EVERYONE Will Get Finasteride Side-Effects Eventually

[Pigeon]

Dihydrotestosterone is the active androgen in the maintenance of nitric oxide

https://academic.oup.com/endo/articl...dFrom=fulltext


The building blocks of erection: Nitric oxide...and more nitric oxide

https://www.eurekalert.org/pub_relea...-tbb031502.php

REVIEWS: Are Androgens Critical for Penile Erections in Humans? Examining the Clinical and Preclinical Evidence​

Data strongly suggest that 5α‐DHT is the important hormone for erectile function

Error - Cookies Turned Off

onlinelibrary.wiley.com

Contribution of dihydrotestosterone to male sexual behaviour​

Conclusions: Differences in concentrations of circulating dihydrotestosterone within the normal range may represent a major predictor of sexual activity in healthy young men.

Contribution of dihydrotestosterone to male sexual behaviour - PubMed

Differences in concentrations of circulating dihydrotestosterone within the normal range may represent a major predictor of sexual activity in healthy young men.

pubmed.ncbi.nlm.nih.gov

 

[Pigeon]

Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm

Abstract

5?-dihydrotestosterone (5?-DHT) is the most potent natural androgen. 5?-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, the physiological role of 5?-DHT in human physiology, remains questionable and, at best, poorly appreciated. Recent emerging literature supports a role for 5?-DHT in the physiological function of liver, pancreatic ?-cell function and survival, ocular function and prevention of dry eye disease and kidney physiological function. Thus, inhibition of 5?-reductases with finasteride or dutasteride to reduce 5?-DHT biosynthesis in the course of treatment of benign prostatic hyperplasia (BPH) or male pattern hair loss, known as androgenetic alopecia (Androgenetic Alopecia) my induces a novel form of tissue specific androgen deficiency and contributes to a host of pathophysiological conditions, that are yet to be fully recognized. Here, we advance the concept that blockade of 5?-reductases by finasteride or dutasteride in a mechanism-based, irreversible, inhabitation of 5?-DHT biosynthesis results in a novel state of androgen deficiency, independent of circulating testosterone levels. Finasteride and dutasteride are frequently prescribed for long-term treatment of lower urinary tract symptoms in men with BPH and in men with Androgenetic Alopecia. This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. We suggest that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease.

https://pubmed.ncbi.nlm.nih.gov/32202088/


DHT, the apex androgen for all men.

https:// men-elite.com/2018/10/23/46-ways-to-increase-dht/

Testosterone is only thought to be a precursor hormone in the body for the synthesis of DHT, which is the most potent alpha hormone. It’s like cholesterol that’s the precursor to pregnenolone and testosterone.


Many of the beneficial effect of testosterone is actually through DHT, and blocking the conversion of testosterone to DHT eliminates those benefits.


Testosterone is converted to DHT via the 5-alpha reductase (5-AR) enzyme in the body. Although testosterone is a major contributor to circulating DHT, DHT can also be created from other precursors, such as DHEA, androstenedione, androsterone, 17-hydroxypregnenolone and 17-hydroxyprogesterone.

A few really cool facts about DHT why it’s superior to testosterone​

DHT is 2.5-10 times more potent than testosterone and here’s why:

1. DHT has 4 times higher affinity to AR (androgen receptors) than testosterone
2. Binding of DHT to the AR transforms the AR to its DNA-binding state
3. DHT upregulates AR synthesis and reduces AR turnover
4. The dissociation rate of testosterone from receptors is 3-5 fold faster than DHT (meaning DHT exerts a much more powerful effect on AR than testosterone)

However, high concentrations of intracellular T can shift AR binding away from DHT by mass action, as only 10% of T converts to DHT via 5-AR and DHT is roughly 7- to 10-fold lower in the circulation than T (R). So DHT is clearly outnumbered.


In the blood, DHT is also bound to SHBG (5 times high affinity and longer binding halflife (43 sec) than T (12 sec)) and more weakly to albumin. In general, protein-bound DHT is inactive except in some reproductive tissues in which megalin, an endocytic receptor, acts as a pathway for cellular uptake of DHT when bound to SHBG.


And finally, DHT can’t be aromatized to estrogen and actually inhibits the aromatase (R) and blocks the estrogen receptors (R).


Ok, enough geeking out.


Let’s discuss why you even want high DHT in the first place.


Like I mentioned, the benefits of high testosterone is mostly due to the conversion of DHT.

So having high DHT will make you feel:​

• Calm and collected
• Confident & non-intimidated by others
• Fearless, but not reckless
• Protective of those you love
• Assertive
• Energetic
• Motivated
• Stress resilient
• Mentally quick and sharp

…and a host of other benefits as well.


It truly is a hormone we want to maximize alongside testosterone, dopamine and thyroid. Keep in mind that the body is complicated and that all hormones need to work together for all the benefits.

 

[Pigeon]

Propecia masks prostate cancer symptoms

Propecia has been proven to mask some of the symptoms and effects of prostate cancer, like prostate enlargement and elevated levels of a chemical called PSA which is produced by the prostate. This may interfere with early detection and diagnosis, meaning that for men taking Propecia prostate cancer may develop into a more advanced and aggressive stage before treatment is begun and therefore result in a worse prognosis. The FDA warns all physicains to be aware of the symptom-masking effects of Propecia and urges patients to discuss screening options with their doctors while taking Propecia.


The FDA has issued several warnings about Propecia and prostate cancer. Federal regulators have issued similar warnings for Proscar, Avodart, Jalyn, generic formulations of Propecia, and other drugs (called 5-ARIs) that are similar to Propecia.
The following Propecia prostate cancer FDA warnings apply to all drugs in this class:
On June 9th, 2011, the FDA issued a Drug Safety Communication warning the public that Propecia may increase the risk of a more serious form of prostate cancer.
The FDA prescribing information product label for Propecia was also updated to include the warning about high-grade prostate cancer. The information cautions that Propecia reduces PSA levels and urges doctors to take this into account when testing for prostate cancer.

http://paact.help/propecia-and-prostate-cancer/

 

[Pigeon]

Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia​

Background: The constellation of persistent sexual, neurological, and physical adverse effects in patients who discontinue 5α-reductase inhibitors (5ARIs) has garnered recent concern. The objective of this study was to evaluate potential penile vascular changes and persistent adverse effects of 5ARIs in men treated for androgenic alopecia (Androgenetic Alopecia).

Methods: This was a prospective case-control study with 25 subjects with a history of 5ARI use for Androgenetic Alopecia and 28 controls. Patient self-reported questionnaires including the International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), Patient Health Questionnaire-9 (PHQ-9), the Epworth Sleepiness Scale (ESS) and the Androgen Deficiency in the Aging Male (ADAM) were used. Penile duplex Doppler ultrasound (PDDU) results were evaluated in men with a history of 5ARI use.

Results: A significant difference in total IIEF score between the 5ARI (median: 35; IQR: 29–43) and control group (median: 29; IQR: 27–32) (P=0.035) was observed. Seventeen 5ARI subjects (68%) had a vascular abnormality on PDDU. The median (IQR) for total IPSS score for the 5ARI group was 10 [5–16] compared to 3 [2–8] for the controls (P<0.01). The 5ARI group had a higher median total PHQ-9 score than controls [10 (6.5–16) vs. 1 (0–2) (P<0.001)]. Two subjects (8%) committed suicide during or after the study.

Conclusions: While the sexual side effects of 5ARIs are well known, there may be persistent genitourinary, physical, psycho-cognitive, anti-androgenic and penile vascular changes after 5ARI discontinuation. Use of 5ARIs for treatment of Androgenetic Alopecia may lead to persistent sexual, genitourinary, physical, psycho-cognitive, and anti-androgenic sequelae even after cessation of 5ARI therapy.

Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia - Khera - Translational Andrology and Urology

Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.

Abstract

Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3?-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3?-diol, 3?-diol and 17?-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'.


https://www.ncbi.nlm.nih.gov/pubmed/24717976

 

[Pigeon]

The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression​

Abstract​

With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia (BPH) with concomitant lower urinary tract symptoms (LUTS). Because the prostate is an androgen target tissue, and transforms testosterone into 5α-dihydrotestosterone (5α-DHT), a potent androgen, via 5α-reductase (5α-R) activity, inhibiting this key metabolic reaction was identified as a target for drug development to treat symptoms of BPH. Two drugs, namely finasteride and dutasteride were developed as specific 5α-reductase inhibitors (5α-RIs) and were approved by the U.S. Food and Drug Administration for the treatment of BPH symptoms. These agents have proven useful in the reducing urinary retention and minimizing surgical intervention in patients with BPH symptoms and considerable literature exists describing the benefits of these agents. In this review we highlight the adverse side effects of 5α-RIs on sexual function, high grade prostate cancer incidence, central nervous system function and on depression. 5α-Rs isoforms (types 1-3) are widely distributed in many tissues including the central nervous system and inhibition of these enzymes results in blockade of synthesis of several key hormones and neuro-active steroids leading to a host of adverse effects, including loss of or reduced libido, erectile dysfunction, orgasmic dysfunction, increased high Gleason grade prostate cancer, observed heart failure and cardiovascular events in clinical trials, and depression. Considerable evidence exists from preclinical and clinical studies, which point to significant and serious adverse effects of 5α-RIs, finasteride and dutasteride, on sexual health, vascular health, psychological health and the overall quality of life. Physicians need to be aware of such potential adverse effects and communicate such information to their patients prior to commencing 5α-RIs therapy.

The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression

With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia (BPH) with concomitant lower urinary tract symptoms (LUTS). Because the prostate is an androgen target tissue, and transforms testosterone into 5α-dihydrotestosterone ...

www.ncbi.nlm.nih.gov

 

[Pigeon]

Professor in this docu about fina agrees with OP's theory.


Another interesting theory why it seems young men are much more sensitive to finasteride is because of the fact; until you're around the age of 25 your brain and endocrine system are still developing. More info and studies about this here: https://www.reddit.com/r/steroids/wiki/index#wiki_why_young_men_should_not_take_aas (and fina is a steroid-like med btw)

Hence most "official" studies are also worthless because most of the test group were older men in those studies. For example the famous japanese fina study, etc.

 

[Pigeon]

Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition​

Abstract​

Persistent alteration of plasma neuroactive steroid levels associated with major depression has been recently reported in men after the suspension of the treatment for androgenetic alopecia with finasteride, an inhibitor of the enzyme 5alpha-reductase. Observations in male rats confirmed persistent alterations in neuroactive steroid levels also in the brain. In the present study, we have ascertained possible effects on depressive-like behavior, neurogenesis, gliosis, neuroinflammation and gut microbiota in male rats after subchronic treatment for 20 days with finasteride and after one month of its withdrawal. At the end of treatment there was an increase in the number of pH3 immunoreactive cells in the subgranular zone of the dentate gyrus together with an increase in the mRNA levels of TNF-α in the hippocampus. By one month after the end of finasteride treatment, rats showed depressive-like behavior coupled with a decrease in the number of pH3 immunoreactive cells in the subgranular zone of the dentate gyrus, a decrease in granule cell density in the granule cell layer and an increase in the number of GFAP immunoreactive astrocytes in the dentate gyrus. Finally, alteration of gut microbiota (i.e., an increase in Bacteroidetes phylum and in Prevotellaceae family at the end of the treatment and a decrease in Ruminococcaceae family, Oscillospira and Lachnospira genus at the end of the withdrawal period) was detected.
In conclusion, finasteride treatment in male rats has long term effects on depressive-like behavior, hippocampal neurogenesis and neuroinflammation and gut microbiota composition.

Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition

Persistent alteration of plasma neuroactive steroid levels associated with major depression has been recently reported in men after the suspension of …

www.sciencedirect.com

 

[Pigeon]

Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis​

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

Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis - PubMed

Available toxicity information from clinical trials of finasteride in men with Androgenetic Alopecia is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of Androgenetic Alopecia, most would have been excluded from the pivotal studies that...

pubmed.ncbi.nlm.nih.gov

 

[Pigeon]

Efficacy and safety of Finasteride (5 alpha-reductase inhibitor) monotherapy in patients with benign prostatic hyperplasia: A critical review of the literature​

Abstract​

Background: Combination therapy with 5 alpha-reductase inhibitor (5-ARI) and alpha-blocker can be considered as a gold standard intervention for medical management of lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH). On the other hand, 5-ARI monotherapy and in particular Finasteride alone is currently getting focus of attention especially due to lack of systematic reviews investigating efficacy outcomes and/or adverse events associated.

Objectives: Aim of the present critical review was to analyze current knowledge of clinical efficacy and incidence of adverse events associated with 5-ARI treatment for LUTS/BPH.

Materials and methods: A systematic review of clinical trials of the literature of the past 20 years was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 8821 patients were included in this study and inclusion criteria for studies selection were: data from randomized clinical trials (RCTs) focusing their attention on the clinical role of Finasteride monotherapy for symptomatic BPH. Parameters of research included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), postvoid residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs).

Results: Overall 12 original articles were included and critically evaluated. Sample sizes of patient actively treated with finasteride varied from 13 to 1524 cases analyzed in a single study. Follow-up after treatments ranged from 3 to 54 months. The effect of finasteride in reducing prostate volume (PV) was moderate (standardized mean difference (SMD) effect between 0.5 to 0.8 for all trials evaluable) while the effect on IPSS score and Qmax was considered significant (SMD in the 0.2 to 0.5 variation range). No severe AEs and/or psychiatric disorders were retrieved among the studies. Sexual health dysfunctions were significantly influenced by finasteride therapy when compared with placebo treated patients.

Conclusions: Although significant clinical benefits of finasteride monotherapy were demonstrated, the effective size of the available reports included in the analysis is limited. Additional head-to-head studies would be needed to re-evaluate clinical efficacy and safety of 5-ARI in combination or not with alpha blockers.

Efficacy and safety of Finasteride (5 alpha-reductase inhibitor) monotherapy in patients with benign prostatic hyperplasia: A critical review of the literature - PubMed

Although significant clinical benefits of finasteride monotherapy were demonstrated, the effective size of the available reports included in the analysis is limited. Additional head-to-head studies would be needed to re-evaluate clinical efficacy and safety of 5-ARI in combination or not with...

pubmed.ncbi.nlm.nih.gov

 

[Pigeon]

Other than thousands upon thousands of anecdotal reports from different men of severe adverse reactions to the drug appearing on the internet in the decades since it was approved for sale, evidence of objective differences between PFS patients and control groups has now been established.

https://journals.plos.org/plosone/ar...0237#abstract0

The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P?=?0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.

https://www.ncbi.nlm.nih.gov/pubmed/28408350

We also reported abnormal somatosensory evoked potentials of the pudendal nerve in PFS patients with severe ED, the first objective evidence of a neuropathy involving peripheral neurogenic control of erection.

Data obtained on neuroactive steroid levels also indicate interesting features. Indeed, decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients.

Finally, finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.

https://www.jsm.jsexmed.org/article/...817-9/fulltext

Using novel ultrasound technology, 96% of men with PFS and ED demonstrated heterogeneity in their corporal tissue at maximal pharmacologic erection. This new protocol is able to show that PFS men complaining of ED may have an underlying biologic pathophysiology.

 

[Pigeon]

The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli​

Abstract ​

Finasteride (finasteride) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. finasteride is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, finasteride has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of finasteride, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of finasteride in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. finasteride reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of finasteride does not primarily reflect changes in gonadal steroids. The effects of finasteride on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that finasteride impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus-pituitary-adrenal (HPA) axis.

The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli - PubMed

Finasteride (finasteride) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. finasteride is clinically approved for the treatment of benign prostatic hyperplasia...

pubmed.ncbi.nlm.nih.gov

 

[Pigeon]

Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study​

Abstract

In the pharmacological treatment of prostate cancer, benign prostatic hyperplasia and androgenetic alopecia finasteride is commonly used. This drug inhibits 5α-reductase type 2, which is why finasteride affects androgen homeostasis, since testosterone (T) cannot be reduced to dihydrotestosterone (DHT). As studies on sex-related renal injuries suggest a high probability of androgen-induced renal dysfunction, the aim of this study was to determine the potential harmful effects of finasteride on the kidneys of rats. The study was performed on sexually mature male Wistar rats given finasteride. Histological sections of the kidneys were used for immunohistochemical visualization of the androgen receptor (AR), junctional proteins (occluding (Occ); E-cad, N-cad, E-/N-cadherin; β-cat, β-catenin; connexin 43 (Cx43)), proliferating cell nuclear antigen (PCNA), IL-6, and lymphocyte markers (CD3 for T cell, CD19 for B cell). The TUNEL method was used for cell apoptosis identification, and picro sirius red staining was used to assess collagen fibers thickness. The levels of T, DHT and estradiol (E2) were determined in blood serum. It was shown that finasteride treatment affected steroid hormone homeostasis, altered the expression of AR and intracellular junction proteins, changed the ratio between cell apoptosis and proliferation, and caused lymphocyte infiltration and an increase of IL-6. The thickening of collagen fibers was observed as tubular fibrosis and glomerulosclerosis. Summarizing, finasteride-induced hormonal imbalance impaired the morphology (i.e., dysplastic glomeruli, swollen proximal convoluted tubules) and physiology (changed level of detected proteins/markers expression) of the kidneys. Therefore, it is suggested that patients with renal dysfunction or following renal transplantation, with androgen or antiandrogen supplementation, should be under special control and covered by extended diagnostics, because the adverse negative effect of DHT deficiency on the progression of kidney disease cannot be ignored.

Finasteride-Induced Inhibition of 5α-Reductase Type 2 Could Lead to Kidney Damage—Animal, Experimental Study

In the pharmacological treatment of prostate cancer, benign prostatic hyperplasia and androgenetic alopecia finasteride is commonly used. This drug inhibits 5α-reductase type 2, which is why finasteride affects androgen homeostasis, since testosterone ...

www.ncbi.nlm.nih.gov

Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study​

The risk of type 2 diabetes was increased by approximately 30% over 11 years in men with benign prostatic hyperplasia who received one of the 5α-reductase inhibitors on the market, finasteride or dutasteride compared with tamsulosin

Additional monitoring might be required for men starting these drugs, particularly in those with other risk factors for type 2 diabetes.

Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study

Objective To investigate the incidence of new onset type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors (dutasteride or finasteride) for long term treatment of benign prostatic hyperplasia. Design Population based cohort study. Setting UK Clinical Practice Research...

www.bmj.com

 

[Pigeon]

Finasteride has been added to the 'list of drugs to avoid in 2021' by a French Medical Journal

Translation from the Journal 'Drugs to be Avoided for Better Care 2021 Report'

'Finasteride 1mg, a 5-alpha-reductase inhibitor, has a very high efficacy in modest androgenic alopecia in men: it increases hair density only slightly on the top of the head (by about 10%), and only for the duration of the treatment. It exposes particular sexual disorders (e.g., sexual dysfunction in erection and ejaculation, decreased libido), depression, suicidal ideation and cancer of the breast. When a drug is the chosen option, local minoxidil used with care is less dangerous.'

(Finasteride is on page 6 of the journal)

The journal is called Prescrire, a medical journal that 'addresses developments in diseases, medications, and in medical techniques and technologies' and 'contains no advertising'.

According to their website their 'editors are healthcare professionals, specially trained in Prescrire's editorial methods and free from conflicts of interest. Exacting quality control procedures are applied to all editorial content.'

 

[Pigeon]

Many doctors who also see more and more guys coming to their clinics to deal with PFS. This is a recent twitter convo between docs:

https://twitter.com/i/web/status/1324770761731657734

Definitely seen this a lot and believe it's real. Anecdotally feel symptoms are worse the younger they started on finasteride. Clomid has helped on a few pts with lower T / FSH/LH levels...

https://twitter.com/i/web/status/1333240440003420160

And I’m 100% certain this effects older guys as well...it’s just more obvious in the younger guys who typically have no co-morbidities.

(so the typical cope of "you're just getting older bro" is nothing more than that, pure cope)

https://twitter.com/i/web/status/1327387622688354305

Post finasteride syndrome is so real! Hundreds of patients coming to #sandiegosexualmedicine with this. Often have low t. Make sure to check dht also! Some recommend andractim, available in Europe (and online). Shockwave therapy for ED. Can take years to get better for some!

 

[Pigeon]

The potential involvement of cholinergic system in finasteride induced cognitive dysfunction​

Abstract​

Objective: Neurosteroids are known to exert diverse functions in the brain. 5α-reductase (5α-R), a rate-limiting enzyme involved in the biosynthesis of neurosteroids is inhibited by finasteride. Clinical studies suggest that administration of finasteride causes the emergence of affective symptoms and cognitive dysfunction. Modeling this in rats would provide an opportunity to understand the mechanisms. Accordingly, in the present study, we evaluated the effects of repeated finasteride administration on spatial learning and memory in the partially baited radial arm maze task (RAM) and social cognitive behavior in the social interaction test. Further, to initiate the quest to understand the mechanisms underlying the effects of finasteride, in a separate group of animals, acetylcholinesterase (AChE) activity in the frontal cortex, hippocampus, septum and striatum was estimated.

Methods: 2 months old male Wistar rats were trained to learn a partially baited radial arm maze task (four trials per day till they reach a choice accuracy of 80 %). Following this, rats were administered with either vehicle (HPβCD) or finasteride (30 or 100 mg/Kg, s.c.) for 7 days and then subjected to retention test on the eighth day. To evaluate the social cognition, finasteride was administered for 7 days, followed by social interaction test on the eighth day. All the sessions were video-recorded and analyzed using Noldus Ethovision XT™ software. Following finasteride administration, on the eighth day, rats were euthanized, and AChE activity was estimated by modified Ellman's method.

Results: Finasteride (100 mg/Kg, s.c.) administration decreased the percent correct choice during the retention trial of the RAM task. This was paralleled by an increase in the number of total number of errors and reference memory errors. In the social interaction test, finasteride (100 mg/Kg, s.c.) administration decreased the time spent with the rat compared to the object, implying decreased sociability and diminished social preference evidenced by similar time spent with the novel and familiar rat. Reduced AChE activity was observed in the frontal cortex, hippocampus and septum.

Conclusion: Our study provides evidence that repeated administration of finasteride decreases social interaction and results in cognitive deficits, potentially through a cholinergic mechanism. Further studies are required to understand the exact link between the cognitive effects and the cholinergic system. A deeper probe of the current findings holds promise for the development of novel neurosteroid-based therapeutics to treat affective and cognitive disorders.

The potential involvement of cholinergic system in finasteride induced cognitive dysfunction - PubMed

Our study provides evidence that repeated administration of finasteride decreases social interaction and results in cognitive deficits, potentially through a cholinergic mechanism. Further studies are required to understand the exact link between the cognitive effects and the cholinergic system...

pubmed.ncbi.nlm.nih.gov

5α-reductase inhibitors really mess with your brain and has an effect on many neurosteroids, here's a nice graph showing only a part of the pathways it influences:

The following reactions are known to be catalyzed by 5α-reductase:[9]

• Cholestenone → 5α-Cholestanone
• Progesterone → 5α-Dihydroprogesterone
• 3α-Dihydroprogesterone → Allopregnanolone
• 3β-Dihydroprogesterone → Isopregnanolone
• Deoxycorticosterone → 5α-Dihydrodeoxycorticosterone
• Corticosterone → 5α-Dihydrocorticosterone
• Cortisol → 5α-Dihydrocortisol
• Aldosterone → 5α-Dihydroaldosterone
• Androstenedione → 5α-Androstanedione
• Testosterone → 5α-Dihydrotestosterone
• Nandrolone → 5α-Dihydronandrolone

Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from progesterone) activate the GABAA receptor in the brain; because finasteride prevents the formation of neurosteroids, it functions as a neurosteroidogenesis inhibitor and may contribute to a reduction of GABAA activity. Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction.[75][76][77]

Finasteride - Wikipedia

en.wikipedia.org

Important new study of androgens and the cascading effects it has become more clear, study from 2020:

Advances in Knowledge of Androgens: How Intentional and Accidental Neurosteroid Changes Inform Us of Their Action and Role - Current Sexual Health Reports

Purpose of Review Here, we summarize current knowledge of androgens’ action gained over the recent years. Recent Findings Neurosteroids are produced in the brain and peripheral nerves, independent of endocrine glands have been investigated for how they are regulated, and have actions via...

link.springer.com

Advances in Knowledge of Androgens: How Intentional and Accidental Neurosteroid Changes Inform Us of Their Action and Role​

In sum, finasteride acting at 5ɑ-R interferes with many downstream or alternative pathways for production of steroids; reducing one pathway increases activity of other enzymes to increase or decrease neurosteroids that have many effects. Perhaps most importantly, these actions of finasteride via 5ɑ-R are not limited to current treatment, but can have lasting effects on patients long after they have discontinued finasteride.

 

[Pigeon]

Post SSRI syndrome has been medically recognized in Europe in 2019 and SSRI's have been on the market much longer than fina or duta too.

Post-SSRI Sexual Dysfunction Recognized as Medical Condition

European regulators recognize a medical condition. Will their U.S. counterparts?

www.psychologytoday.com

Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?

Abstract

Sexual dysfunction is a clinical condition due to different causes including the iatrogenic origin. For instance, it is well known that sexual dysfunction may occur in patients treated with antidepressants like selective serotonin reuptake inhibitors (SSRI). A similar side effect has been also reported during treatment with finasteride, an inhibitor of the enzyme 5alpha-reductase, for androgenetic alopecia. Interestingly, sexual dysfunction persists in both cases after drug discontinuation. These conditions have been named post-SSRI sexual dysfunction (PSSD) and post-finasteride syndrome (PFS). In particular, feeling of a lack of connection between the brain and penis, loss of libido and sex drive, difficulty in achieving an erection and genital paresthesia have been reported by patients of both conditions. It is interesting to note that the incidence of these diseases is probably so far underestimated and their etiopathogenesis is not sufficiently explored. To this aim, the present review will report the state of art of these two different pathologies and discuss, on the basis of the role exerted by three different neuromodulators such as dopamine, serotonin and neuroactive steroids, whether the persistent sexual dysfunction observed could be determined by common mechanisms.

https://pubmed.ncbi.nlm.nih.gov/29675596/

 

[Pigeon]

Effect of androgen deprivation on penile ultrastructure

Abstract

Aim: To investigate the ultrastructural changes of penile corpus cavernosum and tunica albuginea in rats treated with castration or finasteride.

Methods: Eighteen male Sprague-Dawley rats of nine weeks old were randomly divided into three groups with 6 rats each. Group A served as the control, Group B was castrated and Group C, treated with finasteride. Four weeks later, rats were anesthetized and blood samples obtained for the determination of serum testosterone (T) and dihydrotestosterone (DHT) levels; penile tissues were taken for scanning electron microscopy.


Results: The T, free T and DHT levels in Group B and the DHT level in Group C were significantly lower than those in Group A (P<0.05). The tunica albuginea was significantly thinner in Group B than that in Group A (P<0.05), but there was no significant difference between Group C and Group A (P>0.05). Elastic fibers in the tunica albuginea of Group A were very rich and arranged regularly and undulatedly, but in Group B, most of the elastic fibers were replaced by collagenous fibers. In Group C, the tunica albuginea was mainly composed of thick and irregular-arranged collagenous fibers. In Group A, there were abundant smooth muscle fibers in the trabeculae of corpus cavernosum, but they were much less in Group C and scarce or even disappeared in Group B. In Groups B and C, the diminished/disappeared smooth muscle fibers were replaced by irregularly arranged collagenous fibers.


Conclusion: In rats, androgen is essential for maintaining the normal structure of penile tunica albuginea and corpus cavernosum.

https://pubmed.ncbi.nlm.nih.gov/12647000/

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model

Abstract

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116690/

 

[Pigeon]

There are warnings from many medical sources NOT to use Finasteride and have unprotected sex should your partner be pregnant.

1. This information was released by Merck via the FDA in 2011. https://www.google.com/url?sa=t&sour...ognrVif0OszxLF

https://www.accessdata.fda.gov/drugs...MG_MEDR_P1.PDF
"Abnormal male genital development is an expected consequence when conversion of testosterone to 5?dihydrotestosterone (DHT) is inhibited by 5?-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5?-reductase deficiency. Women could be exposed to finasteride through contact with crushed or broken PROPECIA tablets or semen from a male partner taking PROPECIA"


2. The Drugs.com article on Finasteride states: https://www.drugs.com/pregnancy/finasteride.html
"US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits of Finasteride is present in semen and therefore may pose a risk to the fetus. Male patients should be instructed to wear a condom during intercourse with women of childbearing potential or discontinue finasteride. The drug should be discontinued in patients wishing to conceive a child."


3. The electronic medicines compendium https://www.medicines.org.uk/emc/pro...044/smpcstates: "Small amounts of finasteride have been recovered from the semen in subjects receiving finasteride 5 mg/day. It is not known whether a male fetus may be adversely affected if his mother is exposed to the semen of a patient being treated with finasteride. When the patients sexual partner is or may potentially be pregnant, the patient is recommended to minimise exposure of his partner to semen."


4. An extremely high percentage of post-marketing reports of exposure to Finasteride during pregnancy via Semen resulted in genital birth defects. https://www.medicines.org.uk/emc/product/2194/smpc"
"During continual collection of adverse experiences, post-marketing reports of exposure to finasteride during pregnancy via semen of men taking 1 mg or higher doses have been received for eight live male births, and one retrospectively -reported case concerned an infant with simple hypospadias. Causality cannot be assessed on the basis of this single retrospective report and hypospadias is a relatively common congenital anomaly with an incidence ranging from 0.8 to 8 per 1000 live male births. In addition, a further nine live male births occurred during clinical trials following exposure to finasteride via semen, during pregnancy, and no congenital anomalies have been reported."
NOTE: That's 1 out of 17 reports of paternal exposure resulting in a congenital defect which is extremely high.


5. Handbook of Systemic Drug Treatment in Dermatology edited by Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer. "It is not known whether a male fetus may be adversely affected by in utero exposure to the semen of a man treated with finasteride or duasteride, but condom use is advised."


6. Back in 1997 it was requested Merck test and release the No Observable Effect Level dose for oral administration of finasteride. This was never done or they never released the findings: https://www.accessdata.fda.gov/drugs...1MG_PHARMR.PDF
Thus there is NO proven safe amount of finasteride to be received orally at all by pregnant women that has been proven NOT to cause birth defects, including in semen during oral sex.


7. 'Drug related safety issues affecting pregnancy outcome and concerning risk minimisation measures' by Crijns, Hubertina Johanna Maria Josephina. This states "Presence of drugs in seminal fluid could interfere with embryonic or foetal development because of a direct effect on the uterus or the vaginal mucosa during sexual intercourse during pregnancy." Finasteride directly lowers DHT or Dihydrotestosterone, which is the most critical hormone for male genital development during pregnancy in fetuses.

 

[Pigeon]

Alterations of gut microbiota composition in post-finasteride patients: a pilot study​

Abstract​

Purpose​

Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort.

Methods​

Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects.

Results​

Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control.

Conclusion​

Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

Alterations of gut microbiota composition in post-finasteride patients: a pilot study - Journal of Endocrinological Investigation

Purpose Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual...

link.springer.com

I can post many more studies indicating what every rational person already knows, fina is more dangerous than the young, balding guy on the internet desperately wants to believe. Also note that most of the studies I just posted aren't old and quite recent. It's clearer than ever that using 5-alpha-reductase inhibitors brings with it many health risks.

 

[inmyhead]

I wish people spent time trying to figure out hairloss instead of writing random posts with their opinion about finasteride.