Low free testosterone is associated with heart failure mortality in older men referred for coronary angiography

Wehr, Elisabeth; Pilz, Stefan; Boehm, Bernhard O.; März, Winfried; Grammer, Tanja B.; Obermayer–Pietsch, Barbara

doi:10.1093/eurjhf/hfr007

Cited by 74 publications

(61 citation statements)

References 39 publications

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“…Considering the fact that both low vitamin D and low testosterone levels are associated with obesity (1,113), obesity might be a confounding factor when analyzing the association of low vitamin D or androgen status with mortality. However, in the above-mentioned studies (3,111,112), the association of vitamin D and androgens with increased mortality remained significant after adjustment for BMI. Interestingly, accumulating evidence exists for a complex interplay of vitamin D and androgen metabolism.…”

Section: Menmentioning

confidence: 84%

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MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: a systematic review

Lerchbaum

Obermayer-Pietsch

2012

European Journal of Endocrinology

321

252

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Background: Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men. Aim: The aim of this review was to assess the studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals. Methods: We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011. Results and discussion: The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. Vdr knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including IVF outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic, and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, low 25(OH)D levels, and osteoporosis despite normal testosterone levels.

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Section: Menmentioning

confidence: 84%

“…Testosterone Low levels of vitamin D and androgens are both associated with increased mortality in men (3,111,112). Considering the fact that both low vitamin D and low testosterone levels are associated with obesity (1,113), obesity might be a confounding factor when analyzing the association of low vitamin D or androgen status with mortality.…”

Section: Menmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: a systematic review

Lerchbaum

Obermayer-Pietsch

2012

European Journal of Endocrinology

321

252

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“…186 87 2007 In patients with low levels of baseline testosterone, exogenous testosterone did not affect any of the lipid subfractions In patients with normal levels of baseline testosterone, exogenous testosterone resulted in a significant decrease in total cholesterol levels In patients with normal levels of baseline testosterone, exogenous testosterone did not affect the levels of LDL, HDL, or triglyceride levels In patients with chronic disease or in those on glucocorticoid therapy, exogenous testosterone resulted in a small decrease in levels of HDL In patients with chronic disease or in those on glucocorticoid therapy, exogenous testosterone did not affect the levels of total cholesterol, LDL, or triglycerides Isidori et al, 147 2005 Exogenous testosterone resulted in reduced levels of total cholesterol The improvement in total cholesterol was more significant for patients with reduced levels of baseline testosterone No significant change in total cholesterol in patients with baseline testosterone of >10 nmol/L Exogenous testosterone did not affect levels of LDL or HDL The effect of testosterone replacement therapy on triglyceride levels was not examined in this meta-analysis Whitsel et al, 148 2001 Exogenous testosterone resulted in small but significant reduction in the levels of total cholesterol, LDL, and HDL Exogenous testosterone did not affect triglyceride levels HDL ¼ high-density lipoprotein cholesterol; LDL ¼ low-density lipoprotein cholesterol. From J Am Heart Assoc, 106 with permission.…”

Section: Level Of Evidence Ibmentioning

confidence: 99%

Testosterone Therapy and Cardiovascular Risk: Advances and Controversies

Morgentaler

Miner

Caliber

et al. 2015

Mayo Clinic Proceedings

171

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Two recent studies raised new concerns regarding cardiovascular (CV) risks with testosterone (T) therapy. This article reviews those studies as well as the extensive literature on T and CV risks. A MEDLINE search was performed for the years 1940 to August 2014 using the following key words: testosterone, androgens, human, male, cardiovascular, stroke, cerebrovascular accident, myocardial infarction, heart attack, death, and mortality. The weight and direction of evidence was evaluated and level of evidence (LOE) assigned. Only 4 articles were identified that suggested increased CV risks with T prescriptions: 2 retrospective analyses with serious methodological limitations, 1 placebo-controlled trial with few major adverse cardiac events, and 1 meta-analysis that included questionable studies and events. In contrast, several dozen studies have reported a beneficial effect of normal T levels on CV risks and mortality. Mortality and incident coronary artery disease are inversely associated with serum T concentrations (LOE IIa), as is severity of coronary artery disease (LOE IIa). Testosterone therapy is associated with reduced obesity, fat mass, and waist circumference (LOE Ib) and also improves glycemic control (LOE IIa). Mortality was reduced with T therapy in 2 retrospective studies. Several RCTs in men with coronary artery disease or heart failure reported improved function in men who received T compared with placebo. The largest meta-analysis to date revealed no increase in CV risks in men who received T and reduced CV risk among those with metabolic disease. In summary, there is no convincing evidence of increased CV risks with T therapy. On the contrary, there appears to be a strong beneficial relationship between normal T and CV health that has not yet been widely appreciated.

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“…12 It has also been shown that reduced T levels in men with CHF portends a poor prognosis and is associated with increased mortality. 13 …”

Section: 11mentioning

confidence: 99%

Testosterone and the Heart

Goodale

Sadhu

Petak

et al. 2017

Methodist DeBakey Cardiovascular Journal

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Testosterone (T) is the principal male sex hormone, secreted primarily by the testes and transported in the blood by the carrier protein, sex-hormone binding globulin (SHBG). Only 1% to 2% of testosterone circulates in blood as unbound "free" testosterone, but this fraction exhibits the most potent biological activity. Dihydrotestosterone (DHT), the most biologically active androgen, is synthesized from testosterone by 5a-reductase and exerts its effects via a family of androgen receptors. Some biological effects of testosterone may result from its aromatization to estradiol and subsequent interaction with the estrogen receptor. In addition to developing primary and secondary sex characteristics, androgens have diverse anabolic functions such as increasing muscle mass and bone density.1 Testosterone has also demonstrated a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular risk.2,3 However, whether low T causes negative cardiovascular events or is simply associated with them has yet to be determined. 4 This review highlights the evidence underlying the major interrelationships between androgens and the cardiovascular system. Testosterone Actions on Cardiovascular CellsTestosterone and the more potent DHT bind to cytoplasmic androgen receptors (AR) that are chaperoned by heat shock proteins. Once bound, the DHT-AR complex migrates to the nucleus, dimerizes with another DHT-AR complex, associates with coactivator proteins, and transactivates a family of genes with androgen response elements that alter myocardial and vascular cell behavior.1 Evidence also supports a direct rapid membrane effect of T on G-protein-coupled receptors, with an increase in inositol trisphosphate and diacylglycerol and subsequent alterations in cytoplasmic calcium and potassium channel activity. 5 Cardiovascular Risk in Testosterone Deficiency DefinitionTestosterone deficiency (TD) is a well-established major medical condition that negatively impacts male sexuality, general health, and quality of life. Symptoms include decreased libido, erectile dysfunction, decreased energy, depressed mood, irritability, and decreased sense of well-being. In the correct clinical setting, the diagnosis of TD is usually confirmed by low serum concentrations of total T (e.g., < 200 ng/mL) drawn in the early morning. However, there is no specific value that reliably distinguishes men who experience signs and symptoms of TD from those who do not nor those who will likely respond to treatment. Interpretation of total T concentrations is confounded by variation between individuals, variation in serum SHBG, and variation in androgen sensitivity. 6 Furthermore, considerable controversy has arisen regarding the accuracy of currently available commercial testosterone assays, especially those showing T levels at the lower end of the "normal" range. 4 Free testosterone level may be a more reliable indicator of androg...

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Low free testosterone is associated with heart failure mortality in older men referred for coronary angiography

Cited by 74 publications

References 39 publications

MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: a systematic review

MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: a systematic review

Testosterone Therapy and Cardiovascular Risk: Advances and Controversies

Testosterone and the Heart

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