Birute Zilaitiene

Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA

STUDY QUESTION Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe? SUMMARY ANSWER Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels. WHAT IS KNOWN ALREADY High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small sample size and the results have been contradictory. STUDY DESIGN, SIZE, DURATION A coordinated international cross-sectional study among 8344 healthy men. A total of 1872 fertile men aged 18-45 years (with pregnant partners) from four European cities and four US states, and 6472 young men (most with unknown fertility) aged 18-28 years from the general population in six European countries were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS The men were recruited using standardized protocols. A semen analysis was performed and men completed a questionnaire on health and lifestyle, including their intake of beer, wine and liquor during the week prior to their visit. Semen quality (semen volume, sperm concentration, percentage motile and morphologically normal sperm) and serum reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and inhibin B and free testosterone) were examined. MAIN RESULTS AND THE ROLE OF CHANCE The participation rate for our populations was 20-30%. We found no consistent association between any semen variable and alcohol consumption, which was low/moderate in this group (median weekly intake 8 units), either for total consumption or consumption by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7 pmol/l (7.1-32.2) higher free testosterone than men with a weekly intake between 1 and 10 units. Alcohol intake was not significantly associated with serum inhibin B, FSH or LH levels in either group of men. The study is the largest of its kind and has sufficient power to detect changes in semen quality and reproductive hormones. LIMITATIONS, REASONS FOR CAUTION The participation rate was low, but higher than in most previous semen quality studies. In addition, the study was cross-sectional and the men were asked to recall their alcohol intake in the previous week, which was used as a marker of intake up to 3 months before. If consumption in that week differed from the typical weekly intake and the intake 3 months earlier, misclassification of exposure may have occurred. However, the men were unaware of their semen quality when they responded to the questions about alcohol intake. Furthermore, we cannot exclude that our findings are due to unmeasured confounders, including diet, exercise, stress, occupation and risk-taking behavior. WIDER IMPLICATIONS OF THE FINDINGS Our study suggests that moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels which may be due to a changed metabolism of testosterone in the liver. Healthy men may therefore be advised that occasional moderate alcohol intake may not harm their reproductive health; we cannot address the risk of high alcohol consumption of longer duration or binge drinking on semen quality and male reproductive hormones. STUDY FUNDING/COMPETING INTERESTS All funding sources were non-profitable and sponsors of this study played no role in the study design, in data collection, analysis, or interpretation, or in the writing of the article. The authors have no conflicts of interest.

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries

BACKGROUND Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population. OBJECTIVE To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses. RESULTS AND LIMITATIONS A total of 1102 (15.7%) had grade 1-3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment. CONCLUSIONS We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status. PATIENT SUMMARY The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.

Compensated reduction in Leydig cell function is associated with lower semen quality variables: a study of 8182 European young men

STUDY QUESTION Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996-2010. PARTICIPANTS, SETTING AND METHOD Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease the likelihood of detecting associations between reproductive hormone levels and semen variables, suggesting that the presented associations might in reality be even stronger than shown. Although we adjusted for confounders, we cannot of course exclude that our results can be skewed by selection bias or residual confounding. WIDER IMPLICATIONS OF THE FINDINGS Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. This is apparent even within the WHO reference range of semen quality. It is unknown whether impaired Leydig cell function in young men may confer an increased risk of acquired testosterone deficiency later in life. STUDY FUNDING/COMPETING INTERESTS Support from The Research Fund of Rigshospitalet (grant no. R42-A1326) to N.J. made this study possible. The background studies of young men have been supported economically by several grants. ITALIC! Denmark: The European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603 and most recently FP7/2007-2013, DEER Grant agreement no. 212844), The Danish Research Council (grants nos. 9700833 2107-05-0006), The Danish Agency for Science, Technology and Innovation (Grant no. 271070678), Rigshospitalet (Grant no. 961506336), The University of Copenhagen (Grant no. 211-0357/07-3012), The Danish Ministry of Health and the Danish Environmental Protection Agency, A.P. Møller and wife Chastine McKinney Møllers foundation, and Svend Andersens Foundation. ITALIC! Finland: European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT- 2002-00603 and most recently FP7/2008-2012, DEER Grant agreement no. 212844), The Academy of Finland, Turku University Hospital Funds, Sigrid Juselius Foundation. ITALIC! Estonia, Latvia and Lithuania: European Union (QLRT-2001-02911), the Estonian Science Foundation, grant number 2991, Lithuanian Foundation for Research, Organon Agencies B.V. and the Danish Research Council, grant no. 9700833. ITALIC! Germany: European Union (contract numbers QLK4-CT-2002-00603). ITALIC! Spain: European Commission QLK4-1999-01422. M.F. received support from the Spanish Ministry of Science and Innovation (Program Ramon y Cajal). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. None of the authors have any competing interests to declare.

Factors Associated with the Prevalence of Thyroid Nodules and Goiter in Middle-Aged Euthyroid Subjects

The aim of the present study was to determine associations of thyroid hormone levels and different metabolic parameters and anthropometric measurements with volume of nodular and nonnodular thyroid as well as with prevalence of goiter and thyroid nodules in middle-aged euthyroid subjects. Methods. The study consisted of 317 euthyroid subjects aged 48-49 from the Kaunas Cardiovascular Risk Cohort study. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and antithyroid peroxidase antibody (ATPO) levels, as well as anthropometric and metabolic parameters and smoking information, were evaluated. Results. In subjects with and without thyroid nodules, thyroid volume correlated with components of metabolic syndrome, body mass index (BMI), smoking, and TSH levels. In the nonnodular thyroid group, thyroid volume was also positively related to serum insulin and HOMA-IR, whereas a negative correlation between thyroid volume and leptin was identified in the nodular thyroid group. The goiter was identified in 12.3% of subjects. Female gender, thyroid nodules, smoking, BMI, and levels of TSH were independent predictors for goiter. Thyroid nodules were found in 31.2% of participants. Female gender, higher TSH levels, and thyroid volume were independent risk factors for thyroid nodules. Conclusions. Female gender, thyroid nodules, smoking, BMI, and TSH levels were identified as potential predictors of goiter. Female gender, TSH levels, and thyroid volume predicted the presence of thyroid nodules.

Aortopathies in Turner syndrome — new strategies for evaluation and treatment

Turner syndrome is a rare genetic disorder which impairs womens growth, reproductive function, cardiovascular development and other functions. This syndrome has been proposed as an independent risk marker for cardiovascular disease. Despite this, life-threatening cardiovascular outcomes affecting young women are dismissed because of incomplete follow up. During assessment due to their smaller stature, it should be noted that, although the ascending aorta diameter is normal in absolute terms, after indexation for body size, patients with Turner syndrome may have a dilated aorta.Based on recent guidelines and the latest studies, there is new evidence on the use of magnetic resonance imaging in diagnosing aortic lesions. New management possibilities of aortopathies have also been discussed. This approach should optimise medical care for women with Turner syndrome, but many areas of uncertainty still remain in the diagnosis and management of this syndrome, and new prospective studies are needed.

Surgical treatment of stress urinary incontinence and vaginal prolapse for the woman with epispadia

Patient K.L., 32 years old. Menses started at thirteen years old, C 5/28. Patient had two vaginal deliveries in 2004 and 2010. Dysplasia cervicis uteri CIN2-3 was diagnosed in 2007, subsequently diathermoconisation cervicis uteri was performed. The woman was born with epispadia — extrophia of urethra to abdominal wall, without pubic bone. At the age of 8 she underwent an operation in Moscow. During the operation the neck of the bladder was formed as well as urethra, which opens in vulva, place of clitoris. When she was 8 years old, her bladder capacity was 30 ml, in teenage years — 90 ml. The patient also reported history of recurrent urinary tract infections. 2011.08.02 Patient took medical advice in out patient department Kaunas university hospital with a complaint of stress urinary incontinence: when going, coughing, sneezing, doing exercises, having sex and at rest of time. Also it was the sexual intercourse problems with orgasm. She was urinating 8 times per day but none at night. Gynecological examination: absence of pubic bone, vulva is abnormal: absence of labium major and clitoris. Urethra opens into the place of clitoris. Front and back walls of vagina are moving down (POP-Q II-III stage prolapsed). Cervix of uterus is short, epithelised (after diathermoconisation). Uterus is normal in size, in retro-versio-flexio position. — without pathology. Sonography: internal genital organs without pathology. Boney, Valsalva test are positive, Ulmstein test negative. Urodynamic study revealed a bladder capacity of 134 ml, voided volume 173 ml. Pressure of detrusor — 10cmH2O. Compliancenormal, max flow rate 13,8 ml/s, voiding time 24 s. Spontaneous contractions of detrusor were not observed. Surgical treatment: 2011.10.10 TOT (tension obturator tape). Anterior and posterior colporrhaphy and perineoplastic was performed. There were no complications during and after surgery. On the 2 day after operation patient was released from hospital.

Relationship among nutritional patterns, metabolic parameters and reproductive hormones In healthy young men

Introduction: Importance of nutrition in diabetes and other metabolic diseases development is well known, but little has been done to explore whether nutrition affects reproductive health and metabolic parameters in young healthy subjects. The goal of our study was to evaluate a possible relationship between eating patterns, metabolic parameters and androgenisation levels in healthy young men. Methods: A total of 199 men aged 18–26 participated in this sub-study. Anthropometric measurements included height, weight, hip circumference, waist circumference, and calculation of body mass index. Investigation of reproductive function consisted of clinical evaluation, including orchidometry, and measurement of serum total testosterone, sex hormone binding globulin (SHBG), estradiol and inhibin B levels. Body composition analysis was performed by bioelectrical impedance analysis. Nutrition questions included usage of milk and dairy products, eggs, different types of meat and fish, pulses, fruit and vegetables. Results: A weak inverse correlation between beer consumption and SHBG has been observed (r=-0.180, p=0.013). Amount of wine consumed was related to estradiol levels (r=0.211, p=0.007). SHBG levels had inverse correlation with fat mass (r=-0.258, p<0.001), hip circumference (r=-0.249, p=0.001) and waist circumference (r=-0.200, p=0.008). Comparison of distributions among groups showed that milk non-users had lower testosterone (p=0.032) and estradiol (p=0.033) levels and higher waist circumference (p=0.047). Conclusion: