The Effect of Finasteride in Men with Benign Prostatic Hyperplasia

Gormley, G J; Stoner, Elizabeth; Bruskewitz, Reginald C.; Imperato‐McGinley, Julianne; Walsh, Patrick C.; McConnell, John D.; Andriole, Gerald L.; Geller, Jack; Bracken, Bruce; Tenover, Joyce S.

doi:10.1056/nejm199210223271701

Cited by 985 publications

(339 citation statements)

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“…Both androgen receptors and a-adrenoceptors are present in the prostate, and their physiological, pathological and therapeutic implications have been extensively documented (Cheng et al, 1993;Furuya et al, 1982;Gormley et al, 1992;Lepor et al, 1987;Matyus & Horvath, 1997). In principle, secretory and proliferative activities of the prostate are regulated by androgens, whilst the contractile properties of stromal cells are mediated via a-adrenoceptors, with a 1a - Figure 1 Contraction-response curves for phenylephrine with or without prazosin (10 nM) in isolated strips from prostate ventral lobes of intact and castrated rats.…”

Section: Discussionmentioning

confidence: 99%

“…Biological functions such as prostate¯uid secretion and morphological characteristics are aected considerably by androgen deprivation (Cheng et al, 1993). This androgen dependency is a theoretical basis for clinical utility of antiandrogens or ®ve a-reductase inhibitors in benign and malignant diseases of the prostate (Gormley et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Effects of castration on contraction and α₁‐adrenoceptor expression in rat prostate

Homma

Hamada

Nakayama³

et al. 2000

British J Pharmacology

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1 The prostate function is regulated by androgens and a-adrenergic activity. Clinically, antiandrogens and/or a 1 -adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the eects of androgen deprivation on prostate contractility via a 1 -adrenoceptor, the characteristics and expression of a 1 -adrenoceptors were examined in castrated rats. 2 Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 nM), [ 3 H]-prazosin and phenoxybenzamine (3 ± 300 nM) were used for inhibition assay, receptor characterization and partial alkylation of a-adrenoceptor, respectively. The mRNA content of three subtypes of a-adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT ± PCR). 3 Contractile response to phenylephrine increased in castrated rats, which could be explained by a relative increase of the stromal component. A lowered contraction potency was also noted in castrated rats. Receptor binding assay indicated minimal changes in the anity or density of a 1 -adrenoceptor. Escalating alkylation of the a 1 -adrenoceptor population resulted in a rightward shift in the contraction-response curves before depressing maximal contractile force, and the suppression was detected at lower doses in castrated rats. RT ± PCR study con®rmed the expression of three types of a 1 -adrenoceptor, a 1a , a 1b and a 1d -adrenoceptors, in intact rat prostate, and revealed that a 1a -adrenoceptor, but not a 1b or a 1d -adrenoceptors, was down-regulated in castrates. 4 The results show that androgen deprivation suppressed a 1 -adrenergic contractility of rat prostate strips, and the suppression was associated with down-regulation of receptor reserve for the a 1a -adreneroceptor population expressed in intact rat prostate.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of castration on contraction and α₁‐adrenoceptor expression in rat prostate

Homma

Hamada

Nakayama³

et al. 2000

British J Pharmacology

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“…Since the weight of the prostate depends on the 5a-reduced androgens, 20 it was important to determine the effect of the new steroidal compounds (1 -4) on the activity of 5a-reductase and their androgen receptor-binding affinity.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

New Aromatic Esters of Progesterone as Antiandrogens

Bratoeff¹,

Ramı́rez²,

Flores³

et al. 2004

Journal of Enzyme Inhibition and Medicinal Chemistry

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The in vivo and in vitro antiandrogenic activity of four new progesterone derivatives: 4-bromo-17a-( p-fluorobenzoyloxy)-4-pregnene-3,20-dione 1,4-bromo-17a-( pchlorobenzoyloxy)-4-pregnene-3,20-dione 2, 4-bromo17a-( p-bromobenzoyloxy)-4-pregnene-3,20-dione 3 and 4-bromo-17a-( p-toluoyloxy)-4-pregnene-3, 20-dione 4 was determined. These compounds were evaluated as antiandrogens on gonadectomized hamster prostate and reduced the weight of the prostate glands in gonadectomized hamsters treated with testosterone 5 (T) or dihydrotestosterone 6 (DHT) in a similar manner to that of commercially available finasteride, thus indicating a potent in vivo effect. The in vitro studies showed that steroids 1 -4 have a weak inhibitory activity on 5a-reductase with IC 50 values of: 280 (1), 2.6 (2), 1.6 (3) and 114 mM (4). The presence of Cl and Br atoms in the C-17 benzoyloxy group tends to increase the inhibitory potency of the compounds.The binding efficiency of the synthesized steroids 1 -4 to the androgen receptor of the prostate gland is also evaluated. All compounds form a complex with the receptor and this explains the weight reduction of the seminal vesicles in the animals treated with DHT plus steroids 1 -4.

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“…10 The duration of response is variable and patients will inevitably experience a PSA rise. The subsequent effect on PSA doubling time (DT), which represents a key parameter in many surveillance strategies, is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

Chiang

Loblaw

Jethava

et al. 2013

CUAJ

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Introduction: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alphareductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourablerisk prostate cancer. Methods: Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. Results: The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. Conclusion: 5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancerrelated DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.

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The Effect of Finasteride in Men with Benign Prostatic Hyperplasia

Abstract: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

Cited by 985 publications

References 13 publications

Effects of castration on contraction and α₁‐adrenoceptor expression in rat prostate

Effects of castration on contraction and α₁‐adrenoceptor expression in rat prostate

New Aromatic Esters of Progesterone as Antiandrogens

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

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The Effect of Finasteride in Men with Benign Prostatic Hyperplasia

Abstract: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

Cited by 985 publications

References 13 publications

Effects of castration on contraction and α1‐adrenoceptor expression in rat prostate

Effects of castration on contraction and α1‐adrenoceptor expression in rat prostate

New Aromatic Esters of Progesterone as Antiandrogens

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

Contact Info

Product

Resources

About

Effects of castration on contraction and α₁‐adrenoceptor expression in rat prostate

Effects of castration on contraction and α₁‐adrenoceptor expression in rat prostate