Lower urinary tract symptoms (LUTS) are storage, voiding and post-micturition symptoms affecting the lower urinary tract. LUTS may point to serious pathology of the urogenital tract (1). Many adults experience LUTS, and the prevalence of these symptoms increases with age (2). It has been shown that LUTS significantly diminish quality of life in affected men (3). Male LUTS are highly prevalent, occurring in 15% to 60% of males over the age of 40 years in the United States and Europe (4,5,6,7). The prevalence of LUTS is reported as fairly high (ranging from 17.8% to 85.2%) among Turkish patients (8,9). The etiopathogenesis of LUTS is complex and there is more than one hypothesis (10,11,12). Embryologically, genital and urinary systems are related in the sense that they share common passages and are sensitive to sex hormones (13) and androgen receptors are widely distributed in bladder and urethra epithelium cells (14). Estrogens and androgens are known to be important in occurrence of LUTS in men. Components of the insulin-like growth factors (IGF) axis have been found to be associated with the risk of benign prostatic hyperplasia (BPH) and LUTS in previous studies (15,16,17,18,19). It has been shown that high levels of insulin-like growth factor-binding protein 3 (IGFBP3) are inversely correlated with LUTS (20).
LUTS has been studied rather extensively in geriatric males at present. In this study, we aimed to focus on middle-aged males and to investigate a possible association between the severity of LUTS and serum levels of sex hormones, insulin-like growth factor -1 (IGF-1) and IGFBP3.
Forty-nine men with LUTS and 25 healthy men as controls participated in the study. None of the patients had a diagnosis of BPH. All subjects had normal hematocrit, thyroid-stimulating hormone, and prolactin levels as well as normal liver function tests. Subjects were excluded if they had a history of a reproductive disorder or use of medications known to interfere with androgen synthesis/action or glucose homeostasis. Self reports of major comorbidities, including heart conditions, vascular conditions, stroke, transient ischaemic attack, diabetes mellitus, cancer, high blood pressure, high cholesterol and previous urinary tract infection were considered. All patients gave written informed consent to participate in this study which was approved by the Ethics Committee of Bursa Yüksek İhtisas Hospital.
Patients complaining of LUTS who attended the outpatient clinics of the department of urology at Şevket Yılmaz Training and Research Hospital from January 2010 to March 2010 were asked to complete the International Prostate Symptom Score (IPSS). This scoring system is used to assess the severity of symptoms in BPH (21). A total of 49 men aged 25-45 years (mean: 37.9±2.0 years) with LUTS (IPSS ≥9) were included in this prospective study. Considering diurnal variation in hormone values, analyses controlled for the interval between waking and sampling the subjects’ blood. Estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone, dehydroepiandrosterone sulfate (DHEA-SO4), IGFBP3, IGF1 and sex hormone-binding globulin (SHGB) were determined using commercially available assay kits (Dade Behring Inc. -Newark, DE, USA) with an immulite 1000 auto-analyser (Dade Behring Inc. - Newark, DE, USA).
Data were evaluated using SPSS version 13.0 (SPSS Inc, Chicago, IL). Descriptive statistical values (arithmetic means, standard deviation) were calculated. Correlation between serum hormon levels and IPSS was studied using Spearman’s correlation coefficient (r). Comparisons were made by student’s t-test. A p value of less than 0.05 was considered statistically significant.
Demographic data of the study group is demonstrated in Table 1. General characteristics, including age, height, weight and body mass index (BMI) variables were statistically similar between patients and controls.
Biochemical data of the participants are presented in Table 2. There was a remarkable difference in DHEA-SO4 and SHBG between the patients and controls.
Correlations between IPSS scores and clinical and laboratory tests related to the patient group are given in Table 3. Among them, FSH had a statistically significant negative correlation while E2 showed a statistically significant positive correlation with IPSS scores.
Excess E2 may play an important role in the occurrence of LUTS or, stimulus to E2 receptors located in the prostate tissue may take part in the development of BPH (22,23). The results of the present study showed that E2 levels are elevated in LUTS-positive patients. The role of androgens is better studied in case of LUTS but E2 produced from metabolism of androgens or its metabolites is still an issue of discussion. We well know that most of the patients with LUTS recover by using antiandrogen medications but some do not respond to this treatment approach. Therefore, some additional mechanisms are suspected to explain the pathophysiology of LUTS; excess E2 is supposed to be one of them.
Although IGF axis has been shown to be associated with LUTS, the results of the present study did not support this idea. Limited number of the subjects in the study group may be one of the explanations of the situation, but another reason may be characteristics of the participants. In contrast to previous studies, our study group was composed of young males with an average BMI values. Insulin resistance is common among obese persons, and thus, a possible association between IGF and LUTS might have been missed in the study.
In addition to being a precursor of androgens and estrogens, DHEA-S is an active hormone with effects on its own (24). Only a few studies in the literature have evaluated DHEA-SO4 in patients with LUTS, and the results were controversial (25,26,26,27). Rabijewski et al. (25) found that in middle-aged men, the more severe LUTS were associated with low DHEAS. However, Litman et al. (27) showed that this relationship disappeared after statistical adjustment for age. We did not observe any correlation between serum levels of DHEA-SO4 and IPSS scores. Small sample size may have limited our ability to detect modest effects and high DHEA-SO4 levels in patients may account for unknown confounding causality.
Most notably, our study has a small sample size. Thus, findings should be interpreted with caution.
In conclusion, LUTS in men may be in association with E2. Further research are needed to understand the possible role of E2 in enlargement of the prostate.
Ethics Committee Approval: The study were approved by the Bursa Yüksek İhtisas Local Ethics Committee, Informed Consent: Consent form was filled out by all participants.
Peer-review: Externally peer-reviewed.
Medical Practices: Erkan Karadağ, Hakan Demirci, Muhammet Güzelsoy, Soner Çoban, Concept: Yasemin Üstündağ Budak, Kağan Huysal, Erkan Karadağ, Design: Yasemin Üstündağ Budak, Kağan Huysal, Erkan Karadağ, Data Collection or Processing: Yasemin Üstündağ Budak, Kağan Huysal, Hakan Demirci, Erkan Karadağ, Muhammet Güzelsoy, Soner Çoban, Analysis or Interpretation: Yasemin Üstündağ Budak, Hakan Demirci, Literature Search: Yasemin Üstündağ Budak, Hakan Demirci, Writing: Yasemin Üstündağ Budak, Hakan Demirci.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study has received no financial support.
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