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Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss.

BACKGROUND: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. OBJECTIVE: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. METHODS: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. RESULTS: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. CONCLUSION: Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

5-alpha Reductase Inhibitors↗

Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia.

Finasteride is commonly used for the treatment of benign prostatic hyperplasia and has been suggested to prevent prostate cancer development. To gain insight to the molecular effects of finasteride on prostate cancer development, we studied six prostate cancers diagnosed during finasteride treatment for benign prostatic hyperplasia. Comparative genomic hybridization detected genetic alterations in four tumors (1-5 changes/tumor). Xq gains and 6q losses were the most common alterations. The recurrent Xq gains motivated us to study the involvement of the androgen receptor (AR) gene. One tumor with Xq gain had a 3-fold amplification of the AR gene, suggesting that tumor development in finasteride-treated patients may require increased AR copy number and expression, as has previously been shown for prostate cancers recurring during hormonal therapy. Furthermore, in another tumor, an Arg726Leu mutation of the AR gene was found. This mutation was also present in the germ-line DNA of the patient. Arg726Leu mutation has previously been reported to affect the transactivational properties of the AR. In summary, prostate cancers developing during finasteride therapy may have distinct biological properties, such as a low number of chromosomal alterations and frequent involvement of the AR gene. Further studies are needed to explore the role of germ-line AR mutations in these patients.

Chromosome Aberrations↗

A prospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride.

PURPOSE: We prospectively studied the effect of finasteride on chronic hematuria associated with benign prostatic hyperplasia. MATERIALS AND METHODS: We prospectively evaluated 57 patients with chronic intermittent hematuria who were randomized to a finasteride treated or a control arm. RESULTS: In the untreated control group hematuria recurred in 17 patients (63%) within a year but in only 4 (14%) in the finasteride group, which was a statistically significant difference (p <0.05). Surgery was required for bleeding in 7 controls (26%), while no patient on finasteride required surgery. CONCLUSIONS: Hematuria secondary to prostatic bleeding may be significant if not treated. Finasteride appears to be effective for suppressing hematuria caused by benign prostatic hyperplasia and should be considered as treatment.

Aged↗

[Therapy of androgenetic alopecia with finasteride. What must be considered in consultation and drug prescribing].

Androgenetic alopecia in men is genetically determined, but occurs only when the testosterone metabolite dihydrotestosterone (DHT) is present in normal levels. The drug, finasteride, inhibits the enzyme 5-alpha-reductase II, which is responsible for converting testosterone to DHT. One 1 mg tablet (Propecia) of finasteride daily lowers serum DHT levels by about 70%, and increases serum testosterone by 10%. The efficacy of finasteride 1 mg has been demonstrated in a randomized, double-blind, placebo-controlled clinical trial involving more than 1,500 men in whom a significant increase in hair density over a specified area of the scalp, and a significant improvement in appearance was noted. Following one year to treatment 48%, and following 2 years 66%, of the finasteride patients (placebo group 7% after both treatment periods) presented with visibly thicker hair growth. Side effects such as decreased libido, ejaculation disorders and erectile dysfunction were seen in fewer than 2% of the men in both the finasteride and placebo groups.

Alopecia↗

A comparative study of a gonadotropin-releasing hormone agonist and finasteride on idiopathic hirsutism.

OBJECTIVE: To compare the efficacy of finasteride and GnRH agonist in the treatment of idiopathic hirsutism. METHODS: Sixty women with hirsutism were randomly assigned to receive either 5 mg of finasteride or long-acting GnRH agonist (depot leuprolide 3.75 mg) intramuscularly monthly for six months. MAIN OUTCOME MEASURES: Hirsutism scores were measured according to the Ferriman-Gallway scoring system, and side-effects were monitored for six months of treatment. Blood samples were taken at each visit for assessment of endocrine (FSH, LH, estradiol, progesterone, total and free testosterone, androstenedione, DHEAS-S, 17-OH-P. SHBG), biochemical, and hematologic para- meters. RESULTS: All of the patients treated with finasteride or GnRH agonist showed neither menstrual abnormalities nor side-effects. The mean percent change (+/- SD) in hirsutism scores in the GnRH and finasteride groups was 36% +/- 14% and 14% +/- 11% at six months, respectively. Serum total testosterone, free testosterone, androstenedion and DHEA-S showed a meaningful decrease in patients treated with GnRH agonist. On the other hand, only serum total testosterone and free testosterone levels decreased with finasteride treatment (p < 0.05 and p < 0.0001, respectively).

5-alpha Reductase Inhibitors↗

[Finasteride in prolonged therapy of patients with benign prostatic hyperplasia].

The efficiency of finasteride alone and in combination with alpha 1-adrenoblocker tamsulasine in long (2-4 years) treatment of benign prostatic hyperplasia is analyzed, based on published reports and the author's data. Specific features of long finasteride therapy are discussed: decrease in the level of prostatic specific antigen, no effect in case of concomitant infectious chronic prostatitis, more stable result in combination with tamsulasine, higher efficiency of finasteride after a previous course of therapy for prostatitis. Indications for finasteride therapy are defied. The results of finasteride therapy directly correlate with the size of the prostate in 78% patients.

Adult↗

Finasteride. Does it affect spermatogenesis and pregnancy?

QUESTION: A few women have asked me whether finasteride, taken by their partners for male pattern baldness, will affect their pregnancies. The product monograph is very alarming: it sounds as if even handling the medication could cause harm, especially to a male fetus. Should a man stop taking finasteride if his partner is planning pregnancy or is pregnant? What is the risk to the fetus if its mother accidentally handles crushed or broken tablets? ANSWER: To date, there are no reports of adverse pregnancy outcomes among women exposed to finasteride. Taking 1 mg of finasteride daily did not have any clinically significant effect on men's semen. Absorption through the skin while handling tablets is extremely unlikely to cause fetal exposure or harm. There is no reason to discontinue the drug. Motherisk is currently following up women who are pregnant or planning pregnancy and whose partners are taking finasteride.

Administration, Cutaneous↗

Decreased suburethral prostatic microvessel density in finasteride treated prostates: a possible mechanism for reduced bleeding in benign prostatic hyperplasia.

PURPOSE: We evaluated the influence of finasteride on prostatic microvessel density to elucidate a mechanism of decreased bleeding in finasteride treated patients with hematuria secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 22 patients with clinical BPH and gross hematuria who underwent prostate reductive surgery between 1998 and 2000 were prospectively evaluated. The prostate from 10 finasteride treated and 12 untreated patients was immunohistochemically stained for CD-34. Microvessel density analysis was performed by quantifying positive stained blood vessels located within the stroma of hyperplastic nodules as well as in the suburethral portion of the prostate. RESULTS: Mean microvessel density plus or minus standard deviation in finasteride treated patients was significantly lower in the suburethral portion of the prostate versus untreated controls (14.0 +/- 2.8 versus 20.2 +/- 5.3 vessels per high power field, p <0.05). In the nodular hyperplasia there was no statistically significant difference in the treatment and control groups (mean 17.5 +/- 2.8 and 16.7 +/- 4.6 vessels per high power field, respectively). CONCLUSIONS: Finasteride significantly decreases suburethral prostatic microvessel density in patients with BPH, which may explain its efficacy for decreasing BPH associated bleeding.

Aged↗

[Benign prostatic hyperplasia: patients' perception of medical treatment and their expectations. Results of a french survey involving patients treated with finasteride].

Benign prostatic hyperplasia (BPH) is increasingly common in medical practice, as a result of the inevitable aging of the population. The current therapeutic strategy includes three alternatives: watchful waiting, medical treatment and invasive therapy. Finasteride is one of the pharmacological options available. Many clinical studies have demonstrated its efficacy and good safety profile in patients with BPH. The survey we report provides new insights into what has to date been a purely therapeutic approach by taking into consideration patients' expectations and their perception of finasteride treatment. Results indicate that the main preoccupation for patients with BPH is that the pharmacological treatment will reduce the risk of major urological complications and the need for surgery (treatment characteristics considered as very or extremely important by 88 and 93% of patients, respectively). Decreasing symptoms and improving quality of life take second place after these primary concerns. Patient perception of finasteride is excellent. Nearly all patients are satisfied by the efficacy of the treatment, 89% of them reporting good to extremely good improvement of symptoms, the rapid onset of relief being particularly important. The efficacy of finasteride is not hindered by any tolerability issues and is further strengthened by its ease of use. Although this novel survey includes a number of biases, it nevertheless demonstrates that treatment of BPH with finasteride is well accepted by patients and satisfies their expectations. In addition, it provides a mass of general epidemiological data on patients with BPH, as well as on current medical practice regarding this condition.

Aged↗

Effects of finasteride on prostate volume and prostate-specific antigen.

BACKGROUND: Finasteride was introduced to treat patients with benign prostatic hyperplasia (BPH) recently, and it has shown its effects in reduction of prostate volume and decrease of prostate-specific antigen (PSA). We want to know how and how much does finasteride affect prostate volume as well as PSA and prostate-specific antigen density (PSAD), since PSA and PSAD are widely used as screening tools for early detection of prostate cancers. METHODS: Among 166 men with the diagnosis of BPH who received finasteride (5 mg/day) for 6 months, the serum PSA levels were measured. The prostate volumes before and after medication for a subgroup of 86 patients were measured by transrectal ultrasonography (TRUS). Paired t-test was used for the statistical analysis. The median percentage change in PSA of total 166 men and the median percentage changes in prostate volumes and PSAD of 86 men were also calculated. RESULTS: Among 166 men, the average serum PSA level was 2.48+/-2.02 ng/mL at baseline and 1.57+/-1.47 ng/mL at 6 months later. The median percentage change of serum PSA level was -44.26%. For 86 patients who underwent TRUS evaluation the average prostate volume changed from 39.83+/-21.10 mL to 33.62+/-20.52 mL. The median percentage change of prostatic volume was -17.80%. Also, the median percentage change in PSAD for these 86 patients after medication was -38.67%. CONCLUSIONS: Finasteride does decrease the serum PSA level and PSAD as well as prostate volume in men with BPH treated with it for 6 months. Physicians prescribing finasteride for patients with symptomatic BPH should always keep in mind its effect on PSA and PSAD levels in order not to miss potential prostate cancers.

Aged↗

Effect of finasteride (Proscar) on the proliferation of cultured epithelial and stromal cells from normal and hyperplastic human prostates.

Finasteride is a potent 5 alpha-reductase inhibitor which has proven useful in the clinical management of benign prostatic hyperplasia. To determine a potential mode of action for finasteride in prostatic cell proliferation, we have studied the incorporation of [3H]-thymidine into the DNA of cultured epithelial and stromal cells from normal and hyperplastic human prostates. The effects of short treatment with 10(-9) M and 10(-6) M finasteride (48 hrs.) on the incorporation of labelled thymidine were studied. A significant effect of finasteride on prostatic cell proliferation was observed at 10(-6) M for both epithelium and stroma from normal prostate: the rate of thymidine incorporation decreased to 80 +/- 3% (p < 0.001) and 55 +/- 10% (p < 0.01), respectively, compared to the control cells. As observed for normal prostates, this rate of thymidine incorporation was less for hyperplastic epithelium (70 +/- 4%, p < 0.001) than that observed for the hyperplastic stroma (74 +/- 4%, p < 0.01). These data clearly demonstrate that the reduction of the prostate volume observed in BPH treatment by finasteride is partly due to an inhibition of cell proliferation. However, the absence of complete inhibition of cell proliferation at 10(-6) M, a concentration known to strongly inhibit the 5 alpha-reductase activity, supports the hypothesis that factors other than DHT are necessary to induce prostatic cell proliferation.

Adult↗

Treating benign prostatic hyperplasia with finasteride in Chinese men: one-year experience.

To evaluate the long-term efficacy and safety of finasteride in the treatment of symptomatic benign prostatic hyperplasia (BPH), 50 patients with symptomatic BPH were initially evaluated in a double blind, placebo-controlled study for 6 months. The patients were then treated with finasteride in an open extension study in which all received the same dose of finasteride (5 mg/day) for another 6 months. Among the patients (n = 23) who completed the extension study, prostate volume was significantly reduced from baseline by 15%, maximum urine flow rate improved by 1.9 mL/second, symptom scores improved by 37% and serum prostatic specific antigen (PSA) level decreased by 1.34 ng/mL. Other than serum PSA level, these data differed insignificantly from data at the end of the first 6 months. The adverse events observed at the end of the first 6 months (two patients with decreased sexual libido and two with impotency) persisted throughout the study extension period. At the end of the 12 months study, one more patient reported decreased libido. The sustained clinical efficacy and low incidence of side-effects of daily treatment with finasteride 5 mg for 1 year indicate that finasteride is safe and effective for managing symptomatic BPH in Chinese men.

Aged↗

Down-regulation of prostate-specific antigen expression by finasteride through inhibition of complex formation between androgen receptor and steroid receptor-binding consensus in the promoter of the PSA gene in LNCaP cells.

As a specific competitive inhibitor of 5alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone, finasteride is being extensively used for the treatment of benign prostatic hyperplasia and in experimental settings for prostate cancer. In this study, we showed that finasteride markedly inhibited prostate-specific antigen (PSA) secretion and expression. The promoter of the PSA gene contains several well-known cis-regulatory elements. Among them, steroid receptor-binding consensus (SRBC) has been identified as a functional androgen-responsive element. Our previous study showed that PSA was not only present in conditioned medium of the PSA-positive LNCaP cells but was also detectable in small amounts in PSA-negative cell lines, PC-3 and DU-145 (L. G. Wang et al., Oncol. Rep., 3: 911-917, 1996). A strong correlation between binding of nuclear factors to SRBC and the level of PSA present in the conditioned medium and cell extracts was found in these three cell lines, whereas no such correlation with binding was obtained using Sp1 oligonucleotide as a probe. Binding of LNCaP cell nuclear proteins to SRBC was diminished when the cells were exposed to 25 microM finasteride, at which concentration 50% of both PSA mRNA and protein were inhibited. As a major component of DNA-protein complexes, the level of androgen receptor was dramatically decreased in the cells treated with finasteride. Our data indicate that inhibition of complex formation between SRBC and nuclear proteins due to the remarkable decrease in the level of androgen receptor plays a key role in the down-regulation of PSA gene expression by finasteride in LNCaP cells.

Consensus Sequence↗

Effect of finasteride on serum concentrations of dihydrotestosterone and testosterone in three clinically normal sexually intact adult male dogs.

OBJECTIVE: To determine the effect of finasteride at dosages of 0, 10, 0.25, and 0.50 mg/kg of body weight, PO, q 24 h, for 7 days) in a Latin square design with repeated measures. Blood was obtained before and on days 1, 2, 4, and 7 of treatment; 3 blood samples were obtained at 20 minute intervals to detect pulsatile secretion of DHT and T. Dogs were untreated at least 2 weeks between treatments. RESULTS: Finasteride at all doses was associated with a mean decrease in concentration of DHT of 55% (range, 155 +/- 32.3 pg/ml to 70 +/- 15 pg/ml), but had no effect on concentration of T (before treatment, 2.6 +/- 0.38 ng/ml; after treatment, 2.2 +/- 0.63 ng/ml). CONCLUSIONS: Finasteride at these doses significantly decreased serum concentration of DHT in sexually intact adult male dogs. Concentrations of DHT and T before and 7 days after treatment did not differ by dosage of finasteride administered. CLINICAL RELEVANCE: Finasteride (5 mg; 1 tablet) may be a drug of choice for treatment of benign prostatic hypertrophy in 10- to 50-kg dogs.

Analysis of Variance↗

Finasteride in the treatment of patients with moderate symptoms of benign prostatic hyperplasia.

This was a prospective study involving 27 patients with moderate symptoms of benign prostatic hyperplasia (BPH) treated continuously with 5 mg of finasteride daily for one year. There was improvement in clinical BPH symptoms in 22 patients (81.48%), increase in urinary flow rates by a mean of 2.2 mls/sec in 20 patients (74.07%) and a mean decrease in prostate volume of 20.9% in 25 patients (92.59%) comparable to the findings of the other investigators. No patient on finasteride therapy developed acute urinary retention suggesting reduced risk. The reversal in BPH progression stems from the ability of finasteride to reduce prostate volume thus relieving urinary obstruction and to decrease BPH symptoms and increase urinary flow rates. Finasteride therapy was well tolerated in this study. No adverse effect was observed except impotence in one patient (3.7%) and loss of libido in another patient (3.7%). For symptomatic relief in men with moderate obstructive symptoms of BPH, finasteride should be considered an effective alternative to watchful waiting. These findings warrant further investigations and may signal a positive change in the role of medical therapy in the future long term management of BPH.

5-alpha Reductase Inhibitors↗

Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia.

In men who are genetically predisposed to develop androgenetic alopecia (AGA; male pattern hair loss), endogenous androgens alter scalp hair follicles, resulting in production of vellus-like, miniaturised hair, rather than cosmetically significant terminal hair. This change leads to a progressive decline in visible scalp hair density, readily perceived by the patient as thinning and, eventually, baldness. Dihydrotestosterone (DHT), a metabolite of testosterone produced by the enzyme 5alpha-reductase, has been implicated as the specific androgen in the pathogenesis of AGA. Men genetically deficient in the Type 2 isoenzyme of 5alpha-reductase do not develop AGA. Moreover, Type 2 5alpha-reductase has been detected in scalp hair follicles, and balding scalps contain increased Type 2 5alpha-reductase activity and DHT levels. Taken together, these findings provide a rationale for the use of Type 2 5alpha-reductase inhibitors in the treatment of men with AGA. Finasteride, a specific and potent inhibitor of human Type 2 5alpha-reductase, decreases the formation of DHT from testosterone. Originally developed for the treatment of men with benign prostatic hyperplasia (BPH) as a 5 mg tablet, finasteride was subsequently evaluated as a treatment for AGA. Clinical studies in balding men demonstrated that finasteride reduced scalp DHT levels and improved hair growth, confirming the role of DHT in the pathophysiology of AGA. Dose-ranging studies established the optimal dose of 1 mg/day for the treatment of men with this disorder. Large, multicentre studies established the safety and efficacy of finasteride 1 mg, leading to marketing of Propecia (finasteride 1 mg) as a new treatment for men with AGA.

Journal Article↗

Evaluation of sexual function with an international index of erectile function in subjects taking finasteride for androgenetic alopecia.

OBJECTIVE: To evaluate variations in sexual and erectile function in subjects taking 1 mg of finasteride for androgenetic alopecia by administering the abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire before and during treatment. DESIGN: In a multicenter study, 186 patients with androgenetic alopecia were asked to complete the IIEF-5 regarding the domain of erectile function before (at baseline) and 4 to 6 months after beginning finasteride treatment. The test was self-administered. SETTING: The study was conducted in 7 institutional dermatology departments in Italy (Bologna, Rome, Genoa, Cagliari, Milan, Florence, and Bari). PATIENTS: A total of 186 patients with androgenetic alopecia were evaluated before and 4 to 6 months after the initiation of finasteride therapy (1 mg). All patients (age range, 19-43 years; mean age, 28.3 years) were followed up as outpatients. RESULTS: The score on each of the 5 domains of the IIEF-5 did not show any significant change after 4 to 6 months of treatment. CONCLUSIONS: Our results support the clinical impression that sexual side effects are actually much less common than reported in clinical trials. The sexual function of all patients remained stable during treatment with 1 mg of finasteride.

5-alpha Reductase Inhibitors↗

Finasteride treatment of female pattern hair loss.

OBJECTIVE: To evaluate the efficacy of oral finasteride therapy associated with an oral contraceptive containing drospirenone and ethinyl estradiol in premenopausal women with female pattern hair loss. SETTING: Outpatient consultation for hair disorders at the Department of Dermatology, University of Bologna. PATIENTS AND INTERVENTION: Thirty-seven women with female pattern hair loss were treated with oral finasteride, 2.5 mg/d, while taking an oral contraceptive containing drospirenone and ethinyl estradiol. Treatment efficacy was evaluated using global photography and the hair density score from videodermoscopy. A self-administered questionnaire was used to assess patient evaluation of treatment effectiveness. RESULTS: At 12-month follow-up, 23 of the 37 patients were rated as improved using global photography (12 were slightly improved, 8 were moderately improved, and 3 were greatly improved). No improvement was recorded in 13 patients. One patient experienced worsening of the condition. There was a statistically significant (P = .002) increase in the hair density score in 12 patients. No adverse reactions to the drug were reported. CONCLUSIONS: Sixty-two percent of the patients demonstrated some improvement of their hair loss with the use of finasteride, 2.5 mg/d, while taking the oral contraceptive. It is unclear whether the success was due to a higher dosage of finasteride (2.5 mg instead of 1 mg) or to its association with the oral contraceptive containing drospirenone, which has an antiandrogenic effect. Further studies are necessary to understand which patterns of female pattern hair loss respond better to this treatment.

5-alpha Reductase Inhibitors↗