Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study.

PURPOSE: The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. METHODS: This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. RESULTS: After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. CONCLUSIONS: The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.

Seminal microbiome in men with and without prostatitis.

OBJECTIVES: To profile the seminal microbiome applying next generation sequencing. METHODS: Semen samples of 67 men were involved in the study (21 men with and 46 men without prostatitis). Seminal microbiomes were profiled applying the method that uses combinatorial sequence tags attached to polymerase chain reaction primers that amplify the ribosomal ribonucleic acid V6 region. Amplified polymerase chain reaction products were sequenced using an Illumina paired-end protocol on HiSeq2000 platform. RESULTS: The most abundant phylum in semen was Firmicutes, comprising nearly half of the sequences found (median 41.7%, quartiles 28.5-47.2%) followed by Bacteroidetes, Proteobacteria and Actinobacteria. The counts of lactobacilli were higher in healthy men than prostatitis patients (27% [20.2-34.6%] vs 20.2% [4.9-25.0%]; P = 0.05), especially for Lactobacillus iners. Proteobacteria comprised higher proportions in prostatitis patients than healthy men. The species richness was higher in prostatitis patients than healthy men (inverted Simpson index 13.5 ± 5.8 vs 10.3 ± 4.0). CONCLUSIONS: The semen of chronic prostatitis patients contains fewer health-supporting lactobacilli, and has higher species diversity than that of healthy men. Firmicutes (especially lactobacilli), Bacteroidetes, Proteobacteria and Actinobacteria comprise the highest proportion of seminal microbiome.

Semen quality in middle-aged males: associations with prostate-specific antigen and age-related prostate conditions.

OBJECTIVE: To compare markers of semen quality and related reproductive indicators in middle-aged males in relation to serum prostate-specific antigen (PSA) levels. METHODS: A total of 384 voluntary middle-aged men who underwent screening for prostate health were recruited. Reproductive function, semen quality, hormonal parameters, prostate-related pathologies, and PSA levels were measured. RESULTS: Total sperm count and sperm concentration were decreased in men with elevated serum PSA compared with age-matched controls. Serum FSH levels differed significantly in subjects with non-malignant, pre-malignant, and malignant prostate conditions. PSA levels in men with three normal semen variables (semen volume ≥ 1.5 mL, sperm density ≥ 15 × 10(6)/mL, and A + B motility ≥ 40%) were significantly lower compared with subjects with altered parameters (1.51 ng/ml vs. 2.47 ng/ml, respectively, p = 0.002). PSA showed a negative correlation with semen volume and total sperm count, and a positive correlation with semen interleukin-6. CONCLUSIONS: Our data demonstrate that serum PSA levels are related to impaired reproductive parameters in middle-aged subjects. While there is no consensus about the potential link between male factor infertility, impaired reproductive indicators, and prostate pathologies, this topic needs additional research focusing on the interactions between male aging, reproductive function, and the prostate.

Decline of seminal parameters in middle-aged males is associated with lower urinary tract symptoms, prostate enlargement and bladder outlet obstruction.

PURPOSE: We aimed to compare the associations between semen quality, associated reproductive indicators and the main prostate-related parameters in middle-aged men. MATERIALS AND METHODS: This is a prospective study on 422 middle-aged men who underwent the screening for prostate health. Their reproductive function, semen quality and prostate-related pathologies were investigated. RESULTS: Significant associations between semen quality and prostate-related parameters could be seen. Total sperm count and sperm density decreased along with the increase of the I-PSS score and total prostate volume. Also, the related lower urinary tract characteristics showed a negative correlation with main semen parameters for all investigated subjects. No significant differences in age, testicular size, and hormonal parameters were found between the subjects with or without lower urinary tract symptoms and prostate enlargement. CONCLUSIONS: Our study suggests that altered seminal parameters in middle-aged men are associated with LUTS, prostate enlargement and/or bladder outlet obstruction. Although the assessments of prostate and lower urinary tract symptoms may not replace the semen parameters evaluating the male reproductive status, there is a need for further and more detailed investigations about the pathways behind these associations as well as possible related conditions.

Decline of seminal parameters in middle-aged males is associated with lower urinary tract symptoms, prostate enlargement and bladder outlet obstruction

Purpose We aimed to compare the associations between semen quality, associated reproductive indicators and the main prostate-related parameters in middle-aged men. Materials and Methods: This is a prospective study on 422 middle-aged men who underwent the screening for prostate health. Their reproductive function, semen quality and prostate-related pathologies were investigated. Results Significant associations between semen quality and prostate-related parameters could be seen. Total sperm count and sperm density decreased along with the increase of the I-PSS score and total prostate volume. Also, the related lower urinary tract characteristics showed a negative correlation with main semen parameters for all investigated subjects. No significant differences in age, testicular size, and hormonal parameters were found between the subjects with or without lower urinary tract symptoms and prostate enlargement. Conclusions Our study suggests that altered seminal parameters in middle-aged men are associated with LUTS, prostate enlargement and/or bladder outlet obstruction. Although the assessments of prostate and lower urinary tract symptoms may not replace the semen parameters evaluating the male reproductive status, there is a need for further and more detailed investigations about the pathways behind these associations as well as possible related conditions. .

Semen quality and associated reproductive indicators in middle-aged males: the role of non-malignant prostate conditions and genital tract inflammation.

PURPOSE: To compare the associations between non-malignant prostate conditions, genital tract inflammation, and reproductive function in middle-aged men. METHODS: Three-hundred and eighty-two voluntary male subjects who underwent the screening for prostate health were recruited for the study. Semen quality and associated reproductive indicators, seminal inflammation, and prostate-related pathologies were evaluated. RESULTS: Sperm motility and prostate-related parameters were significantly impaired in patients with chronic prostatitis syndromes and lower urinary tract symptoms in comparison with controls. Elevated seminal markers of inflammation were in positive association with body mass index, prostate-specific antigen, and estradiol level in serum while in negative association with semen volume, total sperm count, and sperm motility. According to WHO reference limits, speculative cutoff values for WBC and IL-6 in semen to detect reduced sperm parameters were 0.342 M/mL and 56.8 ng/L, respectively. CONCLUSIONS: According to our data, one of the possible pathways for impaired reproductive quality in male subjects >45 years could be related to infection and inflammation in the genital tract with subsequent (partial) obstruction and damage of prostate and other male accessory glands.

Genetically determined dosage of follicle-stimulating hormone (FSH) affects male reproductive parameters.

CONTEXT: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, -211 bp from the mRNA start) and significantly reduced male serum FSH. OBJECTIVE: In the current study, the T-allele carriers of the FSHB -211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. DESIGN AND SUBJECTS: We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. RESULTS: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10(-6); T-allele effect, -0.41 IU/liter), inhibin-B (P = 2.16 × 10(-3); T-allele effect, -14.67 pg/ml), and total testosterone (P = 9.30 × 10(-3); T-allele effect, -1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10(-4); TT genotype effect, -9.47 ml) and increased serum LH (P = 2.25 × 10(-2); TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. CONCLUSION: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential.

Influence of sexual intercourse on genital tract microbiota in infertile couples.

Several studies have suggested the association of disturbed genital tract microbiota with infertility. Our aim was to clarify the influence of sexual intercourse on partner's genital tract microbiota in infertile couples. Seventeen couples were studied, and in 5 men inflammatory prostatitis (IP) was diagnosed. Semen samples were collected during menstruation of the female counterpart, two self-collected vaginal samples were taken 3-5 days later - before intercourse and 8-12 h after intercourse. Ureaplasma parvum was found in 59% of women, its prevalence was higher in women whose partner had IP, as well as in half of their male partners. Sexual intercourse caused significant shifts in vaginal microbiota - increase of Nugent score and shifts in cultured microbiota (emergence and disappearance of several species). These changes were less expressed in the presence of normal vaginal microbiota but more prominent in the partners of IP men. These changes may interfere with fertilization.

Seminal interleukin-6 and serum prostate-specific antigen as possible predictive biomarkers in asymptomatic inflammatory prostatitis.

OBJECTIVES: To determine the possible predictive values of seminal interleukin-6 (IL-6) and serum prostate-specific antigen (PSA), as well as their combined values, in differentiating between subjects with or without asymptomatic inflammatory prostatitis. METHODS: The study group consisted of 490 men (mean age 18.9 ± 1.8 years, range 16-25). Cytologic examination of all ejaculates (using Bryan-Leishman-stained slides) and clinical examination for possible pathologic findings in the genital region were performed. The subjects with any clinical symptoms of inflammation were excluded. The levels of PSA in the blood serum and IL-6 in the seminal plasma were also determined. The IL-6 and PSA levels for different leukocytospermia status were statistically compared, and receiver operating characteristic curves were designed to determine the sensitivity versus specificity and the positive and negative predictive values of IL-6 and PSA levels against different thresholds of leukocytospermia (0.2, 0.5, and >1.0 × 10(6) leukocytes/mL). RESULTS: The levels of both IL-6 in the seminal plasma and PSA in the blood serum were significantly greater in National Institutes of Health prostatitis IV than in the controls. The receiver operating characteristic curves for seminal IL-6 and serum PSA showed high negative prognostic values for all 3 leukocytospermic subgroups, and positive prognostic values were seen only with IL-6 in the lower leukocytospermic range. CONCLUSIONS: Both seminal IL-6 and serum PSA are excellent negative predictive markers for asymptomatic inflammatory prostatitis in young men, although positive predictive values of these biomarkers remain less indicative in this age group.

Increased Prevalance of the -211 T allele of follicle stimulating hormone (FSH) beta subunit promoter polymorphism and lower serum FSH in infertile men.

CONTEXT: The human FSHB promoter polymorphism (rs10835638; -211 G/T) has been associated with serum FSH in a cohort of young Estonian men. The minor allele carriers had reduced serum FSH (15.7% in GT heterozygotes; 40% in TT homozygotes) compared with GG homozygotes. OBJECTIVE: Because FSH is essential for normal spermatogenesis and fertility, we speculated that abnormalities in FSH action could contribute to male infertility. We sought to study whether genetically inherited constitutively reduced FSH levels may affect male reproduction and replicate the association between rs10835638 and serum FSH among infertile male patients. DESIGN: Genotyping of rs10835638 in a cohort of infertile men (n = 1029; Andrology Center of the Tartu University Clinics, Estonia), including idiopathic infertility cases (IIFC; n = 750). PATIENTS: Patients included male partners (sperm concentration <20 x 10(6)/ml) of infertile couples failing to conceive a child for 12 months or longer. RESULTS: A significant excess of TT homozygotes (1.1 vs. 2.4%) as well as GT heterozygotes (22.4 vs. 25.1%) was detected among infertile men compared with the young male cohort (chi(2) test, P < 0.05). The T allele of rs10835638 was associated with reduced serum FSH (analysis of covariance; full cohort: P = 1.20 x 10(-6), F = 13.8; IIFC: P = 7.70 x 10(-7), F = 14.3) as well as with low FSH to LH ratio (full cohort: P = 1.52 x 10(-11), F = 25.6; IIFC: P = 3.25 x 10(-9), F = 20.4). The median serum FSH levels differed between the GG and TT carriers by 48.5%. All IIFC with TT genotype exhibited low (<1.8) FSH to LH ratio. CONCLUSIONS: In perspective, this genetic marker may have clinical significance in molecular diagnostics of male reproductive success and a potential to identify positive responders to FSH treatment.

FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men.

BACKGROUND: No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters. METHODS: A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 +/- 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia. RESULTS: Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 +/- 1.79 IU/l, n = 423) compared with heterozygotes (2.84 +/- 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 +/- 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 +/- 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups. CONCLUSIONS: The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed.

Prevalence of asymptomatic inflammatory (National Institutes of Health Category IV) prostatitis in young men according to semen analysis.

OBJECTIVES: To determine the prevalence of asymptomatic inflammatory (National Institutes of Health category IV) prostatitis in a cross-sectional community sample of young men. METHODS: The study group consisted of 565 men aged 18.9 +/- 1.8 years (mean +/- standard deviation). Cytologic examination of all ejaculates (using Bryan-Leishman stained slides), as well as analysis for basic semen parameters (volume, concentration, and motility) and clinical examination for possible pathologies in the genital region, were performed. Subjects with any clinical symptoms of inflammation were excluded. Levels of prostate-specific antigen in blood serum and interleukin-6 in seminal plasma were determined as well. RESULTS: The prevalence of asymptomatic inflammatory prostatitis (greater than 1 x 10(6) white blood cells [WBC]/mL in semen, according to World Health Organization guidelines) was 6.0%, but when we used a lower threshold suggested by our previous studies (greater than 0.2 x 10(6) WBC/mL), the prevalence was 19.0%. In this study the analysis did not show any significant effect of leukocytospermia on sperm quality, except higher sperm concentration in subjects with moderate leukocytospermia (0.2-1 x 10(6) WBC/mL). We did not detect any seasonal differences in the prevalence of asymptomatic inflammatory prostatitis. Interleukin-6 and prostate-specific antigen levels were significantly higher in leukocytospermic subjects than in those without leukocytospermia. CONCLUSIONS: Asymptomatic inflammatory prostatitis has a notable prevalence among healthy young men, suggesting the need for further studies to investigate pathogenetic mechanisms of the disease. Lack of negative effect of leukocytospermia on basic semen parameters may indicate higher functional reserve of accessory sex glands in this age group.