Dutasteride.

Hannah C Evans; Karen L Goa

doi:10.2165/00002512-200320120-00005

Home/Archive/PubMed

PubMed · 14565784

Dutasteride.

Hannah C Evans·Karen L Goa

View original source ↗Export metadata ↓

Abstract

Dutasteride, a potent inhibitor of type 1 and 2 5alpha-reductase, reduced dihydrotestosterone levels by >90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day. A combined analysis of three placebo-controlled clinical studies conducted in patients with benign prostatic hyperplasia (BPH) found sustained improvements in American Urological Association- Symptom Index scores and urinary flow rate and a 57% decrease in the risk of acute urinary retention throughout the 2-year treatment period (all p < 0.001 vs placebo). Total prostate and transition zone volume were also reduced (both p < 0.001), as was the risk of BPH-related surgery (by 48%). A nonblind extension study found that dutasteride maintains efficacy for up to 4 years. Dutasteride monotherapy maintained symptom relief following combination treatment with dutasteride and tamsulosin in all patients but those with severe symptoms. Dutasteride was generally well tolerated. Impotence, reduced libido, gynaecomastia and ejaculation disorder occurred significantly more often in dutasteride than placebo recipients, but incidence was generally low. With the exception of gynaecomastia, incidence consistently decreased over time.

Explore related subjects

5-alpha Reductase Inhibitors Azasteroids Drug Therapy, Combination Dutasteride Humans Male Prostate-Specific Antigen Prostatic Hyperplasia Randomized Controlled Trials as Topic Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Hannah C Evans, Karen L Goa. 2003. Dutasteride.. https://doi.org/10.2165/00002512-200320120-00005

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2005

Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression.

The phytotherapeutic agent Serenoa repens is an effective dual inhibitor of 5alpha-reductase isoenzyme activity in the prostate. Unlike other 5alpha-reductase inhibitors, Serenoa repens induces its effects without interfering with the cellular capacity to secrete PSA. Here, we focussed on the possible pathways that might differentiate the action of Permixon from that of synthetic 5alpha-reductase inhibitors. We demonstrate that Serenoa repens, unlike other 5alpha-reductase inhibitors, does not inhibit binding between activated AR and the steroid receptor-binding consensus in the promoter region of the PSA gene. This was shown by a combination of techniques: assessment of the effect of Permixon on androgen action in the LNCaP prostate cancer cell line revealed no suppression of AR and maintenance of PSA protein expression at control levels. This was consistent with reporter gene experiments showing that Permixon failed to interfere with AR-mediated transcriptional activation of PSA and that both testosterone and DHT were equally effective at maintaining this activity. Our results demonstrate that despite Serenoa repens effective inhibition of 5alpha-reductase activity in the prostate, it did not suppress PSA secretion. Therefore, we confirm the therapeutic advantage of Serenoa repens over other 5alpha-reductase inhibitors as treatment with the phytotherapeutic agent will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumour progression.

5-alpha Reductase Inhibitors↗

PubMed2004

The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer.

PURPOSE: The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue is not clearly known. Changes in dihydrotestosterone levels in the prostatic tissue during androgen deprivation therapy in the same patients have not been reported. We analyzed dihydrotestosterone levels in prostatic tissue before and after androgen deprivation therapy. EXPERIMENTAL DESIGN: A total of 103 patients who were suspected of having prostate cancer underwent prostatic biopsy. Sixty-nine patients were diagnosed as having prostate cancer whereas the remaining 34 were negative. Serum samples were collected before biopsy or prostatectomy. Dihydrotestosterone levels in prostatic tissue and serum were analyzed using liquid chromatography/electrospray ionization-mass spectrometry after polar derivatization. In 30 of the patients with prostate cancer, dihydrotestosterone levels in prostatic tissue were determined by performing rebiopsy or with prostate tissues excised after 6 months on androgen deprivation therapy with castration and flutamide. RESULTS: Dihydrotestosterone levels in prostate tissue after androgen deprivation therapy remained at approximately 25% of the amount measured before androgen deprivation therapy. Dihydrotestosterone levels in serum decreased to approximately 7.5% after androgen deprivation therapy. The level of dihydrotestosterone in prostatic tissue before androgen deprivation therapy was not correlated with the serum level of testosterone. Serum levels of adrenal androgens were reduced to approximately 60% after androgen deprivation therapy. CONCLUSIONS: The source of dihydrotestosterone in prostatic tissue after androgen deprivation therapy involves intracrine production within the prostate, converting adrenal androgens to dihydrotestosterone. Dihydrotestosterone still remaining in prostate tissue after androgen deprivation therapy may require new therapies such as treatment with a combination of 5alpha-reductase inhibitors and antiandrogens, as well as castration.

5-alpha Reductase Inhibitors↗

PubMed2004

Effects of PNU157706, a dual 5alpha-reductase inhibitor, on rat epididymal sperm maturation and fertility.

Sperm entering the epididymis gain progressive motility and fertilizing ability in a process termed maturation. The functional dependence of the epididymis on dihydrotestosterone (DHT) is well established, yet few studies have examined the consequences on the epididymis of inhibiting DHT formation. We have shown that inhibition of both isoforms of 5alpha-reductase (types 1 and 2), the enzyme that converts testosterone to DHT, has pronounced effects on epididymal gene expression. In the present study, we investigate whether inhibiting 5alpha-reductase has consequences on epididymal sperm maturation. Rats were treated with vehicle or 10 mg/kg/day PNU157706, a dual-type inhibitor, for 28 days. Fertility and several key facets of sperm maturation were analyzed. Changes in sperm motility were assessed by computer-assisted sperm analysis (CASA). Changes in sperm morphology were assessed by CASA and electron microscopy. The motility of spermatozoa from the cauda epididymidis of treated animals showed a significant decrease in both the percentage of motile and progressively motile sperm as well as altered motion parameters. The morphology of cauda epididymal spermatozoa was also adversely affected by the treatment; the most prominent effect was a markedly elevated proportion of sperm that retained their cytoplasmic droplet. Matings with treated males resulted in fewer successful pregnancies and a higher rate of preimplantation loss. Progeny outcome was unaffected. The compromised sperm motility and morphology likely contribute to the subfertility of inhibitor-treated rats. Our results indicate a role for dual 5alpha-reductase inhibitors in further studies of epididymal physiology and as a potential component of a male contraceptive.

5-alpha Reductase Inhibitors↗