Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men.

Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx (?+?) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods.

Results Men with coronary artery disease had lower total testosterone levels (17.01?±?6.42 vs. 19.37?±?6.58?nmol/l; p?<?0.05), testosterone/estradiol ratio (228.5?±?88.5 vs. 289.8?±?120.1; p?<?0.05) and free androgen index (FAI) (59.49?±?14.79 vs. 83.03?±?25.81; p?<?0.0001), and higher levels of estrone (49.5?±?27.7 vs. 36.6?±?12.7?pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p?<?0.05) between testosterone level and serum level of glucose (r?=??0.29), triglycerides (r?=??0.37), body mass index (r?=??0.55), waist (r?=??0.43), total body fat mass (r?=??0.3) and fasting insulin resistance index. A significant positive association (p?<?0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r?=?0.26).

Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.     

The effects of sex steroids and some elements of lifestyle on the normal variation of bone mineral content in younger versus older healthy Polish males

The aim of the study was to evaluate the independent ‘net’ effects of hormonal variables (estradiol, free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels) and lifestyle variables (alcohol consumption, coffee drinking, cigarette smoking, physical activity and muscle strength) on trabecular, cortical and total bone mineral content (BMC) in a group of 236 healthy males, aged 22–67 years. The men were occupationally active inhabitants of the city of Wroclaw, Lower Silesia, Poland. Trabecular, cortical and total bone mineral content, at the distal radius of the non-dominant hand, were assessed by peripheral quantitative computed tomography (pQCT) using the Stratec 960 apparatus. Sex steroids levels were measured using standard immunoassays. Data on lifestyle variables (alcohol consumption, cigarette smoking, coffee drinking and physical activity) were obtained through a questionnaire. Hand-grip strength of the dominant hand was assessed using a standard dynamometer. All statistical analyses were made separately in two subgroups, younger males (aged 22–39 years) and older males (aged 40 years and over). The impact of a particular independent variable on BMC and the extent of determination on BMC by the complex of chosen variables were evaluated using a path analysis. In younger males, the effects of physical activity and muscle strength were the most important among all the factors that influenced BMC, as they contributed to 16.2%, 16.9% and 16.5% of the variability of trabecular, cortical and total BMC, respectively. Taking into consideration cigarette smoking, alcohol and coffee drinking together, the coefficients of determination of the variability in trabecular, cortical and total BMC were 10.6%, 11.3% and 16.1%, respectively. The variances in trabecular, cortical and total BMC levels were determined in only 5.8%, 11.5% and 13.0% by sex steroids, respectively. The influence of free testosterone on trabecular BMC was greater compared with that of dehydroepiandrosterone sulfate (DHEAS) and estradiol; for cortical BMC, the impacts of estradiol and DHEAS were similar and greater than that of free testosterone, and the variability of total BMC was affected mainly by estradiol. In contrast, in older men the effects of physical activity and muscular strength were the least important among all the complexes of independent variables, as they contributed to 4.5%, 7.8% and 7.0% of the variability in trabecular, cortical and total BMC, respectively. Taking into consideration the influences of cigarette smoking, alcohol and coffee drinking, the coefficients of determination of the variability in trabecular, cortical and total BMC were 16.5%, 14.8% and 17.4%, respectively. Among the older men, the variances in trabecular, cortical and total BMC were determined in only 9.4%, 6.3% and 13.6% by sex steroid levels, respectively. The influence of DHEAS on trabecular BMC was greater when compared with that of estradiol and free testosterone, whereas the variability of both cortical and total BMC in older men was affected mainly by estradiol. It is quite striking that, in younger healthy subjects, both physical activity and muscle strength contributed to a greater extent to BMC variance when compared with sex steroids levels, whereas, in older men, physical activity and muscular strength were less important than androgen- estrogen activity in determining the variability of BMC. This may suggest that the tropic effect of mechanical force influences bone structure mainly in younger men; probably male bone tissue becomes less prone to mechanical stimuli during aging. It is astonishing that both in younger and older men the coefficients of determination of physical activity and muscle strength were the highest for cortical BMC, which would indicate the greatest response of that part of the bone tissue to mechanical force. It is worth noting that the coefficients of determination of the complex of lifestyle factors (alcohol consumption, cigarette smoking and coffee drinking) were higher in older men compared to younger Polish males. This can be explained by the longer exposure of male bone to environmental influences (ethanol, nicotine, caffeine) during a lifetime. Our study revealed that all the evaluated variables were related to the variability in BMC in healthy Polish men, but the coefficients of determination differed depending on the age of the examined subject and on the BMC of a particular bone component. This suggests that the responsiveness of male bone tissue to environmental factors changes with age, and that these effects vary significantly between particular parts of the male bone structure.     

Body mass index,waist/hip ratio and androgen—estrogen activity in younger versus older Polish men

This study was performed to evaluate the associations between estradiol, dehydroepiandrosterone sulfate (DHEAS), free and total testosterone levels, and anthropometric parameters of general adiposity (body mass index, BMI) and fat distribution (waist/hip ratio, WHR), separately in two subgroups of healthy Polish men: younger (aged 22–39 years, n = 95) and older (aged 40 years and over, n = 141) subjects. Sex steroid levels were assessed using radioimmunoassay (RIA). BMI was used as a measure of general adiposity. WHR was used to estimate distribution of adipose depots. The relationships between sex steroids, BMI, WHR and age were evaluated by use of non-parametric statistics (Spearman coefficients). Aging was related to a reduction of all hormone levels (correlation coefficients with age: free testosterone r = -0.52, p < 0.001; total testosterone r = -0.25, p < 0.001; estradiol r = -0.18, p < 0.001; DHEAS r = -0.45, p < 0.001) and an increase of BMI and WHR for BMI r = 0.23, p < 0.001; for WHR r = 0.47, p < 0.001). A one way analysis of co-variance (ANCOVA) was applied separately in the two subgroups of subjects to assess the relationships between hormonal and anthropometric variables. In men aged 22–39 years, the total (but not free) testosterone and DHEAS (when controlled for age) significantly differentiated BMI values. In subjects aged 40 years and over, no associations between sex steroids and BMI were revealed. In younger males DHEAS differentiated WHR values (even when controlled for age and BMI), whereas after the age of 40 years an increased WHR was accompanied by increases in both estradiol and DHEAS levels. The associations between the androgen—estrogen activity and the anthropometric parameters of adiposity vary in younger versus older healthy men.     

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25?mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while β-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment.

The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and β-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain.

In conclusion, the present study demonstrates that 25?mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.     

Hypogonadotrophic hypogonadism in type 2 diabetes

Recent work shows a high prevalence of low testosterone and inappropriately low luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity in patients with type 2 diabetes. However, the duration of diabetes or HbA1c are not related to HH. Furthermore, recent data show that HH is not associated with type 1 diabetes. C-reactive protein concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and C- reactive protein concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is also relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations are also related to an increase in total and regional adiposity. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates insulin resistance and inflammation. In addition, low testosterone levels are associated with an increase in cardiovascular events. Testosterone therapy may therefore, reduce cardiovascular risk. This important aspect requires further investigation.     

Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men

Objective.?The aim of the present study was to analyse the effect of testosterone therapy on bone mineral density in healthy elderly men who had low levels of total testosterone.

Design.?Randomized, double-blind, placebo-controlled study.

Participants.?Forty-eight men over 60 years old with decreased testosterone levels (≤320 ng/dL) comprised the study. Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months; the remaining 23 participants formed the control group. All participants had measurements of bone mineral density (BMD) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels.

Results:?Testosterone treated group exhibited a significant (p < 0.05) increment (from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm²) in lumbar BMD in parallel with a significant (p < 0.001) increment (from 301 ± 32 to 471 ± 107 ng/dL) in testosterone concentrations, whereas no significant change occurred in femoral neck BMD.

Conclusions.?Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels.     

Senility,illness and death in Açvaghosa's ‘Buddhacări˘ta’The Feats of Buddha

Background An age-related decline in growth hormone (GH) level has been established, and this decline is associated with changes in body composition as well as a general increase in susceptibility to illness and a reduced sense of well-being. The current study, a first in Asia, sought to examine the effects of GH therapy on body composition and other endocrine and metabolic functions in a group of healthy elderly Chinese men.

Methods A total of 23 healthy elderly Chinese men, aged between 60 and 69 years, were injected subcutaneously, three times weekly, with 0.08 U/kg of recombinant GH for 6 months. Various hormones and biochemical parameters, together with percentage lean body mass and body fat, were measured before, 3 and 6 months after the start and 3 months after the cessation of GH therapy.

Results A significant increase in lean body mass, up to 9.1% over baseline values at 3 months post-therapy, and a significant decrease in body fat, up to 3.1%, were noted. GH therapy also induced variable and significant increases in levels of insulin growth factor (IGF-I), dehydroepiandrosterone sulfate (DHEAS), insulin, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and triglyceride and significant reductions in glucose and sex hormone binding globulin (SHBG) levels. No changes in testosterone, free androgen index and cholesterol were noted. A significant and independent correlation was noted between IGF-I and insulin, TSH, DHEAS, glucose and triglyceride levels.

Conclusions GH augmentation therapy was effective in improving the body composition of a group of elderly Chinese men. GH-induced positive changes in body composition in the elderly were probably a result of the direct effect of the GH. It is also possible that some of the changes were mediated through GH-induced changes in thyroid hormones, insulin, glucose, triglyceride and DHEAS. However, the mechanism of GH- induced changes in body composition remains to be defined.     

Serum sex steroid hormones and frailty in older American men of the Third National Health and Nutrition Examination Survey (NHANES III)

Objective: To determine whether frailty is associated with circulating total and free testosterone, total and free estradiol, and sex hormone-binding globulin (SHBG) in older men. Methods: With NHANES III data of 461 men aged 60 years and older, we used logistic regression to analyze the associations between serum concentrations of sex steroid hormones, SHBG and frailty. Participants meeting any three or more of the five frailty criteria were classified as “frail”, all others were considered as non-frail. Results: 2.5% of men were frail. Men with SHBG ≥66 nmol/L had three times the odds of frailty (OR = 2.97; 95% CI 1.28–6.86) compared to men with SHBG <66 nmol/L. Men with free testosterone levels below 243 pmol/L had an increased odds of frailty (OR = 3.92; 95% CI 1.29–11.89). None of these associations was statistically significant after additionally adjusting for body mass index, smoking and history of cardiovascular diseases (CVD). Total testosterone, and total and free estradiol serum levels were not statistically significantly associated with frailty. Conclusions: In this US nationally representative study of older men, low free testosterone and high SHBG serum levels were associated with a significantly increased odds of frailty after adjustment for age and race/ethnicity. These associations may, however, be explained by confounding due to obesity, smoking, and the higher prevalence of CVD in frail men or by low hormones or high SHBG mediating the association between obesity, smoking, CVD and frailty.     

Androgen replacement therapy in aging men with secondary hypogonadism

Many animal and human studies show that supraphysiological doses of dehydroepiandrosterone (DHEA) can influence body composition and carbohydrate and lipid metabolism. Most studies have concentrated on women and have not been randomized, thus creating controversial results. With this in mind, we designed a cross-over double-blind placebo-controlled study of 12 men aged 59.0 ± 4.8 years, who received either 50 mg/24 h DHEA or placebo for 3 months to assess the influence of DHEA on the content and distribution of fat tissue and serum insulin, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels, as well as testosterone, estradiol, DHEA-sulfate (S), prostate-specific antigen (PSA) concentrations and indexes of insulin sensitivity and resistance. Patients were recruited from university employees attending for periodic health checks, with normal hepatic and renal function with endogenous DHEA-S level < 1500 ng/dl. Our results did not reveal any significant changes in study parameters, apart from a statistically significant increase in DHEA-S levels after therapy with active substance.     

Insulin resistance,oxidative stress markers and the blood antioxidant system in overweight elderly men

The purpose of the study was to examine in the blood of overweight men aged from 62 to 83 years, the relationships between age and insulin resistance, selected parameters of the oxidative stress, and the antioxidant defense system. The population studied was divided into two groups: the group ‘young-old’ consisted of men aged 62 to 74 years old, and the group ‘old-old’– of men aged between 75 and 83 years. The total antioxidative status (TAS) and concentrations of thiobarbituric acid reactive substances (TBARS) were measured in the blood plasma. In the serum samples, the levels of antibodies against oxidized LDL (oLAB), glucose, total cholesterol, HDL-cholesterol, triglycerides and insulin were measured. Homeostasis Model Assessment of Insulin Resistance (HOMA_IR) was calculated. Concentration of reduced glutathione (GSH) and glutathione peroxidase activity (GPx) were determined in the red blood cells hemolysate. The results of the study did not show significant differences between groups investigated with respect to concentrations of TBARS, TAS, GSH and GPx. However, significantly higher concentrations of glucose and antibodies against oxLDL (p < 0.05) were observed in the group of men over 74 years old in comparison to the group of ‘young-old’ men. It was indicated that the increased insulin resistance and hyperglycemia in elderly men are related to body mass and that they cause intensified oxidative modifications of LDL.     

Association of DHEA-S and estradiol serum levels to symptoms of aging men

Objectives A number of interactions between agerelated changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. Methods In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. Results A total of 375 men with a mean age of 59.9 ± 9.2 years (mean ± standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 ± 90.9 μg/dl and 29.7 ± 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. Conclusion This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.     

Estradiol in elderly men

The role of estrogens in male physiology has become more evident, as a consequence of the discovery of human models of estrogen deficiency such as estrogen resistance or aromatase deficiency. In males, testosterone is the major source of plasma estradiol, the main biologically active estrogen, only 20% of which is secreted by the testes. Plasma estrone, 5% of which is converted to plasma estradiol, originates from tissue aromatization of, mainly adrenal, androstenedione. The plasma concentration of estradiol in males is 2-3 ng/dl and its production rate in blood is 25-40 μg/24 h; both of these values are significantly higher than in postmenopausal women. Plasma levels of estradiol do not necessarily reflect tissue-level activity as peripherally formed estradiol is partially metabolized in situ; thus, not all enters the general circulation, with a fraction remaining only locally active. Of the factors influencing plasma estradiol levels, plasma testosterone is a major determinant. However, the age-associated decrease in testosterone levels is scarcely reflected in plasma estradiol levels, as a result of increasing aromatase activity with age and the age-associated increase in fat mass. Free and bioavailable estradiol levels do decrease modestly with age as does the ratio of free testosterone to free estradiol, the latter testifying to the age-associated increasewd aromatization of testosterone. Estradiol levels are highly significantly positively related to body fat mass and more specifically to subcutaneous abdominal fat, but not to visceral (omental) fat. Indeed, aromatase activity in omental fat is only one-tenth of the activity in gluteal fat. Estrogens in males play an important role in the regulation of the gonadotropin feedback, several brain functions, bone maturation, regulation of bone resorption and in lipid metabolism. Moreover, they affect skin metabolism and are an important factor determining sex interest in man.     

Complex relationship between sex hormones,insulin resistance and leptin in men with and without prostatic disease

Objectives: To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa.

Subjects and methods: Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups.

Results: Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3–28.0) versus 4.8 (1.1–12.3) ng/ml; p?p?=?0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups.

Conclusions: It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.     

Visceral obesity,androgens and the risks of cardiovascular disease and diabetes mellitus

The sex difference in cardiovascular morbidity is traditionally ascribed to the effects of testosterone on the lipid profile. Epidemiological studies show, however, that men with cardiovascular disease have low rather than high circulating testosterone. The factor responsible for both the higher prevalence of cardiovascular disease and the low testosterone might be visceral obesity. Men and women differ in their pattern of fat distribution. Women have predominantly gluteofemoral fat depots and men preferential abdominal/visceral depots. In puberty testosterone favors abdominal/visceral fat deposition. Visceral fat has a high metabolic turnover and the free fatty acids drain on the portal vein. With a large visceral fat depot the liver is flooded with free fatty acids inducing high levels of triglycerides and low high-density lipoprotein cholesterol, impairment of insulin metabolism and reducing insulin sensitivity. These factors contribute to the development of cardiovascular disease and diabetes type II. High insulin levels suppress sex hormone-binding globulin thus lowering circulating testosterone. The fat cell produces leptin signalling to the brain to reduce food intake and increase energy expenditure. High leptin levels suppress testosterone. Some studies suggest that testosterone supplementation reduces visceral obesity and improves cardiovascular risks but more evidence is needed.     

Testosterone deficiency and the metabolic syndrome

Evidence is presented to link components of the metabolic syndrome to testosterone deficiency and obesity. Testosterone deficiency in hypogonadism or testosterone deprivation in normo-gonadotropic men increases fat mass as well as fasting insulin levels. Testosterone supplementation (TS) in a dose dependent manner, increase lean body mass (LBM), reduces fat mass, body mass index (BMI) and waist hip ratio in both young and elderly hypogonadal men. A negative association between T and insulin resistance as well as impaired glucose intolerance has been demonstrated and in type 2 diabetic men TS improves metabolic parameters. TS improves most components of the metabolic syndrome and also reduces inflammatory cytokines.     

Diagnostic significance of free salivary testosterone measurement using a direct luminescence immunoassay in healthy men and in patients with disorders of androgenic status

The accurate measurement of testosterone remains a challenge. The determination of the blood testosterone concentrations in serum by conventional immunoassays is inaccurate in men and even more so in females and children. A new luminescence enzyme immunoassay (LIA) has been developed and validated. The high analytical (8.7 pmol/L) and functional (17.3 pmol/L) sensitivity allows the quantification of the very low concentration in saliva, as well as in serum, after 1/40 dilution. This study measured salivary testosterone levels and compared the results with the free levels calculated from total testosterone and sex hormone-binding globulin in eugonadal and hypogonadal men. Salivary testosterone concentrations in healthy men in morning hours were 369 pmol/L (mean), range 263–544 pmol/L, which was statistically significantly higher than that in men with androgen deficiency, 215 pmol/L (mean), range 51–249 pmol/L.

Repetitive determination of free testosterone concentrations in saliva (once a week for 5 weeks) showed high stability of results over time, with coefficient of variation 9% (range 5–23%).

In this study we showed that free salivary testosterone levels in morning samples correlated well with calculated free testosterone in blood, both in healthy men (R = 0.754, P = 0.001), and in patients with androgen deficiency (R = 0.889, P = 0.0001), though in cases with very low testosterone, salivary concentrations were systematically higher than calculated free testosterone levels in blood.     

Cross-sectional analysis between prostate volumes and serum sex hormones in Japanese men attending a urological clinic

Aim: To evaluate epidemiologically the association between measured prostate volume and sex hormones.

Methods: Between December 2012 and September 2014, 226 patients attending the urological clinic were assessed for the relationship between prostate volume (PV) and, serum sex hormones, physical size, personal habits, etc. Prostate volume was measured by using transabdominal ultrasonography. Statistically, the Pearson correlation coefficients test was used.

Results: Total cases, the cases of PV?≤?25?ml, and the cases of PV?>?25?ml were evaluated respectively. Total cases and the cases of PV?>?25?ml showed a positive significant correlation with testosterone (T), but the cases of PV?≤?25?ml showed no such correlation. The cases of PV?>?25?ml had a positive significant correlation with estradiol (E2), but total cases and cases of PV?≤?25?ml did not. Dehydroepiandrosterone sulfate (DHEAS) showed no correlation with any case of PV, however it decreased significantly with age and had a correlation with alopecia. The E2/T ratio had no correlation with any case of PV, but on the other hand, the T/DHEAS and E2/DHEAS ratios had significant positive correlation with PV?>?25?ml.

Conclusions: Serum T and E2 had significant positive correlation with measured PV especially in larger prostates. This result seems to correspond with the conventional theory that T and E2 have an etiological effect on benign prostatic hyperplasia. DHEAS did not show direct correlation with PV, however it appeared to suppress the role of T and E2 on benign prostatic hyperplasia growth. DHEAS might be a key to understanding the etiology of benign prostatic hyperplasia with aging.     

Mission Statement

Aim.?To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men.

Methods.?The cross-sectional study included 492 elderly men comprising 104 healthy subjects (mean age 71.4 ± 5.2 years), 259 subjects without DM (71.5 ± 5.0 years) and 129 DM patients (73.0 ± 6.3 years). Plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG), estradiol (E₂), luteinising hormone) and follicle-stimulating hormone (FSH) were determined. AR-positive cells were measured by flow cytometry.

Results.?TT concentrations were significantly lower in the DM group (13.8 ± 4.7 nmol/l) than in the healthy (17.1 ± 6.1 nmol/l) and non-diabetes groups (15.8 ± 6.0 nmol/l; all P < 0.01). FT, SHBG, AR-positive proportion (AR%) and AR fluorescence intensity showed a decreasing trend among the healthy, non-DM and DM groups, but the differences were not significant. TT, E₂, E₂/testosterone and SHBG were negatively correlated with blood glucose. SHBG was positively correlated and TT and AR% were negatively correlated with the course of DM. Logistic multiple regression analysis revealed that age, waist/hip ratio, FSH, SHBG and AR% are potential risk factors for DM.

Conclusions.?Low levels of TT, SHBG and AR may be potential risk factors for DM in elderly men.     

The influence of exercise on the functioning of the pituitary–gonadal axis in physically active older and younger men

Age is a meaningful factor modulating the functioning of the human endocrine system. In our research, the factor stimulating the pituitary–gonadal axis was a 400 m race. In this type of effort, glycolytic and lactic acid transformations are dominant and a fundamental increase in lactic acid concentration is noted. The aim of the research was to compare the response of the pituitary–gonadal axis in physically active men of various ages after a 400 m race. Nine men aged 21.7 ± 0.7 years and nine men aged 60.0 ± 3.4 years took part in the study. Blood samples were taken from the elbow vein before the race at 08.00 and immediately after the effort. The levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free testosterone were determined in blood sera. The concentration of lactic acid was measured in full blood at 5 min after the race. Before the effort, statistically significant differences in the concentration of FSH and free testosterone between the two age groups were observed (higher FSH in older men but lower free testosterone). No differences in the level of LH, total testosterone and lactic acid were observed. Immediately after the effort, no changes in the level of FSH were found in both groups; a statistically significant decrease in LH concentration was noted only in the group of younger men. In both groups, statistically significant increases in total testosterone, free testosterone and lactic acid concentrations were observed after the race. In the group of younger men, compared to the older, larger increases in free testosterone and lactic acid concentrations, as well as shorter race time, were revealed after the effort test. Analysis of the two groups after the race showed statistically significant differences in FSH, free testosterone and lactic acid concentrations. A positive correlation (r = 0.57) was demonstrated between the after-effort increase in the concentration of free testosterone and lactic acid, and negative correlation (r = –0.66) between the after-effort increase in the concentration of free testosterone and the time of the 400 m race. In older men, the concentration of free testosterone may play an important function in lowering strength capacities. It must be stressed that the 400 m race was a more significant stimulus for changes in hormone concentrations of the pituitary–gonadal axis in younger men (greater changes in the level of the investigated parameters) than in the older. The results obtained allow us to conclude that, in older men, as compared to the younger ones, the response of the pituitary–gonadal axis to an effort stimulus is to some extent different.     

Testosterone and erectile physiology

The role of testosterone deficiency in sexual dysfunction is an important aspect of aging, because it affects such a large proportion of men over 50 years old. A number of age-related factors can cause sexual dysfunction (in particular erectile dysfunction) and testosterone deficiency, such as chronic illness and multiple medications, and the causative link between hypogonadism and erectile dysfunction is still debated. However, studies in castrated animals have proven that addition of testosterone, and its conversion to dihydrotestosterone, can restore erectile function. It appears that testosterone achieves this by peripheral mechanisms (endothelial dependent and independent) and central mechanisms. Testosterone replacement therapy is therefore effective for erectile dysfunction in men with hypogonadism, with success rates of 35–40%. Testosterone supplementation is also important in men who fail on phosphodiesterase type-5 inhibitors, because a minimum plasma concentration of testosterone is required for the successful restoration of erectile function with these agents. Testosterone gels are now the preferred formulation for testosterone supplementation and they can be highly beneficial in a proportion of men with erectile dysfunction.