The influence of lifestyle and biological factors on semen variability.

PURPOSE: Semen parameters are subjected to within-individual variability over time. The driving factors for this variability are likely multi-factorial, with healthier lifestyle associated with better semen quality. The extent in which variations in individual's lifestyle contributes to within-individual semen variability is unknown. METHODS: A total of 116 repeat semen samples from 29 men aged 19-37 over 6 months were collected. Basic semen analysis as per 5th WHO manual and extended semen parameters (sperm DNA fragmentation, redox potential and lipid peroxidation, sperm binding to hyaluronan and hyperactive motility) were assessed. An additional 39 lifestyle/biological factors (weight, blood pressure, etc.) were collected at each sample including validated health questionnaires SF36 Health Status, Australian Recommend Food Score, and International Physical Activity Questionnaire. RESULTS: Only 10 out of the 39 lifestyle factors varied within men across samples including age (P = 0.0024), systolic blood pressure (P = 0.0080), social functioning (P = 0.0340), energy (P = 0.0069), non-alcoholic caffeinated beverages (P = 0.0010), and nutrition (P < 0.0001). The only semen parameter that varied between collections was sperm morphology (coefficient of variation 23.8 (6.1-72.0), P < 0.05). We only observed weak (r < 0.3) to moderate (r > 0.3- < 0.6) correlations between lifestyle factors, including body mass index, waist circumference, nutrition, exercise, blood pressure and semen parameters including sperm count, progressive motility, and sperm DNA fragmentation (P < 0.05). CONCLUSION: In healthy men from the general population, semen quality and associated lifestyle factors do not significantly vary over 6 months, indicating that one semen sample is likely sufficient for determining male fertility in this population.

MiOXSYS® and OxiSperm® II assays appear to provide no clinical utility for determining oxidative stress in human sperm-results from repeated semen collections.

BACKGROUND: Oxidative stress in semen contributes up to 80% of all infertility diagnosis. Diagnostics to measure oxidative stress in semen was recently added to the 6th edition WHO methods manual, although diagnostic predictive values need to be interpreted with caution as there are still several research questions yet to be answered. OBJECTIVES: To determine the natural fluctuations in semen redox indicators (MiOXSYS® and OxiSperm® II) within and between men and their association with markers of sperm oxidative stress. MATERIALS AND METHODS: Total, 118 repeat semen samples from 31 generally healthy men aged 18-45 years, over 6 months. Standard semen analysis as per 5th WHO manual. Semen redox levels measured via MiOXSYS® and OxiSperm® II. Additional attributes of sperm quality; HBA® binding assay and sperm hyperactivation and oxidative stress; DNA fragmentation (Halo® Sperm) and lipid peroxidation (BODIPY™ 581/591 C11) were assessed. RESULTS: Samples with high redox-potential (MiOXSYS® ≥1.47 sORP/106 sperm/ml) had lower sperm, motility, morphology and higher DNA fragmentation (P < 0.05). Upon further analysis, these associations were driven solely by the adjustment of sperm concentration (106 /ml) in normalised redox-potential. No significant associations between NBT-reactivity (OxiSperm® II) and measures of the sperm function or oxidative stress were observed (P > 0.05). Fluctuations in semen redox levels varied greater between men than within men over the study period. DISCUSSION: Neither MiOXSYS® nor OxiSperm® II assays were predictive of sperm function or sperm oxidative stress. This was likely due at least in part to limited understanding of their biochemistry and clinical application. As a result, these assays seem to provide no additional clinical utility beyond that of a standard semen analysis, highlighting the imperative for the development of new robust point-of-care devices for accurately determining sperm oxidative stress. CONCLUSION: These findings suggest that MiOXSYS® and OxiSperm® II systems for the measurement of sperm oxidative stress may have limited diagnostic potential.

Higher Serum Sex Hormone-Binding Globulin Levels Are Associated With Incident Cardiovascular Disease in Men.

CONTEXT: Sex hormone-binding globulin (SHBG) levels are associated with cardiovascular disease (CVD) risk factors. However, prospective data on the association between SHBG levels and CVD events are sparse, with conflicting results. OBJECTIVES: To examine associations between serum SHBG, total testosterone (TT), and incident CVD and CVD-related mortality in middle-aged to elderly men. DESIGN AND METHODS: Data on 2563 community-dwelling men (35 to 80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress cohort. The analytic sample included 1492 men without baseline (2002 to 2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007 to 2010) and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD mortality, were analyzed using logistic regression for incident CVD and Cox proportional hazard regression for CVD mortality, adjusting for established CVD risk factors. RESULTS: In multivariable models, elevated baseline SHBG and lower baseline TT were independently associated with incident CVD (SHBG: OR, 1.54; 95% CI, 1.15 to 2.06 per SD increase in SHBG, P = 0.003; TT: OR, 0.71; 95% CI, 0.52 to 0.97 per SD decrease in TT; P = 0.03). A decrease in TT between time points was associated with incident CVD (OR, 0.72; 95% CI, 0.56 to 0.92; P = 0.01). Neither SHBG nor TT was significantly associated with all-age CVD mortality [hazard ratio (HR), 0.69; 95% CI, 0.29 to 1.63; P = 0.40; and HR, 0.60; 95% CI, 0.28 to 1.26; P = 0.18, respectively]. CONCLUSIONS: Among all men and men >65 years, elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.

Cross-sectional and longitudinal determinants of serum sex hormone binding globulin (SHBG) in a cohort of community-dwelling men.

Despite its widespread clinical use, there is little data available from population-based studies on the determinants of serum sex hormone binding globulin (SHBG). We aimed to examine multifactorial determinants of circulating SHBG levels in community-dwelling men. Study participants comprised randomly selected 35-80 y.o. men (n = 2563) prospectively-followed for 5 years (n = 2038) in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. After excluding men with illness or medications known to affect SHBG (n = 172), data from 1786 men were available at baseline, and 1476 at follow-up. The relationship between baseline body composition (DXA), serum glucose, insulin, triglycerides, thyroxine (fT4), sex steroids (total testosterone (TT), oestradiol (E2)), and pro-inflammatory cytokines and serum SHBG level at both baseline & follow-up was determined by linear and penalized logistic regression models adjusting for age, lifestyle & demographic, body composition, metabolic, and hormonal factors. Restricted cubic spline analyses was also conducted to capture possible non-linear relationships. At baseline there were positive cross-sectional associations between age (ß = 0.409, p<0.001), TT (ß = 0.560, p<0.001), fT4 (ß = 0.067, p = 0.019) and SHBG, and negative associations between triglycerides (ß = -0.112, p<0.001), abdominal fat mass (ß = -0.068, p = 0.032) and E2 (ß = -0.058, p = 0.050) and SHBG. In longitudinal analysis the positive determinants of SHBG at 4.9 years were age (ß = 0.406, p = <0.001), TT (ß = 0.461, p = <0.001), and fT4 (ß = 0.040, p = 0.034) and negative determinants were triglycerides (ß = -0.065, p = 0.027) and abdominal fat mass (ß = -0.078, p = 0.032). Taken together these data suggest low SHBG is a marker of abdominal obesity and increased serum triglycerides, conditions which are known to have been associated with low testosterone and low T4.

The role of sex hormone-binding globulin (SHBG), testosterone, and other sex steroids, on the development of type 2 diabetes in a cohort of community-dwelling middle-aged to elderly men.

AIMS: Contrasting findings exist regarding the association between circulating sex hormone-binding globulin (SHBG) and testosterone levels and type 2 diabetes (T2D) in men. We examined prospective associations of SHBG and sex steroids with incident T2D in a cohort of community-dwelling men. METHODS: Participants were from a cohort study of community-dwelling (n = 2563), middle-aged to elderly men (35-80 years) from Adelaide, Australia (the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study). The current study included men who were followed for 5 years and with complete SHBG and sex steroid levels (total testosterone (TT), dihydrotestosterone (DHT) and oestradiol (E2)), but without T2D at baseline (n = 1597). T2D was identified by either self-report, fasting glucose (≥ 7.0 mmol/L), HbA1c (≥ 6.5%/48.0 mmol/mol), and/or prescriptions for diabetes medications. Logistic binomial regression was used to assess associations between SHBG, sex steroids and incident T2D, adjusting for confounders including age, smoking status, physical activity, adiposity, glucose, triglycerides, symptomatic depression, SHBG and sex steroid levels. RESULTS: During an average follow-up of 4.95 years, 14.5% (n = 232) of men developed new T2D. Multi-adjusted models revealed an inverse association between baseline SHBG, TT, and DHT levels, and incident T2D (odds ratio (OR) = 0.77, 95% CI [0.62, 0.95], p = 0.02; OR 0.70 [0.57, 0.85], p < 0.001 and OR 0.78 [0.63, 0.96], p = 0.02), respectively. However, SHBG was no longer associated with incident T2D after additional adjustment for TT (OR 0.92 [0.71, 1.17], p = 0.48; TT in incident T2D: OR 0.73 [0.57, 0.92], p = 0.01) and after separate adjustment for DHT (OR 0.83 [0.64, 1.08], p = 0.16; DHT in incident T2D: OR 0.83 [0.65, 1.05], p = 0.13). There was no observed effect of E2 in all models of incident T2D. CONCLUSIONS: In men, low TT, but not SHBG and other sex steroids, best predicts the development of T2D after adjustment for confounders.

Pattern of thyroid dysfunction in patients with metabolic syndrome and its relationship with components of metabolic syndrome.

BACKGROUND: Thyroid dysfunction (TD) and metabolic syndrome (MetS) are known risk factors for atherosclerotic cardiovascular disease (ASCVD). TD is risk factor for ASCVD mediated by the effects of thyroid hormones on lipid metabolism and blood pressure hence the components of MetS. It is possible that coexistence of these two disease entities and unrecognized TD in patients with MetS might substantially increase ASCVD risk. Moreover, little is known about the relationship between TD and the components of MetS. Thus, the purpose of this study was to evaluate the pattern of TD in patients with MetS and its relationship with components of the MetS. METHODS: A total of 358 previously diagnosed patients with MetS were recruited in the study. The thyroid function test parameters were measured to classify TD at Dhulikhel Hospital-Kathmandu University Hospital, Dhulikhel, Nepal. Statistical analyses were performed using SPSS version 16.0 to evaluate pattern and relationship. RESULTS: The overall prevalence of TD in patients with MetS was 31.84% with high prevalence of subclinical hypothyroidism (29.32%). We found no evidence of a relationship between TD and components of MetS, although there was significant difference in waist circumference between four groups of TD. CONCLUSION: Patients with MetS had subclinical hypothyroidism greatly. Although there was no evidence of any relationship between thyroid status and all components of MetS, TD should be taken into account when evaluating and treating patients with MetS to reduce the impending risk.

Oxidative stress and antioxidant defense in oral lichen planus and oral lichenoid reaction.

BACKGROUND: Oral Lichen Planus (OLP) is an inflammatory disease of unknown etiology while Oral Lichenoid Reaction (OLR) is a condition mimicking OLP. As these conditions are exposed to oxidative stress, they could release reactive oxygen species (ROS) which are implicated in the pathogenesis of a plethora of inflammatory conditions to lethal diseases. We evaluated and compared the levels of a series of oxidative stress markers in patients with OLP and OLR with that of normal controls and tried to identify the role of these oxidative stress markers in these conditions. METHODS: Protein thiol oxidation, malondialdehyde (MDA) and total antioxidant activity were estimated in both the groups (OLP and OLR) and compared with that of normal subjects. RESULTS: There were significantly lower levels of serum protein thiols in OLP (p < 0.005) while in patients with OLR the difference was not statistically significant (p < 0.489) when compared with controls. Serum MDA levels were significantly higher in OLP (p < 0.001) and OLR (p < 0.001) than in controls. However, there was no significant difference in serum MDA levels between OLP and OLR patients (p > 0.05), but with a significant difference in serum thiol levels between the two (p < 0.047). Total antioxidant levels were lower in OLP (p < 0.016) and OLR (p < 0.017) when compared to normal subjects, while between the study group total antioxidant levels were not significantly different (p < 0.632). CONCLUSIONS: The findings from the present study demonstrate involvement of ROS in the pathogenesis of OLP and OLR, though both these disease conditions have a different clinical course.