Marek Medras

Anabolic Deficiency in Men With Chronic Heart Failure: Prevalence and Detrimental Impact on Survival

Background— The age-related decline of circulating anabolic hormones in men is associated with increased morbidity and mortality. We studied the prevalence and prognostic consequences of deficiencies in circulating total testosterone (TT) and free testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor-1 (IGF-1) in men with chronic heart failure (CHF). Methods and Results— Serum levels of TT, DHEAS, and IGF-1 were measured with immunoassays in 208 men with CHF (median age 63 years; median left ventricular ejection fraction 33%; New York Heart Association class I/II/III/IV, 19/102/70/17) and in 366 healthy men. Serum levels of free testosterone were estimated (eFT) from levels of TT and sex hormone binding globulin. Deficiencies in DHEAS, TT, eFT, and IGF-1, defined as serum levels at or below the 10th percentile of healthy peers, were seen across all age categories in men with CHF. DHEAS, TT, and eFT were inversely related to New York Heart Association class irrespective of cause (all P<0.01). DHEAS correlated positively with left ventricular ejection fraction and inversely with N-terminal pro-brain natriuretic peptide (both P<0.01). Circulating TT, eFT, DHEAS, and IGF-1 levels were prognostic markers in multivariable models when adjusted for established prognostic factors (all P<0.05). Men with CHF and normal levels of all anabolic hormones had the best 3-year survival rate (83%, 95% CI 67% to 98%) compared with those with deficiencies in 1 (74% survival rate, 95% CI 65% to 84%), 2 (55% survival rate, 95% CI 45% to 66%), or all 3 (27% survival rate, 95% CI 5% to 49%) anabolic endocrine axes (P<0.0001). Conclusions— In male CHF patients, anabolic hormone depletion is common, and a deficiency of each anabolic hormone is an independent marker of poor prognosis. Deficiency of >1 anabolic hormone identifies groups with a higher mortality.

Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism

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.

Gastroesophageal Reflux Disease and Physical Activity

Gastroesophageal reflux disease (GERD) is one of the most common disorders in the general population. In recent years, a marked increase in the occurrence of the disease worldwide has been noted.Intense exercise belongs to factors that are known to exacerbate symptoms of GERD. Episodes of reflux seem to be associated with the length and the intensity of the physical activity undertaken. Experimental studies suggest that the gastroesophageal reflux may be increased in athletes due to: decreased gastrointestinal blood flow; alterations of hormone secretion; changes in the motor function of the oesophagus and the ventricle; and the constrained body position during exercise. Disturbances of the balance between two areas of opposite pressure: intra-abdominal and intrathoracic, have also been proven to influence GERD events.GERD is found in sportspeople of various disciplines, but specific types of exercise may have significantly different impacts on the gastroesophageal reflux.Basic prevention of GERD comprise lifestyle and dietary interventions. Adjustments of the exercise load and avoiding meals and drinks about the time of physical effort may ease the symptoms. Unfortunately, in most patients, pharmacological measures are necessary. These include occasional application of antacids and blockers of histamine H2 receptors in mild forms of the disease, and a regular therapy with proton pump inhibitors (PPI) in the majority of other cases. An average dose of PPI varies from 20 to 40 mg/day and should be continued for 4–8 weeks. Unfortunately, symptoms of GERD frequently return and in these situations long-term acid suppression with PPI is usually necessary.As regular physical activity exerts beneficial health effects, the necessity of establishing associations between moderate, recreational exercise and GERD is needed.

Variation in bone mineral density in adults in Poland: age and sex differences

The decline of mineral bone density with age can lead in more extreme cases to osteopenia and osteoporosis, and is therefore one of the aspects of ageing with great medical and social significance. With this idea in mind a study of age changes in the trabecular and, separately, the cortical bone density of the radius was carried out in 1218 females and 405 males, aged 22 to 60 years, all occupationally active inhabitants of the city of Wroclaw, Poland. The technique used was the peripheral Quantitative Computed Tomography (pQCT). It was found that in females bone densities remain relatively stable throughout the period between 22 and 40 years. They then begin to decline slowly, with a rapid decline after the age of 55. A distinctly different pattern was found among males, with bone densities reaching peak values, markedly higher than those in females, in the third decade of life. After this age the bone density values begin to decline at a rapid rate, so that by the age of 60 years mean trabecular and cortical densities in males have decreased to levels almost equivalent to females of equal age. In view of the small size of the male samples, especially in the older age classes, the above results should be treated with caution and confirmed using larger samples.The decline of mineral bone density with age can lead in more extreme cases to osteopenia and osteoporosis, and is therefore one of the aspects of ageing with great medical and social significance. With this idea in mind a study of age changes in the trabecular and, separately, the cortical bone density of the radius was carried out in 1218 females and 405 males, aged 22 to 60 years, all occupationally active inhabitants of the city of Wroclaw, Poland. The technique used was the peripheral Quantitative Computed Tomography (pQCT). It was found that in females bone densities remain relatively stable throughout the period between 22 and 40 years. They then begin to decline slowly, with a rapid decline after the age of 55. A distinctly different pattern was found among males, with bone densities reaching peak values, markedly higher than those in females, in the third decade of life. After this age the bone density values begin to decline at a rapid rate, so that by the age of 60 years mean trabecular and cortical densities in males have decreased to levels almost equivalent to females of equal age. In view of the small size of the male samples, especially in the older age classes, the above results should be treated with caution and confirmed using larger samples.

Effects of long-term testosterone substitutive therapy on bone mineral content in men with hypergonadotrophic hypogonadism

Summary.  Hypogonadism is one of the crucial risk factors for male osteopenia and osteoporosis. There are few studies on the effects of long‐term and consistently administered testosterone substitutive therapy on bone mineral density in men with gonadal androgen deficiency, and their results have been susceptible to various interpretations. The aim of our study was an evaluation of bone mineral content in 26 men, aged 18–57 years, with hypergonadotrophic hypogonadism who underwent long‐lasting androgen re‐placement therapy with testosterone esters (Omnadren 250), which conditioned proper psychosomatic androgenization. The control group comprised 405 healthy men, aged 20–60 years, a representative sample of the local male population. Among all examined men and in the control group, trabecular, cortical and total bone mineral content at the distal radius of the nondominant hand were assessed by peripheral quantitative computed tomography using the Stratec 960 apparatus. In 11 hypogonadal men (42.3%), the trabecular bone mineral content was found to be within normal ranges; in 15 patients (57.7%) its values were below −1 standard deviation (SD) (osteopenia). In six patients (23.1%), the cortical bone mineral content was between +1 SD and the arithmetic mean, X; in 13 examined men (50%), the cortical bone mineral content was below X and above −1 SD. Osteopenia was diagnosed in six hypogonadal males, whereas osteoporosis was found in one man (cortical bone mineral content below −2.5 SD). Only in seven of the examined men (26.9%) was the total bone mineral content found within normal ranges, whereas in 19 men (73.1%) the total bone mineral content was below −1 SD (osteopenia). Despite the testosterone replacement in hypogonadal men, the greatest reduction of bone mineral content was found in its trabecular and total values. Among all the men examined, the trabecular and total bone mineral contents were below the mean of our own reference values. The results show that long‐term and consecutively administered testosterone replacement in conventional doses, despite the normalization of serum androgen levels and the promotion of proper somatic development, does not simultaneously eliminate hypogonadal osteopenia in every case. The individually differentiated response to exogenous androgens is a characteristic feature of male hypogonadism. This study emphasizes the necessity of regular measurements of bone mineral density in hypogonadal men, as the densitometric parameters should be accepted as an osteologic (and very important) marker of androgenization of the male organism.

The inverse relationship between bone status and blood pressure among Polish men

Primary objective : An evaluation of relationships between bone density and blood pressure in healthy men. Research design : A cross-sectional population-based survey. Methods and procedures : An ethnically homogeneous sample of 208 men, aged 35-63, healthy and occupationally active inhabitants of the city of Wroclaw, Lower Silesia, Poland were studied. Trabecular, cortical and total bone mineral content (BMC) at the ultra-distal radius of the non-dominant hand were assessed by peripheral Quantitative Computed Tomography (pQCT; Stratec 960 apparatus). Body mass index (BMI) was used as a measure of general obesity. Systolic and diastolic blood pressure (BP) were measured using an MPC-350 sphygmomanometer. Multiple linear regression was used to evaluate the relationships between BP and BMC. A two-way analysis of covariance was carried out to test for the significance of inter-group differences in BMC with regard to age and BP with BMI as a continuous covariable. Multiple logistic regression was used to verify whether some select factors (age, BMI, systolic and diastolic BP) could significantly predict male bone status. Results : Systolic BP was not related to bone status at the ultra-distal radius. There were no differences in any BMC between systolic hyper- and normotensive subjects. Additionally, systolic hypertension did not affect the probability of an occurrence of male osteopenia (independently of age and BMI). In contrast, there were significant negative relationships between diastolic BP, and trabecular and total (but not cortical) BMC (even when controlled for age and BMI). Moreover, diastolic hypertensive men had reduced BMC at the ultra-distal radius when compared with normotensive subjects. It is noteworthy that Polish men of diastolic BP exceeding 90 mmHg had an approximately 1.50-fold increased relative risk of being osteopenic when compared with normotensive subjects (even when controlled for age, BMI and systolic BP). Conclusions : In the light of the inverse relationship between BMC and diastolic BP, Polish men with elevated diastolic BP seem to be more prone to the excessive age-related bone loss.

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.

DRD2 C313T and DRD4 48-bp VNTR polymorphisms and physical activity of healthy men in Lower Silesia, Poland (HALS study)

Background: Both animal and human studies have proved that the dopaminergic system of the brain controls many aspects of behavior, e.g. motivation, addiction, motor movement, locomotion. It has been hypothesized that dopamine signalling may regulate spontaneous physical activity as well. Aim: Literature data suggests that an intact function of dopamine receptors (DRD2–DRD4) inhibits physical activity. This study searched for associations between a propensity to be active (or sedentary) and genetic variants of DRD2 and DRD4. Subjects and methods: Invitations to participate in the study were sent to 900 randomly selected, adult men living in Lower Silesia, Poland. Genotyping of DRD2 C313T and DRD4 48-bp VNTR polymorphisms of enrolled subjects (371 (DRD2 C313T) and 397 (DRD4 48-bp VNTR)) was performed. Level of physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). Results: No associations were found between level of physical activity (low, moderate, high) and the two polymorphisms: DRD2 C313T (p = 0.49) and DRD4 48-bp VNTR (p = 0.31). Studied subjects did not differ as to the number of hours spent sitting either. Conclusion: The results exclude the presence of significant relationships between polymorphic variants of the dopamine receptors genes and the level of physical activity in men.

Bone mineral status of Polish men in the course of normal ageing

Summary. Age‐related changes in the bone mineral content (BMC) of men are conditioned by both genetic and environmental factors distinctive for particular populations. This results in considerable differences between various populations concerning the prevalence of osteopenia and osteoporosis, and the occurrence of normal variability in BMC among adult and elderly men. The aim of the study was to evaluate the variation of BMC with age in an ethnically homogenous sample of 405 healthy men, aged 20–60 years, all occupationally active inhabitants of the city of Wroclaw, Lower Silesia, Poland. Trabecular and total BMC at the ultradistal radius of the nondominant hand were assessed by peripheral quantitative computerized tomography using the Stratec 960 densitometer. Among Polish men a distinct phase of maximal BMC values (around the age of 30) was distinguished, with a subsequent, quite rapid decline in bone mass. For example, the peak value of trabecular BMC decreased by approximately 13.2% per decade. In Polish men up to 30–34 years old trabecular and total BMC even exceeded reference values by 10%; however, from 35 years onwards their BMC was lower than standard values. This unfavourable phenomenon of BMC decline was augmented with age, and finally BMC values in men aged 55 and over were 30–35% lower than reference values. The significant discrepancies found between the data presented in this study and reference values probably result from inter‐populational differences in the lifestyles of healthy ageing men. The results also confirm that bone density (with its age‐related changes in the course of normal male ageing) is one of the biological features characteristic of this particular regional population.

Bone mineral content and androgen-estrogen activity in a population of healthy male inhabitants of Wroclaw, Poland

In this study, age-related changes in bone mineral content (BMC) were investigated in the context of alterations of total testosterone, estradiol and dehydroepiandrosterone sulfate (DHEAS) during normal male aging. An anthropologically homogeneous group of 236 males, aged 22–67 years, was subdivided into eight 5-year age categories. The men were healthy and occupationally active inhabitants of the city of Wroclaw, Lower Silesia, Poland. The investigated hormones were measured using standard immunoassays. Trabecular, cortical and total BMC at the distal radius of the non-dominant hand were separately assessed by peripheral quantitative computed tomography (pQCT) using the Stratec 960 apparatus. All correlations among hormone and densitometric parameters and age were evaluated by use of non-parametric statistics (Spearman coefficient). Reductions in trabecular, cortical and total BMC of approximately 40.0%, 28. 1%and 30.8%, respectively, were found in the peak mass between the age category with maximal BMC ...