Finasteride [5ARI] Induced/Associated Effects

[Michael Scally MD]

Belknap SM, Aslam I, Kiguradze T, Temps WH, Yarnold PR, et al. Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis. JAMA Dermatol. http://archderm.jamanetwork.com/article.aspx?articleid=2212246

Importance: Two meta-analyses conclude that finasteride treatment of androgenic alopecia (AGA) is safe but do not assess quality of safety reporting.

Objective: To assess safety reporting for clinical trial reports of finasteride for AGA. Data Sources: MEDLINE, ClinicalTrials.gov, and a clinical data repository for an academic medical center.

Study Selection: Published clinical trial reports for finasteride treatment of AGA.

Data Extraction and Synthesis: For each trial, we assessed quality of adverse event reporting, extracted the number and type of adverse events in treatment and placebo groups, and assessed duration of safety evaluation and adequacy of blinding. Two observers independently extracted the data; differences were resolved by consensus. We assessed generalizability in a large cohort of men prescribed finasteride, 1.25 mg/d or less, by assessing for eligibility in the finasteride-AGA pivotal trials.

Main Outcomes and Measures: Quality was assessed as adequate, partially adequate, inadequate, or no events reported. We used funnel plots of the hazard ratio to assess bias.

Results: Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for AGA, only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer's full prescribing information and 33% took finasteride for more than 1 year.

Conclusions and Relevance: Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.

 

[Michael Scally MD]

Propecia: Hair Growth for Most, Impotence – & Worse – for Some
http://medshadow.org/features/propecia-hair-for-most-impotence-and-worse-for-some/

 

[Michael Scally MD]

Aquila S, Montanaro D, Guido C, Santoro M, Perrotta I, et al. Human sperm molecular anatomy: the enzyme 5alpha-reductase (SRD5A) is present in the sperm and may be involved in the varicocele-related infertility. Histochem Cell Biol. http://link.springer.com/article/10.1007/s00418-015-1320-8

The most common cause of male infertility is the testicular varicocele, a condition that impairs production and decreases quality of sperm. Male fertility also strictly depends on androgens acting through their own receptor.

The enzyme 5alpha-reductase (SRD5A) is involved in the conversion of testosterone to 5alpha-dihydrotestosterone, both required for the development and maintenance of male reproductive function.

Here, we evaluated, by western blotting analysis, the presence of SRD5A in human ejaculated spermatozoa and evidenced differences in sperm SRD5A content between healthy donors and varicocele-affected patients.

Additionally, SRD5A sperm ultrastructural localization was also assessed by transmission electron microscopy and immunogold assay.

We evidenced that SRD5A enzyme is present in the human spermatozoa and that its cellular content is lowered in sperm samples from varicocele patients compared to healthy subjects.

The presence of SRD5A in human ejaculated spermatozoa highlights the potential role of this enzyme in sperm physiopathology suggesting that the decrease in its content, by affecting the conversion of testosterone into 5alpha-dihydrotestosterone, may be an important additional mechanism involved in the harmful effect of varicocele in male fertility.

 

[scuba steve]

It is so hard to make the decision as to whether or not to begin treatment. Nobody wants to go bald. But who wants to deal with sexual problems as a trade off. I want to begin taking finasteride at .25 mg EOD and see how that works for me. It is a horrifying thing however to read all of these studies. especially in my early 20's. I have been very close to getting that prescription for the past 6 months, i have tried ketoconazole it has some effect. Fin has too much risk for the reward it seems. most people say it sexual sides are exaggerated however. Is there any indication that PFS could be in the persons mind as far as ED goes? I want to save my hair!

 

[Deadballs]

It is so hard to make the decision as to whether or not to begin treatment. Nobody wants to go bald. But who wants to deal with sexual problems as a trade off. I want to begin taking finasteride at .25 mg EOD and see how that works for me. It is a horrifying thing however to read all of these studies. especially in my early 20's. I have been very close to getting that prescription for the past 6 months, i have tried ketoconazole it has some effect. Fin has too much risk for the reward it seems. most people say it sexual sides are exaggerated however. Is there any indication that PFS could be in the persons mind as far as ED goes? I want to save my hair!

Dude when I took fin I was prescribed it by a dermatologist and was unaware of the side effects. For the first time in my life I felt a disconnect with my dick and brain. Was weird as hell. Got it immediately. Some people don't get any problems at all. Others get no problem until they stop the medication which is very frightening prospect for anyone taking it as you don't know until you stop.

Fucking weird drug. Does a lot more than just inhibit the conversion of test to dht via AR enzyme. A LOT more. Baffles me it's acceptable to be prescribed for cosmetic reasons. Well it doesn't,,$$$$ is why.

 

[Michael Scally MD]

Irwig MS. Safety concerns regarding 5alpha reductase inhibitors for the treatment of androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. http://journals.lww.com/co-endocrin...cerns_regarding_5_alpha__reductase.99571.aspx

PURPOSE OF REVIEW: To examine the clinical and basic studies regarding persistent adverse effects associated with 5alpha reductase inhibitor treatment for androgenetic alopecia.

RECENT FINDINGS: Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia.

While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5alpha-androstane-3alpha,17beta-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation.

Studies of erectile dysfunction in finasteride-treated rats showed fewer autophagosomes in smooth muscle on transmission electron microscopy, increased apoptosis, decreased smooth muscle, increased collagen deposition and decreased endothelial nitric oxide synthase.

Finally, 5alpha reductase inhibitors have also been found to alter semen parameters in healthy men.

SUMMARY: Multiple animal studies provide a biological basis for many of the persistent effects seen in humans such as erectile dysfunction, depression and decreased alcohol consumption. Prescribers of 5alpha reductase inhibitors should discuss the potential risks with their patients seeking treatment for androgenetic alopecia.

 

[Michael Scally MD]

Nasiri M, Nikolaou N, Parajes S, Krone NP, Valsamakis G, et al. 5α-reductase type 2 regulates glucocorticoid action and metabolic phenotype in human hepatocytes. Endocrinology. http://press.endocrine.org/doi/abs/10.1210/en.2015-1149

Glucocorticoids and androgens have both been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); androgen deficiency in males, androgen excess in females and glucocorticoid excess in both sexes are associated with NAFLD.

Glucocorticoid and androgen action are regulated at a pre-receptor level by the enzyme 5|ga-reductase type 2 (SRD5A2) that inactivates glucocorticoids to their dihydrometabolites and converts testosterone to dihydrotestosterone (DHT). We have therefore explored the role of androgens and glucocorticoids and their metabolism by SRD5A2 upon lipid homeostasis in human hepatocytes.

In both primary human hepatocytes and human hepatoma cell lines, glucocorticoids decreased de novo lipogenesis in a dose-dependent manner. Whilst androgen treatment (testosterone and DHT) increased lipogenesis in cell lines and in primary cultures of human hepatocytes from female donors, it was without effect in primary hepatocyte cultures from men.

SRD5A2 over-expression reduced the effects of cortisol to suppress lipogenesis and this effect was lost following transfection with an inactive mutant construct.

Conversely, pharmacological inhibition using the 5α-reductase inhibitors finasteride and dutasteride, AUGMENTED cortisol action.

We have demonstrated that manipulation of 5α-reductase type 2 activity can regulate lipogenesis in human hepatocytes in vitro. This may have significant clinical implications for those patients prescribed 5α-reductase inhibitors, in particular augmenting the actions of glucocorticoids to modulate hepatic lipid flux.

 

[Michael Scally MD]

Traish AM, Haider KS, Doros G, Haider A. Finasteride, not tamsulosin, increases severity of erectile dysfunction and decreases testosterone levels in men with benign prostatic hyperplasia. Horm Mol Biol Clin Investig. http://www.degruyter.com/view/j/hmbci.ahead-of-print/hmbci-2015-0015/hmbci-2015-0015.xml?format=INT

BACKGROUND: 5alpha-reductase inhibitors (5alpha-RIs) (finasteride and dutasteride) have been proven useful in treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). However, these inhibitors exert undesirable sexual side effects and, in some cases, these effects are persistent. There is considerable disagreement with regard to whether the adverse side effects resolve with continuous treatment.

AIM: To investigate the long-term adverse effects of finasteride treatment in men with BPH on erectile function and to compare these adverse effects in men treated with the alpha1-adrenergic receptor blocker, tamsolusin.

METHODS: In this retrospective registry study, a cohort of 470 men aged between 47 and 68 years (mean 57.78+/-4.81) were treated with finasteride (5 mg/day). A second cohort of 230 men aged between 52 and 72 years (mean 62.62+/-4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 45 months. At intervals of 3 months and at each visit, plasma testosterone (T) levels and the international index of erectile function (IIEF-EF) questionnaire scores were determined.

RESULTS: Long-term treatment with finasteride therapy is associated with worsening of erectile dysfunction (ED) as shown by the significant decrease in the IIEF-EF scores in men treated with finasteride. No worsening of ED was observed in men treated with tamsulosin. The increase in ED due to finasteride did not resolve with continued treatment with finasteride. Most importantly, long-term finasteride therapy resulted in reduction in total T levels, contributing to a state of hypogonadism. On the contrary, no changes in T levels were noted in men treated with tamsolusin.

CONCLUSION: Our findings suggest that in men with BPH, long-term finasteride therapy but not tamsulosin results in worsening of ED and reduces total T concentrations. Clinicians are urged to discuss the impact of 5alpha-RIs therapy on sexual function with their patients before commencing this therapy.

 

[Michael Scally MD]

[Open Access] 5-Alpha Reductase Inhibitors, Benign Prostatic Hyperplasia, and Risk of Male Breast Cancer

Robinson D, Garmo H, Holmberg L, Stattin P. 5-alpha reductase inhibitors, benign prostatic hyperplasia, and risk of male breast cancer. Cancer Causes Control. http://link.springer.com/article/10.1007/s10552-015-0622-4/fulltext.html

PURPOSE: 5-alpha reductase inhibitors (5-ARI) have been suggested to increase the risk of male breast cancer. The aim of this study was to study the risk of breast cancer in men on 5-ARI, in men with benign prostatic hyperplasia (BPH) not on 5-ARI, and in men without BPH.

METHODS: We performed a population-based cohort study in Sweden with data from The Prescribed Drug Register, The Patient Register, and The Cancer Register. Men on 5-ARI, men on alpha-blockers, or men who had undergone a transurethral resection of the prostate (TUR-P) prior to or during 2006-2008 were included as exposed to BPH and a specific treatment thereof. For each exposed man, five unexposed men were selected. Risk of breast cancer was calculated in Cox proportional hazard models.

RESULTS: There were 124,183 exposed men and 545,293 unexposed men, and during follow-up (median 6 years), 99 men with breast cancer were diagnosed. Compared to unexposed men, men on 5-ARI had a hazard ratio (HR) of breast cancer of 0.74 (95 % confidence interval (CI) 0.27-2.03), men on alpha-blockers had HR 1.47 (95 % CI 0.73-2.95), and men with a TUR-P had HR 1.99 (95 % CI 1.05-3.75).

CONCLUSION: No increased risk of breast cancer was observed for men on 5-ARI. However, the increased risk of breast cancer among men who had undergone a TUR-P, a strong indicator of BPH, suggests that the endocrine milieu conducive to BPH is associated with male breast cancer.

 

[Michael Scally MD]

Ali AK, Heran BS, Etminan M. Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study. Pharmacotherapy. http://onlinelibrary.wiley.com/doi/10.1002/phar.1612/abstract

STUDY OBJECTIVE: Finasteride, a 5alpha-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.

DESIGN: Retrospective pharmacovigilance disproportionality analysis.

DATA SOURCE: United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

MEASUREMENTS AND MAIN RESULTS: 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.

CONCLUSION: 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.

 

[blazinshotguns]

Ali AK, Heran BS, Etminan M. Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study. Pharmacotherapy. http://onlinelibrary.wiley.com/doi/10.1002/phar.1612/abstract

STUDY OBJECTIVE: Finasteride, a 5alpha-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.

DESIGN: Retrospective pharmacovigilance disproportionality analysis.

DATA SOURCE: United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

MEASUREMENTS AND MAIN RESULTS: 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.

CONCLUSION: 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.

Not surprised you should see the diet men around age 18-22 eat .

I had around 6 men age 19-21 tell me they had trouble getting it up during sex . This is without fin .

 

[brutus79]

Not surprised you should see the diet men around age 18-22 eat .

I had around 6 men age 19-21 tell me they had trouble getting it up during sex . This is without fin .

Did all 6 men Have their limp dicks on your face?

 

[blazinshotguns]

Did all 6 men Have their limp dicks on your face?

Ya you were one of them actually .

 

[spikehd]

http://www.scbt.com/table-5_alpha-reductase_2.html

No idea what this is exactly but may lead to something.

 

[Michael Scally MD]

Wada N, Hashizume K, Matsumoto S, Kakizaki H. Dutasteride improves bone mineral density in male patients with lower urinary tract symptoms and prostatic enlargement: a preliminary study. Aging Male. http://informahealthcare.com/doi/abs/10.3109/13685538.2015.1072155

INTRODUCTION: We studied the effect of dutasteride on bone mineral density (BMD) in aging male patients with lower urinary tract symptoms (LUTS) and prostatic enlargement.

METHODS: We prospectively studied 17 patients with LUTS and prostatic enlargement. Before and 1 year after dutasteride (0.5 mg daily), we assessed International Prostate Symptom Score (IPSS), prostatic volume (PV), serum prostatic-specific antigen (PSA) and testosterone. BMD in the lumbar and femur was measured by DEXA method.

RESULTS: Dutasteride significantly reduced PV (from 51 +/- 24 to 34 +/- 17 ml, p < 0.001) and improved IPSS (from 15.1 +/- 9.8 to 11.7 +/- 10.3, p < 0.05).

Serum PSA was significantly decreased (from 3.2 +/- 2.6 to 1.0 +/- 0.8 ng/ml, p < 0.001), while serum testosterone "was not changed" significantly.

BMD of the lumbar "was not changed" significantly after dutasteride. BMD of the femur was significantly improved (from 0.75 +/- 0.14 to 0.82 +/- 0.16 g/cm2, p < 0.01).

In nine patients whose testosterone was increased after dutasteride, BMD of the lumbar (from 1.18 +/- 0.26 to 1.22 +/- 0.25 g/cm2, p < 0.05) and femur (from 0.76 +/- 0.12 to 0.84 +/- 0.16 g/cm2, p < 0.05) was significantly improved.

CONCLUSIONS: Dutasteride has a potential to improve BMD with elevation of serum testosterone in aging male patients with LUTS and prostatic enlargement.

 

[Michael Scally MD]

[Open Access] Adverse Effects of Pharmacological Therapy of Benign Prostatic Hyperplasia on Sexual Function in Men

Stojanovic N, Ignjatovic I, Djenic N, Bogdanovic D. Adverse Effects of Pharmacological Therapy of Benign Prostatic Hyperplasia on Sexual Function in Men. Srp Arh Celok Lek. 2015;143(5-6):284-9. http://www.doiserbia.nb.rs/img/doi/0370-8179/2015/0370-81791506284S.pdf

INTRODUCTION: The development of effective medications makes pharmacological therapy of BPH the dominant mode of treatment today. It improves urinary symptoms and prevents disease progression while producing side effects on male sexual function.

OBJECTIVE: The aim of the study is to present the effects of BPH pharmacological treatment on the occurrence of sexually adverse effects in men: changes in sexual desire, erectile, ejaculatory and the orgasmic function.

METHODS: A prospective study involving 156 BPH patients.The average age was 61.16 +/- 2.97. Four groups of 39 patients each were formed.The 4 groups were administered tamsulosin (alpha-blocker), finasteride (5-alpha reductase inhibitor), combination therapy (tamsulosin and finasteride) respectively, while the control group received no treatment. PSS-QoL, IIEF and MSHQ-EjD questionnaires were used to evaluate the symptoms of voiding and sexual function. Follow-up examinations were performed 3 and 6 months into treatment.

RESULTS: Voiding symptoms improved in all groups receiving therapy. The side effects on the sexual function in all these groups include significant disorders of ejaculation and the orgasmic function. Ejaculation disorders: tamsulosin (-4.38 +/- 2.55; p < 0.001), combined therapy (-3.89+/- 2.84) and finasteride (-1.49 +/- 2.52). Orgasmic function disorders: tamsulosin (-1.03 +/- 1.94), combined therapy (-0.76 +/- 2.07) and finasteride (-0.54 +/- 1.68). Complete absence of ejaculation was experienced by 23% of patients on combined therapy, 15% on tamsulosin and 5% on finasteride.

CONCLUSION: Pharmacological therapy of BPH improved voiding symptoms producing different effects on male sexual function. The main adverse effect on sexual function in men is the deterioration in ejaculation or the absence thereof. Clinical consideration of BPH should include the elements of male sexual function, patients' age, the characteristics and effects of each group of drugs.

 

[Michael Scally MD]

Adverse effects of 5alpha-reductase inhibitors: What do we know, don't know, and need to know?
[For Full-Text Email mike.scally@asih.net (Include Title)]


Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M. Adverse effects of 5alpha-reductase inhibitors: What do we know, don't know, and need to know? Rev Endocr Metab Disord. http://link.springer.com/article/10.1007/s11154-015-9319-y

Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions.

One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5alpha-reductase (5alpha-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events.

Indeed, both 5alpha-R inhibition and supplementation of 5alpha-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions.

In particular, the potent 5alpha-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA).

Recent preclinical and clinical findings indicate that 5alpha-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents.

Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH.

In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5alpha-R inhibitors, as well as their biological underpinnings.


5α-Reductases Catalyze A Critical Rate Limiting Step In Steroidogenesis.

Enzymes: 3β- hydroxysteroid dehydrogenase (3β-HSD); 3α-hydroxysteroid dehydrogenase (3α-HSD): 17β- hydroxysteroid dehydrogenase (17β-HSD); Aldosterone synthase (CYP11B2); Steroid 11β-hydroxylase (CYP11B1); Steroid 21-hydroxylase (CYP21A2):17α-hydroxylase/ 17,20 lyase (CYP17A1).

Steroids: 5α-Dihydroaldosterone (5α-DHAldo); 3α,5α- Tetrahydroaldosterone (3α,5α-THAldo); 5α- Dihydrocorticosterone (5α-DHB); 3α,5α- Tetrahydrocorticosterone (3α,5α-THB); Deoxycorticosterone (DOC); 5α-Dihydro deoxycorticosterone (5 α-DHDOC); 3α,5α- Tetrahydrodeoxycorticosterone (3α,5α-THDOC); 5α- Dihydroprogesterone (5α-DHP); 3α,5α-Tetrahydroprogesterone (allopregnanolone; AP); Dehydroepiandrosterone (DHEA); 5α-Dihydrotestosterone (DHT); 5α-Androstane-3α,17 β-diol (3α-diol).

 

[Michael Scally MD]

Morales EE, Grill S, Svatek RS, Kaushik D, Thompson IM, Jr., et al. Finasteride Reduces Risk of Bladder Cancer in a Large Prospective Screening Study. Eur Urol. http://www.europeanurology.com/article/S0302-2838%2815%2900772-1/abstract/finasteride-reduces-risk-of-bladder-cancer-in-a-large-prospective-screening-study

The androgen receptor has been implicated in the development and progression of bladder cancer (BCa), largely based on studies of animal models.

We investigated whether finasteride was associated with a reduced incidence of BCa as observed by self-report in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Cox proportional hazard regression analysis was performed to determine the association of finasteride use with time to diagnosis of BCa, controlling for age and tobacco use.

Of the 72 370 male participants who met inclusion criteria, 6069 (8.4%) had reported the use of finasteride. BCa was diagnosed in 1.07% (65 of 6069) of those who reported finasteride compared with 1.46% (966 of 66 301) of those who reported no use during the trial.

In a multiple Cox regression analysis, self-reported use of finasteride was associated with a decreased risk of development of BCa (hazard ratio: 0.634; 95% confidence interval, 0.493-0.816; p=0.0004), controlling for age and smoking.

Limitations of this study include that it is observational and not randomized, that many of the confounding variables for BCa, such as alcohol use, were not available for use in the analysis, and that finasteride use was by annual self-report, which is subject to missing values and error.

PATIENT SUMMARY: Finasteride is a common medication used to reduce the size of the prostate and to promote hair growth by manipulating testosterone in men. Men are more likely than women to develop bladder cancer (BCa), but our study noted that men using finasteride were less likely to have a BCa diagnosis.

 

[Michael Scally MD]

Alonso JC, Reis LO, Garcia PV, Ferreira U, Matheus WE, et al. Steroid Hormone Receptors as Potential Mediators of the Clinical Effects of Dutasteride: A Prospective, Randomized, Double-Blind Study. Am J Mens Health. http://jmh.sagepub.com/content/early/2015/08/18/1557988315602961.abstract

This study characterizes the clinical and morphofunctional effects of a 5alpha-reductase inhibitor on steroid hormone receptors in normal human prostate tissue, as potential mediators of the clinical effects of dutasteride.

This work was a prospective, double-blind, and randomized study that evaluated 49 men aged between 45 and 70 years, with no alterations in a digital rectal examination and prostate-specific antigen measurements between 2.5 and 4.0 ng/mL.

These patients underwent prostate biopsy guided by transretal ultrasound with prostate neoplasia being ruled out, and the patients were divided into two groups, with one group receiving dutasteride (n = 25) and one group receiving a placebo (n = 24).

The patients were clinically assessed each quarter, and at the end of 12 months they underwent new laboratory tests, prostate rebiopsy, and histopathological, immunohistochemical and clinical analyses.

The estrogen receptor-beta (ERbeta) and androgen receptor immunoreactivities were higher, and the proliferation/apoptotic ratio was significantly lower with predominance of the apoptotic process, followed by a significant reduction in the prostate volume and the total serum prostate-specific antigen levels in the dutasteride group when compared with the placebo group, with a clear supremacy of ERbeta.

There were no significant variations in the serum estrogen and testosterone levels, in the body mass index, or in the ERalpha immunoreactivities in the dutasteride and placebo groups.

The results demonstrated the importance of the ERbeta pathway in the activation mechanisms of apoptosis, exerting a protective effect in the normal prostate, indicating that this receptor might be an important mediator of the clinical effects of dutasteride.

 

[Michael Scally MD]

[Open Access] Oral Finasteride Presents with Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia

Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long-term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT.

A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response.

A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single-therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido).

The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03).

FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients.

Perez-Mora N, Velasco C, Bermudez F. Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men. Skinmed. 2015;13(3):179-83. http://issuu.com/pulsemarketing/docs/skinmed_v13_i3?e=5397957/14071318