Viviana Mesch

Metabolic syndrome throughout the menopausal transition: influence of age and menopausal status

Objective To assess the relationship between the main components of both the metabolic syndrome and insulin resistance and menopausal status in the menopausal transition. Methods A total of 124 healthy women were divided into four groups according to their menstrual status: the first group consisted of 35 women in menopausal transition with menstrual bleeding (MTM) and with cycles between 35 and 80 days; the second group was composed of 29 women in menopausal transition with 3–6 months of amenorrhea (MTA). The third group consisted of 31 postmenopausal women (PostM) and the fourth group of 29 premenopausal women (PreM) with regular cycles. The metabolic syndrome was evaluated following the ATP III criteria. Evaluation of insulin resistance was made through the HOMA, QUICKI and McAuley indices and the triglycerides/high density lipoprotein (HDL) cholesterol ratio. Results The triglycerides/HDL cholesterol ratio increased in MTM, MTA and PostM women in comparison with PreM women. A slight decrease in the QUIKI index (p = 0.06) and a decrease in the McAuley index (p < 0.001) were observed in MTM, MTA and PostM women in comparison to PreM women. The relative frequencies of metabolic syndrome in the four groups were: PreM, 0%; MTM, 20%; MTA, 21%; and PostM, 22% (p = 0.0001). The most frequent markers of the metabolic syndrome were increased waist circumference, low HDL cholesterol levels and hypertension. Linear regression between menopausal status and metabolic syndrome was lost when age was added to the model. Conclusions The frequency of metabolic syndrome increased from the time of the menopausal transition to the postmenopause. Abdominal obesity was the most frequent feature observed. Nevertheless, aging erased the effect of the menopause on the metabolic syndrome. In order to prevent cardiovascular disease, the metabolic syndrome must be evaluated from the time of the menopausal transition.

Androgens in relationship to cardiovascular risk factors in the menopausal transition.

Objective To establish the relationship between androgens and cardiovascular disease (CVD) risk factors in the menopausal transition. Methods A total of 124 women were divided into four groups: 29 premenopausal (PreM), 35 women in the menopausal transition still menstruating (MTM), 29 women in the menopausal transition with 3–6 months amenorrhea (MTA), and 31 postmenopausal women (PostM). Levels of triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, glucose and insulin were assayed in all samples and waist circumference was measured. In a subgroup of 83 women (19 PreM, 21 MTM, 28 MTA and 15 PostM), levels of total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and estradiol were determined. The free androgen index, Homeostasis Model Assessment (HOMA) index, Quantitative Insulin Sensitivity Check Index (QUICKI) and McAuley index, estradiol/total testosterone and triglyceride/HDL cholesterol ratios were calculated. Results Androstenedione was higher in MTA vs. PostM women (p < 0.05); DHEAS was higher in PreM women vs. the other three groups (p < 0.05). Sex hormone binding globulin (SHBG) in MTM women was higher than in MTA women (p < 0.05); the free androgen index was lower in MTM women than in MTA and PostM women. SHBG and the free androgen index showed negative and positive correlations, respectively with waist circumference, insulin resistance and lipids. In a multiple regression analysis, considering waist circumference, neither free androgen index nor SHBG showed significant differences between groups. The waist circumference correlated only with SHBG (p = 0.022) and correlations between SHBG and insulin resistance markers continued to be significant, but relationships between SHBG and lipoproteins and all correlations found with free androgen index were lost. Conclusions An increment in the androgenic milieu that correlates with abdominal fat, insulin resistance and atherogenic lipoproteins becomes evident after the menopausal transition and suggests that evaluation of cardiovascular disease risk in these women should include androgens, considering that abdominal obesity is one of the main determinants of the relationship between androgenic parameters and cardiovascular risk factors.

A comparative study of two hormone replacement therapy regimens on safety and efficacy variables

OBJECTIVE To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women. METHODS In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Students t-test for paired samples, whereas between-group statistics were performed using the Students t-test for independent groups. RESULTS Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups. CONCLUSIONS Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms.

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.

Hair cortisol: A new tool for evaluating stress in programs of stress management.

AIMS Longitudinal and experimental studies have shown that chronic stress contributes to the onset and progression of different diseases. Although it is not possible to eliminate stress completely, people can learn to manage it by participating in different kinds of stress management interventions. This study examined the effectiveness of stress management interventions on neuroendocrine responses in stressed students and health professionals, by measuring hair cortisol in comparison to salivary cortisol. MAIN METHODS Salivary and hair cortisol measurements were performed in 37 subjects (31women, 6 men; mean age 34.0±10.6) who attended to a Coping Stress and Quality of Care Program at the University of Buenos Aires. Cortisol was measured at the beginning and at the end of the program. The State-Trait Anxiety Inventory STAI was used to evaluate state and trait anxiety. KEY FINDINGS In subjects who completed the program, no differences were observed in salivary cortisol levels between the first and the last session. However, in these subjects, hair cortisol obtained in the last session was significantly lower than hair cortisol in the first session. SIGNIFICANCE Hair cortisol appears to be a better biomarker than salivary cortisol for evaluation of the effectiveness of a stress reduction program and it seems to be a better indicator of stress system dysregulation as well.

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.

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.

HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

Tuberculosis (TB) is the leading cause of death among HIV‐positive patients. The decreasing frequencies of terminal effector (TTE) CD8+T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV–TB patients. Here, we aimed to study Mtb‐specific cytotoxicity, IFN‐γ secretion, memory status of CD8+T cells, and their modulation by DHEA during HIV–TB coinfection. CD8+T cells from HIV–TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T‐cell frequencies compared to healthy donors both in total and Mtb‐specific CD8+T cells. Notably, CD8+T cells from HIV–TB patients displayed higher Terminal Effector (TTE) CD45RAdim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD‐1 expression levels on CD8+T cells from HIV–TB patients increased although restricted to the CD27+ population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8+T cells and in vitro DHEA treatment enhanced Mtb‐specific cytotoxic responses and terminal differentiation in CD8+T cells from HIV–TB patients. Our data suggest that HIV–TB coinfection promotes a deficient CD8+ T‐cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8+T‐cell functions during HIV–TB coinfection.

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.