Age-related morphological peculiarities of human testes.

BACKGROUND: This study aimed to compare the isolated testes size, volume, weight and density changes with age and to establish the suitability of three formulas of testicular volume calculation for 18-50 and 51-70-year-old men groups. MATERIALS AND METHODS: Two hundred and six testes of 103 men (59 of 18-50-year-old and 44 of 51-70-year-old men) were weighed and their size was measured by the sliding calliper. The accurate volume was determined by water displacement and compared with volume calculated using three formulas, and the density of testicular tissues was calculated. RESULTS: The mean length and height of both testes and length and height of right and left testes decreased significantly with age. The mean width of both testes and width of right and left testes decreased with age insignificantly. The mean of water displacement volume and weight and volume and weight of right and left testes decreased with age significantly. The mean density of testicular tissues and the density of the right and left testes increased significantly with age. In the same age group, the size, water displacement volume and weight of right testes was insignificantly higher than that of the left ones, and the density of testicular tissues was similar in the right and left testes. CONCLUSIONS: The prolate spheroid formula was most suitable for calculation of testicular volume for 18-50-year-old men and prolate ellipsoid formula was most suitable for calculation of testicular volume in 51-70-year-old men.

Emotional state, cognitive functioning and quality of life of adult women with Turner syndrome in Lithuania.

AIM: The aim was to analyze emotional state, cognitive functioning and quality of life (QoL) of adult women with Turner syndrome (TS) in Lithuania. PATIENTS AND METHODS: Of all invited adult TS patients from Lithuanian TS database (n = 150), 68 (age 18-60, average 30.2 ±â€¯9.0 years) agreed and were recruited for the study, as well as 68 age-matched healthy control women. Emotional state was evaluated by Profile of Mood States (POMS) questionnaire, cognitive functioning by Trail Making Test and Digit Span Test (DST) of Wechsler Adult Intelligence Scale, and QoL by WHO Brief Quality of Life Questionnaire (WHO QoL). RESULTS: Patients with TS were of a significantly shorter stature (p < .001) than age-matched control women and than the 3rd percentile of the National Standards of Lithuania. After the adjustment for height, weight and body mass index (BMI), no significant differences in emotional state were detected, though without the adjustment, depression-dejection (p = .004) score was significantly higher in TS women than in age-matched controls. Significantly worse cognitive functioning (attention capacity, visual scanning abilities, executive function and psychomotor speed, p < .001), as well as worse psychological (p = .002) and social (p = .006) aspects of QoL were found after the adjustment for height, weight and BMI in adult women with TS than in age-matched controls. CONCLUSION: In conclusion, after the adjustment for height, weight and BMI, adult women with Turner syndrome in Lithuania have impaired cognitive functioning and worse psychological and social aspects of QoL, but not emotional state and physical and environmental aspects of QoL in comparison to age-matched healthy women.

The number of CAG and GGN triplet repeats in the Androgen Receptor gene exert combinatorial effect on hormonal and sperm parameters in young men.

Androgen receptor (AR) is a transcription factor that is activated upon binding to testosterone (T) and is implicated in regulating the expression of reproduction-related genes. The human AR gene (Xq11-12) spans 186,588 bp and eight exons. N-terminal transactivation domain of the encoded AR protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8-37 CAG-repeats) and a polyglycine tract (encoded by 10-30 GGN-repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population-based cohort of Baltic young men (n = 974; aged 20.1 ± 2.1 years). We designed an assay to amplify and detect simultaneously the variants of both polymorphic repeats. The study revealed that elongated AR CAG tract was associated with lower FSH (linear regression: p = 0.0002, effect per repeat -0.056 IU/L). As a novel finding, the carriers of GGN-stretch with ≥24 repeats showed a trend for decreased sperm concentration (p = 0.027). Although neither of the variants exhibited an isolated effect on circulating T, their allelic combinations modulated serum T levels, as well as sperm concentration. The lowest T was measured for men carrying the AR gene with long CAG (n ≥ 25) and short GGN (n ≤ 21) repeat tracts (mean 18.8 vs. 25.5-28.6 nmol/L for the other AR variants, p = 0.017). The lowest sperm concentration was detected among individuals with both elongated repetitive stretches (CAG, n ≥ 25 and GGN, n ≥ 24; mean 49.0 vs. 68.4-72.1 mill/mL for the other variants; p = 0.00059). The innovative study design enabled to clearly demonstrate a combinatory impact of CAG and GGN repeat lengths at male reproductive parameters. As AR regulates transcription of over 900 genes in many tissues and organs, the combinatory effects of these common repeat-length variants on male physiology in the wider context and across lifetime are still to be assessed.

Effects of two-year testosterone replacement therapy on cognition, emotions and quality of life in young and middle-aged hypogonadal men.

The aim of the study was to examine the effects of two-year testosterone replacement therapy on cognitive functioning, emotional state and quality of life in young and middle-aged men with hypogonadotropic hypogonadism. Nineteen males diagnosed with hypogonadotropic hypogonadism participated in the study. Cognitive functions were assessed by Trail Making Test and Digit Span Test of Wechsler Adult Intelligence Scale. Emotional state was evaluated by Profile of Mood States. Quality of life was evaluated by WHO Brief Quality of Life Questionnaire. Changes after two-year testosterone replacement therapy were detected in Trail Making A (42.9 ± 22.3 vs. 36.2 ± 22.5, p = .050) and B (90.6 ± 55.3 vs. 65.6 ± 21.4, p = .025) tests, showing improvement in attention and visual scanning abilities, executive function and psychomotor speed, as well as in Digit Span Test forward score (5.4 ± 2.0 vs. 6.1 ± 2.6, p = .046), showing improvement in attention capacity and psychomotor speed. No significant differences were observed in emotional state and quality of life. In conclusion, beneficial effect in cognitive functioning (improved attention and visual scanning ability, executive function and psychomotor speed), but not in emotional state and quality of life, was observed in young and middle-aged hypogonadal men after two-year testosterone replacement therapy.

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.

APPROACHES TO THE 26-36-YEAR-OLD LITHUANIAN MEN'S SEXUAL FUNCTION.

CONTEXT: In the year 2003-2004 a circumstantial investigation of young men reproductive health parameters was performed in Nordic and Baltic countries, but sexuality remained undetermined. OBJECTIVE: To determine the suitability of the European Male Ageing Study - Sexual Function Questionnaire (EMAS - SFQ) for investigation of sexuality of 26-36 year aged general population and to investigate sexuality of Kaunas participants in the project "The reproductive function of Estonian, Latvian and Lithuanian Young men (2003-2004)" (KELLY), using EMAS - SFQ. DESIGN: Sixty one 26-36 year aged KELLY men were recaptured from the list of participants in a 2003-2004 study and completed EMAS - SFQ. Their anthropometric characteristics, scores of sexuality (22 parameters from EMAS - SFQ, 3 calculated parameters and 2 parameters consisting from answers to the only question - masturbation and erectile function-for each participant) were analysed, in conjunction with anthropometric, sperm quality and hormone levels of 2003-2004 18-25 year old general population. RESULTS: Overall sexual functioning and masturbation were higher as compared to all the published data for different age men and different testosterone concentration groups of EMAS study. CONCLUSIONS: KELLY sexuality results, obtained using EMAS - SFQ, would be considered as referral values for young men in countries with generally good reproductive health.

The current management of Turner syndrome.

Turner syndrome is a rare disease, with the incidence of 1 of 2500 life born females. Characteristic features are: growth retardation, gonadal dysgenesis and impairment, congenital and acquired cardiovascular disorders. New management possibilities in Turner syndrome are coming along with the new scientific evidence on the pathogenesis of TS developmental, metabolic, cardiovascular and reproductive issues. Attitude to the growth retardation treatment and hormone replacement therapy is changing. The effectiveness of additional androgen doses for growth improvement and low Estrogen doses in the early childhood for better puberty induction and metabolic outcomes has been demonstrated recently. There are some new concerns about pregnancy induced progression of cardiovascular pathology in Turner syndrome. Inadequate follow-up despite strict and clear guidelines of TS patients is still an issue in the health care system in many countries. This rare disorder requires multidiscipline approach of experienced professionals. The aim of this review is to overview recent studies evaluating Turner syndrome, to focus on the possibilities to avoid crucial outcomes of this disorder and to improve management and follow-up.

'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH ß-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V-LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.

Impaired emotional state, quality of life and cognitive functions in young hypogonadal men.

The study aimed to analyse emotional state, quality of life and cognitive functions in young hypogonadal men. Thirty-four males with hypogonadism (age 29.1 ± 10.5 years) and 34 age-matched healthy males (age 30.5 ± 11.0 years) were recruited. Their emotional state was evaluated by Profile of Mood States, quality of life - by WHO Brief Quality of Life Questionnaire - and cognitive functioning - by Trail Making Test and Digit Span Test of Wechsler Adult Intelligence Scale. It was found that young men with hypogonadism had higher depression-dejection (13.1 ± 8.8 versus 7.4 ± 5.9, P = 0.003), fatigue-inertia (10.0 ± 5.8 versus 7.0 ± 4.9, P = 0.030), confusion-bewilderment (5.1 ± 4.6 versus 2.3 ± 3.1, P = 0.004) and lower vigour-activity (14.3 ± 5.1 versus 17.7 ± 4.3, P = 0.008) levels than age- and sex-matched controls. Quality of life psychological (13.1 ± 2.8 versus 15.1 ± 1.9, P = 0.005) and social (13.6 ± 2.4 versus 15.7 ± 2.0, P < 0.001) domains were significantly worse in men with hypogonadism than in controls. Cognitive functions were significantly worse (P < 0.001) in men with hypogonadism than in controls, showing worse executive function, attention, visual scanning abilities and psychomotor speed. A significant correlation was found between testosterone concentration and quality of life psychological domain. Cognitive functioning scores were significantly related with FT4 concentration. It is concluded that young hypogonadal patients have impaired emotional state and quality of life, but the most severe impairment was found in cognitive functioning.

Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume.

Follicle-stimulating hormone receptor (FSHR) contains two common linked polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), shown to modulate ovarian function in women. The effect on male fertility and reproductive parameters has been inconclusive. We studied FSHR Asn680Ser polymorphism in a large study group (n = 1790) from the Baltic countries. The population-based Baltic male cohort (Estonians, Latvians, Lithuanians; n = 1052) and Estonian oligo-/azoospermic (sperm concentration <20 × 10(6) /mL) idiopathic infertile patients (n = 738) were genotyped for the FSHR Asn680Ser using PCR-RFLP. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No statistical difference was detected in allelic distribution of the FSHR Asn680Ser between the Baltic cohort and Estonian male infertility group. A consistent significant association was detected between the FSHR Ser680 allele and lower total testes volume in both, the Baltic cohort (p = 0.010, effect = -1.16 mL) and Estonian idiopathic infertility group (p = 0.007, effect = -1.77 mL). In meta-analysis, the statistical significance was enhanced (p = 0.000066, effect = -1.40 mL). Meta-analysis supported further associations with moderate effect between the FSHR Ser680 variant and higher serum FSH (p = 0.072), lower Inhibin B (p = 0.037) and total testosterone (p = 0.034). No statistically significant associations were identified with serum LH and estradiol, and sperm parameters. In conclusion, the study in 1790 Baltic men shows statistically highly significant association of the FSHR Asn680Ser with total testes volume and supportive association with serum reproductive hormone levels indicative to the functional effect of the alternative FSHR variants on male reproductive physiology.

Sexual function, mood and menopause symptoms in Lithuanian postmenopausal women.

OBJECTIVES: To assess sexual function in a clinical sample of Lithuanian postmenopausal women and identify the most important determinants of sexual function, including the use of hormone replacement therapy (HT), emotional status and menopausal symptoms. METHODS: Three hundred postmenopausal women who were referred to a gynecologist for a routine yearly check-up were enrolled for the study. Data for 246 women were appropriate for statistical analysis. Participants filled the Female Sexual Function Index for evaluation of sexual function, the Greene Climacteric Scale for the assessment of menopause symptoms and the Hospital Anxiety and Depression Scale for the evaluation of depression and anxiety symptoms. RESULTS: Sexual function was better in younger women and in HT users compared with non-users. Thus, to analyze the other variables, an adjustment for age was applied. HT significantly increased the likelihood of higher desire, lubrication, satisfaction, and lower pain when adjusting results for age. HT reduced the likelihood of psychological and depression symptoms and increased the likelihood of vasomotor symptoms of menopause when results adjusted for age were analyzed. HT did not appear to affect anxiety symptoms after the results were adjusted for age. CONCLUSIONS: HT increased chances for better sexual desire, lubrication, satisfaction, less pain and lower depression symptoms in postmenopausal women, even when the results were adjusted by age. HT did not improve sexual arousal, orgasm, menopausal and anxiety symptoms. Depression, anxiety, menopausal symptoms and age were the main risk factors for the possible development of sexual dysfunction.

Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up.

BACKGROUND: Cryptorchidism at birth is one of the symptoms of testicular dysgenesis syndrome (TDS). The aim of the study was to detect prevalence of cryptorchidism in Lithuanian newborn boys. METHODS: A total of 1204 consecutively born boys were examined within the first days after birth in one regional hospital. Boys cryptorchid at birth were reexamined 1 year later. RESULTS: The prevalence of cryptorchidism at birth was 5.7% (69 cases). Cryptorchidism was associated with low birth weight (P < 0.0001), preterm delivery (P < 0.0001), small gestational weight (P = 0.03) and other congenital abnormalities of genitalia (P = 0.0001). No correlation between cryptorchidism at birth and maternal age, birth order or mode of delivery was demonstrated in this study, but paternal body mass index <20 kg/m2 was found to be a significant risk factor (P = 0.001). The prevalence of congenital cryptorchidism at 1 year of age was 1.4%. CONCLUSIONS: We detected lower frequency of cryptorchidism at birth in Lithuanian boys than in Danes (9.0%), but higher than in Finns (2.4%). We had expected the frequencies in Lithuania and Finland to be relatively similar because the other symptoms of TDS (incidence of testicular cancer and semen quality) are close in these countries.

Inter-observer variation in the results of the clinical andrological examination including estimation of testicular size.

Inter-observer variation in andrological examination by 10 clinical investigators from five Nordic and Baltic countries was investigated. In addition, information on intra-observer variation was obtained for six of the 10 investigators. Testicular size was measured using Prader's orchidometer and one of the investigators also performed an ultrasound estimate of testicular size. A highly significant difference (p < 0.001) between observers was found with an inter-observer error of 16% in estimating testicular size in 23 young men. The difference in the estimate tended to increase with increasing testicular size. There was no significant intra-observer difference in two measurements performed on consecutive days. Only differences in median testis size, which were greater than 31% between measurements by two investigators, were found to be significant at the 5% level. The ultrasound estimate of testicular size was significantly lower than the orchidometer estimate, with a mean difference of 3.6 mL for the left testis and 4.3 mL for the right testis. Tanner staging of genitalia and diagnosis of a varicocele was subject to great inter-observer variation, and for the diagnosis of varicocele only one-third of the investigators was able to reproduce their results on a second examination. In conclusion, it was found that the clinical andrological examination of young men is subject to great inter-observer variation. This should be kept in mind when results from different studies are compared as well as in daily clinical practice.