Dramatically deteriorated quality of life in men with prostatitis-like symptoms.

BACKGROUND: Despite widespread occurrence and poor comprehension, prostatitis has been largely under-researched. OBJECTIVE: To compare complaints, general and sexual health, co-morbidities, risk factors, and lifestyle in men with and without prostatitis-like symptoms (PLS). MATERIAL AND METHODS: The cross-sectional study included 20- to 59-year-old male residents of Estonia. Questionnaire data of 82 men with PLS and of 711 men without PLS were compared. RESULTS AND DISCUSSION: A third of men with PLS considered their health poor, with more frequently diagnosed renal diseases, benign prostate hyperplasia, STDs, chronic nervous system diseases, and depression in them than in controls. They reported more cystitis and gynecological inflammations in their partners, and more prostatitis in their close relatives. This familial predisposition indicates possible genetic and immunologic background of PLS that may be associated also with susceptibility to respiratory tract infections revealed for the first time in our study. By the personality type, the men in the PLS group were less calm but more worrying. Hard drinks, antidepressants, sedative, and sleeping pills were more frequently consumed, and nightshift working and continuous stress were more commonly seen among men with than without PLS. PLS disturbed the sexual life as well as everyday activities. CONCLUSIONS: The men with PLS are characterized by remarkable complex of co-morbidities, habits, and attitudes. PLS possess substantial negative impact on quality of life. Successful work-up of these patients needs multidimensional treatment modalities that take into consideration major factors of syndrome. Genetic factors and central nervous system imbalance but also partner's genital tract microbiota as the potential contributing and/or perpetuating factors to PLS need more scientific attention.

Impact of sexual debut on culturable human seminal microbiota.

Micro-organisms are tightly integrated into host-microbiota ecosystem. Microbiota of human semen has been studied so far mostly in case of infertility or prostatitis. We aimed to reveal possible impact of sexual debut on seminal microbiota in healthy young men. The study group included 68 young healthy men, of them 12 men without sexual experience, 11 men with single lifetime sexual partner and 45 men with multiple lifetime sexual partners. Basic semen parameters were similar for all subgroups, and no correlation between sexual experience and WBC counts in semen was found. A man could harbour one to nine different bacteria in his semen; the total concentration of bacteria ranged from 2.3 to 7.3 log10 CFU/mL of semen. Lower total bacterial concentration and lower bacterial diversity was observed in men without sexual experience than in sexually experienced men (p < 0.05), with significant positive correlation between these two parameters (r = 0.54; p < 0.0001). In conclusion, the sexual debut is associated with the enrichment of seminal microbiota but not with the influx of WBC or changes in basic seminal parameters.

Inflammatory reaction found in prostate-specific material - method standardization and proposed optimal cut-off points.

Prostatitis classification as well as treatment decisions are primarily based on differentiation of the inflammatory status in prostate-specific material. At the same time, methods used for detection of inflammation are semi-quantitative and not finally standardized. The main aim of this study was to suggest more precise methods for detection of prostate inflammatory status. Additional aims were to define optimal cut-off points of various tests in order to discriminate between inflammatory and non-inflammatory condition and to analyze the prevalence of inflammatory prostatitis in the groups of symptomatic prostatitis, lower urinary tract symptoms and control subjects. This prospective study included 541 patients (with prostatitis symptoms, with lower urinary tract symptoms and controls) at Tartu University Hospital, Estonia. Leukocyte counts in first-void urine, expressed prostatic secretion and post-massage urine as well as interleukin-6 in prostate secretion specimens were determined. Based on ROC curve analysis, we detected potential normal values for leukocytes in expressed prostatic secretion (<0.5 m/mL), leukocytes in post-massage urine (<4 WBCs per HPF) and IL-6 in prostatic secretion (<50 nmol/mL). Using these newly defined normal values, we detected inflammatory reaction in prostate-specific materials in 24.3%, 53.4% and 69% in control, lower urinary tract symptoms and prostatitis group, respectively. LIMITATION: only subjects with prostatic fluid volume >0.04 mL were included. We propose standardized method for analysis of inflammatory reaction in prostate-specific materials. Based on these newly defined normal values, we verified high prevalence of inflammatory forms of disease in both study groups, but also high prevalence of asymptomatic inflammatory prostatitis among control group of Estonian men. Combining results of analysis of the different inflammatory markers from available prostate-specific materials allows us to differentiate better between inflammatory and non-inflammatory forms of prostate diseases and hence to choose more precise treatment strategies.

Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts.

STUDY QUESTION: What are the primary causes of severe male factor infertility? SUMMARY ANSWER: Although 40% of all patients showed primary causes of infertility, which could be subdivided into three groups based on the severity of their effect, ~75% of oligozoospermia cases remained idiopathic. WHAT IS KNOWN ALREADY: There are few large-scale epidemiological studies analyzing the causes of male factor infertility. STUDY DESIGN, SIZE, DURATION: A prospective clinical-epidemiological study was conducted at the Andrology Centre, Tartu University Hospital between 2005 and 2013, recruiting male partners of couples failing to conceive a child for over ≥12 months. Among 8518 patients, 1737 (20.4%) were diagnosed with severe male factor infertility. A reference group of fertile controls was comprised of 325 partners of pregnant women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean age of infertility patients and fertile controls was 33.2 ± 7.3 and 31.7 ± 6.3 years, respectively. All participants were examined using a standardized andrology workup, accompanied by a structured medical interview. Hormonal analysis included serum FSH, LH and testosterone. Semen quality was determined in accordance to the World Health Organization recommendations. Cases with spermatozoa concentrations of ≤5 million/ml were screened for chromosomal aberrations and Y-chromosomal microdeletions. MAIN RESULTS AND THE ROLE OF CHANCE: The primary cause of infertility was defined for 695 of 1737 patients (~40%). The analyzed causal factors could be divided into absolute (secondary hypogonadism, genetic causes, seminal tract obstruction), severe (oncological diseases, severe sexual dysfunction) and plausible causal factors (congenital anomalies in uro-genital tract, acquired or secondary testicular damage). The latter were also detected for 11 (3.4%) men with proven fertility (diagnoses: unilateral cryptorchidism, testis cancer, orchitis, mumps orchitis). The causal factors behind the most severe forms of impaired spermatogenesis were relatively well understood; causes were assigned: for aspermia in 46/46 cases (100%), for azoospermia in 321/388 cases (82.7%), and for cryptozoospermia in 54/130 cases (41.5%). In contrast, 75% of oligozoospermia cases remained unexplained. The main cause of aspermia was severe sexual dysfunction (71.7% of aspermia patients). Azoospermia patients accounted for 86.4% of all cases diagnosed with secondary hypogonadism and 97.1% of patients with seminal tract obstruction. Of patients with a known genetic factor, 87.4% had extreme infertility (azoo-, crypto- or aspermia). The prevalence of congenital anomalies in the uro-genital tract was not clearly correlated with the severity of impaired sperm production. Previously defined 'potential contributing factors' varicocele and leukocytospermia were excluded as the primary causes of male infertility. However, their incidence was >2-fold higher (31.0 vs 13.5% and 16.1 vs 7.4%; P < 0.001) in the idiopathic infertility group compared to controls. In addition, the proportions of overweight (or obese) patients and patients suffering from a chronic disease were significantly increased in almost all of the patient subgroups. LIMITATIONS REASONS FOR CAUTION: The study included only subjects with reduced total spermatozoa counts. Thus, these findings cannot be automatically applied to all male factor infertility cases. WIDER IMPLICATIONS OF THE FINDINGS: The novel insights and improved clarity achieved in the comprehensive analysis regarding the absolute, causative and plausible factors behind male infertility, as well as the 'potential contributing factors', will be valuable tools in updating the current clinical guidelines. The study highlights knowledge gaps and reiterates an urgent need to uncover the causes and mechanisms behind, and potential treatments of, oligozoospermic cases, representing the majority of idiopathic infertility patients (86.3%). STUDY FUNDING/COMPETING INTERESTS: The project was financed by the EU through the ERDF, project HAPPY PREGNANCY, no. 3.2.0701.12-004 (M.P., M.L.) and the Estonian Research Council: grants PUT181 (M.P.) and IUT34-12 (M.L.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. TRAIL  REGISTRATION NUMBER: Not applicable.

Couple-related factors of ART outcome.

PURPOSE OF INVESTIGATION: Although assisted reproductive technologies (ART) are the current mainstay of infertility treatment, several mechanisms leading to ART failure are still unclear. The aim of the present study was to determine possible health-related risk factors in both counterparts of the couple affecting the ART outcome. MATERIAL AND METHODS: The authors recruited 100 consecutive couples who were undergoing ART procedure. All subjects filled out a health questionnaire, and the presence of bacterial vaginosis in females and/or prostatitis in males was evaluated. RESULTS: Success of the ART procedure was 30.2%, failure being most significantly related to woman's age (OR = 0.24, 95% CI 0.09-0.66, p = 0.003) and excess body weight (OR = 0.08, 95% CI 0.01-0.63, p = 0.002). Male factors, previous conceptions, and presence of children increased the likelihood of ART success. Bacterial vaginosis and prostatitis did not significantly compromise the effectiveness of the ART procedure in this study. CONCLUSION: In 100 consecutive infertile couples scheduled for ART procedure, pregnancy was achieved in 30.2%, with female age and overweight and previous children from male side being the most significant factors affecting the ART outcome.

Systemic oxidative stress could predict assisted reproductive technique outcome.

PURPOSE: Previous studies have indicated that OxS (oxidative stress) may appear as a possible reason for poor ART outcome. Our aim was to study OxS levels in both partners of couples seeking Assisted reproduction Technology (ART). METHODS: Altogether 79 couples were recruited. Oxidative DNA damage (8-OHdG) and lipid peroxidation (8-EPI) were measured, and clinical background and ART outcomes were recorded. RESULTS: Both OxS markers accurately reflected clinical conditions with prominent negative effects attributable to genital tract infections, endometriosis, uterine myoma and smoking. Furthermore, the level of OxS was also affected by partner's state of health. The highest 8-EPI levels were detected in both partners when biochemically detectable pregnancies did not develop into clinically detectable pregnancies (in women, 97,8 ± 16,7 vs 72.9 ± 22,9, p = 0.007; in men, 89.6 ± 20,4 vs 72,1 ± 22,6, p = 0.049). CONCLUSIONS: To conclude, high grade systemix OxS in both partners may negatively affect the maintenance and outcome of pregnancy. Applying the detection of OxS in ART patients may select patients with higher success rate and/or those who require antioxidant therapy. This would lead to improvement of ART outcome as well as natural fertility.

Reproductive function in middle-aged males: healthy men versus male partners of infertile couples.

The aim of this study was to compare the reproductive parameters and the health-related, lifestyle and educational factors in middle-aged healthy men and male partners of infertile couples. Our patient group included 164 male partners of infertile couples with a preceding period of infertility of at least 12 months and 61 men attending a prostate health screening and considering themselves healthy. Significant differences between the groups were found in testicular volume, total sperm output, density and morphology as well as oestradiol levels in serum. The analysis showed significant positive correlations between testicular volume and semen quality, while negative correlations were observed between gonadotrophin levels and sperm parameters in both groups. Physical activity and sexual capability were higher in healthy men, while coital frequency and a history of sexually transmitted diseases were higher in male partners of infertile couples. The impact of physical activity and sexual capability on semen quality for all subjects was revealed. We can conclude that impaired reproductive function, that is, semen quality, in men >45 years is related not only with general male ageing but obvious differences between subjects of infertile couples and healthy middle-aged men can be seen. Their relations with lifestyle, environmental or physiological factors need further study.

Oxidative stress in leucocytospermic prostatitis patients: preliminary results.

The aim of this study was to contribute to the knowledge concerning pathogenesis of inflammatory chronic prostatitis by revealing possible shifts in the balance of markers of oxidative stress and anti-oxidative activity in case of leucocytospermic prostatitis. We also attempted to identify possible relations between seminal micro-organisms and oxidative stress parameters. A many-sided complex of local (spermatozoa, seminal plasma) and general (blood, urine) markers in 21 prostatitis patients and nine controls was compared. In both spermatozoa and seminal plasma, the content of diene conjugates was significantly higher in prostatitis patients compared with healthy controls. At the same time total anti-oxidative status in spermatozoa and total anti-oxidative activity in seminal plasma were lower in prostatitis patients than in controls. In urine, the level of 8-isoprostanes was significantly higher in prostatitis patients than in healthy controls, correlating well with 8-hydroxy-2'-deoxyguanosine. The latter correlated with cellular Fe and Ni contents as well, confirming that these metals with varying valency may cause DNA damage. Reduced glutathione showed higher levels in blood of controls than in prostatitis patients. Coryneform bacteria appeared to be associated with prostatitis-related oxidative stress. In conclusion, leucocytospermic prostatitis patients are characterised by oxidative stress at all levels: systemic (general), seminal plasma and cellular.

The Estonian version of the National Institutes of Health chronic prostatitis symptom index.

Our aim was to establish the Estonian version of the National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and to examine its validity and applicability in chronic prostatitis patients as well as in community-based study. The questionnaire was tested in 54 category III prostatitis patients. In addition, 452 men were enrolled into a community-based study that resulted in 83 completed questionnaires. The discriminatory power, psychometric properties and internal correlations of the questionnaire were tested. The questionnaire demonstrated good internal consistency, with Cronbach's alpha coefficient 0.82. The pain and quality of life domains demonstrated high correlations with each other and with the entire questionnaire. The total score and the scores of pain and quality of life domains of the Estonian NIH-CPSI differed significantly between the chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients and the men without CP/CPPS, and so the index proved a good discriminant validity. We can conclude that the Estonian NIH-CPSI is easily understood and reflects accurately the clinical symptoms and the quality of life in patients with chronic prostatitis. The similarity of the psychometric properties of the English and Estonian versions of the NIH-CPSI supports their measurement equivalence.

Evidence that orexigenic effects of melanocortin 4 receptor antagonist HS014 are mediated by neuropeptide Y.

Recent studies using melanocortin-4 receptor (MC4R) knockout mice and MC4R antagonists have shown that weakening of MC4R-ergic tone increases food intake and causes obesity. In this study, we used the newly discovered selective MC4R antagonist HS014 for increasing food intake in free-feeding rats and evaluated the effects of the NPY Y1 receptor antagonist 1229U91 and the selective serotonin uptake inhibitor fluoxetine on this increased feeding behavior. 1229U91 (12 nmol, i.c.v.), which alone does not affect food intake, significantly attenuated the orexigenic effects of HS014, whereas 1 and 3 nmol doses of 1229U91 were ineffective. Fluoxetine, which has been shown to inhibit NPY release, inhibited spontaneous food intake and completely blocked the stimulation of food intake by HS014. These data suggest that feeding induced by weakening of the MC4R-ergic tone may be mediated through activation of the NPY-ergic system. This is the first report showing that physiological feeding response evoked by MC4R blockage is influenced by NPY signalling.