Effect of Androgens on Atherosclerotic Risk in Hypogonadism
Effect of Androgens on Atherosclerotic Risk in Hypogonadism
Objective Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder.
Design and methods Forty-three male patients aged 30 (range: 24–39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26–39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness.
Results The carotid intima-media thickness (P < 0·001) was higher and the brachial flow-mediated diameter (P = 0·002) was lower in patients with idiopathic hypogonadotropic hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = −0·556, P = <0·001). The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after the androgen replacement therapy (P = 0·002 and 0·026, respectively).
Conclusions This study indicated that low total testosterone levels can be considered a significant marker of atherosclerosis in patients with idiopathic hypogonadotropic hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months.
Hypogonadotropic hypogonadism (HH) is characterized by clinical symptoms related to hypogonadism, such as low total testosterone (TT) levels and low or nonelevated levels of gonadotrophins (1). HH is the result of congenital or acquired disorders that affect the hypothalamus and/or the pituitary gland. Congenital HH is separated into two main categories: anosmic HH (Kallmann syndrome), which is based on the presence of an impaired sense of smell, and congenital normosmic idiopathic hypogonadotropic hypogonadism (IHH). The prevalence of IHH has been estimated to range from 1:10 000 to 1:86 000 individuals.
Several studies have shown an association between androgen deficiency and increased mortality in men. Over the last decade, many studies have also demonstrated a relationship between androgen deficiency and cardiovascular disease. Androgen deficiency influences the development of metabolic syndrome. Some studies demonstrated that it increases total cholesterol, triglycerides and low-density lipid cholesterol (LDL-C) and reduces high-density lipid cholesterol (HDL-C). They also showed that androgen replacement therapy (ART) improves the lipid profile, suggesting that androgens may help to prevent the development and/or advance of atherosclerosis.
There is clinical evidence of an association between endothelial dysfunction and androgen deficiency. Several studies showed that the TT level is inversely correlated with the carotid intima-media thickness (IMT), which is an indicator of endothelial damage, independent of other atherosclerotic risk markers, such as body mass index (BMI), smoking, lipid parameters, hypertension and diabetes. A number of clinical studies have also demonstrated that TT was related to the brachial flow-mediated diameter (FMD%), which is an early indicator of endothelial dysfunction, independent of other atherosclerotic risk markers, and suggested that supplementation with TT increased the FMD%.
The previous studies of androgen deficiency and atherosclerosis included mostly elderly hypogonadal men. There is some clinical evidence of a relationship between androgen deficiency and atherosclerosis in young hypogonadal men, with one study showing that middle-aged men with low TT have increased carotid atherosclerosis. Another study indicates that testosterone replacement therapy improves endothelial function in young patients with IHH. We aimed to investigate the efficacy of ART in ameliorating several predefined atherosclerotic risk markers in young-to-middle-aged men with IHH.
Abstract and Introduction
Abstract
Objective Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder.
Design and methods Forty-three male patients aged 30 (range: 24–39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26–39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness.
Results The carotid intima-media thickness (P < 0·001) was higher and the brachial flow-mediated diameter (P = 0·002) was lower in patients with idiopathic hypogonadotropic hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = −0·556, P = <0·001). The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after the androgen replacement therapy (P = 0·002 and 0·026, respectively).
Conclusions This study indicated that low total testosterone levels can be considered a significant marker of atherosclerosis in patients with idiopathic hypogonadotropic hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months.
Introduction
Hypogonadotropic hypogonadism (HH) is characterized by clinical symptoms related to hypogonadism, such as low total testosterone (TT) levels and low or nonelevated levels of gonadotrophins (1). HH is the result of congenital or acquired disorders that affect the hypothalamus and/or the pituitary gland. Congenital HH is separated into two main categories: anosmic HH (Kallmann syndrome), which is based on the presence of an impaired sense of smell, and congenital normosmic idiopathic hypogonadotropic hypogonadism (IHH). The prevalence of IHH has been estimated to range from 1:10 000 to 1:86 000 individuals.
Several studies have shown an association between androgen deficiency and increased mortality in men. Over the last decade, many studies have also demonstrated a relationship between androgen deficiency and cardiovascular disease. Androgen deficiency influences the development of metabolic syndrome. Some studies demonstrated that it increases total cholesterol, triglycerides and low-density lipid cholesterol (LDL-C) and reduces high-density lipid cholesterol (HDL-C). They also showed that androgen replacement therapy (ART) improves the lipid profile, suggesting that androgens may help to prevent the development and/or advance of atherosclerosis.
There is clinical evidence of an association between endothelial dysfunction and androgen deficiency. Several studies showed that the TT level is inversely correlated with the carotid intima-media thickness (IMT), which is an indicator of endothelial damage, independent of other atherosclerotic risk markers, such as body mass index (BMI), smoking, lipid parameters, hypertension and diabetes. A number of clinical studies have also demonstrated that TT was related to the brachial flow-mediated diameter (FMD%), which is an early indicator of endothelial dysfunction, independent of other atherosclerotic risk markers, and suggested that supplementation with TT increased the FMD%.
The previous studies of androgen deficiency and atherosclerosis included mostly elderly hypogonadal men. There is some clinical evidence of a relationship between androgen deficiency and atherosclerosis in young hypogonadal men, with one study showing that middle-aged men with low TT have increased carotid atherosclerosis. Another study indicates that testosterone replacement therapy improves endothelial function in young patients with IHH. We aimed to investigate the efficacy of ART in ameliorating several predefined atherosclerotic risk markers in young-to-middle-aged men with IHH.
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