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Testosterone Replacement, Low T, HCG, & Beyond
When Testosterone Is Not Enough
Lower TRT dosage when adding hCG to keep blood work stable?
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<blockquote data-quote="madman" data-source="post: 275007" data-attributes="member: 13851"><p><strong><em>Urology professor: "DR. TED SCHAEFFER: There’s significant pathology <u>ASSOCIATED</u> with taking finasteride. We used to think that it was predominantly in those main structures, follicles of your hair, prostate, et cetera, but now we know there’s profound potential impact centrally in your nervous system, it can affect your sex drive, it can affect your sex performance, et cetera."</em></strong></p><p></p><p>Associated.</p><p></p><p></p><p></p><p></p><p><strong><em>*It also does much more than only reducing DHT</em></strong></p><p></p><p>No shit Sherlock look up the numerous studies I have been posting on here over the years!</p><p></p><p></p><p></p><p></p><p></p><p></p><p><em>.<strong> Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.</strong></em></p><p><em><strong>a substantial body of evidence exists </strong></em><strong><em>which points to serious and <u>POTENTIALLY</u> ill-health effects of 5A-RIs' therapy. These include loss or reduced libido, erectile dysfunction, orgasmic and ejaculatory dysfunction (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/table/T2/?report=objectonly" target="_blank">Table 2</a>) [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/#B99" target="_blank">99</a>], development of high grade PCa tumors (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/figure/F4/?report=objectonly" target="_blank">Fig. 4</a>), <u>POTENTIAL</u> negative cardiovascular events, and depression. The side effects are <u>POTENTIALLY</u> harmful in <u>SOME INDIVIDUALS</u> and in young men <u>MAY</u> <u>BE</u> persistent or irreversible [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/#B100" target="_blank">100</a>]. The argument that the benefits of these drugs outweighs the risks is slowly eroding in the face of new emerging scientific evidence from preclinical (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/figure/F2/?report=objectonly" target="_blank">Figs. 2</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/figure/F3/?report=objectonly" target="_blank">?,3;3</a>; <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/table/T1/?report=objectonly" target="_blank">Table 1</a>) and clinical studies (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/table/T2/?report=objectonly" target="_blank">Table 2</a>).</em></strong></p><p></p><p></p><p><em><strong>Educate yourself. You have no clue.</strong></em></p><p></p><p></p><p></p><p></p><p>LMFAO!</p><p></p><p>Again dig a lil deeper!</p><p></p><p>No one is denying that the use of 5ARs (finasteride/dutasteride) can cause sexual/mental sides which can be common but again it's not a given that everyone will experience such.</p><p></p><p>Even then the short-term sides are reversible for the majority once the medication is stopped.</p><p></p><p><em><strong>*The sexual side effects are common and transient, but in a <u>SMALL SUBGROUP OF PATIENTS</u>, these side effects can persist even years after discontinuation of the drug</strong></em><strong><em> [48, 88, 89].</em></strong></p><p></p><p><em><strong>*Symptoms generally improve after discontinuation, but patients with <u>EPIGENETIC SUSCEPTIBILITY may experience</u> persistent effects regardless of age or dosage</strong></em></p><p></p><p></p><p>Some men continue to use 5ARs and suffer from minimal sides.</p><p></p><p>Comes down to the individual as many other factors are at play here.</p><p></p><p>Again when it comes to long-term sides/PFS this is far from common.</p><p></p><p>The genetically prone which is the minority would be the susceptible individuals.</p><p></p><p>No one can say for sure if you will be one of the unlucky ones.</p><p></p><p>Again no one here is denying the short/long-term sides!</p><p></p><p>Common f**KING theme here!</p><p></p><p></p><p><em><strong>*PFS IN INDIVIDUALS <u>PREDISPOSED TO EPIGENETIC SUSCEPTIBILITY</u></strong></em></p><p><em><strong></strong></em></p><p><em><strong>*MAY PERSIST IN A <u>SUBSET OF MEN</u></strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/sexual-problems-in-men-with-alopecia-treated-with-oral-finasteride-are-topical-solutions-better.16571/[/URL]</p><p></p><p><strong>CONCLUSION</strong></p><p></p><p><em><strong>*AGA is a common situation that men are interested and seeking solutions. 5-ARIs—some of the FDA-approved medicines—have been increasingly used in this context in the treatment of AGA. <u>However, 5-ARIs have well-defined side effects that can negatively affect sexual life</u>. <u>The real problem is that it is unknown and unpredictable as to which men using these drugs may be subject to these side effects and when these effects may appear</u>. Studies have been insufficient to give a clear answer to this question. More genetic and clinical studies are needed to understand the pathophysiological pathways leading to the onset and continuation of side effects in men who have used finasteride.</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/controversies-in-the-treatment-of-androgenetic-alopecia-the-history-of-finasteride.16573/[/URL]</p><p></p><p><em><strong>*<em><strong><u>Together these questions help assess the risk a patient has or is likely to develop sexual dysfunction</u>. <u>Patients that are not suffering from sexual dysfunction or are less likely to develop sexual dysfunction, are good candidates for finasteride</u>. In patients that are candidates for finasteride, it would be appropriate to explain the evidence from the controlled studies presented on the finasteride FDA label. <u>It is ultimately up to the patient to decide if the relatively low risk of sexual dysfunction outweighs the benefit of finasteride in the treatment of AGA, but the evidence speaks for itself</u>.</strong></em></strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome-a-surmountable-challenge-for-clinicians.20491/[/URL]</p><p></p><p><em><strong>Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? <u>One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that the use of these drugs is associated with the development of sexual dysfunction, which MAY PERSIST IN A SUBSET OF MEN, irrespective of age, drug dose or duration of study</u>. <u>Also, increased depression, anxiety, and suicidal ideation in a SUBSET OF MEN treated with these drugs were commonly reported in a number of studies</u>. <u>It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm</u>. <u>Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological, and physical adverse side effects, in a SUBSET OF MEN</u>. <u>These constellations of symptoms constitute the basis for PFS in INDIVIDUALS PREDISPOSED TO EPIGENETIC SUSCEPTIBILITY.</u> Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.</strong></em></p><p></p><p></p><p><strong>DISCUSSION</strong></p><p><strong></strong></p><p><strong><em>It is time to acknowledge and recognize that patients who are suffering from PFS are not psychotic or delusional, as some in the clinical community wish to label them (65, 66). </em></strong><em><strong>It is time for action, and this necessitates the development of more effective approaches to understanding the pathophysiological mechanism of PFS and the development of novel therapeutic options. The medical community has an obligation not to turn a blind eye to this rare yet debilitating condition in young men. Patients with this condition should not be stereotyped or stigmatized by untrained and unprepared clinicians, due to <u>lack of awareness and knowledge pertaining to this new and rare syndrome</u>. Greater awareness and education are needed among the medical and scientific communities in order to develop better approaches for managing men with PFS. It is paramount that steps are taken to develop a better understanding of the underlying mechanisms contributing to the onset and progression of PFS and to promote educational and training programs to increase awareness and improve the management of this condition.</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/finasteride-propecia-for-scalp-hair-loss-and-excess-facial-hair-in-women-safe-and-effective.22467/[/URL]</p><p></p><p><em><strong>*<u>Concerns regarding the adverse effects of finasteride and dutasteride used in </u>men have led the NIH to add the <u>controversial “post-finasteride syndrome”</u>, <u>described as a persistent sexual, neurological, and physical adverse reaction, to its GENETIC AND RARE DISEASE Information website</u>.16,18</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/finasteride-suicidality-and-psychological-adverse-events-in-men-taking-propecia-or-proscar.22493/[/URL]</p><p></p><p><strong>Conclusions</strong></p><p><strong></strong></p><p><strong><u><em>Using validated pharmacovigilance methods, we found significant disproportional signals for suicidality associated with finasteride use</em></u><em>.</em></strong><em> <strong><u>In stratified analyses, these signals were not present in older patients prescribed finasteride for BPH but were only present among younger patients using finasteride for alopecia</u>.</strong> In sensitivity analyses, drugs with similar indications but different mechanisms of action and drugs with similar mechanisms of action and adverse effect profiles did not have disproportional reporting of suicidality nor psychological adverse events. Disproportional reporting of suicidality associated with finasteride use was observed after 2012.<strong> <u>In light of these exploratory findings, disproportional signals associated with finasteride may be attributed to reporting biases, namely, stimulated reporting, or to greater repercussions of adverse effects and/or inherent psychological morbidities among younger men</u>. <u>Suicidality and psychological adverse events associated with finasteride use by young patients undergoing treatment for alopecia and potential biases confounding this association merit further investigation</u>.</strong></em></p><p></p><p></p><p></p><p></p><p><strong>CONCLUSION</strong></p><p></p><p><em>This study is the first to consider gene expression differences in men with PFS in explaining the etiology of this condition. <strong>Given gene expression per se is not mechanistic and does not imply causality, experiments with downstream processes of protein expression and activity should be undertaken to provide mechanistic data and clarify the results of this work</strong></em><strong><em>. </em></strong><em><strong><u>Further investigation should also explore upstream processes including the mechanisms regulating gene expression in the setting of PFS and identify RISK FACTORS FOR INDIVIDUALS, with a potential focus on GENETIC RISK FACTORS</u>.</strong> </em><strong><em><u>At this time, patients should be informed regarding POSSIBLE SIDE EFFECTS of 5ARI that MAY PERSIST even following discontinuation of treatment as part of their counseling</u>.</em></strong></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/finasteride-for-hair-loss.23828/#post-205500[/URL]</p><p></p><p><em><strong>12.2 Post finasteride syndrome (PFS)</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Several groups around the world have coined the term <u>“Post finasteride syndrome (PFS)” in a SUBSET OF MEN who used finasteride</u>, who experienced persistent sexual dysfunction (decreased libido and ejaculation disorder) and psychological effects (increased depression, anxiety, and suicidal ideas) after cessation of therapy, irrespective of age, drug, or duration of treatment (81,83). Men using finasteride for more than 205 days had a higher risk for persistent erectile dysfunction (76,84).</strong></em></p><p><em><strong></strong></em></p><p><em><strong>The association of sexual and nonsexual side effects in former finasteride users may be due to the fact that</strong></em><strong><em> <u><strong>fi</strong>nasteride irreversibly inhibits 5AR with a slow rate of dissociation</u>, probably leading to a long-lasting effect on the body, regardless of the time and dose of administration (83).<u> Additionally, an alteration in the brain neurosteroids such as progesterone and dihydroprogesterone </u>could possibly contribute to the persistent psychological effects, as the inhibition of 5AR is a rate-limiting step in the production of neurosteroids (76,85). </em></strong><em><strong>Preclinical animal studies showed that finasteride lowered plasma and hippocampal neurosteroids and increased depression (86,87).</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/the-connection-of-5ar-inhibitors-like-finasteride-to-the-development-of-depression.24336/[/URL]</p><p></p><p><em><strong><em><u>Molecular mechanisms and/or GENETIC DETERMINANTS behind 5-ARIs-induced neuropsychiatric effects should be further explored in both preclinical and clinical studies</u>. Other possible links such as obesity [29, 97] and the derivation of neurotrophic factors in the brain of FIN users need examination.<strong> Although a causal relationship has not been clearly established, <u>particular care needs to be taken in a patient with an existing psychiatric diagnosis, a patient confirmed as having a first-degree relative with a psychiatric history, and adolescents</u>. <u>These groups are more prone to develop depression than other populations</u> [15,19,40]. <u>In all cases, it is paramount that physicians need to carefully assess the risk of depression and other adverse effects, including neuropsychiatric and sexual effects before prescribing 5-ARIs</u>.</strong></em></strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome.24345/[/URL]</p><p></p><p><em><strong><em><strong>*<em><strong><u>Post-Finasteride Syndrome is the current term for a RARE SYNDROME of devastating physical, neurological, and sexual side effects that persist and progress after stopping finasteride</u>. The condition occurs primarily in younger men who have taken the drug to treat hair loss. <u>There is currently no effective treatment for this disease</u>.</strong></em></strong></em></strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/mpb-and-finasteride-side-effects-dosing-theory.24661/#post-215047[/URL]</p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/persistent-adverse-sexual-effects-of-finasteride.24844/[/URL]</p><p></p><p><em><strong>*<em>When confronted with data that their product could cause persistent erectile dysfunction, the Risk Management Safety Team at Merck, in 2009, had the opportunity to take further action to sort out the issue. Realizing that many adverse event reports lacked adequate information, the team could have recommended conducting additional rigorous prospective studies on finasteride to obtain needed information using validated instruments to assess sexual symptoms. <strong>Instead of seeking out the truth regarding a serious and life-altering adverse effect, the Risk Management Safety Team’s planned action was routine pharmacovigilance for another 2 years.5 It is difficult to justify this decision since routine pharmacovigilance was unable to provide adequate information on hundreds of cases from 1998 to 2008.</strong> <strong><u>The FDA also bears some responsibility as it did not advise or require Merck to conduct additional safety studies to adequately address the signal of persistent erectile dysfunction</u>. <u>Although we cannot turn back the clock to alter Merck’s approach and decision in 2009, prescribers of finasteride and male patients with androgenetic alopecia deserve to know how an opportunity was lost to seek the truth regarding this medication’s persistent sexual side effects</u>.</strong></em></strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/how-avodart-and-proscar-affect-libido.24985/#post-219331[/URL]</p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/persistent-sexual-dysfunction-after-finasteride.25186/[/URL]</p><p></p><p><strong>CONCLUSIONS</strong></p><p></p><p><em><strong>In a large series, we replicated Khera’s findings of <u>persistent physical sequelae associated with changes in SF in men after DC FIN</u>. While more research is needed, this <u>population is young, ED is most often severe, and testing shows a high prevalence of vascular, neurologic, and hormonal pathologies</u>.</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome-current-views-and-where-do-we-stand.25450/[/URL]</p><p></p><p><em><strong>*Many clinicians are unaware of the scope of the persistent physical and psychological adverse effects of finasteride while it is in use and despite its discontinuation. <u>The treating clinician should have knowledge and awareness about the higher prevalence of depression and sexual dysfunction in the SUBSET OF MEN seeking treatment for AGA in comparison to the general population</u>. <u>Hence, it is mandatory to ask about patients’ histories of preexisting depression or sexual dysfunction before starting finasteride treatment</u>. <u>Studies agree that 5-alpha reductase inhibitors are well-tolerated, but not without risk</u>. Accordingly, patient education prior to treatment is of the utmost importance, and alternative therapies for treating alopecia may be considered during patient counseling.</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Conclusion</strong></p><p><strong></strong></p><p><strong><em>Post-Finasteride Syndrome (PFS) is considered a serious group of adverse effects that range between persistent, irreversible sexual, neurological, physical, and psychological symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men. <u>Based on the existing literature and clinical research, the medical community believes that these patterns of symptoms constitute the basis for PFS in INDIVIDUALS PREDISPOSED TO EPIGENETIC SUSCEPTIBILITY</u>. The medical community must define and characterize the pathophysiological mechanisms underlying PFS, and more attention should be devoted to patient education and counseling as well as to developing novel management modalities. In addition, further high-quality clinical studies are needed to evaluate potential neuropsychiatric side effects of finasteride in humans and to establish whether finasteride has any exact causal relationship with suicide ideation and other reported side effects.</em></strong></p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/sexual-dysfunction-post-ssri-and-5-alpha-reductase-inhibitors.25515/[/URL]</p><p></p><p><strong>PFS</strong></p><p><strong></strong></p><p><strong><em>*SUBSET OF MEN</em></strong></p><p></p><p>[ATTACH=full]41100[/ATTACH]</p><p>[ATTACH=full]41101[/ATTACH]</p><p>[ATTACH=full]41102[/ATTACH]</p><p>[ATTACH=full]41103[/ATTACH]</p><p>[ATTACH=full]41104[/ATTACH]</p><p>[ATTACH=full]41105[/ATTACH]</p><p>[ATTACH=full]41106[/ATTACH]</p><p>[ATTACH=full]41107[/ATTACH]</p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/dht-lowering-medications.25929/#post-231807[/URL]</p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/5-alpha-reductase-inhibitors-use-in-prostatic-disease-and-beyond.27399/[/URL]</p><p></p><p><strong>*</strong><em><strong>Both finasteride and dutasteride are generally well-tolerated medications, with most adverse effects reported as mild and transient (2). The most frequently reported adverse effects are related to sexual dysfunction, mainly decreased sexual libido, impotence, and ejaculatory disorders</strong></em></p><p><em><strong></strong></em></p><p><em><strong>*<em><strong>Several other adverse effects have been described, including depression, cardiovascular disease, and metabolic syndrome.</strong> <strong>Suggestions of an increase in the incidence of male breast cancer and dementia have not been supported by current literature (15,16)</strong></em></strong></em></p><p><em><strong><em><strong></strong></em></strong></em></p><p><em><strong><em><strong>*<em><strong>It is reported 5-ARIs may increase insulin resistance, leading to high rates of diabetes, metabolic disease, and cardiovascular disease (18)</strong></em></strong></em></strong></em></p><p><em><strong><em><strong><em><strong></strong></em></strong></em></strong></em></p><p><em><strong><em><strong><em><strong>*<em><strong>Currently, there remains no well-established relationship between 5-ARIs and metabolic syndrome or cardiovascular disease</strong></em></strong></em></strong></em></strong></em></p><p><em><strong><em><strong><em><strong><em><strong></strong></em></strong></em></strong></em></strong></em></p><p><em><strong><em><strong><em><strong><em><strong>*<em><strong>A growing chorus of consumers has reported persistent adverse side effects from 5-ARIs, despite the discontinuation of the medication. These persistent symptoms have been labeled post-finasteride syndrome (PFS), embodying a constellation of sexual, physical, and neuropsychiatric symptoms that developed during or after the use of 5-ARIs</strong></em></strong></em></strong></em></strong></em></strong></em></p><p><em><strong><em><strong><em><strong><em><strong><em><strong></strong></em></strong></em></strong></em></strong></em></strong></em></p><p><em><strong><em><strong><em><strong><em><strong><em><strong>*<em><strong>The pathological mechanism of PFS is unclear, though it is theorized 5-ARIs inhibit the synthesis of neurosteroids known to affect mood, cognition, and libido (17)</strong></em></strong></em></strong></em></strong></em></strong></em></strong></em></p><p><em><strong></strong></em></p><p><em><strong>*Current evidence in support of PFS consists of case reports, surveys, or low-volume observation data. <u>It is, for this reason, that the existence, incidence, and mechanism of PFS remain debated</u> (13,21,22). <u>To establish the existence of PFS, quality prospective data, including placebo trials, is required</u>.</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/us-fda-warning-regarding-finasteride-and-suicidal-ideation.27770/[/URL]</p><p></p><p><em><strong>*Urologists prescribing 5-ARIs should be aware of the recent addition of suicide and SI risk to the list of AEs. A mental health screen should be performed and appropriate resources provided to all patients starting on finasteride. A timely review should be arranged with the general practitioner to assess new-onset mental health or SI symptoms. <u>Dose titration adjustments for AGA indications or discontinuation of the medication in these circumstances may be appropriate</u>.</strong></em></p><p></p><p><strong><em>*Further research is required to establish causation between finasteride and SI.</em></strong></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/transforming-dermatology-with-5-alpha-reductase-inhibitors.28050/[/URL]</p><p></p><p><strong>Safety concerns and harmful effects:</strong></p><p></p><ul> <li data-xf-list-type="ul"><em>The use of 5ARIs for androgenetic alopecia (AGA) or benign prostatic hyperplasia in men is associated with serious adverse effects</em></li> <li data-xf-list-type="ul"><em>Adverse effects include sexual, physical, and mental symptoms, leading to post-finasteride syndrome (PFS)</em></li> <li data-xf-list-type="ul"><em>Scientific evidence supports the link between 5ARI use and adverse effects, including libido loss, erectile dysfunction, depression, anxiety, and suicidal ideation</em></li> <li data-xf-list-type="ul"><em><strong>Symptoms generally improve after discontinuation, but patients with <u>EPIGENETIC SUSCEPTIBILITY may experience persistent effects regardless of age or dosage</u></strong></em></li> <li data-xf-list-type="ul"><em>Finasteride and minoxidil use in alopecia treatment result in significant adverse effect reports, negatively impacting the reproductive system in both genders</em></li> <li data-xf-list-type="ul"><em>Men commonly report sexual adverse effects, while women report reproductive toxicity effects such as fetal toxicity and induced abortion</em></li> <li data-xf-list-type="ul"><em>The FDA warns about potential adverse effects of finasteride, including increased risk of high-grade prostate cancer and male fetal genital malformation in women of reproductive age, pregnant women, or nursing mothers</em></li> </ul><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/finasteride-and-antidepressant-induced-sexual-dysfunction-in-men.28107/[/URL]</p><p>[ATTACH=full]41108[/ATTACH]</p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/clinical-guide-to-rare-male-sexual-disorders.28436/[/URL]</p><p></p><p><em>Post-finasteride syndrome 5α reductase inhibitors (5-ARIs), specifically finasteride and dutasteride, have long been used to treat androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH) with proven efficacy and safety profile30–32. Their mechanism of action is via inhibition of the conversion of testosterone into dihydrotestosterone (DHT). <strong>However, the adverse effects profile of these agents has led to debate around their use owing to the possible onset of a rare sexual dysfunction, so-called PFS, which is defined as the persistence of common adverse effects associated with 5-ARI treatment, even after the agent has been discontinued.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>These agents can cause a wide range of effects — emotional, psychological, physical, and sexual — all of which are collectively included in the definition of PFS. Symptoms attributed to this syndrome, including sexual effects (ED, decreased libido, chronic testicular pain, and penis shrinkage), physical effects (gynaecomastia, penis shrinkage, penile curvature, testicular reduction, muscle atrophy, and dry skin), and psychiatric symptoms (depression, anxiety, suicidal thoughts, and insomnia), were highlighted by young patients who had been regularly using finasteride for the treatment of AGA33</strong>.<strong> Notably, the definition of PFS extends to patients in whom the symptoms persist months or even years after treatment discontinuation33</strong></em></p><p><em></em></p><p><em>The etiology of the varied symptoms that characterize this syndrome can be explained by the wide localization of the 5-ARI enzyme in the body, including the brain, bones, and muscles34, which leads to the reduction of DHT in related tissues. In fact, reduced levels of tetrahydroprogesterone, isopregnanolone, and DHT and increased levels of testosterone and 17β-oestradiol have been observed in the cerebrospinal fluid of patients with PFS after long-term 5-ARI use35.In addition, reduced levels of dihydroprogesterone and increased 5α-androstane-3α, 17β-diol and 17β-oestradiol were seen in plasma from the same group of patients.</em></p><p></p><p></p><p></p><p></p><p><strong>Aetiology, pathophysiology, and diagnosis</strong></p><p></p><p><em><strong>5-ARIs inhibit the 5α reductase enzyme nearly irreversibly, with high affinity and a slow rate of dissociation, resulting in long-lasting effects, regardless of the dose administered36</strong>. They are rapidly absorbed after oral administration with a peak plasma concentration (Cmax) of 9.2 μg/occurring 1–2 h (Tmax) after administration of finasteride at a dose of 1 mg/day (ref. 37) and steady-state trough plasma finasteride concentrations are obtained after 3 days38. Although finasteride is used to decrease prostate size for the treatment of BPH, animal studies in rats revealed changes in penile histology and architecture following the use of 5-ARIs (0.5 mg/rat/day), with a decrease in smooth muscle and an increase in collagen along with decreased expression of neuronal and endothelial nitric oxide synthase levels in the penis following treatment with dutasteride39. A separate study demonstrated that rats treated with dutasteride for 12 weeks demonstrated a diminished in vivo erectile response, which did not improve following the washout period40</em></p><p><em></em></p><p><em>A phase II, blinded placebo-controlled study in 42 healthy male volunteers with no sexual or other disorders showed that administering finasteride 0.4–100 mg/day for up to 2 weeks reduced serum DHT levels from 2.02 nmol/l to 0.44 nmol/l in volunteers taking 50 mg, twice daily, which returned to pretreatment levels after 14 days41. Furthermore, slight increases in serum total testosterone and oestradiol levels (10–15%) were observed in the participants after finasteride treatment, although the oestradiol concentration remained within the normal range and the relationship between testosterone and oestradiol remained unchanged37. <strong>The authors concluded that finasteride is very well tolerated, without altering the levels of other steroid hormones, and that it depresses DHT levels in healthy volunteers.</strong></em></p><p><em><strong>Supporting the role of 5-ARIs in sexual dysfunction,</strong> a 2016 meta-analysis focused on the clinical efficacy of 5-ARIs in a group of 5,956 patients with BPH (2,947 in the α-blocker (α-adrenergic receptor antagonist) group and <strong>2,965 in the 5-ARI group) showed that 5-ARI therapy (dutasteride 0.5 mg or finasteride 5 mg daily) was associated with an increased risk of development of de novo ED (6.47% versus 4.71%, OR 1.42) as well as libido loss (3.37% versus 2.3%; OR 1.49)42</strong></em></p><p><em></em></p><p><em>To date, the most interesting information on this topic has come from a pharmacovigilance study published in 2015, which analyzed the United States Food and Drug Administration Adverse Event Reporting System database for adverse effects in patients aged 18–45 years treated with low-dose finasteride for AGA between 1998 and 2013. <strong>The authors reported 4,910 persistent effects, 577 of which were sexual dysfunctions (11.8%). On average, sexual dysfunctions occurred 1.8 years after starting low-dose finasteride and lasted for 5.4 months after stopping treatment and included disturbances in sexual dysfunction, including ED, ejaculation disorders, and orgasmic abnormalities. Interestingly, the study showed a substantial increase in persistent sexual adverse effects in 2011–2013, which was not explained by any clear hypothesis43</strong></em></p><p><em></em></p><p><em>In an Italian survey of 79 patients who had experienced >6 months of PFS syndrome, 40.5% of patients reported ED, 16.5% difficulties in reaching orgasm and 87.3% loss of penis sensitivity, as well as reduced mental concentration (72.2%), and loss of muscle tone and/or mass (51.9%)44. Similarly, Irwig and Kolukula33 reported new-onset persistent sexual dysfunctions associated with finasteride use in 71 men aged 21–46 years; overall, 94% of men reported low libido, 92% ED, 92% decreased arousal and 69% problems with orgasm. <strong>Interestingly, the mean number of reported sexual episodes per month dropped from 25.8 ± 18.0 to 8.8 ± 7.1 (P < 0.0001) and the total sexual dysfunction score increased before and after finasteride (from 7.4 ± 2.3 to 21.6 ± 3.4) use according to the Arizona Sexual Experience Scale (P < 0.0001)33.</strong></em></p><p><em></em></p><p><em>Furthermore, a prospective case–control study of 25 patients receiving 1 mg of finasteride for AGA and 28 control patients who did not receive 5-ARIs reported vascular abnormalities on penile Doppler ultrasound in 17 of the patients in the 5-ARI group (68%).<strong> However, these data could not be compared with controls as penile Doppler was performed only in those who had been treated with 5-ARIs45. Even so, this study further highlights the development of possible persistent anti-androgenic sequelae even after cessation of 5-ARI therapy</strong></em></p><p><em>Changes in penile morphology have also been shown in animal studies. For example, in rats, both finasteride (5 mg/kg) and dutasteride(0.5 mg/kg) usage promoted penile morphological changes such as reduced sinusoidal space and smooth muscle in the corpus cavernosumon post-mortem histology compared with untreated control rats46. Although this particular study did not assess intracavernosal pressures directly, the observed alterations in penile morphology couldpotentially be attributed to a decline in intracavernosal pressures. A separate study conducted in rats found that decreased intracavernosal pressure was linked to a reduction in sinusoidal space density caused by various substances (such as enalapril or sildenafil or a combination thereof)47. <strong><u>However, some evidence has also suggested that some 5-ARI-related effects can also arise owing to GENETIC VARIABILITY as well</u>.</strong> <strong>In a small cohort of 8 patients with PFS, histological examination of tissue alteration in the skin from prepuce showed significant differences in the percentages of epithelial cells (basal cells of the epidermis) positive for nuclear androgen receptor (AR) in patients with PFS (80.66%) compared with controls (65.06%) (P = 0.043) and greater expression of stromal cells in PFS (40.06%) compared with controls (23.46%) (P = 0.023). <u>However, the ratio of AR-positive stromal cells to serum testosterone concentrations was twofold higher in patients with PFS than in control patients (P = 0.001)48, emphasizing how LOCAL VARIABILITY of AR EXPRESSION could be responsible for the persistent side effects of 5-ARI treatment</u>48</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Two polymorphisms in AR have been shown to be related to PFS. (CAG) rs4045402 and (GGN) rs3138869 extreme-length alleles were more frequent among patients with PFS (OR 5.88) who had AGA(OR 3.55) than patients with AGA who had not received treatment49. I<u>n particular, the length of two trinucleotide repeats in AR — the polyglutamine (CAG)n repeat and the imperfect polyglycine (GGN)n repeat, both located in exon 1 of AR — might contribute to the frequency of some specific symptoms reported by patients with PFS</u>.</strong> In this study, the onset of PFS symptoms soon after finasteride discontinuation occurred more frequently in subjects with the long (GGN) >23 repeats (28.6%) versus the medium (GGN) 23 (4.5%, OR 8.4) repeats and medium-to-short(GGN) ≤23 (5.7%, OR 6.4) repeats haplotype. <strong>Furthermore, in patients with PFS, short (CAG)n repeats showed a greater decrease in sexual desire and libido than medium repeats, whereas long (CAG)n repeats were associated with worse orgasms than short repeats50</strong></em></p><p><em><strong></strong></em></p><p><em><strong>The fecal microbiota has also been implicated in the pathogenesis of PFS.</strong> A 2021 study demonstrated that patients with PFS had a reduction of richness and diversity of gut microbiota structure, in particular, Faecalibacterium spp. and Ruminococcaceae UCG-005, whereas Alloprevotella and Odoribacter spp. were increased compared with healthy controls51. <strong>Alterations in the steroid environment might explain fecal microbiota changes in patients receiving 5-ARIs.</strong> For example, microbial species, such as Clostridium scindens, mediate the conversion of glucocorticoids to androgens and can, therefore, be considered a potential target for finasteride. Furthermore, the brain–gut microbiota axis might be affected, as 5α-reduced metabolites have been reported in plasma and cerebrospinal fluid of patients with PFS. <strong>However, this hypothesis has not been fully clarified, and further studies are required35,52</strong></em></p><p><em><strong></strong></em></p><p><em><strong><u>Thus, numerous controversies surround this syndrome, as studies have failed to shed light on the onset of male sexual dysfunctions in the short and long term after the suspension of 5-ARI treatment</u>. <u>Notably, the BIOLOGICAL BASIS of the relationship between these disorders and 5-ARI therapy is not yet convincing and some patients report symptoms cannot be adequately explained BIOLOGICALLY, with the frequency of consultations for the conditions paralleling the respective media coverage, indicating a high degree of suggestibility</u>53,54</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Furthermore, reports from drug control agencies are also affected by selection bias, artifact, and sometimes even confusion regarding the objectivity of the symptoms reported55,56. <u>When considering the studies, one must keep in mind that voluntary reporting of these disturbances considerably distorts the scientific data as the participants were a self-selected population</u>.</strong></em></p><p><em>PFS is primarily associated with the use of finasteride, a medication that was approved for treating male pattern baldness in 1997. In 2011, the US product label for finasteride products Propecia and Proscar included a warning about persistent ED following the discontinuation of treatment. In 2012, the label was further updated to include persistent libido disorders, ejaculation disorders, orgasm disorders after stopping Propecia, and decreased libido after stopping Proscar.<strong> Notably, a PFS diagnosis should not be made if prior use of isotretinoin an SSRI is reported.</strong> <strong>Sexual dysfunction that occurs while taking finasteride but resolves after discontinuing the treatment is not considered PFS. A multidisciplinary panel of experts has established criteria for diagnosing PFS, which include the prior treatment with a 5-ARI and enduring sexual dysfunction that persists after discontinuing the treatment. Additional criteria provide further guidance for diagnosing PFS (Box 1).</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Treatment of PFS</strong></p><p></p><p><em>Contrasting evidence in the literature means that the treatment of PFS is still under discussion. Thus, practical recommendations must be offered before starting long-term therapy based on patients’ eligibility, including appropriate informed consent and advice on adverse effects, and proposing alternatives, such as switching to topical finasteride.<strong> Treatment with 5-ARIs is contraindicated in patients with a previous history of sexual dysfunction, infertility, or psychiatric disorders, which can worsen with these agents. <u>Unfortunately, specific risk factors for PFS are not yet identified and no specific recommendations to treat this syndrome are available, owing to the combined influence of psychological effects, nocebo reactions, comorbidities and other factors</u>.</strong></em></p><p><em></em></p><p><em>One published case report described the use of different treatment modalities in three patients. The first patient was managed with Sabal fruit extract soft capsules, Wuling capsules, letrozole, HCG+HMG injections, and 11-ketotestosterone; the second received took tadalafil, Wu Ling capsules, Bushen Yinao pills, zopiclone and clomiphene citrate; and the third took sildenafil, zopiclone, Wu Lingcapsules and Bushen Yinao pills57. However, this report did not describe the patients’ outcomes. <strong>In another case report, one patient was prescribed HCGu 6,000 IU/week, split into three applications of 2,000 UI/week, in conjunction with anastrozole 2 mg/week, divided into two doses of 1 mg. <u>His symptoms gradually but steadily got better over the course of 2 months, including less penile rigidity in a flaccid state, a warmer penis, more morning erections (without any changes in the rigidity of the erections), some growth in penile girth, absence of post-ejaculatory asthenia, increased libido, increased muscular tone and strength, and better mood and self-esteem</u>58</strong>. The second patient was started on tadalafil 5 mg/daily. He saw partial improvements in penile size and erectile function after a few weeks of tadalafil use; however, he had to stop treatment owing to adverse effects of headache and tinnitus and was then referred for psychotherapy owing to increased sexual anxiety.</em></p><p><em></em></p><p><em><strong>In terms of practical recommendations, the presence of previous psychiatric or sexual disorders, family history of psychiatric illnesses, and the presence of previous sexual dysfunction should all be considered in patients receiving finasteride treatment who report relevant PFS symptoms. After ruling out these aspects, patients referred with PFS should be offered support for their sexual symptoms, through both psychological and pharmaceutical approaches.</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/the-post-finasteride-syndrome.28481/#post-264852[/URL]</p><p></p><p><em>The 5ARIs finasteride and dutasteride are widely used drugs over 20 years for alopecia and BPH/LUTS with a variety of side effects like sexual, neurological, psychiatric, endocrine, metabolic, ophthalmological, testicular dysfunctions and the increased incidence of high-grade prostate cancer [17, 21, 54]. <strong><u>The sexual side effects are common and transient, but in a small subgroup of patients, these side effects can persist even years after discontinuation of the drug</u> [48, 88, 89]. This so-called PFS has serious implications for the quality of life and unfortunately, till now no effective therapy exists [17, 54].</strong></em></p><p><em></em></p><p><em>The physiological mechanisms of PED and genital anesthesia are yet to be understood; is there an endocrinological, psychological, or neurological cause (central or peripheral) [90]? <strong>The above-mentioned etiological mechanisms like the change in neurochemistry and neurogenesis, the novel state of androgen deficiency, and the nocebo-effect are steps further <u>but by far insufficient to explain why there are subgroups of patients with side effects during and after use of 5ARIs and to reach in the end a concrete therapy</u>.</strong></em></p><p><em></em></p><p><em>For a better understanding of the existing relations between hormonal and cerebral symptoms a consistent cross-consultation is needed between urologists/sexologists/endocrinologists/dermatologists on one end and psychiatrists/neurologists/researchers on the other hand.<strong> <u>In general, it is sometimes difficult for patients and professionals to recognize the link between symptoms and the 5ARIs because symptoms exist or appear (a long time) after discontinuation of the drug</u>. <u>A very interesting and promising development is the identification of genetically influenced metabotypes, so-called GIMS [91], that represent the genetic basis of chemical individuality, which gave new biological insights</u>. With the help of these GIMS it was possible to prove a consistent genetic association between greater 5α-reductase activity and the risk of male-pattern hair loss [61]. The investigators also observed genetic associations consistent with lower 5α-reductase activity with lower levels of metabolites downstream of 5α-reduction of androgenic steroids.</strong> <strong>Another study identified a separate genetic association between androsterone sulfate, epiandrosterone sulfate, and depression [92]. <u>This chemical individuality might be the way to identify subgroups of patients at risk for side effects due to 5ARIs</u>.</strong></em></p><p><em><strong></strong></em></p><p><em><strong><u>The lack of quality studies is a major problem in assessing the presence and frequency of the side effects</u>.</strong> Further research is warranted with PCRCT including validated questionnaires at baseline with detailed history regarding past psychiatric disorders, the use of medications or drugs, and relevant comorbidities, and with a follow-up for several years. However, this is unlikely to happen due to a lack of funding. <strong><u>Until then it is of utmost importance to identify individuals with a previous history of depression, sexual dysfunction, or infertility who may be more susceptible to the various side effects</u> [93]. <u>The possible risks should then be discussed with the patient and weighed out against the benefits of the use of 5ARIs as mentioned in the introduction</u>. Men under the age of 40 who use finasteride for alopecia are at risk for suicide if they develop persistent sexual adverse effects and insomnia [94]. </strong>Physicians need more awareness regarding the decrease of PSA due to 5ARIs of 50% after 6 to 12 months of use [6] which can mask high-grade prostate cancer [21]. They should restrict the 5ARIs to patients with a prostate volume of >40 ml according to the EAU guideline 2023 [12]. Therapeutic innovation is urgently needed that might cure or relieve this wide range of health risks.</em></p><p></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/finasteride-and-dutasteride-for-the-treatment-of-male-androgenetic-alopecia.28894/[/URL]</p><p></p><p><em><strong>Both finasteride and dutasteride are effective at treating hair loss in male AGA, with studies finding dutasteride is more efficacious than finasteride. <u>Overall, there remains no consensus with respect to the presence, severity, or duration of sexual adverse effects induced by 5-ARIs, although many studies suggest that sexual adverse effects are uncommon and resolve spontaneously</u>. Furthermore, it has been suggested that the reports of sexual dysfunction may be a result of a nocebo effect, drug dosage, duration of treatment, or disease process. <u>For patients concerned about systemic adverse effects of oral 5-ARIs, topical administration may be effective at treating AGA with less potential for sexual adverse effects</u>. <u>5-ARIs may have a negative impact on spermatogenesis and discontinuation of these medications results in improved sperm parameters in most patients</u>. <u>Teratogenicity after paternal exposure is unlikely due to the low concentration of 5-ARIs absorbed in semen</u>. Further research is needed to clarify the effects of 5-ARI use on reproduction.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>It is important for physicians treating AGA to counsel patients about the efficacy of 5-ARIs and the potential adverse effects prior to starting treatment. <u>It is reasonable to consider screening patients taking finasteride for sexual adverse effects, even when using a low dose</u>. <u>If patients experience adverse effects, discontinuation should be considered and patients should be monitored for recovery of sexual function</u>. <u>Finasteride and dutasteride should be used with caution in men who desire fertility and should be considered on the differential during infertility evaluations</u>. Barrier contraception during intercourse is recommended for female partners who are pregnant or may become pregnant. <u>Furthermore, topical application of finasteride and dutasteride may be considered as a treatment option if patients want to avoid systematic reproductive adverse effects</u>.</strong></em></p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/accomplished-molecular-biologist-nadine-hornig-discusses-finasteride-syndrome.29050/[/URL]</p><p></p><p></p><p></p><p></p><p>[URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome-and-upcoming-research.29698/[/URL]</p></blockquote><p></p>
[QUOTE="madman, post: 275007, member: 13851"] [B][I]Urology professor: "DR. TED SCHAEFFER: There’s significant pathology [U]ASSOCIATED[/U] with taking finasteride. We used to think that it was predominantly in those main structures, follicles of your hair, prostate, et cetera, but now we know there’s profound potential impact centrally in your nervous system, it can affect your sex drive, it can affect your sex performance, et cetera."[/I][/B] Associated. [B][I]*It also does much more than only reducing DHT[/I][/B] No shit Sherlock look up the numerous studies I have been posting on here over the years! [I].[B] Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA. a substantial body of evidence exists [/B][/I][B][I]which points to serious and [U]POTENTIALLY[/U] ill-health effects of 5A-RIs' therapy. These include loss or reduced libido, erectile dysfunction, orgasmic and ejaculatory dysfunction ([URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/table/T2/?report=objectonly']Table 2[/URL]) [[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/#B99']99[/URL]], development of high grade PCa tumors ([URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/figure/F4/?report=objectonly']Fig. 4[/URL]), [U]POTENTIAL[/U] negative cardiovascular events, and depression. The side effects are [U]POTENTIALLY[/U] harmful in [U]SOME INDIVIDUALS[/U] and in young men [U]MAY[/U] [U]BE[/U] persistent or irreversible [[URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/#B100']100[/URL]]. The argument that the benefits of these drugs outweighs the risks is slowly eroding in the face of new emerging scientific evidence from preclinical ([URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/figure/F2/?report=objectonly']Figs. 2[/URL], [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/figure/F3/?report=objectonly']?,3;3[/URL]; [URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/table/T1/?report=objectonly']Table 1[/URL]) and clinical studies ([URL='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064044/table/T2/?report=objectonly']Table 2[/URL]).[/I][/B] [I][B]Educate yourself. You have no clue.[/B][/I] LMFAO! Again dig a lil deeper! No one is denying that the use of 5ARs (finasteride/dutasteride) can cause sexual/mental sides which can be common but again it's not a given that everyone will experience such. Even then the short-term sides are reversible for the majority once the medication is stopped. [I][B]*The sexual side effects are common and transient, but in a [U]SMALL SUBGROUP OF PATIENTS[/U], these side effects can persist even years after discontinuation of the drug[/B][/I][B][I] [48, 88, 89].[/I][/B] [I][B]*Symptoms generally improve after discontinuation, but patients with [U]EPIGENETIC SUSCEPTIBILITY may experience[/U] persistent effects regardless of age or dosage[/B][/I] Some men continue to use 5ARs and suffer from minimal sides. Comes down to the individual as many other factors are at play here. Again when it comes to long-term sides/PFS this is far from common. The genetically prone which is the minority would be the susceptible individuals. No one can say for sure if you will be one of the unlucky ones. Again no one here is denying the short/long-term sides! Common f**KING theme here! [I][B]*PFS IN INDIVIDUALS [U]PREDISPOSED TO EPIGENETIC SUSCEPTIBILITY[/U] *MAY PERSIST IN A [U]SUBSET OF MEN[/U][/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/sexual-problems-in-men-with-alopecia-treated-with-oral-finasteride-are-topical-solutions-better.16571/[/URL] [B]CONCLUSION[/B] [I][B]*AGA is a common situation that men are interested and seeking solutions. 5-ARIs—some of the FDA-approved medicines—have been increasingly used in this context in the treatment of AGA. [U]However, 5-ARIs have well-defined side effects that can negatively affect sexual life[/U]. [U]The real problem is that it is unknown and unpredictable as to which men using these drugs may be subject to these side effects and when these effects may appear[/U]. Studies have been insufficient to give a clear answer to this question. More genetic and clinical studies are needed to understand the pathophysiological pathways leading to the onset and continuation of side effects in men who have used finasteride.[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/controversies-in-the-treatment-of-androgenetic-alopecia-the-history-of-finasteride.16573/[/URL] [I][B]*[I][B][U]Together these questions help assess the risk a patient has or is likely to develop sexual dysfunction[/U]. [U]Patients that are not suffering from sexual dysfunction or are less likely to develop sexual dysfunction, are good candidates for finasteride[/U]. In patients that are candidates for finasteride, it would be appropriate to explain the evidence from the controlled studies presented on the finasteride FDA label. [U]It is ultimately up to the patient to decide if the relatively low risk of sexual dysfunction outweighs the benefit of finasteride in the treatment of AGA, but the evidence speaks for itself[/U].[/B][/I][/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome-a-surmountable-challenge-for-clinicians.20491/[/URL] [I][B]Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? [U]One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that the use of these drugs is associated with the development of sexual dysfunction, which MAY PERSIST IN A SUBSET OF MEN, irrespective of age, drug dose or duration of study[/U]. [U]Also, increased depression, anxiety, and suicidal ideation in a SUBSET OF MEN treated with these drugs were commonly reported in a number of studies[/U]. [U]It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm[/U]. [U]Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological, and physical adverse side effects, in a SUBSET OF MEN[/U]. [U]These constellations of symptoms constitute the basis for PFS in INDIVIDUALS PREDISPOSED TO EPIGENETIC SUSCEPTIBILITY.[/U] Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.[/B][/I] [B]DISCUSSION [I]It is time to acknowledge and recognize that patients who are suffering from PFS are not psychotic or delusional, as some in the clinical community wish to label them (65, 66). [/I][/B][I][B]It is time for action, and this necessitates the development of more effective approaches to understanding the pathophysiological mechanism of PFS and the development of novel therapeutic options. The medical community has an obligation not to turn a blind eye to this rare yet debilitating condition in young men. Patients with this condition should not be stereotyped or stigmatized by untrained and unprepared clinicians, due to [U]lack of awareness and knowledge pertaining to this new and rare syndrome[/U]. Greater awareness and education are needed among the medical and scientific communities in order to develop better approaches for managing men with PFS. It is paramount that steps are taken to develop a better understanding of the underlying mechanisms contributing to the onset and progression of PFS and to promote educational and training programs to increase awareness and improve the management of this condition.[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/finasteride-propecia-for-scalp-hair-loss-and-excess-facial-hair-in-women-safe-and-effective.22467/[/URL] [I][B]*[U]Concerns regarding the adverse effects of finasteride and dutasteride used in [/U]men have led the NIH to add the [U]controversial “post-finasteride syndrome”[/U], [U]described as a persistent sexual, neurological, and physical adverse reaction, to its GENETIC AND RARE DISEASE Information website[/U].16,18[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/finasteride-suicidality-and-psychological-adverse-events-in-men-taking-propecia-or-proscar.22493/[/URL] [B]Conclusions [U][I]Using validated pharmacovigilance methods, we found significant disproportional signals for suicidality associated with finasteride use[/I][/U][I].[/I][/B][I] [B][U]In stratified analyses, these signals were not present in older patients prescribed finasteride for BPH but were only present among younger patients using finasteride for alopecia[/U].[/B] In sensitivity analyses, drugs with similar indications but different mechanisms of action and drugs with similar mechanisms of action and adverse effect profiles did not have disproportional reporting of suicidality nor psychological adverse events. Disproportional reporting of suicidality associated with finasteride use was observed after 2012.[B] [U]In light of these exploratory findings, disproportional signals associated with finasteride may be attributed to reporting biases, namely, stimulated reporting, or to greater repercussions of adverse effects and/or inherent psychological morbidities among younger men[/U]. [U]Suicidality and psychological adverse events associated with finasteride use by young patients undergoing treatment for alopecia and potential biases confounding this association merit further investigation[/U].[/B][/I] [B]CONCLUSION[/B] [I]This study is the first to consider gene expression differences in men with PFS in explaining the etiology of this condition. [B]Given gene expression per se is not mechanistic and does not imply causality, experiments with downstream processes of protein expression and activity should be undertaken to provide mechanistic data and clarify the results of this work[/B][/I][B][I]. [/I][/B][I][B][U]Further investigation should also explore upstream processes including the mechanisms regulating gene expression in the setting of PFS and identify RISK FACTORS FOR INDIVIDUALS, with a potential focus on GENETIC RISK FACTORS[/U].[/B] [/I][B][I][U]At this time, patients should be informed regarding POSSIBLE SIDE EFFECTS of 5ARI that MAY PERSIST even following discontinuation of treatment as part of their counseling[/U].[/I][/B] [URL unfurl="true"]https://www.excelmale.com/threads/finasteride-for-hair-loss.23828/#post-205500[/URL] [I][B]12.2 Post finasteride syndrome (PFS) Several groups around the world have coined the term [U]“Post finasteride syndrome (PFS)” in a SUBSET OF MEN who used finasteride[/U], who experienced persistent sexual dysfunction (decreased libido and ejaculation disorder) and psychological effects (increased depression, anxiety, and suicidal ideas) after cessation of therapy, irrespective of age, drug, or duration of treatment (81,83). Men using finasteride for more than 205 days had a higher risk for persistent erectile dysfunction (76,84). The association of sexual and nonsexual side effects in former finasteride users may be due to the fact that[/B][/I][B][I] [U][B]fi[/B]nasteride irreversibly inhibits 5AR with a slow rate of dissociation[/U], probably leading to a long-lasting effect on the body, regardless of the time and dose of administration (83).[U] Additionally, an alteration in the brain neurosteroids such as progesterone and dihydroprogesterone [/U]could possibly contribute to the persistent psychological effects, as the inhibition of 5AR is a rate-limiting step in the production of neurosteroids (76,85). [/I][/B][I][B]Preclinical animal studies showed that finasteride lowered plasma and hippocampal neurosteroids and increased depression (86,87).[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/the-connection-of-5ar-inhibitors-like-finasteride-to-the-development-of-depression.24336/[/URL] [I][B][I][U]Molecular mechanisms and/or GENETIC DETERMINANTS behind 5-ARIs-induced neuropsychiatric effects should be further explored in both preclinical and clinical studies[/U]. Other possible links such as obesity [29, 97] and the derivation of neurotrophic factors in the brain of FIN users need examination.[B] Although a causal relationship has not been clearly established, [U]particular care needs to be taken in a patient with an existing psychiatric diagnosis, a patient confirmed as having a first-degree relative with a psychiatric history, and adolescents[/U]. [U]These groups are more prone to develop depression than other populations[/U] [15,19,40]. [U]In all cases, it is paramount that physicians need to carefully assess the risk of depression and other adverse effects, including neuropsychiatric and sexual effects before prescribing 5-ARIs[/U].[/B][/I][/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome.24345/[/URL] [I][B][I][B]*[I][B][U]Post-Finasteride Syndrome is the current term for a RARE SYNDROME of devastating physical, neurological, and sexual side effects that persist and progress after stopping finasteride[/U]. The condition occurs primarily in younger men who have taken the drug to treat hair loss. [U]There is currently no effective treatment for this disease[/U].[/B][/I][/B][/I][/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/mpb-and-finasteride-side-effects-dosing-theory.24661/#post-215047[/URL] [URL unfurl="true"]https://www.excelmale.com/threads/persistent-adverse-sexual-effects-of-finasteride.24844/[/URL] [I][B]*[I]When confronted with data that their product could cause persistent erectile dysfunction, the Risk Management Safety Team at Merck, in 2009, had the opportunity to take further action to sort out the issue. Realizing that many adverse event reports lacked adequate information, the team could have recommended conducting additional rigorous prospective studies on finasteride to obtain needed information using validated instruments to assess sexual symptoms. [B]Instead of seeking out the truth regarding a serious and life-altering adverse effect, the Risk Management Safety Team’s planned action was routine pharmacovigilance for another 2 years.5 It is difficult to justify this decision since routine pharmacovigilance was unable to provide adequate information on hundreds of cases from 1998 to 2008.[/B] [B][U]The FDA also bears some responsibility as it did not advise or require Merck to conduct additional safety studies to adequately address the signal of persistent erectile dysfunction[/U]. [U]Although we cannot turn back the clock to alter Merck’s approach and decision in 2009, prescribers of finasteride and male patients with androgenetic alopecia deserve to know how an opportunity was lost to seek the truth regarding this medication’s persistent sexual side effects[/U].[/B][/I][/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/how-avodart-and-proscar-affect-libido.24985/#post-219331[/URL] [URL unfurl="true"]https://www.excelmale.com/threads/persistent-sexual-dysfunction-after-finasteride.25186/[/URL] [B]CONCLUSIONS[/B] [I][B]In a large series, we replicated Khera’s findings of [U]persistent physical sequelae associated with changes in SF in men after DC FIN[/U]. While more research is needed, this [U]population is young, ED is most often severe, and testing shows a high prevalence of vascular, neurologic, and hormonal pathologies[/U].[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome-current-views-and-where-do-we-stand.25450/[/URL] [I][B]*Many clinicians are unaware of the scope of the persistent physical and psychological adverse effects of finasteride while it is in use and despite its discontinuation. [U]The treating clinician should have knowledge and awareness about the higher prevalence of depression and sexual dysfunction in the SUBSET OF MEN seeking treatment for AGA in comparison to the general population[/U]. [U]Hence, it is mandatory to ask about patients’ histories of preexisting depression or sexual dysfunction before starting finasteride treatment[/U]. [U]Studies agree that 5-alpha reductase inhibitors are well-tolerated, but not without risk[/U]. Accordingly, patient education prior to treatment is of the utmost importance, and alternative therapies for treating alopecia may be considered during patient counseling.[/B][/I] [B]Conclusion [I]Post-Finasteride Syndrome (PFS) is considered a serious group of adverse effects that range between persistent, irreversible sexual, neurological, physical, and psychological symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men. [U]Based on the existing literature and clinical research, the medical community believes that these patterns of symptoms constitute the basis for PFS in INDIVIDUALS PREDISPOSED TO EPIGENETIC SUSCEPTIBILITY[/U]. The medical community must define and characterize the pathophysiological mechanisms underlying PFS, and more attention should be devoted to patient education and counseling as well as to developing novel management modalities. In addition, further high-quality clinical studies are needed to evaluate potential neuropsychiatric side effects of finasteride in humans and to establish whether finasteride has any exact causal relationship with suicide ideation and other reported side effects.[/I][/B] [URL unfurl="true"]https://www.excelmale.com/threads/sexual-dysfunction-post-ssri-and-5-alpha-reductase-inhibitors.25515/[/URL] [B]PFS [I]*SUBSET OF MEN[/I][/B] [ATTACH type="full" alt="Screenshot (32631).png"]41100[/ATTACH] [ATTACH type="full" alt="Screenshot (32632).png"]41101[/ATTACH] [ATTACH type="full" alt="Screenshot (32633).png"]41102[/ATTACH] [ATTACH type="full" alt="Screenshot (32634).png"]41103[/ATTACH] [ATTACH type="full" alt="Screenshot (32636).png"]41104[/ATTACH] [ATTACH type="full" alt="Screenshot (32637).png"]41105[/ATTACH] [ATTACH type="full" alt="Screenshot (32638).png"]41106[/ATTACH] [ATTACH type="full" alt="Screenshot (32639).png"]41107[/ATTACH] [URL unfurl="true"]https://www.excelmale.com/threads/dht-lowering-medications.25929/#post-231807[/URL] [URL unfurl="true"]https://www.excelmale.com/threads/5-alpha-reductase-inhibitors-use-in-prostatic-disease-and-beyond.27399/[/URL] [B]*[/B][I][B]Both finasteride and dutasteride are generally well-tolerated medications, with most adverse effects reported as mild and transient (2). The most frequently reported adverse effects are related to sexual dysfunction, mainly decreased sexual libido, impotence, and ejaculatory disorders *[I][B]Several other adverse effects have been described, including depression, cardiovascular disease, and metabolic syndrome.[/B] [B]Suggestions of an increase in the incidence of male breast cancer and dementia have not been supported by current literature (15,16) *[I][B]It is reported 5-ARIs may increase insulin resistance, leading to high rates of diabetes, metabolic disease, and cardiovascular disease (18) *[I][B]Currently, there remains no well-established relationship between 5-ARIs and metabolic syndrome or cardiovascular disease *[I][B]A growing chorus of consumers has reported persistent adverse side effects from 5-ARIs, despite the discontinuation of the medication. These persistent symptoms have been labeled post-finasteride syndrome (PFS), embodying a constellation of sexual, physical, and neuropsychiatric symptoms that developed during or after the use of 5-ARIs *[I][B]The pathological mechanism of PFS is unclear, though it is theorized 5-ARIs inhibit the synthesis of neurosteroids known to affect mood, cognition, and libido (17)[/B][/I][/B][/I][/B][/I][/B][/I][/B][/I] *Current evidence in support of PFS consists of case reports, surveys, or low-volume observation data. [U]It is, for this reason, that the existence, incidence, and mechanism of PFS remain debated[/U] (13,21,22). [U]To establish the existence of PFS, quality prospective data, including placebo trials, is required[/U].[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/us-fda-warning-regarding-finasteride-and-suicidal-ideation.27770/[/URL] [I][B]*Urologists prescribing 5-ARIs should be aware of the recent addition of suicide and SI risk to the list of AEs. A mental health screen should be performed and appropriate resources provided to all patients starting on finasteride. A timely review should be arranged with the general practitioner to assess new-onset mental health or SI symptoms. [U]Dose titration adjustments for AGA indications or discontinuation of the medication in these circumstances may be appropriate[/U].[/B][/I] [B][I]*Further research is required to establish causation between finasteride and SI.[/I][/B] [URL unfurl="true"]https://www.excelmale.com/threads/transforming-dermatology-with-5-alpha-reductase-inhibitors.28050/[/URL] [B]Safety concerns and harmful effects:[/B] [LIST] [*][I]The use of 5ARIs for androgenetic alopecia (AGA) or benign prostatic hyperplasia in men is associated with serious adverse effects[/I] [*][I]Adverse effects include sexual, physical, and mental symptoms, leading to post-finasteride syndrome (PFS)[/I] [*][I]Scientific evidence supports the link between 5ARI use and adverse effects, including libido loss, erectile dysfunction, depression, anxiety, and suicidal ideation[/I] [*][I][B]Symptoms generally improve after discontinuation, but patients with [U]EPIGENETIC SUSCEPTIBILITY may experience persistent effects regardless of age or dosage[/U][/B][/I] [*][I]Finasteride and minoxidil use in alopecia treatment result in significant adverse effect reports, negatively impacting the reproductive system in both genders[/I] [*][I]Men commonly report sexual adverse effects, while women report reproductive toxicity effects such as fetal toxicity and induced abortion[/I] [*][I]The FDA warns about potential adverse effects of finasteride, including increased risk of high-grade prostate cancer and male fetal genital malformation in women of reproductive age, pregnant women, or nursing mothers[/I] [/LIST] [URL unfurl="true"]https://www.excelmale.com/threads/finasteride-and-antidepressant-induced-sexual-dysfunction-in-men.28107/[/URL] [ATTACH type="full" alt="Screenshot (32641).png"]41108[/ATTACH] [URL unfurl="true"]https://www.excelmale.com/threads/clinical-guide-to-rare-male-sexual-disorders.28436/[/URL] [I]Post-finasteride syndrome 5α reductase inhibitors (5-ARIs), specifically finasteride and dutasteride, have long been used to treat androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH) with proven efficacy and safety profile30–32. Their mechanism of action is via inhibition of the conversion of testosterone into dihydrotestosterone (DHT). [B]However, the adverse effects profile of these agents has led to debate around their use owing to the possible onset of a rare sexual dysfunction, so-called PFS, which is defined as the persistence of common adverse effects associated with 5-ARI treatment, even after the agent has been discontinued. These agents can cause a wide range of effects — emotional, psychological, physical, and sexual — all of which are collectively included in the definition of PFS. Symptoms attributed to this syndrome, including sexual effects (ED, decreased libido, chronic testicular pain, and penis shrinkage), physical effects (gynaecomastia, penis shrinkage, penile curvature, testicular reduction, muscle atrophy, and dry skin), and psychiatric symptoms (depression, anxiety, suicidal thoughts, and insomnia), were highlighted by young patients who had been regularly using finasteride for the treatment of AGA33[/B].[B] Notably, the definition of PFS extends to patients in whom the symptoms persist months or even years after treatment discontinuation33[/B] The etiology of the varied symptoms that characterize this syndrome can be explained by the wide localization of the 5-ARI enzyme in the body, including the brain, bones, and muscles34, which leads to the reduction of DHT in related tissues. In fact, reduced levels of tetrahydroprogesterone, isopregnanolone, and DHT and increased levels of testosterone and 17β-oestradiol have been observed in the cerebrospinal fluid of patients with PFS after long-term 5-ARI use35.In addition, reduced levels of dihydroprogesterone and increased 5α-androstane-3α, 17β-diol and 17β-oestradiol were seen in plasma from the same group of patients.[/I] [B]Aetiology, pathophysiology, and diagnosis[/B] [I][B]5-ARIs inhibit the 5α reductase enzyme nearly irreversibly, with high affinity and a slow rate of dissociation, resulting in long-lasting effects, regardless of the dose administered36[/B]. They are rapidly absorbed after oral administration with a peak plasma concentration (Cmax) of 9.2 μg/occurring 1–2 h (Tmax) after administration of finasteride at a dose of 1 mg/day (ref. 37) and steady-state trough plasma finasteride concentrations are obtained after 3 days38. Although finasteride is used to decrease prostate size for the treatment of BPH, animal studies in rats revealed changes in penile histology and architecture following the use of 5-ARIs (0.5 mg/rat/day), with a decrease in smooth muscle and an increase in collagen along with decreased expression of neuronal and endothelial nitric oxide synthase levels in the penis following treatment with dutasteride39. A separate study demonstrated that rats treated with dutasteride for 12 weeks demonstrated a diminished in vivo erectile response, which did not improve following the washout period40 A phase II, blinded placebo-controlled study in 42 healthy male volunteers with no sexual or other disorders showed that administering finasteride 0.4–100 mg/day for up to 2 weeks reduced serum DHT levels from 2.02 nmol/l to 0.44 nmol/l in volunteers taking 50 mg, twice daily, which returned to pretreatment levels after 14 days41. Furthermore, slight increases in serum total testosterone and oestradiol levels (10–15%) were observed in the participants after finasteride treatment, although the oestradiol concentration remained within the normal range and the relationship between testosterone and oestradiol remained unchanged37. [B]The authors concluded that finasteride is very well tolerated, without altering the levels of other steroid hormones, and that it depresses DHT levels in healthy volunteers. Supporting the role of 5-ARIs in sexual dysfunction,[/B] a 2016 meta-analysis focused on the clinical efficacy of 5-ARIs in a group of 5,956 patients with BPH (2,947 in the α-blocker (α-adrenergic receptor antagonist) group and [B]2,965 in the 5-ARI group) showed that 5-ARI therapy (dutasteride 0.5 mg or finasteride 5 mg daily) was associated with an increased risk of development of de novo ED (6.47% versus 4.71%, OR 1.42) as well as libido loss (3.37% versus 2.3%; OR 1.49)42[/B] To date, the most interesting information on this topic has come from a pharmacovigilance study published in 2015, which analyzed the United States Food and Drug Administration Adverse Event Reporting System database for adverse effects in patients aged 18–45 years treated with low-dose finasteride for AGA between 1998 and 2013. [B]The authors reported 4,910 persistent effects, 577 of which were sexual dysfunctions (11.8%). On average, sexual dysfunctions occurred 1.8 years after starting low-dose finasteride and lasted for 5.4 months after stopping treatment and included disturbances in sexual dysfunction, including ED, ejaculation disorders, and orgasmic abnormalities. Interestingly, the study showed a substantial increase in persistent sexual adverse effects in 2011–2013, which was not explained by any clear hypothesis43[/B] In an Italian survey of 79 patients who had experienced >6 months of PFS syndrome, 40.5% of patients reported ED, 16.5% difficulties in reaching orgasm and 87.3% loss of penis sensitivity, as well as reduced mental concentration (72.2%), and loss of muscle tone and/or mass (51.9%)44. Similarly, Irwig and Kolukula33 reported new-onset persistent sexual dysfunctions associated with finasteride use in 71 men aged 21–46 years; overall, 94% of men reported low libido, 92% ED, 92% decreased arousal and 69% problems with orgasm. [B]Interestingly, the mean number of reported sexual episodes per month dropped from 25.8 ± 18.0 to 8.8 ± 7.1 (P < 0.0001) and the total sexual dysfunction score increased before and after finasteride (from 7.4 ± 2.3 to 21.6 ± 3.4) use according to the Arizona Sexual Experience Scale (P < 0.0001)33.[/B] Furthermore, a prospective case–control study of 25 patients receiving 1 mg of finasteride for AGA and 28 control patients who did not receive 5-ARIs reported vascular abnormalities on penile Doppler ultrasound in 17 of the patients in the 5-ARI group (68%).[B] However, these data could not be compared with controls as penile Doppler was performed only in those who had been treated with 5-ARIs45. Even so, this study further highlights the development of possible persistent anti-androgenic sequelae even after cessation of 5-ARI therapy[/B] Changes in penile morphology have also been shown in animal studies. For example, in rats, both finasteride (5 mg/kg) and dutasteride(0.5 mg/kg) usage promoted penile morphological changes such as reduced sinusoidal space and smooth muscle in the corpus cavernosumon post-mortem histology compared with untreated control rats46. Although this particular study did not assess intracavernosal pressures directly, the observed alterations in penile morphology couldpotentially be attributed to a decline in intracavernosal pressures. A separate study conducted in rats found that decreased intracavernosal pressure was linked to a reduction in sinusoidal space density caused by various substances (such as enalapril or sildenafil or a combination thereof)47. [B][U]However, some evidence has also suggested that some 5-ARI-related effects can also arise owing to GENETIC VARIABILITY as well[/U].[/B] [B]In a small cohort of 8 patients with PFS, histological examination of tissue alteration in the skin from prepuce showed significant differences in the percentages of epithelial cells (basal cells of the epidermis) positive for nuclear androgen receptor (AR) in patients with PFS (80.66%) compared with controls (65.06%) (P = 0.043) and greater expression of stromal cells in PFS (40.06%) compared with controls (23.46%) (P = 0.023). [U]However, the ratio of AR-positive stromal cells to serum testosterone concentrations was twofold higher in patients with PFS than in control patients (P = 0.001)48, emphasizing how LOCAL VARIABILITY of AR EXPRESSION could be responsible for the persistent side effects of 5-ARI treatment[/U]48 Two polymorphisms in AR have been shown to be related to PFS. (CAG) rs4045402 and (GGN) rs3138869 extreme-length alleles were more frequent among patients with PFS (OR 5.88) who had AGA(OR 3.55) than patients with AGA who had not received treatment49. I[U]n particular, the length of two trinucleotide repeats in AR — the polyglutamine (CAG)n repeat and the imperfect polyglycine (GGN)n repeat, both located in exon 1 of AR — might contribute to the frequency of some specific symptoms reported by patients with PFS[/U].[/B] In this study, the onset of PFS symptoms soon after finasteride discontinuation occurred more frequently in subjects with the long (GGN) >23 repeats (28.6%) versus the medium (GGN) 23 (4.5%, OR 8.4) repeats and medium-to-short(GGN) ≤23 (5.7%, OR 6.4) repeats haplotype. [B]Furthermore, in patients with PFS, short (CAG)n repeats showed a greater decrease in sexual desire and libido than medium repeats, whereas long (CAG)n repeats were associated with worse orgasms than short repeats50 The fecal microbiota has also been implicated in the pathogenesis of PFS.[/B] A 2021 study demonstrated that patients with PFS had a reduction of richness and diversity of gut microbiota structure, in particular, Faecalibacterium spp. and Ruminococcaceae UCG-005, whereas Alloprevotella and Odoribacter spp. were increased compared with healthy controls51. [B]Alterations in the steroid environment might explain fecal microbiota changes in patients receiving 5-ARIs.[/B] For example, microbial species, such as Clostridium scindens, mediate the conversion of glucocorticoids to androgens and can, therefore, be considered a potential target for finasteride. Furthermore, the brain–gut microbiota axis might be affected, as 5α-reduced metabolites have been reported in plasma and cerebrospinal fluid of patients with PFS. [B]However, this hypothesis has not been fully clarified, and further studies are required35,52 [U]Thus, numerous controversies surround this syndrome, as studies have failed to shed light on the onset of male sexual dysfunctions in the short and long term after the suspension of 5-ARI treatment[/U]. [U]Notably, the BIOLOGICAL BASIS of the relationship between these disorders and 5-ARI therapy is not yet convincing and some patients report symptoms cannot be adequately explained BIOLOGICALLY, with the frequency of consultations for the conditions paralleling the respective media coverage, indicating a high degree of suggestibility[/U]53,54 Furthermore, reports from drug control agencies are also affected by selection bias, artifact, and sometimes even confusion regarding the objectivity of the symptoms reported55,56. [U]When considering the studies, one must keep in mind that voluntary reporting of these disturbances considerably distorts the scientific data as the participants were a self-selected population[/U].[/B] PFS is primarily associated with the use of finasteride, a medication that was approved for treating male pattern baldness in 1997. In 2011, the US product label for finasteride products Propecia and Proscar included a warning about persistent ED following the discontinuation of treatment. In 2012, the label was further updated to include persistent libido disorders, ejaculation disorders, orgasm disorders after stopping Propecia, and decreased libido after stopping Proscar.[B] Notably, a PFS diagnosis should not be made if prior use of isotretinoin an SSRI is reported.[/B] [B]Sexual dysfunction that occurs while taking finasteride but resolves after discontinuing the treatment is not considered PFS. A multidisciplinary panel of experts has established criteria for diagnosing PFS, which include the prior treatment with a 5-ARI and enduring sexual dysfunction that persists after discontinuing the treatment. Additional criteria provide further guidance for diagnosing PFS (Box 1).[/B][/I] [B]Treatment of PFS[/B] [I]Contrasting evidence in the literature means that the treatment of PFS is still under discussion. Thus, practical recommendations must be offered before starting long-term therapy based on patients’ eligibility, including appropriate informed consent and advice on adverse effects, and proposing alternatives, such as switching to topical finasteride.[B] Treatment with 5-ARIs is contraindicated in patients with a previous history of sexual dysfunction, infertility, or psychiatric disorders, which can worsen with these agents. [U]Unfortunately, specific risk factors for PFS are not yet identified and no specific recommendations to treat this syndrome are available, owing to the combined influence of psychological effects, nocebo reactions, comorbidities and other factors[/U].[/B] One published case report described the use of different treatment modalities in three patients. The first patient was managed with Sabal fruit extract soft capsules, Wuling capsules, letrozole, HCG+HMG injections, and 11-ketotestosterone; the second received took tadalafil, Wu Ling capsules, Bushen Yinao pills, zopiclone and clomiphene citrate; and the third took sildenafil, zopiclone, Wu Lingcapsules and Bushen Yinao pills57. However, this report did not describe the patients’ outcomes. [B]In another case report, one patient was prescribed HCGu 6,000 IU/week, split into three applications of 2,000 UI/week, in conjunction with anastrozole 2 mg/week, divided into two doses of 1 mg. [U]His symptoms gradually but steadily got better over the course of 2 months, including less penile rigidity in a flaccid state, a warmer penis, more morning erections (without any changes in the rigidity of the erections), some growth in penile girth, absence of post-ejaculatory asthenia, increased libido, increased muscular tone and strength, and better mood and self-esteem[/U]58[/B]. The second patient was started on tadalafil 5 mg/daily. He saw partial improvements in penile size and erectile function after a few weeks of tadalafil use; however, he had to stop treatment owing to adverse effects of headache and tinnitus and was then referred for psychotherapy owing to increased sexual anxiety. [B]In terms of practical recommendations, the presence of previous psychiatric or sexual disorders, family history of psychiatric illnesses, and the presence of previous sexual dysfunction should all be considered in patients receiving finasteride treatment who report relevant PFS symptoms. After ruling out these aspects, patients referred with PFS should be offered support for their sexual symptoms, through both psychological and pharmaceutical approaches.[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/the-post-finasteride-syndrome.28481/#post-264852[/URL] [I]The 5ARIs finasteride and dutasteride are widely used drugs over 20 years for alopecia and BPH/LUTS with a variety of side effects like sexual, neurological, psychiatric, endocrine, metabolic, ophthalmological, testicular dysfunctions and the increased incidence of high-grade prostate cancer [17, 21, 54]. [B][U]The sexual side effects are common and transient, but in a small subgroup of patients, these side effects can persist even years after discontinuation of the drug[/U] [48, 88, 89]. This so-called PFS has serious implications for the quality of life and unfortunately, till now no effective therapy exists [17, 54].[/B] The physiological mechanisms of PED and genital anesthesia are yet to be understood; is there an endocrinological, psychological, or neurological cause (central or peripheral) [90]? [B]The above-mentioned etiological mechanisms like the change in neurochemistry and neurogenesis, the novel state of androgen deficiency, and the nocebo-effect are steps further [U]but by far insufficient to explain why there are subgroups of patients with side effects during and after use of 5ARIs and to reach in the end a concrete therapy[/U].[/B] For a better understanding of the existing relations between hormonal and cerebral symptoms a consistent cross-consultation is needed between urologists/sexologists/endocrinologists/dermatologists on one end and psychiatrists/neurologists/researchers on the other hand.[B] [U]In general, it is sometimes difficult for patients and professionals to recognize the link between symptoms and the 5ARIs because symptoms exist or appear (a long time) after discontinuation of the drug[/U]. [U]A very interesting and promising development is the identification of genetically influenced metabotypes, so-called GIMS [91], that represent the genetic basis of chemical individuality, which gave new biological insights[/U]. With the help of these GIMS it was possible to prove a consistent genetic association between greater 5α-reductase activity and the risk of male-pattern hair loss [61]. The investigators also observed genetic associations consistent with lower 5α-reductase activity with lower levels of metabolites downstream of 5α-reduction of androgenic steroids.[/B] [B]Another study identified a separate genetic association between androsterone sulfate, epiandrosterone sulfate, and depression [92]. [U]This chemical individuality might be the way to identify subgroups of patients at risk for side effects due to 5ARIs[/U]. [U]The lack of quality studies is a major problem in assessing the presence and frequency of the side effects[/U].[/B] Further research is warranted with PCRCT including validated questionnaires at baseline with detailed history regarding past psychiatric disorders, the use of medications or drugs, and relevant comorbidities, and with a follow-up for several years. However, this is unlikely to happen due to a lack of funding. [B][U]Until then it is of utmost importance to identify individuals with a previous history of depression, sexual dysfunction, or infertility who may be more susceptible to the various side effects[/U] [93]. [U]The possible risks should then be discussed with the patient and weighed out against the benefits of the use of 5ARIs as mentioned in the introduction[/U]. Men under the age of 40 who use finasteride for alopecia are at risk for suicide if they develop persistent sexual adverse effects and insomnia [94]. [/B]Physicians need more awareness regarding the decrease of PSA due to 5ARIs of 50% after 6 to 12 months of use [6] which can mask high-grade prostate cancer [21]. They should restrict the 5ARIs to patients with a prostate volume of >40 ml according to the EAU guideline 2023 [12]. Therapeutic innovation is urgently needed that might cure or relieve this wide range of health risks.[/I] [URL unfurl="true"]https://www.excelmale.com/threads/finasteride-and-dutasteride-for-the-treatment-of-male-androgenetic-alopecia.28894/[/URL] [I][B]Both finasteride and dutasteride are effective at treating hair loss in male AGA, with studies finding dutasteride is more efficacious than finasteride. [U]Overall, there remains no consensus with respect to the presence, severity, or duration of sexual adverse effects induced by 5-ARIs, although many studies suggest that sexual adverse effects are uncommon and resolve spontaneously[/U]. Furthermore, it has been suggested that the reports of sexual dysfunction may be a result of a nocebo effect, drug dosage, duration of treatment, or disease process. [U]For patients concerned about systemic adverse effects of oral 5-ARIs, topical administration may be effective at treating AGA with less potential for sexual adverse effects[/U]. [U]5-ARIs may have a negative impact on spermatogenesis and discontinuation of these medications results in improved sperm parameters in most patients[/U]. [U]Teratogenicity after paternal exposure is unlikely due to the low concentration of 5-ARIs absorbed in semen[/U]. Further research is needed to clarify the effects of 5-ARI use on reproduction. It is important for physicians treating AGA to counsel patients about the efficacy of 5-ARIs and the potential adverse effects prior to starting treatment. [U]It is reasonable to consider screening patients taking finasteride for sexual adverse effects, even when using a low dose[/U]. [U]If patients experience adverse effects, discontinuation should be considered and patients should be monitored for recovery of sexual function[/U]. [U]Finasteride and dutasteride should be used with caution in men who desire fertility and should be considered on the differential during infertility evaluations[/U]. Barrier contraception during intercourse is recommended for female partners who are pregnant or may become pregnant. [U]Furthermore, topical application of finasteride and dutasteride may be considered as a treatment option if patients want to avoid systematic reproductive adverse effects[/U].[/B][/I] [URL unfurl="true"]https://www.excelmale.com/threads/accomplished-molecular-biologist-nadine-hornig-discusses-finasteride-syndrome.29050/[/URL] [URL unfurl="true"]https://www.excelmale.com/threads/post-finasteride-syndrome-and-upcoming-research.29698/[/URL] [/QUOTE]
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