Low-dose Finasteride Research Articles

Persistent Gynecomastia due to Short-term Low-dose Finasteride for Androgenetic Alopecia.

We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator. One year later, bilateral mammoplasty was performed to remove the remaining breast tissue. Finasteride, a 5-alpha-reductase inhibitor, is widely used for the treatment of androgenetic alopecia. Gynecomastia is an expected side effect of this therapy given its mechanism of action. However, only 8 cases of gynecomastia have been reported with low-dose (1 mg daily) finasteride treatment since its approval for androgenetic alopecia in 1997. This raises the concern that gynecomastia resulting from low-dose finasteride is significantly underreported, causing inadequately informed patients. Further, because of the risk of gynecomastia, it is important for prescribing physicians to counsel patients regarding this complication and to consider early intervention when finasteride-induced gynecomastia first arises to prevent fibrosis and thus irreversible gynecomastia.

Long-term treatment with finasteride induces apoptosis and pathological changes in female mice.

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study.

Finasteride, a 5α-reductase inhibitor, is marketed in a low dose (1 mg) as a popular therapy for androgenic alopecia in young men. As case reports and small surveys have suggested a link between persistent sexual dysfunction (SD) and suicidal ideation (SI) with low-dose finasteride, the aim of this study was to detect signals of SD and SI secondary to low-dose finasteride use in young men. Retrospective pharmacovigilance disproportionality analysis. United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Low-dose finasteride-related adverse event reports for men aged 18-45 years that were submitted to the FAERS between 1998 and 2013 were retrieved. Multi-item Gamma Poisson Shrinker disproportionality analysis was applied to calculate the empirical Bayes geometric mean (EBGM) and corresponding 95% confidence interval (CI) as an association metric between low-dose finasteride and the events of interest. Signals were defined as associations with thresholds of a CI lower limit of 2.0 or greater. Medical Dictionary for Regulatory Activities Preferred Terms denoting to SD and SI were identified to reflect the outcome of interest. In total, of 4910 reports, 577 persistent SD and 39 SI adverse event reports (11.8% and 7.9%, respectively) were identified for young men using low-dose finasteride; 34 (87.2%) of the 39 men with SI also experienced SD. The majority of these events were serious (e.g., contributed to the patient's death, hospitalization, or disability). Low-dose finasteride was associated with more than expected reporting of SD in young men compared with reporting of these events with all other drugs within the database (EBGM 28.0, 95% CI 26.1-30.0). Disproportional reporting in SI events was noted, although it did not reach signal threshold (EBGM 1.72; 95% CI 1.31-2.23). Among serious SD events, 43% led to disability; 28% required medical intervention, including hospitalization; and 5% were life-threatening. Six fatal SD reports were identified. Persistent SD might be a potential risk of low-dose finasteride for androgenic alopecia therapy in young men, and this risk might contribute to SI. Our findings provide a strong hypothesis for pharmacoepidemiologic studies to further examine this association.

Intermittent Low-Dose Finasteride Administration Is Effective for Treatment of Hirsutism in Adolescent Girls: A Pilot Study

Study ObjectiveHirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH). Design and ParticipantsTwenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups. ResultsIn patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P < .0001 for both). Similarly, the 3α-17 β-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset. ConclusionsA low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive.

Secondary infertility due to use of low-dose finasteride

Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.

Finasteride-induced secondary infertility associated with sperm DNA damage

To report a case of low-dose finasteride-induced secondary infertility with associated elevated sperm DNA fragmentation index (DFI) and otherwise normal semen parameters. Case report. University hospital. A 48-year-old man on low-dose finasteride and his 37-year-old wife with normal menses and normal gynecologic exam. Determination of sperm DFI and discontinuation of low-dose finasteride. Sperm DFI. The sperm DFI done a year earlier was 30%. This value was unchanged when repeated 2 months later. The patient was advised to stop finasteride. Three months after discontinuing the finasteride, the DFI decreased to 21% and subsequent DFI after another 3 months improved to 16.5%. To date, there is still no documented full-term pregnancy or live birth. The significant reduction in DFI within 3 months of finasteride cessation and continued improvement suggests a causal link between finasteride and sperm DNA damage. We hypothesize that low-dose finasteride may exert a negative influence on sperm DNA integrity, resulting in increased pregnancy losses. We suggest that in infertile men using finasteride, sperm DFI should be measured in addition to semen parameters, and a trial of discontinuation of finasteride may be warranted.

Abstract PR-03: Randomized presurgical trial of finasteride vs. flutamide vs. placebo in prostate cancer

Abstract Background: Prostate cancer (PC) is an ideal target for chemoprevention, with high-grade prostatic intraepithelial neoplasia (HGPIN) as its most likely precursor finasteride, a 5α-reductase inhibitor, reduced prostate cancer incidence by 25% in average-risk men. However, a higher proportion of high-grade PC has been noted whose biological significance is unclear. An alternative targeted approach is the use of androgen receptor antagonists such as flutamide. Presurgical window-of-opportunity trials have been proposed as a model to assess the activity of preventive interventions in a cost-effective manner in PC. In this study we test the effect of minimal low-dose flutamide exposure or finasteride in comparison to placebo on biomarkers associated with PC, HGPIN, and normal prostate tissue. Materials and Methods: This is a prospective randomized phase IIB placebo-controlled double-blind presurgical trial of finasteride 5 mg/day (FIN) vs. flutamide 250 mg/day (FLU) vs. placebo (PLA) in men with PC. Patients with biopsy proven PC, clinical stage ≤T2, candidates to radical retropubic prostatectomy were enrolled. Drugs and placebo were administered for 4 to 6 weeks before surgery. A sample size of 120 patients (40 per arm) was calculated to detect significant differences on change in nuclear area (NA) of epithelial cells between treatment and placebo arms (primary endpoint). To establish a direction of NA change from normal to malignancy a discriminant function derived from differences in morphometric parameters in the pretreatment biopsies between the normal epithelium and the PC tissue was applied to the posttreatment groups. Secondary endpoints include change in proliferation markers (Ki67 labeling index, topoisomerase-IIα), in serum PSA and hormones, safety, and toxicity. Results: 125 patients were randomized at four cooperating institutions (41 FIN, 42 FLU, and 42 PLA). Mean age and PSA at baseline were 64 years and 8.7 ng/mL, respectively, without differences among arms. There were significant differences in NA and Ki67LI of normal and neoplastic cells both before and after treatment (NA interquartile range: 27-40µ2 in normal tissue, 30-50µ2 in HGPIN and 36-55µ2 in cancer tissue) but no differences were detected among arms. Image and discriminant analysis performed in a subgroup of patients (16 FIN, 24 FLU, and 20 PLA) showed in the PLA and FLU arms a higher discriminant function score after treatment, with a significant increase of the mean score by 90% and 50%, respectively, meaning that cases treated with placebo or flutamide undergo a statistically significant further progression of karyometric features. Conversely, FIN-treated PC exhibited only a small further progressive change, with a net increase of the mean score by only 8%. LH significantly increased in the FLU arm; PSA and fPSA decreased while T increased significantly in both treatment arms compared to placebo. Treatment was well tolerated. Conclusion: NA and KI67LI were significantly different among normal, HGPIN and PC tissue and between pre- and posttreatment biopsies. Discriminant analysis detected an inhibition of progressive karyometric pattern in patients treated with finasteride relative to low-dose flutamide and placebo. Our results support the use of nuclear changes as measured by karyometry in presurgical models to assess the activity of preventive agents. This talk is also presented as Poster A68. Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-03.

The influence of low dose finasteride, a type II 5α-reductase inhibitor, on circulating neuroactive steroids.

Finasteride is a 5α-reductase inhibitor that has received clinical approval for the treatment of human benign prostatic hyperplasia and androgenetic alopecia. The treatment is practically without side effects, although some occasional cases of depression syndrome have been reported. 5α-Reductase is an enzyme responsible for the reduction of testosterone, progesterone or deoxycorticosterone to their 5α-reduced derivatives possessing anticonvulsant, antidepressant, and anxiolytic activity. Therefore, the formation of GABAergic neuroactive steroids is likely to be impacted by finasteride. The objective of the study was to show how the treatment of premature androgenetic alopecia with low doses (1mg/day) of finasteride influences the broad spectrum of steroids with potential neuroactivity. A group of 12 men with premature androgenetic alopecia participated in the present study. The steroid hormone profile was determined for all individuals. Finasteride was administered for 4 months at a daily dose of 1mg. After the treatment, the same hormonal profile was determined again. 5α-Reduced steroids, e.g., 5α-dihydrotestosterone, androsterone, epiandrosterone, 5α-androstene-3α,17β-diol, allopregnanolone, isopregnaolone, and some 5-ene steroids, such as dehydroepiandrosterone and pregnenolone, decreased gradually during treatment. The decrease of 5α-reduced steroids, especially of allopregnanediol, dihydrotestosterone, and pregnenolone, is probably one of the factors responsible for the increased occurrence of depression in men treated with finasteride, even at low doses.

Effect of Low-Dose Finasteride on Serum PSA Concentrations

Finasteride, a type II 5α-reductase inhibitor, lowers serum prostate-cancer antigen (PSA) levels in recipients. It is approved in the U.S. at two

LONG-TERM EFFECTS OF FINASTERIDE ON PROSTATE SPECIFIC ANTIGEN LEVELS: RESULTS FROM THE PROSTATE CANCER PREVENTION TRIAL

Studies have shown that finasteride decreases prostate specific antigen (PSA) by approximately 50% during the first 12 months of use. We estimated the long-term effects of finasteride on PSA in men with and without a prostate cancer diagnosis at the end of the study. We analyzed serial PSA in participants in the Prostate Cancer Prevention Trial who had an end of study biopsy (928 with cancer and 8,620 with negative biopsy) or an interim diagnosis of prostate cancer (671). Linear mixed effects regression models were fit to longitudinal PSA values beginning 1 year after randomization. In subjects with no cancer in the end of study biopsy PSA in the finasteride arm showed a median annual decrease of 2% [corrected] after year 1, while PSA in the control arm showed an annual increase of 3% (p <0.001). In end of study cases PSA increased annually by 6% (placebo) and 7% (finasteride). In those with interim diagnoses PSA increased by 11% (placebo) and 15% (finasteride) each year prior to diagnosis. Cases with high grade disease (Gleason 7 and above) had greater PSA increases than cases with low grade disease (p <0.001). In men who have been receiving finasteride for more than 1 year time varying adjustment factors may be needed to determine whether PSA is in the normal range. In the Prostate Cancer Prevention Trial cohort the adjustment factor required to preserve median PSA increased from 2 at 24 months to 2.5 at 7 years after the initiation of finasteride.

Intermittent low-dose finasteride is as effective as daily administration for the treatment of hirsute women

In a prospective randomized study 38 women with idiopathic hirsutism or polycystic ovary syndrome (PCOS) received 2.5 mg of finasteride every day or every 3 days. Intermittent low-dose administration of finasteride was as effective as continuous administration in reducing hirsutism score and was accompanied by a lower incidence of side effects.

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 hirsutism 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, 17α-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.

Effect of Castration and Finasteride on Urinary Oxalate Excretion in Male Rats

We investigated the effects of castration and finasteride administration on urinary oxalate (Ox) excretion in a rat ethylene glycol (EG) model of urolithiasis. Male adult SD rats were divided into six groups. Group 1 were normal, untreated rats. The other five groups, all treated with 0.75% EG for 4 weeks; were as follows: group 2, non-castrated (intact) rats; group 3, castrated rats; group 4, castrated rats with a 4-cm testosterone implant; group 5, intact rats treated with high-dose finasteride (7.5 mg%); and group 6, intact rats treated with low-dose finasteride (0.75 mg%). Urinary Ox excretion increased 12.8-fold after 4 weeks of EG treatment (group 2 vs group 1). Both castration (group 3) and finasteride administration (groups 5 and 6) significantly decreased urinary Ox excretion compared with intact rats (group 2). We conclude that dihydrotestosterone is partially responsible for the exaggerated hyperoxaluria observed in the rat EG model of urolithiasis.

Effect of castration and finasteride on urinary oxalate excretion in male rats

We investigated the effects of castration and finasteride administration on urinary oxalate (Ox) excretion in a rat ethylene glycol (EG) model of urolithiasis. Male adult SD rats were divided into six groups. Group 1 were normal, untreated rats. The other five groups, all treated with 0.75% EG for 4 weeks; were as follows: group 2, non-castrated (intact) rats; group 3, castrated rats; group 4, castrated rats with a 4-cm testosterone implant; group 5, intact rats treated with high-dose finasteride (7.5 mg%); and group 6, intact rats treated with low-dose finasteride (0.75 mg%). Urinary Ox excretion increased 12.8-fold after 4 weeks of EG treatment (group 2 vs group 1). Both castration (group 3) and finasteride administration (groups 5 and 6) significantly decreased urinary Ox excretion compared with intact rats (group 2). We conclude that dihydrotestosterone is partially responsible for the exaggerated hyperoxaluria observed in the rat EG model of urolithiasis.

The Effect of Low Dose Finasteride Therapy in a Man with Prostatism

The Effect of Low Dose Finasteride Therapy in a Man with Prostatism

The Effect of Low Dose Finasteride Therapy in a Man with Prostatism

No AccessJournal of UrologyClinical Urology: Case Report1 Feb 1996The Effect of Low Dose Finasteride Therapy in a Man with Prostatism Michael J. Sullivan and Richard C. Smith Michael J. SullivanMichael J. Sullivan More articles by this author and Richard C. SmithRichard C. Smith More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)66485-1AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "The Effect of Low Dose Finasteride Therapy in a Man with Prostatism." The Journal of Urology, 155(2), p. 652 References 1 : The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. New Engl. J. Med.1992; 327: 1185. Crossref, Medline, Google Scholar 2 : Finasteride. A review of its potential in the treatment of benign prostatic hyperplasia. Drugs1993; 46: 177. Google Scholar 3 : Hormonal effects of an orally active 4-azasteroid inhibitor of 5 alpha-reductase in humans. Prostate1989; 14: 45. Google Scholar Center for Clinical and Biological Research Inc., San Diego, California.© 1996 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 155Issue 2February 1996Page: 652 Advertisement Copyright & Permissions© 1996 by American Urological Association, Inc.MetricsAuthor Information Michael J. Sullivan More articles by this author Richard C. Smith More articles by this author Expand All Advertisement PDF downloadLoading ...