Halina Grosman

Lipoproteins, sex hormones and inflammatory markers in association with prostate cancer

Objective. To evaluate lipoprotein profile and sex hormones in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their possible associations with some inflammatory markers linked to PCa. Methods. A total of 150 men (50–65 years), matched by age and body mass index (BMI), included in this study and divided into three groups according to total prostate specific antigen (PSA), digital rectal examination and prostate biopsy: 50 PCa, 50 BPH and 50 controls. Total cholesterol (Chol), HDL-chol, LDL-chol, triglycerides (TG), total testosterone (T), free T (FT), bioavailable T (BioT), estradiol and SHBG were measured. The free androgen index (FAI) and TG/HDL-chol were calculated. In 25 PCa and 25 controls, C-reactive protein (hs-CRP), adiponectin and insulin were determined. Results. Patients with PCa showed higher TG/HDL-chol and diminished HDL-chol than Controls and BPH. PSA correlated inversely with HDL-chol and directly with TG/HDL-chol. FAI, FT, BioT and estradiol levels were higher, and SHBG and adiponectin were lower in PCa than in Controls. No differences were found in androgens between BPH and PCa. Conclusion. Our most novel findings are that the patients with PCa presented lower total Chol and HDL-chol and higher TG/HDL-chol than BPH and Controls. Patients with PCa showed higher androgens and lower adiponectin than Controls.

Association between testosterone levels and the metabolic syndrome in adult men

Abstract Objective: To evaluate the relationship between testosterone levels and the metabolic syndrome (MS) in men older than 45 years. Methods: Six hundred and sixty men (45–70 years) selected from 2906 participants of a population screening for prostate cancer were included in this study. Testosterone and the components of MS were assessed in all men. MS was diagnosed according to NCEP-ATP III criteria. Triglycerides (TG)/HDL-cholesterol (chol) index was calculated. Results: The presence of MS was inversely associated with testosterone (χ2, p < 0.001), independently of age (OR 0.802, CI 95%: 0.724–0.887, p < 0.0001). Hypertension was the most frequent abnormality observed followed by elevated TG and waist circumference (WC). Testosterone correlated positively with HDL-chol (r: 0.14, p < 0.0001) and negatively with body mass index (BMI)(r: −0.29, p < 0.0001), WC (r: −0.26, p < 0.0001), TG (r: −0.20, p < 0.0001), TG/HDL-chol (r: −0.20, p < 0.0001), glucose (r: −0.11, p = 0.005) and MS score (r: −0.23, p < 0.0001). Conclusions: Our results show that in men older than 45 years, as long as testosterone levels decline, the prevalence of MS increases, independently of age. The correlations found between testosterone and four of the five components of MS, as well as with BMI and TG/HDL-chol ratio, a surrogate marker of insulin resistance, suggest considering male hypogonadism as a determinant of developmental abnormalities typical of MS.

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

Abstract 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 < 0.01] and estradiol [median (range) 37.0 (20–90) versus 29.0 (20–118) pg/ml; 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.

Relationship between cortisol, life events and metabolic syndrome in men

Psychological factors and stressful life events (LE) are considered to play a role in the onset of the metabolic syndrome (MS). We tested the association between LE and cortisol, a marker of chronic stress, with the risk of developing MS and their interaction. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 149 healthy men (mean ± SD age, 58.6 ± 7.7 years) were included in this study. Participants were assessed by the Holmes and Rahe questionnaire about their experience of LE during the previous 1–5 years. MS was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III (ATP-III) and International Diabetes Federation (IDF) criteria. Serum cortisol was measured at 08:00–09:00 h. Participants with MS (IDF criteria) reported significantly more past LE (p = 0.009) and greater summed weight of LE (p = 0.049) than those without MS. Furthermore, LE interacted with cortisol in relation to MS: in men with increased serum cortisol levels ( ≥ 13.7 μg/dl), number of LE significantly predicted MS-status (relative risk (RR) = 1.16, p = 0.03), whereas in men with low cortisol, LE were unrelated to MS (p = 0.52). We conclude that LE were significantly more prevalent in men with the MS than without the MS, according to IDF criteria, independent of the effects of age and body mass index, especially in men with increased serum cortisol levels.

Life events, cortisol and levels of prostate specific antigen: a story of synergism.

BACKGROUND Previous studies have tested the relationship between stressful life events (LE) and cancer onset, but inconsistent results have been found. One possibility is that the LE-cancer relation may depend on other biological factors pertinent to stress and cancer. METHODS This study examined the relationship between LE and prostate specific antigen (PSA) levels, a tumor marker, and whether cortisol mediates or moderates a LE-PSA relationship. During a voluntary screening for prostate cancer risk, 139 men (mean age=57.3 years) were assessed with the Holmes and Rahe questionnaire about their LE during the past 1-5 years, and their PSA and serum cortisol levels were measured. RESULTS LE and cortisol alone were unrelated to PSA. However, statistically controlling for age, body mass index and the ratio of triglycerides to HDL cholesterol, we found evidence for a synergistic interaction between LE and cortisol. Among men with low cortisol, number of LE were inversely and significantly correlated with PSA (r=-0.265, p<0.05), while in men with high cortisol, number of LE were positively and significantly correlated with PSA (r=0.344, p<0.01). These results more consistently stemmed from the effects of uncontrollable LE. Similar results were found, using a clinically significant PSA cut-off. CONCLUSIONS These results suggest considering the joint effects of psychosocial and biological factors in relation to possible cancer risk, where the hypothalamic pituitary adrenal axis may moderate stress-cancer risk associations.

Expression of Caveolin-1 in Penile Cavernosal Tissue in a Denervated Animal Model after Treatment with Sildenafil Citrate

INTRODUCTION Radical pelvic surgery is a major cause of erectile dysfunction due to iatrogenic cavernous nerve damage. Endothelial nitric oxide synthase, which generates nitric oxide (NO) in the cavernosal tissues, localizes to specialized plasma membrane invaginations known as caveolae. Growing evidence suggests that caveolae are major components of signal trafficking and that stimuli that affect the concentration of the main structural protein of caveolae, caveolin-1 influence NO signaling. AIM To evaluate caveolin-1 expression as a marker of cavernous tissue damage and determine the impact of early sildenafil administration on caveolin-1 expression in animal models of partial and total surgical penile denervation. METHODS Thirty-six rats were divided into six groups (N = 6 per group) that received bilateral or unilateral penile denervation or sham surgery, with and without sildenafil 10 mg daily for 7 weeks. MAIN OUTCOME MEASURES Sections were taken from the proximal middle portion of the penis of all animals. Cavernous tissue was delineated by the tunica albuginea, then the extent of immunostaining for the following parameters was quantitated to determine (i) cavernous smooth muscle layer in the cavernous space expressed as the percentage of alpha-smooth muscle actin (alpha-SMA) positive immunostaining per area and (ii) caveolin-1 expressed as a percentage of area. RESULTS A marked decrease in both caveolin-1 and alpha-SMA expression in cavernous smooth muscle tissue and in the endothelium of rats was noted after a bilateral and unilateral neurotomy. Specimens from animals receiving sildenafil exhibited higher mean immunostaining values for both proteins in cavernous tissue. The differences were statistically significant compared with groups receiving the same surgical treatment without sildenafil. CONCLUSION Caveolin-1 and alpha-SMA expression in cavernous tissue is significantly reduced by pelvic nerve injury, and the loss is related to the extent of the neural damage. Early administration of sildenafil elicits caveolin-1 expression, which appears to preserve cavernous tissue.

Life events are positively associated with luteinizing hormone in middle age adult men: role of cortisol as a third variable.

Abstract Previous studies have tested the relationship between chronic stress and sex hormones, but inconsistent results have been found. One possibility is that this association may depend on other biological factors. This study examined the relationship between stressful life events (LE) and sex hormones in men, and whether cortisol is involved in this relationship. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 139 healthy men (mean ± SD age, 57.8 ± 5.7 years) were included in this study. Participants were assessed with the Holmes and Rahe questionnaire in relation to their experience of LE during the previous 1–5 years. Salivary and serum cortisol was measured at 08:00–09:00 h, as well as luteinizing hormone (LH), total testosterone, epinephrine (E) and norepinephrine (NE). LE weight sum and LE number positively correlated with LH (r = 0.293, p = 0.004; r = 0.220, p = 0.031, respectively). In a multiple regression analysis, LE-sum explained an additional and significant 10.4% of the variance in LH levels, after statistically controlling for the effects of age, waist circumference (WC) and BMI (F(1,90) = 6.61, p < 0.05). Importantly, cortisol interacted with LE in relation to total testosterone. In men with high cortisol values (≥15.4 µg/dl), there was a statistically significant positive relationship between LE number and total testosterone levels (p = 0.05), while LE were unrelated to total testosterone in men with low cortisol. LE correlated with sex hormones, predicting LH values, and in men with high cortisol levels shows a possible moderator effect of cortisol on the relationship between LE and total testosterone.