Finasteride [5ARI] Induced/Associated Effects

Discussion in 'Men's Health Forum' started by madclown, Dec 18, 2006.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Sexual Side Effects of 5-Alpha-Reductase Inhibitors finasteride and dutasteride

    The 5-alpha-reductase inhibitors finasteride and dutasteride are frequently used in the treatment of androgenetic alopecia and benign prostatic hyperplasia.

    These drugs are effective at reducing levels of dihydrotestosterone, the primary androgen responsible for the pathogenesis of both these conditions.

    However, finasteride and dutasteride have also been shown to produce an increase in the incidence of sexual dysfunction, namely, impotence, decreased libido, and ejaculation disorder.

    The purpose of this study is to review the existing medical literature with regard to the sexual side effects of 5-alpha-reductase inhibitor therapy.

    This review is an extensive look at the sexual effects of 5-alpha-reductase inhibitors and compares outcomes for finasteride versus dutasteride in addition to comparing sexualside effects for each of the different dosages prescribed of finasteride and dutasteride.

    Fertig RM, Gamret AC, Darwin E, Gaudi S. Sexual side effects of 5-alpha-reductase inhibitors finasteride and dutasteride: A comprehensive review. Dermatology online journal 2017;23. Sexual side effects of 5-α-reductase inhibitors finasteride and dutasteride: A comprehensive review
     
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Mosher LJ, Godar SC, Morissette M, et al. Steroid 5alpha-reductase 2 deficiency leads to reduced dominance-related and impulse-control behaviors. Psychoneuroendocrinology 2018;91:95-104. http://www.psyneuen-journal.com/article/S0306-4530(17)31394-X/abstract

    Highlights
    · 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into DHT.
    · We found that 5αR2 knockout (KO) mice have reduced dominance-related behaviors.
    · These deficits are accompanied by lower novelty-seeking and risk-taking.
    · 5αR2 KO mice exhibit reduced D2-like receptor binding in the nucleus accumbens.

    The enzyme steroid 5alpha-reductase 2 (5alphaR2) catalyzes the conversion of testosterone into the potent androgen 5alpha-dihydrotestosterone. Previous investigations showed that 5alphaR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5alphaR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates.

    While male 5alphaR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses. Furthermore, male 5alphaR2 KO mice exhibited reduced D2-like dopamine receptor binding in the shell of the nucleus accumbens - a well-recognized molecular signature of social dominance.

    Collectively, these results suggest that 5alphaR2 is involved in the establishment of social dominance and its behavioral manifestations. Further studies are warranted to understand how the metabolic actions of 5alphaR2 on steroid profile may be implicated in social ranking, impulse control, and the modulation of dopamine receptor expression in the nucleus accumbens.
     
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  3. Old

    Old Member

    Do you have a copy of the complete article? Am particularly interested in CNS effects/functions of DHT ... this article suggesting DHT influences D2 binding. Thanks
     
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  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    5alpha-Reductase Inhibitors (5ARIs) and Male Reproduction

    The 5ARIs, finasteride and dutasteride, are used to treat benign prostate hyperplasia and lower urinary tract symptoms. At much lower doses, 5ARI treatment reduces male hair loss. These drugs inhibit the conversion of testosterone to the more active dihydrotestosterone (DHT).

    In men taking these medications, DHT levels are reduced by some 90% while testosterone levels remain relatively stable. Well known for their negative effects on libido and erectile function, 5ARIs also cause ejaculatory dysfunction in some men, having the potential to decrease semen quality.

    In fact, some studies of men treated with these drugs have reported lower total sperm count, along with lower sperm motility, although the changes are probably insufficient to reduce fertility in men with normal semen before treatment. There is a population of men with more severely decreased sperm numbers; as low as 10% of pretreatment values.

    Fewer studies have looked at the lower doses used for male alopecia, indicating little affect in men with normal semen quality, but a negative effect on sperm numbers in men with oligozoospermia. There have been no studies looking at fertility endpoints for these medications.

    Drobnis EZ, Nangia AK. 5alpha-Reductase Inhibitors (5ARIs) and Male Reproduction. Advances in experimental medicine and biology 2017;1034:59-61. 5α-Reductase Inhibitors (5ARIs) and Male Reproduction
     
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Baas WR, Butcher MJ, Lwin A, et al. A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Post-finasteride Syndrome. Urology 2018. https://www.goldjournal.net/article/S0090-4295(18)30590-9/abstract

    OBJECTIVE: To quantify reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS), create a demographic of patient reports, and examine the cluster of symptoms to correlate consistency of post-finasteride syndrome (PFS) complaints. PFS is a provisional diagnosis encompassing a cluster of sexual, physical, and psychological/neurologic symptoms associated with 5-alpha reductase inhibitor (5ARI) use that emerge or continue after discontinuation of medication.

    MATERIALS AND METHODS: FAERS dataset of 5ARI's from April 2011 to October 2014 was obtained. Each FAERS report had 16 categories for completion, but not every report was fully completed. Statistical analysis compared variables of interest between the two doses of finasteride (1mg vs 5mg).

    RESULTS: From FAERS, 2,048 monotherapy cases were identified: 1581 of finasteride 1mg, 240 of finasteride 5mg, and 226 of unreported doses. Possibly related to labeling changes, from 2011 to 2014, there was a significant increase in adverse events (AEs) reported involving 1mg dosing. Finasteride use was reported with many sexual AEs including diminished libido, erectile dysfunction and ejaculatory complaints. Other common AEs included dermatologic, metabolic and psychological/neurological complaints. There were more AE reports with the 1mg dose than the 5mg dose. One case of dutasteride reported back pain, not generally attributed to PFS.

    CONCLUSIONS: FAERS data suggests that finasteride exposure is reported with a diverse collection of symptoms, particularly in younger men on 1 mg dosage compared to older men on 5mg. Many of these complaints fall well out of the realm of previously established AEs from long-term controlled studies.
     
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Maksym RB, Kajdy A, Rabijewski M. Post-finasteride syndrome - does it really exist? The aging male: the official journal of the International Society for the Study of the Aging Male 2019:1-10. https://www.tandfonline.com/doi/full/10.1080/13685538.2018.1548589

    Inhibitors of 5alpha-steroid reductase are drugs used to treat androgen-dependent conditions including prostate diseases and androgenic alopecia. Finasteride was the first on the market and is currently the most widely used inhibitor. dutasteride was the second inhibitor to be approved and has a similar safety profile.

    Common adverse events of treatment consist of sexual disorders and a negative affect balance. It was described that the prolonged use of 5alpha-steroid reductase inhibitors in patients with alopecia can cause persistent side effects called a post-finasteride syndrome (PFS), that is not just a simple coexistence of events, but rather a definite syndrome with an iatrogenic background.

    PFS occurs in susceptible individuals even after small doses of the drug and can last for a long time after the discontinuation of treatment. A deterioration in the quality of life in affected individuals does not justify use of the drug.

    Wider recognition of PFS symptoms, its incidence, course, prevention, and treatment possibilities will allow the indications for drug use to be reconsidered and treatment to be more personalized. Knowledge about PFS will also help to provide the best treatment for affected individuals and to properly educate patients before obtaining an informed consent for therapy with 5alpha-steroid reductase inhibitors.
     

    Attached Files:

  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] A Comment on the Post-finasteride Syndrome

    The post-Finasteride syndrome (PFS) has been claimed to occur in men who have taken oral finasteride to treat hair loss or benign prostatic hyperplasia. While the incidence of persistent sexual, mental, and physical side effects despite quitting finasteride is unknown, and the condition is not recognized by the scientific community, individuals who suffer from PFS do present with very distinctive and homogenous symptoms.

    The concept has emerged from reports of nondermatologists, neuroendocrinological research, case reports, and uncontrolled studies. These have been scrutinized by hair experts who found that persistent sexual side effects were only documented in low-quality studies with a strong bias selection and a significant nocebo effect. Others totally dispute the credibility of the PFS.

    In any case, the PFS is a problem that has to be dealt with. Low-quality studies neither confirm nor refute the condition as a valid nosologic entity. Therefore, it is as inappropriate to dismiss the condition, as it would be to demonize finasteride for the treatment of male pattern hair loss. Whether the PFS represents a nocebo reaction or a real drug adverse event is irrelevant, while the best way to alleviate the emotional distress related to hair loss is to effectively treat the condition causing the problem. It is not sufficient to only discuss the plausibility of the PFS.

    There is a need for practical recommendations to include such important issues as patient selection and risk assessment, appropriate patient information, how to react in case of drug-related adverse events, issues of fertility and malignancy, management of the PFS, and alternatives, specifically the use of topical finasteride. It is the aim of this commentary to provide the respective information.

    Rezende HD, Dias M, Trueb RM. A Comment on the Post-Finasteride Syndrome. International journal of trichology 2018;10:255-61. A comment on the post-finasteride syndrome Rezende HD, Dias MF, Trueb RM - Int J Trichol
     
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Haber RS, Gupta AK, Epstein E, Carviel JL, Foley KA. finasteride for androgenetic alopecia is not associated with sexual dysfunction: A survey-based, single-center, controlled study. Journal of the European Academy of Dermatology and Venereology : JEADV 2019. https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.15548

    BACKGROUND: The occurrence of sexual dysfunction side effects associated with finasteride use in men with androgenetic alopecia (AGA) is thought to be less prevalent than is publicized. There is a need to investigate sexual dysfunction among finasteride users with population-based controls.

    OBJECTIVE: To evaluate presence of sexual dysfunction in men using finasteride or not using finasteride.

    METHOD: Adult men visiting a dermatologist's office for any reason were asked to complete a survey including a modified version of the Arizona Sexual Experience Scale (ASEX) to assess presence of sexual dysfunction with and without finasteride use.

    RESULTS: Data from 762 men aged 18 to 82 was collected; 663 finasteride users and 99 non-finasteride users. There were no significant differences between finasteride users and non-user controls in reporting sexual dysfunction using the ASEX scale. Regression analysis indicated that self-reporting libido loss and reduced sexual performance, not finasteride use, predicts a higher ASEX score.

    CONCLUSION: Use of finasteride does not result in sexual dysfunction in men with AGA. This data is consistent with other large survey-based controlled studies.
     
  9. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Zakhem GA, Goldberg JE, Motosko CC, Cohen BE, Ho RS. Sexual Dysfunction in Men Taking Systemic Dermatologic Medication: A Systematic Review. Journal of the American Academy of Dermatology 2019. https://www.jaad.org/article/S0190-9622(19)30459-1/pdf

    BACKGROUND: Prescription medications are among the most common causes of sexual dysfunction, and patients are often hesitant to seek help when experiencing these symptoms.

    OBJECTIVE: In this review, we identified the available evidence of sexual side effects in men using systemic dermatologic medications and suggest screening protocols and actions that may improve a patient's symptom where possible.

    METHODS: A systematic review was conducted of all articles in the PubMed database published from the time of inception to May 2018 to identify studies evaluating use of systemic dermatologic medications in men with evidence of sexual side effects. Subsequently, a secondary in-depth literature review was performed for each individual medication.

    RESULTS: 5497 articles were reviewed in the primary systematic review. A total of 59 articles covering 11 systemic dermatologic medications met inclusion criteria. We identified level 1 evidence for sexual side effects as a primary outcome in patients taking finasteride.

    LIMITATIONS: Many included studies were limited by sample size and methodology.

    CONCLUSION: The information in this review may serve as a reference of side effects when deciding on a therapeutic agent and a guide to identify patients to screen for sexual dysfunction.
     
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Incidence of Type 2 Diabetes Mellitus in Men Receiving Steroid 5α-Reductase Inhibitors

    Objective To investigate the incidence of new onset type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors (dutasteride or finasteride) for long term treatment of benign prostatic hyperplasia.

    Design Population based cohort study.

    Setting UK Clinical Practice Research Datalink (CPRD; 2003-14) and Taiwanese National Health Insurance Research Database (NHIRD; 2002-12).Participants Men in the CPRD who received dutasteride (n=8231), finasteride (n=30 774), or tamsulosin (n=16 270) were evaluated.

    Propensity score matching (2:1; dutasteride to finasteride or tamsulosin) produced cohorts of 2090, 3445, and 4018, respectively. In the NHIRD, initial numbers were 1251 (dutasteride), 4194 (finasteride), and 86 263 (tamsulosin), reducing to 1251, 2445, and 2502, respectively, after propensity score matching.

    Main outcomes measure Incident type 2 diabetes using a Cox proportional hazard model.

    Results In the CPRD, 2081 new onset type 2 diabetes events (368 dutasteride, 1207 finasteride, and 506 tamsulosin) were recorded during a mean follow-up time of 5.2 years (SD 3.1 years). The event rate per 10 000 person years was 76.2 (95% confidence interval 68.4 to 84.0) for dutasteride, 76.6 (72.3 to 80.9) for finasteride, and 60.3 (55.1 to 65.5) for tamsulosin.

    There was a modest increased risk of type 2 diabetes for dutasteride (adjusted hazard ratio 1.32, 95% confidence interval 1.08 to 1.61) and finasteride (1.26, 1.10 to 1.45) compared with tamsulosin. Results for the NHIRD were consistent with the findings for the CPRD (adjusted hazard ratio 1.34, 95% confidence interval 1.17 to 1.54 for dutasteride, and 1.49, 1.38 to 1.61 for finasteride compared with tamsulosin). Propensity score matched analyses showed similar results.

    Conclusions The risk of developing new onset type 2 diabetes appears to be higher in men with benign prostatic hyperplasia exposed to 5α-reductase inhibitors than in men receiving tamsulosin, but did not differ between men receiving dutasteride and those receiving finasteride. Additional monitoring might be required for men starting these drugs, particularly in those with other risk factors for type 2 diabetes.

    Wei L, Lai EC-C, Kao-Yang Y-H, Walker BR, MacDonald TM, Andrew R. Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study. BMJ (Clinical research ed) 2019;365:l1204. Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study
     
  11. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Reducing the risk of type 2 diabetes in men with benign prostatic hyperplasia—old steroids, new tricks
    Reducing the risk of type 2 diabetes in men with benign prostatic hyperplasia—old steroids, new tricks - The BMJ

    Troublesome symptoms from benign prostatic hypertrophy (BPH) are common. 5α-Reductase inhibitors (5αRI) are increasingly prescribed to alleviate these problems. Unfortunately, like many other treatments, 5αRI medicines have adverse effects that may modify clinicians enthusiasm to prescribe these medicines.

    Clinicians aspire to do no harm and alleviating one condition while causing another important morbidity requires a careful evaluation of the benefits and risks. We now have to add increasing the risk of diabetes to the list of adverse effects caused by 5αRIs.

     
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] [5ARi] Infertility and Teratogenicity After Paternal Exposure to Systemic Dermatologic Medications

    BACKGROUND: This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark.

    OBJECTIVE: To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men.

    METHODS: Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure.

    RESULTS: A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications.

    LIMITATIONS: We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects.

    CONCLUSIONS: Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better-quality studies are required in this area, particularly studies assessing potential teratogenicity.

    Zakhem GA, Motosko CC, Mu EW, Ho RS. Infertility and teratogenicity after paternal exposure to systemic dermatologic medications: A systematic review. Journal of the American Academy of Dermatology 2019;80:957-69. https://www.jaad.org/article/S0190-9622(18)32641-0/fulltext
     
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