Increased heart rate and atherosclerosis: potential implications of ivabradine therapy

Despite all the therapeutic advances in the field of cardiology, cardiovascular diseases, and in particular coronary artery disease, remain the leading cause of death and disability worldwide, thereby underlining the importance of acquiring new therapeutic options in this field. A reduction in elevated resting heart rate (HR) has long been postulated as a therapeutic approach in the management of cardiovascular disease. An increased HR has been shown to be associated with increased progression of coronary atherosclerosis in animal models and patients. A high HR has also been associated with a greatly increased risk of plaque rupture in patients with coronary atherosclerosis. Endothelial function may be an important link between HR and atherosclerosis. An increased HR has been shown experimentally to cause endothelial dysfunction. Inflammation plays a significant role in the pathogenesis and progression of atherosclerosis. In the literature, there is data that shows an association between HR and circulating markers of vascular inflammation. In addition, HR reduction by pharmacological intervention with ivabradine (a selective HR-lowering agent that acts by inhibiting the pacemaker ionic current If in sinoatrial node cells) reduces the formation of atherosclerotic plaques in animal models of lipid-induced atherosclerosis. The aim of this editorial is to review the possible role of ivabradine on atherosclerosis.     

Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly

The nation’s aging population is growing rapidly. By 2030, the number of adults age 65 and older will nearly double to 70 million. Americans are living longer and older adults can now live for many years with multiple chronic illnesses but with a substantial cost to health care. Twenty percent of the Medicare population has at least five chronic conditions i.e., hypertension, diabetes, arthritis, etc. Studies in experimental models and even humans reveal that constitutive production of nitric oxide (NO) is reduced with aging and this circumstance may be relevant to a number of diseases that plague the aging population. NO is a multifunctional signaling molecule, intricately involved with maintaining a host of physiological processes including, but not limited to, host defense, neuronal communication and the regulation of vascular tone. NO is one of the most important signaling molecules in our body, and loss of NO function is one of the earliest indicators or markers of disease. Clinical studies provide evidence that insufficient NO production is associated with all major cardiovascular risk factors, such as hyperlipidemia, diabetes, hypertension, smoking and severity of atherosclerosis, and also has a profound predictive value for disease progression including cardiovascular and Alzheimers disease. Thirty plus years after its discovery and over 13 years since a Nobel Prize was awarded for its discovery, there have been no hallmark therapeutic breakthroughs or even NO based diagnostics. We will review the current state of the science surrounding NO in the etiology of a number of different diseases in the geriatric patient. From these observations, it can be concluded that enzymatic production of NO declines steadily with increasing age in healthy human subjects. Implementing strategies to diagnose and treat NO insufficiency may provide enormous benefit to the geriatric patient.     

Considerations of elderly factors to manage the complication of liver cirrhosis in elderly patients

The aging of the organ function causes sensitivity to the disease progression and need careful consideration for the medical treatment. With the increase of aging population, the opportunity to provide medical treatment for people in very old age is rapidly increasing therefore, the understanding of the various physiological changes of cellular function, size and function of organs are essential for the decision of therapeutic options. Among the various chronic conditions seen in elderly people, we have focused on liver cirrhosis, since despite specific therapeutic options for many of liver diseases including direct acting antivirals for hepatitis C virus, nucleoside analogs for hepatitis B, and corticosteroids for autoimmune hepatitis, there is currently no standard therapy to treat liver cirrhosis, which is the final stage of these liver diseases. Therefore,management of the various symptoms of liver cirrhosis is essential, and agingrelated parameters must be considered in the decision making for therapeutic strategies and dosage of the available medicine. In this mini-review, we have summarized the therapeutic options to manage various symptoms of liver cirrhosis, carefully considering the physiological changes of various organs associated with aging.     

Molecular mechanisms of cardiac aging

Age-associated changes in cardiovascular structure/ function are implicated in the markedly increased risk for cardiovascular disease in older persons. Aging not only prolongs exposure to several other cardiovascular risks, but also leads to intrinsic cardiac changes, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, includ- ing left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenu- ated in mice overexpressing catalase targeted to mitochondria （mCAT）. These findings demonstrate the critical role of rnitochondrial reactive oxygen species （ROS） in cardiac ag ing and support the potential antioxidants to cardiac aging lar diseases. application of mitochondrial and age-related cardiovascular diseases.     

Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men

Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity, sexual dysfunction, increase body fat, weight gain and the development of cardiac disease. Objective We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks factors. Methods Fifty-six self referred men without diabetes mellitus, hypertension, or cardiovascular disease (ages 52.3 ± 7.8 years) were randomly selected from a large cohort. Baseline weight, body fat composition, fasting glucose, hemoglobin A1c and fasting lipid levels, as well as free and total testosterone levels were assessed. All patients were assessed and followed 6–18 months after initiation of the program. The program consisted of a low glycemic load balanced nutrition diet, a recommended structured daily exercise program of 30–60 minutes, as well as once to twice weekly intramuscular testosterone injections (113.0 ± 27.8 mg). Results At follow up, weight was reduced from 233.9 ± 30.0 pounds (lbs) to 221.3 ± 25.1 lbs (P < 0.001), BMI was reduced from 33.2 ± 3.3 kg/m² to 31.3 ± 2.8 kg/m² (P < 0.0001). Total body fat was 27.1% ± 5.2% vs. 34.3% ± 5.7% at baseline (P < 0.0001). Fasting glucose was reduced from 95.3 ± 14.4 mg/dL to 87.5 ± 12.6 mg/dL (P < 0.0001). Total cholesterol was reduced from 195.4 ± 33.0 mg/dL to 172.7 ± 35.0 mg/dL (P < 0.005). No clinically significant adverse events were recorded. Conclusions Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was granted. The combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.     

Androgen deficiency in elderly men with systolic chronic heart failure

Objective Several previous studies have shown androgens deficiency in men with CHF, and 2 studies on the prognostic significance of serum levels of androgens in CHF patients have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHE Methods A total of 175 elderly （age ≥ 60 years） men with CHF were recruited. Total testosterone fiT） and sex hormone binding globulin （SHBG） were measured, and free serum testosterone （eFT） was calculated. The median follow-up time was 1262 days. Results During follow-up 54 （30.9%） patients died. TT and eFF deficiency was found in 21.7% （38/175） and 27.4% （48/175） patients, respectively. Both TT and eFT were inversely associated with LVEF and NT-proBNP （all P〈0.01）. Kaplan-Meier curves for patients in low, medium and high tertiles according to TF and eFT level showed significantly different cumulative survival rate （both P〈0.01 by log-rank test）. However, after adjustment for clinical variables, there were no significant associations between either Tr or eFT levels or survival time （OR=0.97, 95% CI, 0.84-1.12, P--0.28; and OR=0.92, 95% CI, 0.82-1.06,/＇=0.14, respectively）. Conclusion Our study showed that although levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, they are not independent predictors for mortality     

Sex Hormones Affect Aging Process by Influencing Lipid Profiles, Cellular Immunological Function and Lipid Peroxides and Oxidation System

Objectives To investigate the correlation between sex hormones(SH) and aging. Methods Through epidemiological investigation in our country, the levels of SH were measured by radioimmunoassy; lipid profile, glucose and apolipoprotein by automatic biochemic analytical instrument; T cell subsets by flow cytometer; and MDA, SOD were evaluated by the thiobarbituric acid (TBA) test and the nitrite method modified by Oyanagui respectively using spectrophotometry. Results In men, the serum levels of follicle stimulating hormone ( FSH)、luteinizing hormone(LH) increased significantly with aging, but serum prolactin(PRL) and progesterone(P) levels remained unchanged in all life; Both testosterone (T) and free testosterone (FT) all decreased greatly with aging, but 17β - estradiol( 17β - E_2) was reverse ; E_2 was negatively correlated with T and E_2/T increased with aging. The level of serum total cholesterol (TC) increased with aging, but triglycerides (TG) remain unchanged; compared with young group, high - d     

Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion?

Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures- as diets, physical activity, behavior therapy and pharmacotherapy- have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.     

Ghrelin and Helicobacter pylori infection

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primar- ily influence changes in plasma ghrelin concentrations. Helicobacter pylori （H pylor/~ infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lym- phoid tissue lymphoma. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in Hpylori infected sub- jects than in Hpylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in associa- tion with atrophic gastritis induced by Hpylori infection accounts for the decrease in plasma ghrelin concentra- tion. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may re- sult from the＇ compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations be- fore and after Hpylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.     

Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.     

Endogenous sex hormones and cardiovascular disease in men

Unlike women, men do not experience an abrupt reduction in endogenous sex hormone production. It has, however, become clear that an age-associated decrease in the levels of (bioactive) sex hormones does occur. Whether endogenous sex hormones have an impact on cardiovascular disease has for many years remained largely unknown, but during the last decade more attention has been drawn to the importance of testosterone, estrogens, and adrenal androgens in etiology, prevention, and treatment of male cardiovascular disease. The purpose of this article is to summarize the evidence currently available on the association between endogenous sex hormones and cardiovascular disease in males. Published studies dealing with the relationship between circulating levels of sex hormones and cardiovascular disease in males were reviewed. The studies reviewed in this article suggest that circulating endogenous sex hormones and estrogens have a neutral or beneficial effect on cardiovascular disease in men.     

Hormones and health outcomes in aging men

Increasing age is a predictor of ill-health and mortality related to cardiovascular disease and to frailty, a syndrome characterized by deterioration of multiple organ systems leading to loss of physiological reserve, diminished capacity to cope with stressors, and increased risk of disability and death. As men grow older, their levels of testosterone decline while the prevalence of ill-health increases. Observational studies have linked lower testosterone levels with cardiovascular disease and mortality in middle-aged and older men. More recently, lower testosterone has been shown to predict reduced sexual activity and frailty in aging men. Additional studies are needed to determine whether lower testosterone is a biomarker or a potentially treatable risk factor for poorer health outcomes in older men. During aging, the response of the pituitary–thyroid axis alters to manifest higher thyrotropin levels. The presences of subclinical hypo- and hyper-thyroidism predict adverse cardiovascular outcomes. Newer results indicate that in euthyroid older men, differences in free thyroxine levels within the normal range predict specific health outcomes including frailty. Clarification of the roles of endogenous testosterone and thyroxine in the genesis of ill-health during male aging offers the prospect of future intervention to preserve health and well-being in this growing population.     

Androgens and cardiovascular disease

Globally, cardiovascular disease will continue causing most human deaths for the foreseeable future. The consistent gender gap in life span of approximately 5.6 yr in all advanced economies must derive from gender differences in age-specific cardiovascular death rates, which rise steeply in parallel for both genders but 5-10 yr earlier in men. The lack of inflection point at modal age of menopause, contrasting with unequivocally estrogen-dependent biological markers like breast cancer or bone density, makes estrogen protection of premenopausal women an unlikely explanation. Limited human data suggest that testosterone exposure does not shorten life span in either gender, and oral estrogen treatment increases risk of cardiovascular death in men as it does in women. Alternatively, androgen exposure in early life (perinatal androgen imprinting) may predispose males to earlier onset of atherosclerosis. Following the recent reevaluation of the estrogen-protection orthodoxy, empirical research has flourished into the role of androgens in the progression of cardiovascular disease, highlighting the need to better understand androgen receptor (AR) coregulators, nongenomic androgen effects, tissue-specific metabolic activation of androgens, and androgen sensitivity. Novel therapeutic targets may arise from understanding how androgens enhance early plaque formation and cause vasodilatation via nongenomic androgen effects on vascular smooth muscle, and how tissue-specific variations in androgen effects are modulated by AR coregulators as well as metabolic activation of testosterone to amplify (via 5alpha-reductase to form dihydrotestosterone acting on AR) or diversify (via aromatization to estradiol acting upon estrogen receptor alpha/beta) the biological effects of testosterone on the vasculature. Observational studies show that blood testosterone concentrations are consistently lower among men with cardiovascular disease, suggesting a possible preventive role for testosterone therapy, which requires critical evaluation by further prospective studies. Short-term interventional studies show that testosterone produces a modest but consistent improvement in cardiac ischemia over placebo, comparable to the effects of existing antianginal drugs. By contrast, testosterone therapy has no beneficial effects in peripheral arterial disease but has not been evaluated in cerebrovascular disease. Erectile dysfunction is most frequently caused by pelvic arterial insufficiency due to atherosclerosis, and its sentinel relationship to generalized atherosclerosis is insufficiently appreciated. The commonality of risk factor patterns and mechanisms (including endothelial dysfunction) suggests that the efficacy of antiatherogenic therapy is an important challenge with the potential to enhance men's motivation for prevention and treatment of cardiovascular diseases.     

New perspectives on Mars and Venus: unravelling the role of androgens in gender differences in cardiovascular biology and disease

There are substantial gender differences in the pattern, severity and clinical outcomes of coronary heart disease independent of environmental risk factor exposure. As a consequence, there has been considerable interest in the potential role of sex hormones in atherogenesis, particularly the potential protective effects of oestrogen. However, the failure of the recent clinical randomised trials to show a cardioprotective effect for oestrogen coupled with a growing interest in androgen replacement therapy in elderly men has refocused interest on the role of androgens in cardiovascular biology and disease. Over the last decade, compelling evidence has emerged that sex differences in vascular biology are not only determined by gender-related differences in sex steroid levels but also by gender-specific tissue and cellular characteristics which mediate sex-specific responses to a variety of stimuli. In the vasculature, androgens often act in a gender-specific manner, with differential effects in male and female cells. This gender-dependent regulation may have important implications for understanding the basis of the gender gap in atherosclerosis and may eventually lead to the development of sex-specific treatments for cardiovascular disease. This review will summarise the current data for the role of androgens in gender differences in coronary heart disease and cardiovascular biology.     

Endogenous testosterone and endothelial function in postmenopausal women

OBJECTIVE: It is well known that coronary heart disease incidence increases in women after menopause. This phenomenon was related to reduced levels of female sex hormones. Estrogen decline, however, is not the only hormonal change during the postmenopausal period and estrogen administration did not protect women from cardiovascular disease. Therefore, it is justified to explore other hormonal changes. The role of androgens is still controversial. The aim of the present study was to investigate the relationship between endogenous sex hormones and endothelial function, measuring the brachial artery flow-mediated dilation. METHODS AND RESULTS: Sixty postmenopausal women were consecutively enrolled and underwent a clinical and biochemical examination. Brachial artery flow-mediated dilation was also evaluated by ultrasound. After correction for confounding variables, testosterone was positively correlated to flow-mediated dilation (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow-mediated dilation smaller than that in the highest tertile (P=0.02). CONCLUSIONS: This result could suggest that the development of cardiovascular disease after menopause is due not only to estrogen decline but also to androgen decline. More studies are needed to evaluate the role of androgen replacement therapy on postmenopausal women with low level of this hormone.     

Cardiovascular alteration and treatment of hypertension: do men and women differ?

Cardiovascular disease is one of the most common causes of mortality affecting both men and women in industrialized nations. Sex-related differences have been well established with regard to heart and vascular function as well as cardiovascular disease processes. Nevertheless, the precise mechanisms of action behind these gender-related differences are poorly understood. Premenopausal women have a relatively lower arterial blood pressure compared to age-matched men and post-menopausal women, suggesting a role of ovarian hormones in blood pressure regulation. Sex-related differences in vasculature and neuroendocrine systems are also present that can affect hemostasis, vascular reactivity, and vascular tone. Treatment for cardiovascular disease and hypertension has been challenging and unsatisfactory. Men and women may require different antihypertensive regimens due to differences in the progression and presentation of hypertension. Additionally, hormone replacement therapy in postmenopausal women has been controversial, producing both beneficial and detrimental effects. Therefore, this review will focus on sex-related differences in the heart and vasculature, and treatments for cardiovascular disease, such as hypertension.     

Significance of oestrogens in male (patho)physiology

Traditionally conceptualized as 'female hormones', oestrogens appear to have significant effects in the male biological system. Favorable effects have been noted on bone, brain and cardiovascular physiology while a potential role in the prostate pathology of the aging male has been seriously suspected. Oestrogens in male are predominantly the products of peripheral aromatization of testicular and adrenal androgens. While the testicular and adrenal production of androgens declines with aging, levels of total plasma oestradiol do not decline. This is to be ascribed to the common increase in fat mass with aging (the substrate of peripheral aromatization) and an increased aromatase activity with aging. But free or bioavailable oestrogens may decline due to an increase in sex hormone binding globulin. Oestrogens produce significant beneficial effects on skeletal growth and bone maturation. In old age oestrogens are better predictors of bone fractures than androgens. Oestrogens exert effects on the brain: on cognitive function, co-ordination of movement, pain and affective state, and are maybe protective of Alzheimer's disease. Oestrogen effects on the cardiovascular system include those on lipid profiles, fat distribution, endocrine/paracrine factors produced by the vascular wall (such as endothelins, nitric oxide), blood platelets, inflammatory factors and coagulation. The potentially adverse effects of oestrogens on the prostate may be due to a shift in the oestrogen / androgen ratio with aging. Sources of estrogens in men are endogenous androgens, or in case of androgen deficiency, exogenous androgens. Dietary phytoestrogens or selective estrogen receptor modulators, as drugs, may be significant as well.     

Testosterone supplementation therapy for older men: potential benefits and risks

Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded. In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased. Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials.     

Androgens and male sexual behavior from mice to men.

Exogenous androgenic hormones or drugs that affect endogenous androgen levels are now used in a variety of human applications [cf. Bardin et al. (1991)]. Therefore, an increasing number of well-controlled physiological, clinical, and psychological studies have examined the effects of androgens on muscle, prostate, lipids, and bone, as well as the cardiovascular, immune, and nervous systems. The increasing number of androgens and delivery systems that are currently available or under development should also increase the prevalence of androgen therapy (Table 1). As androgen use increases, a crucial area of research is the effect of androgens on sexual behavior, which encompasses sexual desire, motivation, performance, and satisfaction. There is a large body of animal data documenting hormonal regulation of male sexual behavior and the neural sites of action of these hormones. Clinical data on the effects of androgens on human male sexuality come from correlative studies of endogenous testosterone levels and sexual function, treatment of men who are testosterone deficient, and men using hormonal contraceptives.     

The effect of supraphysiologic doses of testosterone on fasting total homocysteine levels in normal men

Elevated total homocysteine (tHcy) levels are associated with increased risk for atherosclerotic cardiovascular disease. tHcy levels are higher in men than in women, and estrogen replacement therapy may reduce tHcy levels in postmenopausal women. The effect of androgenic hormones on tHcy levels in men has not been examined. The present study determined the effect of supraphysiologic doses of testosterone, with or without its aromatization to estradiol, on fasting tHcy levels in 14 normal male weightlifters aged 19–42 years. Subjects received testosterone enanthate (200 mg/week intramuscularly), the aromatase inhibitor, testolactone (1 g/day orally), or both drugs together in a crossover design. Each treatment lasted 3 weeks and each treatment was separated by a 4-week washout. Both testosterone regimens increased serum testosterone levels, whereas estradiol increased only during testosterone alone. Mean tHcy levels were not significantly altered when testosterone was given alone or together with testolactone. Testolactone did not significantly influence tHcy levels. We conclude that short-term, high-dose testosterone administration does not affect fasting tHcy levels in normal men.