJ, Hankey GJ, Hannemann A, Haring R, Hsu B, Karlsson M, Martin SA, Matsumoto AM, Mellström D, Ohlsson C, O'Neill TW, Orwoll ES, Quartagno M, Shores MM, Steveling A, Tivesten Å, Travison TG, Vanderschueren D, Wittert GA, Wu FCW, Yeap BB.   Factors Associated With Circulating Sex Hormones in Men: Individual Participant Data Meta-analyses.  Annals of Internal Medicine. 2023 Sep;176(9):1221-1234.    

Svedlund Eriksson E, Johansson I, Mårtensson AKF, Lantero Rodriguez M, Schilperoort M, Kroon J, Kooijman S, Omerovic E, Andersson L, Levin MC, Rensen PCN, Tivesten Å.  Castration of Male Mice Induces Metabolic Remodeling of the Heart.   Journal of the Endocrine Society. 2022 Sep 1;6(11):bvac132.      

Wilhelmson AS, Johansson I, Fogelstrand L, Fagman JB, Arnal JF, Karlsson MCI, Tivesten Å.  Deficiency of mature B cells does not alter the atherogenic response to castration in male mice.   Scientific Reports. 2022 Jul 28;12(1):12931. doi: 10.1038/s41598-022-16846-4.    

Ohlsson C, Langenskiöld M, Smidfelt K, Poutanen M, Ryberg H, Norlén AK, Nordanstig J, Bergström G, Tivesten Å.   Low Progesterone and Low Estradiol Levels Associate with Abdominal Aortic Aneurysms in Men.  Journal of Clinical Endocrinology and Metabolism. 2022 Mar 24;107(4):e1413-e1425    

Lantero Rodriguez M, Schilperoort M, Johansson I, Svedlund Eriksson E, Palsdottir V, Kroon J, Henricsson M, Kooijman S, Ericson M, Borén J, Ohlsson C, Jansson JO, Levin MC, Rensen PCN, Tivesten Å.   Testosterone reduces metabolic brown fat activity in male mice.  Journal of Endocrinology 2021 Sep 3;251(1):83-96.    

 Langenskiöld M, Smidfelt K, Nordanstig J, Bergström G, Tivesten Å.  Leukocyte subsets and abdominal aortic aneurysms detected by screening in men.    Journal of Internal Medicine. 2020 Sep;288(3):345-355.    

Wu PH, Westerberg PA, Kindmark A, Tivesten Å, Karlsson MK, Mellström D, Ohlsson C, Fellström B, Linde T, Ljunggren Ö.   The association between Single Nucleotide Polymorphisms of Klotho Gene and Mortality in Elderly Men: The MrOS Sweden Study.  Scientific Reports. 2020 Jun 24;10(1):10243.    

 Wilhelmson AS, Lantero Rodriguez M, Johansson I, Svedlund Eriksson E, Stubelius A, Lindgren S, Fagman JB, Fink PJ, Carlsten H, Ekwall O, Tivesten Å.   Androgen Receptors in Epithelial Cells Regulate Thymopoiesis and Recent Thymic Emigrants in Male Mice   Frontiers in Immunology 2020 Jun 29;11:1342    

 Wilhelmson AS, Lantero Rodriguez M, Stubelius A, Fogelstrand P, Johansson I, Buechler MB, Lianoglou S, Kapoor VN, Johansson ME, Fagman JB, Duhlin A, Tripathi P, Camponeschi A, Porse BT, Rolink AG, Nissbrandt H, Turley SJ, Carlsten H, Mårtensson IL, Karlsson MCI, Tivesten Å.  Testosterone is an endogenous regulator of BAFF and splenic B cell number.  Nature Communications 2018 May 25;9(1):2067.      

Wilhelmson AS, Lantero Rodriguez M, Svedlund Eriksson E, Johansson I, Fogelstrand P, Stubelius A, Lindgren S, Fagman JB, Hansson GK, Carlsten H, Karlsson MCI, Ekwall O, Tivesten Å.   Testosterone protects against atherosclerosis in male mice by targeting thymic epithelial cells.  Arteriosclerosis, Thrombosis, and Vascular Biology 2018 Jul;38(7):1519-1527.    

Olivius C, Landin-Wilhelmsen K, Olsson DS, Johannsson G, Tivesten Å.  Prevalence and treatment of central hypogonadism and hypoandrogenism in women with hypopituitarism.  Pituitary 2018 Oct;21(5):445-453.    

Lundell AC, Ryberg H, Vandenput L, Rudin A, Ohlsson C, Tivesten Å.  Umbilical cord blood androgen levels in girls and boys assessed by gas chromatography-tandem mass spectrometry.  Journal of Steroid Biochemistry and Molecular Biology 2017 Jul;171:195-200.    

Lundell AC, Nordström I, Andersson K, Strömbeck A, Ohlsson C, Tivesten Å, Rudin A.  Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys.  Scientific Reports. 2017 Nov 14;7(1):15503.    

Svensson J, Sjögren K, Levin M, Borén J, Tivesten Å*, Ohlsson C*.  Increased diet-induced fatty streak formation in female mice with deficiency of liver-derived insulin-like growth factor-I. *Shared last authorship  Endocrine. 2016 Jun; 52(3):550-60    

Eriksson AL, Wilhelmson AS, Fagman JB, Ryberg H, Koskela A, Tuukkanen J, Tivesten Å, Ohlsson C.  The bone sparing effects of 2-methoxyestradiol are mediated via estrogen receptor-α in male mice.  Endocrinology. 2016 Nov;157(11):4200-4205.    

Wilhelmson AS, Fagman JB, Johansson I, Zou ZV, Andersson AG, Svedlund Eriksson E, Johansson ME, Lindahl P, Fogelstrand P, Tivesten Å.  Increased intimal hyperplasia after vascular injury in male androgen receptor-deficient mice.  Endocrinology. 2016 Oct;157(10):3915-3923.    

Fagman JB, Wilhelmson AS, Motta BM, Pirazzi C, Alexanderson C, De Gendt K, Verhoeven G, Holmäng A, Anesten F, Jansson JO, Levin M, Borén J, Ohlsson C, Krettek A, Romeo S, Tivesten Å.  The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.   FASEB J. (2015); 29(4):1540-50.    

Wilhelmson AS, Stubelius A, Börjesson AE, Wu J, Stern A, Malin S, Mårtensson IL, Ohlsson C, Carlsten H, Tivesten Å.  Androgens regulate bone marrow B lymphopoiesis in male mice by targeting osteoblast-lineage cells.  Endocrinology. (2015); 156(4):1228-36.    

Nilsson ME, Vandenput L, Tivesten Å, Norlén AK, Lagerquist MK, Windahl SH, Börjesson AE, Farman HH, Poutanen M, Benrick A, Maliqueo M, Stener-Victorin E, Ryberg H, Ohlsson C.  Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry.  Endocrinology. (2015); 156(4):1228-36    

Tivesten Å, Nilsson M, Carlzon D, Vandenput L, Karlsson MK, Ljunggren Ö, Barrett-Connor E, Mellström D, Ohlsson C.    Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men.   Journal of the American College of Cardiology (2014) 64(17):1801-10.      

Ohlsson C, Nilsson ME, Tivesten Å, Ryberg H, Mellström D, Karlsson MK, Ljunggren Ö, Labrie F, Orwoll ES, Lee DM, Pye SR, O’Neill TW, Finn JD, Adams JE, Ward KA, Boonen S, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean MEJ, Pendleton N, Punab M, Vanderschueren D, Wu FCW, the EMAS study group, Vandenput L.   Comparisons of immunoassay and mass spectrometry measurements of serum estradiol levels and their influence on clinical association studies in men.  Journal of Clinical Endocrinology and Metabolism (2013); 98(6):E1097-102    

Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellström D, Tivesten Å.   High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden.    Journal of the American College of Cardiology (2011); 58(16):1674-81      

Wilhelmson AS, Bourghardt-Fagman J, Gogos JA, Fogelstrand P, Tivesten Å.   Catechol-O-methyltransferase is dispensable for vascular protection by estradiol in mouse models of atherosclerosis and neointima formation.    Endocrinology (2011);152(12):4683-90    

Bourghardt J, Wilhelmson A, Alexanderson C, De Gendt K, Verhoeven G, Krettek A, Ohlsson C, Tivesten Å.   Androgen receptor-dependent and independent atheroprotection by testosterone in male mice.    Endocrinology (2010);151(11):5428-37    

Ohlsson C, Labrie F, Barrett-Connor E, Karlsson MK, Ljunggren O, Vandenput L, Mellström D, Tivesten Å.   Low serum levels of dehydroepiandrosterone predict all-cause and cardiovascular mortality in elderly Swedish men.    Journal of Clinical Endocrinology and Metabolism (2010) 95(9): 4406-4414    

Tivesten Å, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellström D, Ohlsson C.     Low serum testosterone and estradiol predict mortality in elderly men.    Journal of Clinical Endocrinology and Metabolism (2009) 94(7):2482-8.    

Bourghardt J, Bergström G, Krettek A, Sjöberg S, Borén J, Tivesten Å.   The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-deficient mice.    Endocrinology (2007) 148(9):4128-32    

Tivesten Å, Mellström D, Jutberger H, Fagerberg B, Lernfelt B, Orwoll E, Karlsson MK, Ljunggren Ö, Ohlsson C.   Low serum testosterone and high serum estradiol levels associate with lower extremity peripheral arterial disease in elderly men: The MrOS study in Sweden.   Journal of the American College of Cardiology (2007) 50(11):1070-6