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PubMed1999

Finasteride treatment for one year in 35 hirsute patients.

This study was performed to confirm the favourable therapeutic effects of finasteride in hirsute women as described by previous publications of different research groups. Our study was a non-randomized, prospective clinical trial. Thirty five patients with hirsutism were included in the study. The patients received 5 mg finasteride orally once per day over a period of 12 months. Hirsutism score, FSH, LH, E2, total T, free T, androstenedione (A), DHEAS, 17-hydroxyprogesterone (17-OHP) and sex hormone-binding globulin (SHBG) levels were determined in all the patients before treatment and every 6 months during treatment. The modified Ferriman-Gallwey score decreased from a mean of 19.06 +/- 6.12 to 11.31 +/- 4.93 during the study. Clinical improvement in the degree of hirsutism was observed in 26 of 35 patients. The percent reductions in hirsutism scores (mean% +/- SD) at 6 and at 12 months were 25.8 +/- 11.3 and 41.3 +/- 18.5, respectively. During the finasteride therapy E2 and SHBG were increased significantly while DHEAS was decreased significantly at 12 months. There were no significant changes in the values of the other hormones and no serious side effects were observed in the study. In conclusion, finasteride is a well tolerated therapeutic agent without significant side pathological laboratory findings and can be used in the treatment of hirsutism.

17-alpha-Hydroxyprogesterone↗
PubMed2006

Protein profiling of rat ventral prostate following chronic finasteride administration: identification and localization of a novel putative androgen-regulated protein.

To better understand the effects of antiandrogens on the prostate, we investigated the changes in the proteome of rat ventral prostate (VP) following treatment with a well characterized 5alpha-reductase inhibitor, finasteride. Sprague-Dawley rats were treated daily by gavage with finasteride at 0, 1, 5, 25, and 125 mg/kg/day. Changes in plasma hormone levels as well as the weight and histology of sex accessory tissues were determined after 28 days of treatment and showed a dose-related decrease of VP weights together with a marked atrophy of the tissue visible at the macroscopic and microscopic levels. In addition, significant reductions in seminal vesicle and epididymis weights were noted. VP proteins were analyzed by two-dimensional gel electrophoresis: 37 proteins, mainly involved in protein synthesis, processing, and cellular trafficking and in metabolism, detoxification, and oxidative stress, were identified as modulated by finasteride. The prominent feature of this study is the demonstration of finasteride dose-dependent up-regulation of a protein similar to l-amino-acid oxidase 1 (Lao1). An up-regulation of this protein was also observed with the antiandrogen flutamide. Lao1 expression occurred as early as 48 h after antiandrogen administration and persisted throughout the treatment duration. Immunohistochemistry showed that this protein was only detectable in epithelial cells and secretory vesicles. Altogether these data point to a potential use of Lao1 to reveal antiandrogen-induced prostate injury.

5-alpha Reductase Inhibitors↗
PubMed2003

Low-dose (2.5 mg/day) finasteride treatment in hirsutism.

This study was performed to confirm the therapeutic effects of low-dose, (2.5 mg/day) finasteride in hirsute women. Our study was a non-randomized prospective clinical trial. Twenty-nine patients with hirustism were included in the study. The patients received 2.5 mg finasteride once a day over a period of 12 months. Follicle stimulating hormone, luteinizing hormone, sex hormone binding globulin, 17 alpha-hydroxyprogesterone, estradiol, androstenedione, total and free testosterone, dehydroepiandrosterone sulfate levels and hirsutism scores were determined in all patients before treatment and at every 6 months during the therapy. The hirsutism score decreased from a mean of 18.4 +/- 4.6 to 8.4 +/- 4.2 during the study. The per cent reduction in hirsutism score (mean +/- SD) at 6 and 12 months was 29.2 +/- 14.5 and 55.7 +/- 14.9%, respectively. There were no significant differences in any of the hormone levels and no serious side-effects were observed during the treatment. In conclusion, low-dose finasteride (2.5 mg/day) is a cost-effective, well-tolerated therapeutic agent without significant abnormal biochemical findings and can be used in place of high-dose (5 mg/day) finasteride in the treatment of hirsutism.

5-alpha Reductase Inhibitors↗
PubMed2005

Hidradenitis suppurativa treated with finasteride.

BACKGROUND: Hidradenitis suppurativa (HS) is a distressing condition for which no satisfactory treatment is available. Studies on hormonal mechanisms responsible for HS point towards altered end-organ sensitivity, probably related to the enzyme 5a reductase that converts testosterone to dihydrotestosterone. Finasteride, an inhibitor of type II 5a reductase, has been reported to be effective in recalcitrant HS. AIM: To study the effectiveness and tolerability of finasteride in patients with HS in a preliminary trial. METHODS: Seven patients (five women and two men) with HS that was not responding well to antibiotics were treated with finasteride at a dose of 5 mg/day as monotherapy. Clinical response was assessed at regular intervals. Patients were followed up for periods varying from 8 months to 2 years. RESULTS: Six patients improved significantly and three of them had complete healing of lesions. Two patients who were followed up for more than 1 year experienced remissions lasting 8-18 months. The drug was generally well tolerated; however, two women complained of breast enlargement. CONCLUSION: The results of this preliminary study suggest that finasteride is an effective therapeutic option in HS.

5-alpha Reductase Inhibitors↗
PubMed1995

Local and systemic reduction by topical finasteride or flutamide of hamster flank organ size and enzyme activity.

The hamster flank organ is a widely used model of the control of sebaceous gland activity by androgens and anti-androgens. Finasteride, a 5 alpha-reductase inhibitor, was administered locally on the surface of the right flank organ and right ear twice daily for 4 weeks. The treatment caused similar 12% to 30% reductions in the size of the sebaceous glands in both flank organs. Moreover, relative mRNA levels of the androgen-regulated FAR-17a gene measured by in situ hybridization as well as [3H]-thymidine incorporation and 5 alpha-reductase activity were similarly decreased in the two flank organs after topical application. The pure anti-androgen flutamide, at the same doses, exerted a more potent effect on all the same parameters, and the effect was also comparable on both the treated and untreated sides of flank organs. Finasteride and flutamide significantly decreased ventral and dorsal prostatic weights after topical application. The present data show that the topical administration of finasteride, in analogy with flutamide, causes local inhibition of sebaceous gland growth in both the costovertebral organs and ears. However, as demonstrated by the similar inhibitory effect in the contralateral untreated side and the reduced weight of the dorsal and ventral lobes of the prostate and seminal vesicles, finasteride and flutamide both exert significant systemic effects.

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

Effectiveness of finasteride on patients with male pattern baldness who have different androgen receptor gene polymorphism.

Finasteride is not necessarily effective on all of the male pattern baldness (MPB) patients. To know any factor which correlates with the effectiveness of finasteride, the polymorphism of androgen receptor (AR) gene was analyzed. Symptoms of the 488 MPB patients (18-62 y) before and after treatment with total dose of 10 mg or more of finasteride was typed by photographic method. The number of CAG and GGC repeats in AR gene of MPB patients was determined by DNA sequencing. When the number of the triplet repeats (CAG + GGC) was plotted against the degree of symptom improvement after treatment with this drug, a broad correlation between these variables was observed. The smaller the repeat number, the higher the improvement with finasteride. The group of patients with shorter repeat region in AR gene responded better to this drug than that with longer repeat region, although the former patients tended to reveal severe initial symptoms. Determination of such polymorphism is thought to be useful in the drug choice for MPB patients.

Adult↗
PubMed2004

Follow-up of 1 mg finasteride treatment of male pattern baldness-difference between clinical trials and private office follow-up: influences on prescribing habits evaluated.

BACKGROUND: Finasteride (Propecia) was approved by the FDA in 1998 for treating men with androgenetic alopecia. The published clinical trials demonstrated statistical differences between drug and placebo. Rarely do new drugs undergo further non-drug-company-sponsored studies of efficacy. Concerns about clinical studies and marketing of drugs prompted this evaluation of a large group of patients taking this medication. OBJECTIVE: Finasteride usage offered an opportunity not only to understand the acceptance of a cosmetically oriented medication, but also to evaluate subjective comments and compliance after a long period of time. METHODS: A total of 1261 patients were monitored with phone calls every 3 months after finasteride was initially prescribed. After 12 months, a detailed questionnaire was sent to all patients with an additional letter and two telephone calls if no response was received. Statistical analysis of the patients' data was made. RESULTS: Thirty-two percent or 414 men continued to take finasteride daily for 1 to 3 years. Twenty-four percent or 297 men discontinued the drug between 3 and 15 months owing to poor results. The remaining 44% or 549 men were lost to follow-up despite numerous attempts to contact them. CONCLUSION: A total of 414 men continued to take the medication, but only 211 returned detailed questionnaires. A small percentage of this group felt that they grew hair. The remaining patients noted poor results.

Alopecia↗
PubMed2006

A new look at the 5alpha-reductase inhibitor finasteride.

Finasteride is the first 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern hair loss). These clinical applications are based on the ability of finasteride to inhibit the Type II isoform of the 5alpha-reductase enzyme, which is the predominant form in human prostate and hair follicles, and the concomitant reduction of testosterone to dihydrotestosterone (DHT). In addition to catalyzing the rate-limiting step in the reduction of testosterone, both isoforms of the 5alpha-reductase enzyme are responsible for the reduction of progesterone and deoxycorticosterone to dihydroprogesterone (DHP) and dihydrodeoxycorticosterone (DHDOC), respectively. Recent preclinical data indicate that the subsequent 3alpha-reduction of DHT, DHP and DHDOC produces steroid metabolites with rapid non-genomic effects on brain function and behavior, primarily via an enhancement of gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Consistent with their ability to enhance the action of GABA at GABA(A) receptors, these steroid derivatives (termed neuroactive steroids) possess anticonvulsant, antidepressant and anxiolytic effects in addition to altering aspects of sexual- and alcohol-related behaviors. Thus, finasteride, which inhibits both isoforms of 5alpha-reductase in rodents, has been used as a tool to manipulate neuroactive steroid levels and determine the impact on behavior. Results of some preclinical studies and clinical observations with finasteride are described in this review article. The data suggest that endogenous neuroactive steroid levels may be inversely related to symptoms of premenstrual and postpartum dysphoric disorder, catamenial epilepsy, depression, and alcohol withdrawal.

Alcohol-Related Disorders↗
PubMed2005

Pre-surgical finasteride therapy in patients treated endoscopically for benign prostatic hyperplasia.

INTRODUCTION: Transurethral resection of the prostate is considered the standard technique for patients with moderate or severe lower urinary tract symptoms related to benign prostatic hyperplasia (BPH). Pathologically BPH is characterized by an increased proliferation of stromal and acinar cells, sustained by increased vascularization (neoangiogenesis). Recent studies have also shown that finasteride reduces angiogenesis and prostatic bleeding associated with BPH. Reducing the volume as a final step in reducing neoangiogenesis could thus represent a fundamental advance in limiting intra- and postoperative bleeding in patients undergoing transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Our study included 60 patients undergoing TURP between January 2001 and January 2002. Of the patients, 30 received pretreatment with finasteride while 30 did not undergo any pretreatment (control group). In all the patients we evaluated the degree of peri-surgical bleeding, intended as a reduction in hemoglobin values in the 24 h following surgery. RESULTS AND CONCLUSIONS: In the group of patients pretreated with finasteride, blood loss, evaluated as a reduction in hemoglobin values, was minimal, and none of the patients required blood transfusion. The average hemoglobin loss in the 24 h following surgery was 0.9%. In the control group (average age 67 years), 4 patients (12%) required blood transfusion. The loss of hemoglobin was 2.36%. Finasteride, therefore, seems to play a fundamental role in the pretreatment of TURP patients, since by reducing dihydrotestosterone synthesis, it interacts with endothelial growth factors, thus reducing angiogenesis and preventing bleeding.

Aged↗
PubMed1992

Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia.

The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study.

5-alpha Reductase Inhibitors↗
PubMedDate not supplied

Comparison of tamsulosin and finasteride for lower urinary tract symptoms associated with benign prostatic hyperplasia in Korean patients.

Tamsulosin (0.2 mg) and finasteride (5 mg) once daily for 24 weeks were compared in a single-blind, randomized study as initial treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) in 205 Korean patients. Symptom and quality of life (QOL) assessment by the International Prostatic Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and adverse events were analysed at 4 weeks and 24 weeks. On intention-to-treat analysis, both drugs showed similar efficacy at endpoint (decreased I-PSS, increased Qmax and improved QOL score; 34.7%, 23.9% and 34.1% for tamsulosin, and 30.5%, 22.2% and 23.1% for finasteride, respectively). However, tamsulosin produced significant improvements in I-PSS and Qmax at 4 weeks compared with finasteride (17.6% versus 10.0% and 10.9% versus 3.1%, respectively), and a superior QOL score improvement during the study. Adverse events were observed significantly more frequently among finasteride than tamsulosin patients (23 versus four). Both were equally effective in long-term treatment of urinary outflow obstruction symptoms associated with BPH in Korean patients, but tamsulosin was more effective for short-term treatment, with a better safety profile.

Aged↗
PubMed2004

Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia.

Tissue-selective androgen receptor modulators (SARMs) demonstrate tissue selectivity in both castrated and intact male rats, behaving as partial agonists in androgenic tissues (i.e. prostate and seminal vesicle), but full agonists in anabolic tissues (i.e. levator ani muscle). The partial agonist activity of SARMs (compounds S-1 and S-4) in the prostate of intact rats suggested that SARM could be used for androgen suppression in the treatment of benign prostate hyperplasia (BPH). This study was designed to explore the mechanisms of action of SARM and to characterize the tissue selectivity of S-1 in intact male rats compared with that of hydroxyflutamide (antiandrogen) and finasteride (5alpha-reductase inhibitor), two major drugs used for androgen suppression treatment of BPH. In intact male rats, S-1 (5, 10, and 25 mg/kg) selectively decreased the prostate weight with similar efficacy to finasteride (5 mg/kg), without affecting the levator ani muscle or increasing the plasma levels of testosterone, LH, and FSH. Hydroxyflutamide (0.5, 1, 5, 10, and 25 mg/kg), however, decreased both the prostate and levator ani muscle weights without any selectivity and increased plasma hormone levels in a dose-dependent manner. Furthermore, S-1 and S-4 showed very weak inhibitory effects toward transiently expressed type I and II human 5alpha-reductase (Ki, >20 microm) during in vitro assays. Therefore, although S-1 and finasteride showed very similar suppressive effects in the prostate of intact male rats, they decreased prostate size via different mechanisms of action. S-1 simply worked as androgen receptor partial agonist, whereas finasteride inhibited prostatic 5alpha-reductase. These studies indicate that SARMs may demonstrate clinical utility as single agent or combination therapy for BPH.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1992

Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies.

Studies were performed to compare the effects of 5 alpha-reductase inhibition and antiandrogen receptor blockade on differentiation of male internal and external genital structures and prostate in the rat. Dose-response studies were performed on male rats treated in utero during the period of sexual differentiation with either the potent 5 alpha-reductase inhibitor finasteride or the antiandrogen flutamide. The treated animals were raised to adulthood and killed, and genital structures were evaluated. Treatment with the 5 alpha-reductase inhibitor finasteride at a dose of 25 mg/kg.day resulted in significant feminization of the external genitalia. There was no further feminization of the genitalia at doses up to 300 mg/kg.day. Wolffian ductal differentiation occurred at all doses evaluated. Seminal vesicle weight, however, significantly decreased at 25 mg/kg.day, but without a further decrease at higher doses of the 5 alpha-reductase inhibitor. Vas deferens and epididymal weights were unchanged at all doses evaluated. There was a significant decrease in prostate size at 25 and 50 mg/kg.day, with no further decrease at higher doses. In flutamide-treated animals, complete feminization of the genitalia occurred at 24 mg/kg.day in all animals. At 18 mg/kg.day, Wolffian ductal differentiation occurred, but seminal vesicle weight was decreased. At dosages of 100, 200, and 300 mg/kg.day flutamide, the vas deferens was absent unilaterally or bilaterally, with small remnants of epididymal head and tail present. At dosages of 24 mg/kg.day and above, the prostate was absent. Studies with the 5 alpha-reductase inhibitor finasteride demonstrate the dependency of prostate and male external genital differentiation on dihydrotestosterone (DHT). However, unlike androgen receptor blockade with flutamide, finasteride did not totally abolish prostate differentiation or completely feminize the external genitalia, despite increasingly higher doses. Since there is no evidence of multiple 5 alpha-reductase isoenzymes to date in the rat, these results suggest that testosterone (T) can compensate for DHT to some degree at the level of the androgen receptor. Wolffian differentiation, however, was not affected by inhibition of DHT, demonstrating its T dependency, but seminal vesicle growth was impaired. Thus, inhibition of 5 alpha-reductase activity limits seminal growth potential in adulthood. Studies with the antiandrogen flutamide show that at doses significantly above that required to completely block prostate differentiation and cause genital feminization, Wolffian ductal differentiation is significantly impaired. Thus, higher doses of flutamide are needed to block the paracrine effect of T on the Wolffian ducts.

5-alpha Reductase Inhibitors↗
PubMed1994

Clinical and hormonal effects of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism.

Hyperactivity of 5 alpha-reductase in the skin is considered a major mechanism of excessive hair growth in hirsute women with normal levels of serum androgens (idiopathic hirsutism). Preventing the conversion of testosterone to dihydrotestosterone by inhibiting 5 alpha-reductase activity could thus be the most rational and effective treatment in this condition. The present study evaluated the effects of the oral administration of finasteride (5 mg once daily) for 6 months in 17 young women with idiopathic hirsutism, 5 of whom were also given an oral contraceptive. The degree of hirsutism (graded by a modified Ferriman-Gallwey score), serum sex hormone levels, and serum and urinary 5 alpha-metabolism steroid profiles were determined basally and periodically during the treatment period. The modified Ferriman-Gallwey score showed a remarkable reduction after 6 months of finasteride treatment (5.9 +/- 0.6 vs. 11.7 +/- 1.3; P < 0.01). Serum 5 alpha-dihydrotestosterone and 3 alpha-androstanediol glucuronide levels were decreased, and urinary C19 and C21 5 beta/5 alpha metabolite ratios were increased compared with pretreatment values. No significant adverse effect was reported. In women treated with finasteride and oral contraceptive, clinical efficacy was slightly more pronounced. In conclusion, the 5 alpha-reductase inhibitor finasteride is well tolerated and seems to be a useful tool in the treatment of idiopathic hirsutism.

Adult↗
PubMed1996

Finasteride therapy does not alter bone turnover in men with benign prostatic hyperplasia--a Clinical Research Center study.

Benign prostatic hyperplasia is often treated with finasteride, which inhibits the conversion of testosterone to dihydrotestosterone (DHT). Aside from the prostate, other androgen-dependent tissues seem to be unaffected by selective DHT deficiency, but the effect on bone density in humans has not yet been defined. To study this question, we compared indices of bone turnover and bone mineral density in 35 men treated with finasteride with controls. Bone resorption was assessed by measuring urinary excretion of N-telopeptide cross-links of type I collagen and hydroxyproline, and bone formation was assessed by measuring serum osteoncalcin and bone-specific alkaline phosphatase. Bone density of the spine and hip were assessed by dual energy x-ray absorptiometry. We found that finasteride-treated patients had mean DHT levels 81% lower than controls (P < 0.0001). There were no significant differences between the two groups in any of the markers of bone turnover or measures of bone density. These results suggest that testosterone can maintain bone density in men even in the absence of DHT. Although long term studies are needed, our results suggest that men who take finasteride are not at increased risk for bone loss.

Aged↗
PubMed2004

Combination of finasteride and doxazosin for the treatment of benign prostatic hyperplasia.

Finasteride, which inhibits the enzyme 5 alpha-reductase, reduces prostate size and relieves the symptoms of benign prostatic hyperplasia (BPH) in men with enlarged prostates. alpha 1 -Adrenoceptor antagonists, such as doxazosin and terazosin, are also effective in the treatment of BPH. Previous clinical studies in which finasteride had little or no effect alone, have shown little or no additive effect with alpha 1 -adrenoceptor antagonists. The Medical Therapy of Prostatic Symptoms study showed a considerable benefit with finasteride alone and an additive effect when administered with doxazosin. One interpretation of these results is that if finasteride is effective alone in BPH, the combination with an alpha 1 -adrenoceptor antagonist will give an additive effect.

Clinical Trials as Topic↗
PubMed1998

Identification of genes expressed in the rat prostate that are modulated differently by castration and Finasteride treatment.

In mammals, testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens). Testosterone is the most abundant circulating androgen, and is converted in specific tissues to DHT by the 5alpha-reductase enzymes. Although each of these androgens binds to the same receptor protein (androgen receptor, AR), each exerts biologically distinct effects. Theories to explain the specific effects of testosterone and DHT have centered on kinetic differences of binding of androgens to the receptor or differences in the metabolic fates of the two hormones. In the current experiments, differential display PCR (ddPCR) was used to identify genes regulated differently by testosterone and DHT. Adult male rats were treated as follows: castrated, treated with Finasteride (an inhibitor of 5alpha-reductase) or left intact for ten days. RNA was prepared from the dissected prostates of these animals and used for ddPCR. Genes exhibiting four distinct patterns of regulation were observed among the mRNAs. Class 1 genes showed equivalent expression in intact and Finasteride-treated animals, but were absent in castrated animals (mRNAs D1, D2, D6, D10). Class 2 genes showed higher expression in intact animals, intermediate levels following Finasteride treatment, but were absent in castrated animals (mRNA D8). Two classes of gene were particularly intriguing: class 3 showed gene expression only in the intact animal (mRNA D7, D9) and class 4 showed increased gene expression following Finasteride treatment (mRNA D3). While the patterns observed for some of these genes (e.g. D8) suggest that the different biological effects of testosterone and DHT may be due to the lower affinity of the AR for testosterone and limiting tissue concentrations of androgen, our results also suggest that some genes expressed in the rat prostate may be regulated in fundamentally different ways in response to testosterone and DHT.

5-alpha Reductase Inhibitors↗
PubMed2004

Does finasteride alter the pathology of the prostate and cancer grading?

All forms of androgen-deprivation therapy, including finasteride, induce distinctive histologic changes in benign and neoplastic prostatic epithelial cells, including cytoplasmic clearing, nuclear and nucleolar shrinkage, and chromatin condensation. Treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nucleolar diameter than untreated controls, creating the potential for grading bias. Recognition of these changes may be difficult in needle biopsies and lymph node metastases with treated cancer because of the subtle infiltrative pattern and inconspicuous nucleoli. The effects of finasteride may be less pronounced than other forms of therapy with variable distribution throughout the prostate; further, there may be greater sensitivity of low and intermediate-grade cancer than high-grade cancer. The Gleason grading system for cancer should not be used after finasteride treatment as it is not validated in this setting and is likely to overestimate the biologic potential of high-grade cancer observed after therapy. Chemoprevention trials with agents such as finasteride that alter morphology should not rely on cancer grading as a secondary endpoint owing to grading bias.

5-alpha Reductase Inhibitors↗