Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Finasteride”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1999

Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359.

BACKGROUND: Medical management of benign prostatic hyperplasia (BPH) giving rise to lower urinary tract symptomatology (LUTS) has emerged as the mainstay for first-line therapy. Prostate-specific antigen (PSA) is the most important method of detecting prostate carcinoma. The effect of finasteride on PSA has been widely reported. Little data exist with respect to alpha-adrenergic blocking therapy in men treated for BPH. In the present investigation we set out to evaluate the effect of these two forms of therapy. METHODS: Patients enrolled in the VA Cooperative Study #359 trial were evaluated. This study evaluated men with moderate LUTS owing to BPH in four treatment groups: placebo (P), finasteride (F), terazosin (T), and combination of finasteride plus terazosin (C). Men were recruited at 31 VA medical centers and had a baseline in 52-week PSA determination at the respective sites. RESULTS: There was no significant difference in baseline PSA between four groups (mean range, 2.0-2.9 ng/ml). Statistically significant reduction in PSA levels was observed at 52 weeks in the F and C arms (P < 0.001), whereas significant increases were observed in the T and P arms (P < 0.01). Additionally, there was no significant difference in PSA response between the T and P arms. Thirty percent of men in the C or F arms had more than 40-60% reduction of PSA. In contrast, the majority of men on T or P had less than 40% change in PSA. Only 35% of men on F or C had the expected 40-60% reduction in PSA level. CONCLUSIONS: These data demonstrate no clinically significant effect of T on PSA level. The heterogeneity of PSA response to F may make monitoring patients for the development of prostate cancer problematic.

Adrenergic alpha-Antagonists↗
PubMed1992

Castration-like effects on the human prostate of a 5 alpha-reductase inhibitor, finasteride.

Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BPH) and prostate cancer. 5 alpha-Reductase deficiency in humans, an experiment of nature, is an uncommon genetically transmitted disorder in which prostate size remains very small throughout adult life. A 5 alpha-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trials in patients with BPH to statistically decrease prostate size and improve clinical symptoms in comparison to placebo controls. In the untreated BPH prostate, tissue levels of dihydrotestosterone (DHT) and testosterone (T) averaged 4.2 and 0.2 ng/g, respectively. Following one week of finasteride therapy, T levels rose to a mean of 1.32 ng/g while DHT levels decreased to 0.62 ng/g. These values contrast with values in prostate tissue from surgical castrates in which DHT and T values average 1.14 ng/g and 0.1 ng/g, respectively. If we use the relative binding affinity of T and DHT to the androgen receptor as a criterion of biological androgen potency, T would appear to be one-fourth as potent as DHT. Using this 1:4 ratio to convert prostatic T to a biologically equivalent amount of prostatic DHT, the total biologically active DHT equivalent in the prostate following one week of finasteride averages 0.95 ng/g compared to a mean of 1.14 ng/g in surgical castrates.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1996

Lack of correlation between prostate-specific antigen density and prostatic shrinkage in response to finasteride therapy.

We attempted to correlate prostate volume reduction in response to finasteride treatment with initial prostate-specific antigen (PSA) levels and PSA density in men with symptomatic benign prostatic hyperplasia (BPH). The average reductions in prostatic volume (transrectal ultrasonography) were 27% and 34% after 6 and 12 months of finasteride therapy, respectively. Serum PSA levels decreased by 45% (6 months) and 50% (12 months). There was a positive correlation between initial serum PSA values and initial prostate volumes (r = 0.57, P < 0.001). There was no correlation, however, between the initial serum PSA or PSA-density values and prostate volume reduction. These data indicate that initial serum PSA and PSA-density values are not predictive of the response to finasteride therapy in terms of prostate size reduction.

Aged↗
PubMed2002

Effects of finasteride on apoptosis and regulation of the human hair cycle.

BACKGROUND: A number of studies have provided evidence that apoptosis is a central element in the regulation of hair follicle regression. In androgenetic alopecia (AGA), the exact location and control of key players in the apoptotic pathways remains obscure. OBJECTIVE: In the present study, we used a panel of antibodies and investigated the spatial and cellular pattern of expression of caspases and inhibitors of apoptosis (IAPs), such as XIAP and FLIP, in men with normal scalp and in men with AGA before and after 6 months of treatment with 1 mg oral finasteride treatment. METHODS AND RESULTS: Constitutive expression of caspases-1, -3, -8, and -9 and XIAP was detected predominantly within the isthmic and infundibular hair follicle area, basilar layer of the epidermis, and eccrine and sebaceous glands. AGA-affected tissues showed an increase in caspase (-1, -3, -6, -9) immunoreactivity with a concomitant decrease in XIAP staining. After 6 months of finasteride treatment, both caspases and XIAP were similar to levels exhibited by normal subjects. Immunoblot analysis was performed to determine antibody specificity and cellular expression of caspases. Purified populations of keratinocytes, melanocytes, dermal papilla, and dermal fibroblasts derived from human hair follicles were cultured in vitro and treated with 0.5 mm staurosporin. Time-course experiments revealed that processing of caspase-3 is a principal event during apoptosis of these hair cell types. CONCLUSION: These data suggest that alterations in levels of caspases and IAPs regulate hair follicle homeostasis. Moreover, finasteride appears to influence caspase and XIAP expression in hair follicle cells thus signaling anagen, active growth in the hair cycle.

Adolescent↗
PubMed2006

Should finasteride be used to prevent prostate cancer?

Prostate cancer is an important public health problem. Chemoprevention offers an attractive solution because it may lead to decreased disease-specific mortality. Furthermore, because many men are treated radically for prostate cancers that pose little or no threat to life, chemoprevention may also provide an excellent strategy for diminishing treatment-related costs and adverse effects such as erectile and urinary dysfunction. The Prostate Cancer Prevention Trial was a 7-year randomized study of finasteride versus placebo among men aged older than 55 years. All men were intended to have a prostate biopsy at study conclusion. At trial's end, there was a 25% reduction in period prevalence in all prostate cancers (24.4% for placebo vs 18.4% for finasteride). This represents a 6% absolute risk reduction. A larger number of higher-grade cancers were noted among men randomized to finasteride, which post hoc analyses and studies suggest are almost certainly related to previously unrecognized biases in trial design. There continues to be great debate as to the clinical significance of the cancers prevented. It is our opinion that among men who warrant 5-alpha reductase inhibitors (5ARIs) as part of their benign prostatic hyperplasia regimen, cancer prevention should be recognized as an additional benefit of treatment. Furthermore, men with high risk of clinically significant prostate cancer, such as significant family history, abnormal prostate biopsy histologies, and African descent, should be made aware of these findings. Men with significant anxiety or concern about prostate cancer should also be made aware of the risks and benefits of this therapy. Additional trials of antiestrogens, micronutrients, and other 5ARIs, which will mature over the next 2 to 5 years, will better define the role of 5ARIs in prostate cancer chemoprevention.

Clinical Trials as Topic↗
PubMed1995

Finasteride dose-dependently reduces the proliferation rate of the LnCap human prostatic cancer cell line in vitro.

OBJECTIVES: To assess the effects of finasteride, a 5-alpha-reductase inhibitor, and of classic antiandrogens on the growth rate of the LnCap human prostate carcinoma cell line, derived from a primary and well-differentiated neoplasm. METHODS: Cell proliferation experiments in vitro with and without the antiandrogens cyproterone acetate, hydroxyflutamide, and finasteride in the 0.0001 to 10.0 microM range. RESULTS: The growth rate of the LnCap cell line can be dose-dependently inhibited by 5-alpha-reductase inhibition (finasteride) and by antiandrogens (cyproterone acetate and hydroxyflutamide) in vitro, in defined conditions. CONCLUSIONS: Besides other human prostate cell lines derived from metastatic sites (PC3, DU145), also in the LnCap cell line an autonomous androgen-dependent mechanism of growth stimulation can be hypothesized, since testosterone and dihydrotestosterone are unable to stimulate the cell proliferation rate at the same molar concentrations. The clinical implications of these results in prostate cancer therapy and the possible future use of these molecules in the prevention of cancer incidence are discussed.

Androgen Antagonists↗
PubMed1993

Altered brain and pituitary androgen metabolism by prenatal, perinatal or pre- and postnatal finasteride, flutamide or dihydrotestosterone treatment in juvenile male rats.

1. The authors investigated the administration of finasteride, a 5 alpha-reductase inhibitor; flutamide, an androgen receptor blocker and; exogenous dihydrotestosterone (DHT) during intervals covering different portions of the "critical period" of neural development (i.e. prenatal, perinatal or pre- and postnatal development) to determine the long-term effects of these agents on altering androgen metabolism in hypothalamic and pituitary tissue of juvenile (30 day-old) male rats. 2. The efficacy of the treatments and hypothalamic-pituitary axis function was monitored by measuring luteinizing hormone levels by radioimmunoassay. 5 alpha-Reductase and aromatase activity was determined in hypothalamic and pituitary tissue. 3. Significant alterations in pituitary 5 alpha-reductase activity was detected in DHT-treated animals, whereas, hypothalamic 5 alpha-reductase activity was significantly decreased by finasteride treatment and significantly increased by DHT treatment. Hypothalamic aromatase activity was significantly decreased in flutamide-treated animals. 4. These results suggest that: a) prenatal exposure to exogenous DHT stimulates hypothalamic (but inhibits pituitary) 5 alpha-reductase activity long-term and b) basal 5 alpha-reductase activity levels can be inhibited by finasteride treatment in hypothalamic but not in pituitary tissue, suggesting that a different regulatory mechanism exists for 5 alpha-reductase in hypothalamic versus pituitary tissue.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

The finasteride prostate cancer prevention trial (PCPT)--what have we learned?

In 2003, the first of two large NCI-sponsored prostate cancer chemoprevention trials was reported. The prostate cancer prevention trial (PCPT) demonstrated a 24.8% reduction in the prevalence of prostate cancer in men taking finasteride 5mg/d for 7 years. However, despite the overall reduced risk of prostate cancer, men in the finasteride-treated arm of the study were more likely to develop high-grade disease. This article examines some of the controversies aroused by the PCPT and evaluates some of the arguments that have been advanced in an attempt to explain some of the unexpected outcomes of the study. In addition, some of the recent studies assessing the potential impact of an effective chemopreventive strategy on population mortality are reviewed. To conclude, there is some discussion of factors, which need to be openly discussed with male patients who might be considered for finasteride therapy.

Enzyme Inhibitors↗
PubMed2001

Pharmacokinetic parameters and mechanisms of inhibition of rat type 1 and 2 steroid 5alpha-reductases: determinants for different in vivo activities of GI198745 and finasteride in the rat.

The interaction of baculovirus expressed rat steroid 5alpha-reductase types 1 and 2 (r5AR1 and r5AR2) with 17beta-N-(2,5-bis(trifluoromethyl)phenyl)carbamoyl-4-aza-5alpha-androst-1-en-3-one (GI198745) was investigated at pH 7 and 37 degrees. This 5alpha-reductase inhibitor was found previously to be a time-dependent inhibitor of the two human 5alpha-reductase isozymes. In contrast, we demonstrate in the present study that although GI198745 is a potent time-dependent inhibitor of r5AR2, it is a classical rapid-equilibrium inhibitor of r5AR1. This type of behavior with human and rat 5alpha-reductases has been shown for the inhibitor 17beta-(N-tert-butylcarbamoyl)-4-aza-5alpha-androst-1-en-3-one (finasteride), a current therapy for benign prostatic hyperplasia. Inhibition of r5AR1 by GI198745 was competitive with testosterone and followed Michaelis-Menten kinetics with a K(i) value of 0.3 +/- 0.02 nM. Data for the inhibition of r5AR2 by GI198745 were consistent with a two-step mechanism, where K(i) is the dissociation constant for an initial enzyme-inhibitor complex and k(3) is the rate constant for the second slow step. The pseudo-bimolecular rate constant (k(3)/K(i)) for the association of GI198745 with r5AR2 was (2.0 +/- 0.4) x 10(7) M(-1) sec(-1). The high affinity of this inhibitor for r5AR2 was further demonstrated by the inability of the enzyme-inhibitor complex to dissociate after approximately 7 days of dialysis at 4 degrees. Both GI198745 and finasteride appear to inactivate r5AR2 by apparent irreversible modification, but are classical, reversible inhibitors of r5AR1. Therefore, we hypothesize that because of its pharmacokinetic parameters and increased potency against r5AR1, GI198745 is more effective than finasteride in preventing the growth of the rat prostate.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Polarographic behavior and determination of finasteride.

The polarographic behavior of finasteride at the dropping mercury electrode (DME) was studied adopting direct current (DC(t)), alternating current (AC(t)) and differential-pulse polarography (DPP) modes. In Britton-Robinson buffer (BRb), finasteride exhibited cathodic waves over the pH range 6-12. At pH 10, a well-defined cathodic wave was obtained. The latter could be characterized as being irreversible, diffusion-controlled and partially affected by adsorption phenomenon. The number of electrons involved in the reduction process was accomplished and a proposal of the electrode reaction was presented. The current-concentration plots were rectilinear over the ranges 8-40 and 2-30 microg ml(-1) using DC(t) and DPP modes, respectively. The minimum delectability was 0.2 microg ml(-1) (5.4 x 10(-7) M), for the latter. The proposed method was successfully applied to the determination of finasteride in its commercial capsules and the results obtained were in good agreement with those given with a reference method.

Finasteride↗
PubMed2000

A prospective, randomized trial comparing flutamide (250 mg/d) and finasteride (5 mg/d) in the treatment of hirsutism.

OBJECTIVE: To compare the long-term (1 year) effects of flutamide (250 mg/d) and finasteride (5 mg/d) for the treatment of hirsutism in women. DESIGN: Randomized, prospective clinical study. SETTING: Departments of Gynecology and Obstetrics and Endocrinology at Erciyes University Medical Faculty, Kayseri, Turkey. PATIENT(S): Seventy patients with hirsutism were studied. INTERVENTION(S): Thirty-five patients were treated with flutamide (250 mg/d) and 35 patients with finasteride (5 mg/d) for 12 months. Hirsutism score, hormone levels, and multiscreen blood chemistry were measured at 3-month intervals. MAIN OUTCOME MEASURE(S): Reduction in hair growth. RESULT(S): The modified Ferriman-Gallwey scores for hirsutism decreased significantly at months 6 and 12 from a mean +/- SD of 17. 8 +/- 5.8 to 6.0 +/- 3.4 and 17.8 +/- 5.8 to 4.8 +/- 3.2, respectively, in group 1; and from 19.1 +/- 6.1 to 14.2 +/- 4.9 and 19.1 +/- 6.1 to 11.3 +/- 5.0 in group 2, respectively. There were no statistically significant differences in any of the hormonal indices in group 1, but in group 2, E(2) and sex hormone-binding globulin increased significantly while DHEAS decreased significantly at 12 months of therapy. CONCLUSION(S): This study shows that flutamide (250 mg/d) is more effective than finasteride (5 mg/d) in reducing hair growth. We conclude that flutamide (250 mg/d) may represent a more effective and well tolerated treatment for patients.

Adult↗
PubMed2000

Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH).

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

Aged↗
PubMed2006

Do the benefits of finasteride outweigh the risks in the prostate cancer prevention trial?

PURPOSE: The Prostate Cancer Prevention Trial demonstrated that finasteride could reduce the incidence of prostate cancer by 25%. However, its use was also associated with an increased risk of high grade cancer resulting in uncertainty surrounding the net benefits of therapy. MATERIALS AND METHODS: We used the Montreal Prostate Cancer Model, a validated Markov model of prostate cancer progression, to compare the forecasted survival in treated and untreated men. The conditions of the model were varied to reflect different assumptions about whether the cancer grade difference observed in the PCPT was real or a treatment associated artifact, and whether cancers detected on end of study biopsies were clinically significant. RESULTS: For a hypothetical cohort of 1,000, 62-year-old men treated with finasteride, an increased survival of 140 life-years (0.14 years per individual) is forecasted if all diagnosed cancers are considered. If tumor grade differences are held to be artifactual, the forecasted benefits increase to 200 life-years. However, if the tumor grade difference is real and only clinically detected cancers are considered, estimated increased survival is only 20 life-years (0.02 years per individual). CONCLUSIONS: The primary prevention of prostate cancer with finasteride looks promising. However, at the present time it should only be considered with caution until we have answered critical questions surrounding the difference in cancer grade observed in the PCPT and the clinical significance of cancers detected on protocol directed end of study biopsies.

Aged↗
PubMed2003

Combination of low-dose flutamide and finasteride for PSA-only recurrent prostate cancer after primary therapy.

OBJECTIVES: To evaluate the efficacy and tolerability of combined finasteride and low-dose flutamide for prostate-specific antigen (PSA)-only recurrence after definitive therapy and to determine the predictors of recurrence-free survival. METHODS: Seventy-one men with biochemical recurrence after primary therapy for prostate cancer were prospectively enrolled from 1996 to 1998. Forty-two patients had undergone radical retropubic prostatectomy and 29 had undergone external beam radiotherapy. Radionuclide bone scans and computed tomography of the abdomen and pelvis showed no metastasis. The initial treatment with finasteride (5 mg twice daily) and flutamide (125 mg twice daily) was continued unless participants were unable to tolerate the agents or experienced PSA progression. RESULTS: At a mean of 44.4 months (range 12 to 92) of follow-up, 54 (76%) of 71 patients were available for measurement of disease status and response to therapy. Three patients had died of unrelated causes; 5 men withdrew from the study because of side effects and 1 patient for protocol violation. Eight patients were lost to follow-up. Twenty-seven patients (38%) continued receiving therapy with no evidence of PSA progression (PSA level less than 0.4 ng/mL), 6 patients maintained a more than 50% reduction in their baseline PSA level at the time of analysis, and 21 (29%) had PSA progression (ie, elevated PSA level on three consecutive tests more than 4 weeks apart). Major side effects were breast tenderness (90%), gynecomastia (72%), gastrointestinal disturbances (22%), fatigue (10%), and decreased libido (4%). The side effects were mild and well tolerated by most patients. CONCLUSIONS: The combination of finasteride and flutamide showed a moderate efficacy in patients with PSA-only recurrence after definitive therapy. The efficacy appears to be greater in patients who can achieve a PSA nadir of 0.1 ng/mL or less after the start of treatment.

5-alpha Reductase Inhibitors↗
PubMed2003

[Finasteride: 10 years of clinical use. Systematic review of the literature].

INTRODUCTION: After ten years of clinical use of Finasteride in patients with BPH, we carried out a systematic review of the literature including the assessment of their quality and grading the level of evidence for clinical recommendations. METHODS: Using Medline, Embase, Healthstar and Cochrane Library from 1990 until 2002, we select all the studies referring patients between 50 to 85 with symptoms of BPH, metrics of flow, prostatic volume, postmictional residue, detrusor pressure, adverse effects, cost-effectiveness and quality of life. RESULTS: We found out 135 references, of which 36 accomplish the inclusion criteria. Of those, 3 have got level I of evidence, 12 level II, 6 level III and 10 level IV. Three are economic studies and two evaluate the quality of life. DISCUSSION: With a high level of evidence and after ten years of clinical use, Finasteride shows its effectiveness in reducing the symptoms of patients with prostate bigger than 40 ml and/or PSA of more than 1.4 ngr/ml, with scarce adverse effects with a clear improvement of quality of life. Therefore, it is recommended (grade A) for clinical use. CONCLUSIONS: Finasteride, through prostate volume reduction, modify natural evolution of BPH, decreasing the risk of acute urine retention and surgery.

5-alpha Reductase Inhibitors↗
PubMed2001

Effect of finasteride on behavioural arousal and somatosensory evoked potentials in fetal sheep.

This study examines the effect of inhibiting the synthesis of gamma-aminobutyric acid(A) (GABA(A)) agonist steroids on behavioural activity and somatosensory evoked potentials (SEP) in late gestation fetuses. Pregnane steroid production was suppressed by infusion of the 5alpha-reductase inhibitor, finasteride in chronically catheterised fetal sheep, 130-135 days gestation. Finasteride treatment (160 mg in 10 ml of vehicle over 2 h) significantly increased the incidence of fetal arousal during the period 4-10 h after commencing the infusion (P<0.05, n=6), whereas other behavioural parameters were not effected. In three of four animals, finasteride produced an increase in the amplitude of the N22 peak of the SEP during high voltage electrocortical activity. We conclude that suppression of pregnane steroid synthesis, by inhibition of the 5alpha-reductase enzyme, increases arousal activity in the fetus which is consistent with a reduction in GABA(A) receptor mediated inhibition.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

A rapid method for obtaining finasteride, a 5alpha-reductase inhibitor, from commercial tablets.

To study the effects of allopregnanolone (AP) depletion on stress-induced dopamine changes in cortical dopamine, the 5alpha-reductase inhibitor finasteride on a gram-scale is required. Two procedures for the extraction of finasteride from tablets are outlined (method A and B). In method A, a suspension of powdered tablets was preliminary extracted with chloroform and the extracts dried and evaporated. The resulting residue was then purified on column chromatography. Method B involves a direct chromatographic separation of the powdered tablets. In terms of isolated yields, the second procedure works well, is cheaper, and less time-consuming. The efficiency of the method was tested by measuring progesterone, AP and THDOC content in plasma and cerebral cortex of rats. The protocol enables the prompt availability of sufficient amount of finasteride in experimental grade, useful in examining the role of endogenous cerebrocortical AP in brain homeostasis.

5-alpha Reductase Inhibitors↗
PubMed2002

Phenytoin-mediated androgen metabolism in gingival fibroblasts. Effects of the antiandrogen finasteride and the alkaline phosphatase inhibitor levamisole.

OBJECTIVES: This investigation attempts to identify the role of the alkaline phosphatase inhibitor levamisole (L) and the antiandrogen finasteride (F) on 5alpha-reductase activity in gingival fibroblasts, to elucidate mechanisms for phenytoin-induced gingival overgrowth. MATERIAL AND METHODS: Human gingival fibroblasts were incubated with Eagle's MEM and 14C-testosterone/14C-4-androstenedione as substrates; effective concentrations of phenytoin (Ph), levamisole (L) and finasteride (F), alone and in combinations of (Ph + F) (Ph + L) were added to the incubate. After 24 h, the medium was analysed for steroid metabolites and quantified using a radioisotope scanner. RESULTS: The metabolites isolated were 5alpha-dihydrotestosterone (DHT), 4-androstenedione (4-A) or testosterone (T) from each substrate. With 14C-T as substrate, Ph stimulated DHT synthesis by 1.7-fold, while F and L inhibited this activity by 1.8-fold and 34%, respectively (n = 6; P < 0.001). The combination of Ph + F reduced yields by 2.7-fold compared with Ph alone and Ph + L reduced DHT synthesis by 2.4-fold compared with Ph alone (n = 6; P < 0.001). When 14C-4-androstenedione was used as substrate, similar trends were identified. CONCLUSION: These results suggest that the alkaline phosphatase inhibitor levamisole and the 5alpha-reductase inhibitor finasteride can substantially decrease the yields of DHT in fibroblasts, stimulated by phenytoin. This could be a potential target for reducing the gingival overgrowth caused by phenytoin.

5-alpha Reductase Inhibitors↗