Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacologic strategies for the treatment of BPH are at present directed toward relaxing prostate smooth muscle and reducing prostate volume. Historically, the primary limitation of pharmacotherapy for BPH has been that the symptomatic improvement achieved was overshadowed by the morbidity of treatment. However, the morbidity has been markedly diminished based on a more precise understanding of the embryology, physiology, and pharmacology of the prostate. The origins and pharmacologic properties of the smooth musculature of the prostate and bladder are unique. Therefore, drugs such as alpha blockers may relax the prostate selectively without altering bladder function. Although phenoxybenzamine, a nonselective alpha blocker, relieves infravesical obstruction secondary to BPH, the severity of the adverse reactions limits the use of this drug. The contractile properties of the prostate smooth muscle are mediated by alpha-1 adrenoceptors. The effectiveness of phenoxybenzamine and selective alpha-1 blockers such as prazosin and terazosin are similar. The side effects of the selective alpha-1 blockers are negligible. Androgen suppression, which lowers testosterone, produces intolerable side effects such as gynecomastia, erectile dysfunction, and impaired libido. The androgen dependency of the prostate provides the rationale for using 5 alpha-reductase inhibitors for the treatment of BPH. Reduction of prostate volume can be achieved by blocking the action or synthesis of dihydrotestosterone without impotence, gynecomastia, and hot flashes. These recent advances in pharmacotherapy for BPH are based on understanding of the fundamental developmental properties of the prostate.
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PMID:Embryologic development of the prostate. Insights into the etiology and treatment of benign prostatic hyperplasia. 169 77

The effects of depot medroxyprogesterone (DMPA), a 5 alpha-reductase, luteinizing-hormone release and human androgen receptor adhesion inhibitor, were assessed in 80 patients with benign prostatic hyperplasia (BPH) in a double-blind, placebo-controlled study. Patients were randomized to DMPA 150 mg single-dose intramuscular injection or placebo in a similar fashion. The following changes were seen with DMPA after 3 months (duration of DMPA effect): (1) serum testosterone reached castration levels within 3 days as compared to no changes in the placebo group; (2) the prostate volume was reduced by 25% compared to a 3% decrease with placebo (p < 0.001); (3) maximum urinary-flow rates increased by 3.7 ml/s compared to placebo (p < 0.001); (4) total urinary symptom scores decreased by 4.9 points compared to a nonsignificant decrease with placebo (p < 0.005). There was a 2.5-point decrease in irritative symptoms (urinary frequency, nocturia and urgency) as compared to a nonsignificant decrease with placebo (p < 0.005). After 3 months, the urinary symptoms and urodynamic changes were reversed but significantly greater than the baseline values (p < 0.001). The prostates showed regrowth to the initial sizes within 18-36 weeks. DMPA was better tolerated, except for a higher incidence of impotence, decreased libido and ejaculatory disorders, than in the placebo group. The quality of life is improved with DMPA since it did not produce hot flashes. It was concluded that single-dose DMPA 150 mg is a safe and effective treatment for prostatic obstruction where potency is a secondary consideration.
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PMID:Depot medroxyprogesterone in the management of benign prostatic hyperplasia. 853 77

Intermittent androgen deprivation therapy (IADT) is an alternative to continuous androgen deprivation therapy (ADT) in prostate cancer patients with nonmetastatic disease. ADT is associated with numerous side effects such as hot flashes, sexual dysfunction, anemia, fatigue, loss of muscle mass, osteoporosis, metabolic syndrome and premature cardiovascular disease. IADT was developed with the intention of improving the quality of life and to delay progression of prostate cancer to castration resistance. The benefits of slightly improved quality of life by IADT compared to ADT were demonstrated in multiple clinical trials. IADT was noted to be noninferior to ADT in patients with biochemical recurrence of prostate cancer but in studies performed in patients with metastatic prostate cancer, the results were inconclusive. Our recent studies suggested that the administration of 5 alpha-reductase inhibitors during the off-cycle of IADT can significantly prolong the survival of mice bearing androgen-sensitive prostate tumors when off-cycle duration was short. This review discusses the survival benefit of 5 alpha-reductase inhibition in IADT in animal models and the potential translation of this finding into clinic.
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PMID:Improving intermittent androgen deprivation therapy: lessons learned from basic and translational research. 2475 77