cholecalciferol and Prostatic-Hyperplasia

To explore the role of cholecalciferol for the prophylaxis against recurrent urinary tract infection (UTI) in patients with benign prostatic hyperplasia (BPH).. Our randomized, uncontrolled prospective study included 389 naïve BPH patients with moderate/severe symptoms, consecutively. The patients were randomly allocated to two groups; group-A included 193 patients who received tamsulosin, while group-B included another 196 patients who received tamsulosin with cholecalciferol. The study population was followed up for 2 years after the start of the treatment. For all the patients enrolled, clinical evaluation, imaging studies (abdominal and trans-rectal ultrasonography), and laboratory investigations [including urinalysis, urine culture with antibiotic susceptibility testing for positive cultures and estimation of prostate-specific antigen (PSA) level] were provided.. The incidence rate of recurrent UTI was 9% among the study population; it was significantly higher among group-A patients compared to those of group-B (13.5% vs. 4.6%, p 0.003, OR 2.7, 95% CI 1.5-4.3). Compared to patients of group-A, those of group-B developed a significantly lower level of PSA at the end of treatment period (0.16 ± 0.03 ng/mL vs. 0.27 ± 0.08 ng/mL, p 0.043, OR 1.9, 95% CI 1.2-6.8).. Adjuvant cholecalciferol supplementation may be protective against recurrent UTI among patients with BPH receiving tamsulosin therapy without extra adverse effects.

Topics: Aged; Cholecalciferol; Drug Therapy, Combination; Humans; Incidence; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Recurrence; Tamsulosin; Treatment Outcome; Urinary Tract Infections; Urological Agents; Vitamins

To evaluate the effect of BXL628, a vitamin D3 analog, on prostate volume in patients with benign prostatic hyperplasia (BPH).. We conducted a phase II, double blind, randomized, placebo controlled, clinical study. Patients eligible were aged>or=50 years, had a diagnosis of BPH and a prostate volume>or=40 ml. Eligible patients were randomized and given either BXL628 150 mcg daily or placebo for 12 weeks. All randomized patients underwent at baseline and at the end of study pelvic MRI to measure prostatic volume, uroflowmetry (Qmax), American Urological Association Symptom Index (AUASI), serum PSA, testosterone, dihydrotestosterone and luteizing hormone.. A total of 119 patients were randomized: 57 patients to BXL628 and 62 to placebo. The percentage change of prostate volume at 12 week was -2.90 in the BXL628 group vs. +4.32 in the placebo group (p-value<0.0001). The estimated difference between treatments (BXL628 minus placebo) was -7.22% (95% confidence limit -9.27 to -5.18). Considering Qmax, mean change vs. baseline was -0.30 in BXL628 vs. +1.50 in the placebo group: this finding was not statistically significant. The mean change of the AUASI total score at final visit vs. baseline was -1.77 in the BXL628 group vs. -3.45 in the placebo group (p=not significant).. BXL628 was able to arrest prostate growth within 12 weeks in men aged>or=50 years with prostatic volume>or=40 ml. Its unprecedented mechanism of action may offer a new opportunity for the treatment of BPH.

Topics: Aged; Aged, 80 and over; Calcitriol; Cell Division; Cholecalciferol; Double-Blind Method; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia

Prostate growth and differentiation is under the control of androgens not only during fetal life and childhood but also in adulthood, and it has been proposed that increased prostatic concentration of androgens, or increased androgen responsiveness, causes benign prostatic hyperplasia (BPH). However, different androgen ablation strategies such as treatment with GnRH agonists and finasteride resulted in a modest decrease of the hyperplastic prostate volume. In the last few years it became evident that both androgen-dependent and androgen-independent growth factors promote prostate enlargement by inducing cell proliferation or reducing apoptosis. Therefore, new therapeutic strategies, aimed at reducing intraprostatic growth factor signaling, are under investigation. In this study, we report further evidence that a non hypercalcemic-analogue of vitamin D(3), analogue (V) decreases growth factor-induced human BPH cell proliferation and survival. We found that Des (1-3) insulin-like growth factor [Des (1-3) IGF-I], an IGF-I analogue, which does not bind to IGF-binding proteins, is a potent mitogen for BPH stromal cells via a dual mechanism: stimulation of cell growth and inhibition of apoptosis. Similar results were previously reported for another growth factor for BPH cells, keratinocyte growth factor (KGF). Accordingly, we speculate that both KGF and IGF might be involved in the pathogenesis of BPH. We also found analogue (V) not only inhibits the mitogenic activity of growth factors on BPH cells, but even decreased the basal expression of bcl-2, and induced apoptosis. Therefore, vitamin D(3) analogues might be considered for the medical treatment of BPH.

Topics: Animals; Apoptosis; Cell Division; Cells, Cultured; Cholecalciferol; Humans; Insulin-Like Growth Factor I; Male; Peptide Fragments; Prostatic Hyperplasia; Proto-Oncogene Proteins c-bcl-2; Stromal Cells

Prostate enlargement and function is under the dual control of androgens and intraprostatic growth factors. They regulate, in concert, prostate cell proliferation and apoptosis. An increased signaling of both growth factors and androgens are supposed to underlie benign prostate hyperplasia (BPH), one of the more common disorders of the aging male. Since, in clinical practice, androgen ablation resulted in a rather limited decrease in prostate volume, therapeutic strategies targeting intraprostatic growth factors are emerging. The activated form of vitamin D, vitamin D3, and some of its analogues have been described as potent regulators of cell growth and differentiation. In this study, we report the effects of one of these vitamin D3 analogues, 1,25-dihydroxy-16ene-23yne D3, or analogue (V), on the fate of isolated epithelial cells derived from patients with BPH. We essentially found that analogue (V), as well as vitamin D3, inhibited BPH cell proliferation and counteracted the mitogenic activity of a potent growth factor for BPH cells, such as keratinocyte growth factor (KGF). Moreover, analogue (V) induced bcl-2 protein expression, intracellular calcium mobilization, and apoptosis in both unstimulated and KGF-stimulated BPH cells. Since a short-term (5-min) incubation with analogue (V) reduced the KGF-induced tyrosine phosphorylation of a 120-kDA protein, corresponding to the KGF receptor, a rapid and direct cross-talk between these two molecules is suggested. Such a rapid effect of analogue (V), together with the transient induction of intracellular calcium waves, seems to indicate the partial involvement of a membrane, nongenomic receptor for vitamin D3. In conclusion, we demonstrated the antiproliferative and proapoptotic effect of analogue (V) in BPH cells and speculated on its possible use in the therapy of BPH.

Topics: Blotting, Western; Calcitriol; Calcium; Cell Death; Cell Division; Cholecalciferol; Electrophoresis, Polyacrylamide Gel; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Growth Substances; Humans; Immunohistochemistry; Keratinocytes; Male; Microscopy, Electron; Phosphorylation; Primed In Situ Labeling; Prostatic Hyperplasia; Proto-Oncogene Proteins c-bcl-2; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor; Receptors, Growth Factor; Tyrosine