Finasteride [5ARI] Induced/Associated Effects

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

  1. Dr JIM

    Dr JIM Member

     
    kgwamd and James23 like this.
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Motofei IG, Rowland DL, Georgescu SR, et al. Post-finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo. Skin Pharmacol Physiol 2017;30(1):42-5. https://www.karger.com/Article/Abstract/455972

    Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome.

    Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome.

    Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account.
     
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Risk of gynecomastia and Breast Cancer Associated with The Use Of 5-Alpha Reductase Inhibitors

    BACKGROUND: Clinical trial results suggest that 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) may increase the risk of gynecomastia and male breast cancer, but epidemiological studies have been limited.

    PATIENTS AND METHODS: We conducted a cohort study with nested case-control analyses using the UK Clinical Practice Research Datalink. We identified men diagnosed with BPH who were free from Klinefelter syndrome, prostate, genital or urinary cancer, prostatectomy or orchiectomy, or evidence of gynecomastia or breast cancer. Patients entered the cohort at age >/=40 years and at least 3 years after the start of their electronic medical record.

    We classified exposure as 5ARIs (alone or in combination with alpha blockers [ABs]), AB only, or unexposed to 5ARIs and ABs. Cases were men who had a first-time diagnosis of gynecomastia or breast cancer. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) in the gynecomastia analysis and crude and adjusted odds ratios (ORs) with 95% CIs in both analyses were calculated.

    RESULTS: Compared to no exposure, gynecomastia risk was elevated for users of 5ARIs (alone or in combination with ABs) in both the cohort (IRR=3.55, 95% CI 3.05-4.14) and case-control analyses (OR=3.31, 95% CI 2.66-4.10), whereas the risk was null for users of AB only.

    The increased risk of gynecomastia with the use of 5ARIs persisted regardless of the number of prescriptions, exposure timing, and presence or absence of concomitant prescriptions for drugs known to be associated with gynecomastia.

    The risk was higher for dutasteride than for finasteride.

    5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61-3.80).

    CONCLUSION: In men with BPH, 5ARIs significantly increased the risk of gynecomastia, but not breast cancer, compared to AB use and no exposure.

    Hagberg KW, Divan HA, Fang SC, Nickel JC, Jick SS. Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia. Clin Epidemiol 2017;9:83-91. https://www.dovepress.com/risk-of-gynecomastia-and-breast-cancer-associated-with-the-use-of-5-al-peer-reviewed-fulltext-article-CLEP
     
    Dr JIM, Rockclimber and James23 like this.
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Gupta AK, Carviel J, MacLeod MA, Shear N. Assessing finasteride-associated sexual dysfunction using the FAERS database. J Eur Acad Dermatol Venereol. Assessing finasteride‐associated sexual dysfunction using the FAERS database

    BACKGROUND: Post-marketing reports suggest that finasteride causes sexual dysfunction despite a low incidence reported in clinical trials. Therefore, the extent of risk remains unknown.

    OBJECTIVE: To determine whether the risk of sexual dysfunction is higher among individuals treated with finasteride compared to a baseline risk for all other drugs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.

    METHODS: A case by non-case disproportionality approach was used whereby a Reporting Odds Ratio (ROR) with 95% confidence interval (CI) was calculated. The National Ambulatory Medical Care Survey (NAMCS) was used to confirm results.

    RESULTS: A significant disproportionality in reporting of sexual dysfunction with the use of finasteride was observed whether finasteride was indicated for hair loss (ROR = 138.17, 95% CI: 133.13, 143.4), prostatic hyperplasia (ROR= 93.88, 95% CI: 84.62, 104.16) or any indication (ROR= 173.18, 95% CI: 171.08, 175.31). When these results were stratified by age, disproportionality was strongest at 31-45 years.

    CONCLUSION: Use of finasteride has led to an increase in reports of sexual dysfunction where it is believed to be the primary suspect.


     
    James23 likes this.
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Association of Suicidality and Depression With 5alpha-Reductase Inhibitors

    Importance: There have been concerns raised by patients and regulatory agencies regarding serious psychiatric adverse effects associated with 5alpha-reductase inhibitors.

    Objective: To determine if there is an increased risk of suicide, self-harm, or depression among older men starting a 5alpha-reductase inhibitor for prostatic enlargement.

    Design, Setting, and Participants: A population-based, retrospective, matched cohort study using linked administrative data for 93197 men ages 66 years or older (median [IQR] age, 75 [70-80] years) in Ontario, Canada, who initiated a new prescription for a 5alpha-reductase inhibitor during the study period (2003 through 2013).

    Participants were matched (using a propensity score that included 44 of our 96 covariates that included medical comorbidities, medication usage, and health care system utilization) to an equal number of men not prescribed a 5alpha-reductase inhibitor. Exposures: Duration of finasteride or dutasteride usage.

    Main Outcomes and Measures: Suicide. Secondary outcomes were self-harm and depression.

    Results: Men who used 5alpha-reductase inhibitors were not at a significantly increased risk of suicide (HR, 0.88; 95% CI, 0.53-1.45). Risk of self-harm was significantly increased during the initial 18 months after 5alpha-reductase inhibitor initiation (HR, 1.88; 95% CI, 1.34-2.64), but not thereafter.

    Incident depression risk was elevated during the initial 18 months after 5alpha-reductase inhibitor initiation (HR, 1.94; 95% CI, 1.73-2.16), and continued to be elevated, but to a lesser degree, for the remainder of the follow-up period (HR, 1.22; 95% CI, 1.08-1.37).

    The absolute increases in the event rates for these 2 outcomes were 17 per 100000 patient-years and 237 per 100000 patient-years, respectively.

    The type of 5alpha-reductase inhibitor (finasteride or dutasteride) did not significantly modify the observed associations with suicide, self-harm, and depression.

    Conclusions and Relevance: In a large cohort of men ages 66 years or older, we did not demonstrate an increased risk of suicide associated with 5alpha-reductase inhibitor use. However, the risk of self-harm and depression were increased compared with unexposed men.

    This is in keeping with postmarketing experience and patient concerns, and discontinuation of the medication in these circ umstances may be appropriate.

    Welk B, McArthur E, Ordon M, Anderson KK, Hayward J, Dixon S. Association of Suicidality and Depression With 5alpha-Reductase Inhibitors. JAMA Intern Med. http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2610105
     
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Thielke S. The Risk of Suicidality and Depression From 5-α Reductase Inhibitors. JAMA Intern Med. Published online March 20, 2017. Risk of Suicidality and Depression From 5-α Reductase Inhibitors

    In this issue of JAMA Internal Medicine, the findings reported by Welk et al1 about mental health effects of 5-α reductase inhibitors (5ARIs) illustrate this dilemma.

    The authors discovered, using more precise methods than in any previous research, a clear association between 5ARI prescription and some negative mental health outcomes among older men with lower urinary tract symptoms (LUTS).

    Comparing 5ARI users and carefully matched nonusers, there was no difference in risk of suicide.

    Risk of self-harm was increased by 17 per 100 000 patient-years, but only during the first 18 months of treatment. Risk of incident depression was increased by 272 per 100 000 patient-years, with a mitigated risk after 18 months.

    Based on these numbers, clinicians would occasionally encounter patients with depression, and would very rarely encounter cases of self-harm, that could be attributed to 5ARIs.

    What ought a clinician to do with these findings?

    Some options include
    (1) prescribing other medications for LUTS that are not known to increase risk of depression,
    (2) giving clear warning to all patients about the possible risks,
    (3) warning those who have had prior depression about the risks,
    (4) monitoring carefully for depression during 5ARI use, or
    (5) doing nothing, insofar as the absolute differences in risk were small and the events rare.


     
    James23 likes this.
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Wu C, Forbes E, Jarvi KA. clomiphene citrate rescue of spermatogenesis in men with infertility while remaining on finasteride: A case report. Can Urol Assoc J 2017;11(3-4):E122-E3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365389/

    Finasteride is a selective inhibitor of type-2 5-alpha reductase enzyme, preventing the conversion of testosterone to dihydrotestosterone (DHT).

    Finasteride is used as an oral drug for the treatment of benign prostatic hyperplasia at the 5 mg/day dose and is also used for the treatment of androgenic alopecia, or male pattern hair loss, at a dosage of 1 mg orally.

    There are now a number of studies documenting that finasteride, even at the low dose of 1mg, may have an adverse effect on fertility for some men.

    In the largest study, Samplaski et al reported that sperm counts improved over 11-fold once the men had stopped the finasteride, but most of the men did not recover to normal sperm parameters.

    Presently, if men using finasteride are subfertile, the recommendation is to stop the finasteride and wait for a recovery of spermatogenesis.

    There has been no report of the use of any hormone therapy, such as clomiphene citrate, gonadotropin, or aromatase inhibitors, to treat subfertile men on finasteride.

    This is the first case report of the use of clomiphene citrate to improve fertilty for a man on finasteride.
     
    James23 likes this.
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Melcangi RC, Santi D, Spezzano R, et al. Neuroactive Steroid Levels and Psychiatric and Andrological Features in Post-finasteride Patients. J Steroid Biochem Mol Biol. NEUROACTIVE STEROID LEVELS AND PSYCHIATRIC AND ANDROLOGICAL FEATURES IN POST-FINASTERIDE PATIENTS.

    Highlights
    · In patients treated with finasteride for male pattern hair loss, persistent side effects may occur.
    · Erectile dysfunction and abnormal somatosensory evoked potentials of the pudendal nerve were reported.
    · Major depressive disorder and altered levels of neuroactive steroids were observed.

    Recent reports show that, in patients treated with finasteride for male pattern hair loss, persistent side effects including sexual side effects, depression, anxiety and cognitive complaints may occur. We here explored the psychiatric and andrological features of patients affected by post-finasteride syndrome (PFS) and verified whether the cerebrospinal fluid (CSF) and plasma levels of neuroactive steroids (i.e., important regulators of nervous function) are modified.

    We found that eight out of sixteen PFS male patients considered suffered from a DSM-IV major depressive disorder (MDD). In addition, all PFS patients showed erectile dysfunction (ED); in particular, ten patients showed a severe and six a mild-moderate ED. We also reported abnormal somatosensory evoked potentials of the pudendal nerve in PFS patients with severe ED, the first objective evidence of a neuropathy involving peripheral neurogenic control of erection. Testicular volume by ultrasonography was normal in PFS patients.

    Data obtained on neuroactive steroid levels also indicate interesting features. Indeed, decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients. Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF.

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


     
    James23 likes this.
  9. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Long-Term dutasteride Therapy in Men with Benign Prostatic Hyperplasia Alters Glucose and Lipid Profiles and Increases Severity of Erectile Dysfunction

    Background Dutasteride has been successfully used in treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, dutasteride inhibits 5alpha-reductase type 1 and type 2 enzymes and may compromises glucocorticoids and androgen metabolism and alters metabolic function resulting in undesirable metabolic and sexual adverse side effects.

    Aim The aim of this study was to investigate the long-term adverse effects of dutasteride therapy in men with BPH on:
    i) blood glucose,
    ii) glycated hemoglobin (HbA1c),
    iii) low density lipoprotein-cholesterol (LDL-C); high density lipoprotein-cholesterol (HDL-C) and total cholesterol (TC),
    iv) testosterone (T),
    v) liver alanine and aspartate aminotransferases (ALT and AST) and
    vi) erectile dysfunction (ED).

    Methods A retrospective registry study, with a cohort of 230 men aged between 47 and 68 years (mean 57.78 +/- 4.81) were treated with dutasteride (0.5 mg/day) for LUTS, secondary to BPH. A second cohort of 230 men aged between 52 and 72 years (mean 62.62 +/- 4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 36-42 months.

    At intervals of 3-6 months, and at each visit, plasma glucose, HbA1c, TC, LDL-cholesterol, T levels and liver alanine amino transferase (ALT) and aspartate aminotransferase (AST) were determined.

    Further patient assessment was made by the International Index of Erectile Function (IIEF-EF) questionnaire, the Aging Male Symptom (AMS) and International Prostate Symptom Scores (IPSS).

    Results Long-term treatment with dutasteride therapy is associated with significant improvements in LUTS, as assessed by reduction in prostate volume, IPSS and prostate specific antigen (PSA).

    Long-term dutasteride therapy, however, resulted in increased blood glucose, HbA1c, TC and LDL levels, ALT and AST activities, AMS Score and reduced T levels and worsened ED as assessed by the IIEF-EF scores.

    No worsening of ED, glucose, HbA1c, ALT, AST, AMS were observed in men treated with tamsulosin.

    Most importantly, long-term dutasteride therapy resulted in reduction in total T levels, contributing to a state of hypogonadism.

    Conclusion Our findings suggest that long-term dutasteride therapy produces worsening of ED, reduced T levels and increased glucose, HbA1c and alters lipid profiles, suggesting induced imbalance in metabolic function. We strongly recommend that physicians discuss with their patients these potential serious adverse effects of long-term dutasteride therapy prior to instituting this form of treatment.

    Traish A, Haider KS, Doros G, Haider A. Long-term dutasteride therapy in men with benign prostatic hyperplasia alters glucose and lipid profiles and increases severity of erectile dysfunction. Horm Mol Biol Clin Investig. https://www.degruyter.com/view/j/hmbci.ahead-of-print/hmbci-2017-0015/hmbci-2017-0015.xml
     
    Dr JIM likes this.
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    finasteride Drug Safety Alert

    The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a safety alert after receiving reports of depression and, in rare cases, suicidal thoughts in men taking finasteride 1mg. The MHRA has also reminded healthcare professionals that depression is also associated with finasteride 5mg.

    Finasteride drug safety alert. Drug Ther Bull. http://dtb.bmj.com/content/early/2017/08/02/dtb.2017.8.0509
     
    Dr JIM and James23 like this.
  11. holyhead

    holyhead Junior Member

    I have been dealing with it pfs for last year and saw Dr mark Gordon in LA via Tele medicine and have improved mentally on clomid and supplements now on TRT..I didn't get sexual sides but devastating physical sides of massive weight and body changes of fat and fluid..I started in Feb on Clomid and been on his low dose testosterone cypionate since july..I have improved more in last two weeks than since I started..

    Mainly mental sides improve with more energy..Hes very expensive with exhaustive labs but I gave him the dough he's only one that does Tele medicine..All my hormones were back up now but the physical sides won't go back..Like the tissue and receptors are only metabolising a small percent of androgens and that's why they don't..

    NO One seems to know for sure..But the changes in my body and also hair has changed dramatically is disturbing..i weighed 165 for 10 plus years..Now around 220..Wtf
     
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Hematuria and Hematospermia Associated with the Use of finasteride for the Treatment of Androgenic Alopecia: A Case Report

    In this report we address an unusual adverse effect of finasteride (propecia 1 mg tablets) that was associated with painless hematuria and hematospermia in a 38-year-old healthy male during treatment of androgenic alopecia at a dose of 1 mg/day.

    It was found that the bleeding was linked to finasteride use as it occurred 2-3 days after use and stopped upon discontinuation of the drug.

    The patient was subjected to urological examination, laboratory investigations, and radiological imaging to identify the probable cause of bleeding. It appeared the bleeding was most probably of prostatic origin in the absence of obvious underlying pathology.

    The frequency of such unusual bleeding remains to be investigated in large clinical trials to address its exact mechanism, predisposing factors, clinical significance, and potential long-term consequences.

    Fouda AM, Bazeed AM. Hematuria and Hematospermia Associated with the Use of Finasteride for the Treatment of Androgenic Alopecia: A Case Report. Drug Saf Case Rep 2017;4(1):14. Hematuria and Hematospermia Associated with the Use of Finasteride for the Treatment of Androgenic Alopecia: A Case Report
     
    Dr JIM likes this.
  13. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    5α-Reductase Inhibitors and Depression

    The risk of suicide and depression associated to the use of5-[1] reductase inhibitors (5-ARI) and the potential adverse neurological effects of these drugs have long been a concern. A retrospective cohort study has recently been published using linked administrative data for 93,197 66-year-old men or older with lower urinary tract symptoms(LUTS) in Ontario, Canada, who started treatment with a 5-ARI during the study period (2003---2013). The authors found, using more precise methods than in any previous research, a clear association between 5-ARI prescription and some negative mental health outcomes.



    In conclusion, the recognition of depression and self-injury as possible effects of 5-ARI is important given its significant impact. However, the relatively small magnitude of these risks should not deter physicians from prescribing these drugs in appropriate patients, since the potential benefits of 5-ARI outweigh these risks in most cases. How-ever, we should advise patients on the risks of 5-ARI. 5-ARIsuspension may be appropriate in the context of the new onset of depression or self-injury after initiation of treatment, especially in patients with no history of depression.

    Alcantara Montero A. 5α-reductase inhibitors and depression. Actas Urológicas Españolas (English Edition). https://www.sciencedirect.com/science/article/pii/S2173578617301518
     
    James23 likes this.
  14. Dr JIM

    Dr JIM Member

    And such an occurrence is RARE from any drug IME
     
  15. ulfbehrt

    ulfbehrt Member

    Well I was going to try this stuff one day, but after reading all this NOPE lol. I'm not bald, but shit is thinning from 20 years of running gear......but that's ok with me. Besides plenty of ladies out there like us older, hardened fellas ;)
     
    James23 likes this.
  16. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Gupta AK, Carviel J, Gupta MA, Shear NH. Assessing dutasteride-associated sexual dysfunction using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). J Eur Acad Dermatol Venereol 2017. Assessing dutasteride‐associated sexual dysfunction using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)

    BACKGROUND: Incidences of sexual dysfunction due to the use of 5 alpha-reductase inhibitors have been suggested. Despite low sexual dysfunction reported in clinical trials, an analysis of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database revealed a significant disproportionality in the reporting of sexual dysfunction with the use of finasteride. Therefore, it is likely that a similar relationship with dutasteride may exist.

    OBJECTIVE: To determine whether dutasteride use leads to a higher risk of sexual dysfunction compared to a baseline risk for all other drugs using the FAERS database.

    METHODS: A case by non-case disproportionality approach was used whereby a Reporting Odds Ratio (ROR) with 95% confidence interval (CI) was calculated. Cases of dutasteride-associated sexual dysfunction were compared to a reference risk of sexual dysfunction for all other drugs in the database.

    RESULTS: A significant disproportionality in reporting of sexual dysfunction with the use of dutasteride was observed. The disproportionality was present for all age ranges except for 31-45 years where there were few overall reports of adverse events.

    LIMITATIONS: Adverse events can be underreported and selection bias is inherent in the FAERS.

    CONCLUSION: Dutasteride use is associated with an increase in reports of sexual dysfunction.
     
    James23 likes this.
  17. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Traish AM. Negative Impact of testosterone Deficiency and 5alpha-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men. Advances in experimental medicine and biology 2017;1043:473-526. Negative Impact of Testosterone Deficiency and 5α-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men

    Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent metabolite 5alpha-dihydrotestosterone (5alpha-DHT) or via aromatization into estradiol (E2) modulates important biochemical signaling pathways of human physiology and plays a critical role in the growth and/or maintenance of functions in a host of tissues and organs. T and 5alpha-DHT play an important role in regulating physiology of the muscle, adipose tissue, liver, bone, and central nervous system, as well as reproductive and sexual functions. Thus, androgen deficiency (also referred to as hypogonadism) is a well-recognized medical condition and if remained untreated will have a negative impact on human health and quality of life.

    In this chapter, we have summarized the negative impact of T deficiency (TD) on a host of physiological functions including reduced lean body mass (LBM), increased fat mass (FM), increased insulin resistance (IR), metabolic syndrome (MetS) and adiposity, reduced bone mineral density (BMD), anemia, sexual dysfunction, and reduced quality of life and increased mortality. In addition, we discuss another critical aspect of unrecognized form of androgen deficiency resulting from inhibition of 5alpha-reductases with drugs, such as finasteride and dutasteride, to block transformation of T into 5alpha-DHT in the course of treatment of benign prostatic hyperplasia (BPH) and male pattern hair loss, also known as androgenetic alopecia (AGA). The negative impact of drugs that inhibit transformation of T to 5alpha-DHT by 5alpha-reductases on metabolic function is manifested in fat accumulation in the liver, which may predispose to nonalcoholic fatty liver disease (NAFLD). Also, inhibition of 5alpha-DHT formation increases glucose synthesis and reduces glucose disposal potentially contributing to hyperglycemia, IR, and elevated activities of liver function enzymes concomitant with reduction in circulating T levels, worsening erectile dysfunction (ED), and reduced quality of life.

    Although we have attempted to summarize the current literature pertaining to this critical topic "androgen deficiency" and its impact on men's health and quality of life, there remain many gaps in the knowledge regarding the biochemical pathways that are involved in the pathophysiology of androgen deficiency. We wish to clearly state that there are areas of controversies, including whether age-related androgen deficiency (functional hypogonadism) merits treatment and whether T therapy provided real proven benefits. Finally, considerable debate exists with respect to the potential and purported cardiovascular (CV) risks of treating TD with exogenous T. For brevity sake, we will not discuss in detail the benefits of T therapy in men with TD since this topic is comprehensively covered by Dr. F. Saad's chapter in this book, entitled "Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency (Hypogonadism)."

    We have made a concerted effort to address the controversy of T therapy in men with TD in the discussion. However, we wish to acknowledge that these issues will remain a matter of debate for some time to come. Only with advances in fundamental basic science and clinical research, some of these controversial issues may be laid to rest. Nevertheless, we believe that there is considerable body of credible evidence to suggest that T therapy of men with TD is safe and effective and provides a host of health benefits and therefore merits considerations in men with TD, irrespective of the underlying cause or etiology. An additional aspect of androgen deficiency is the drug-induced reduction in 5alpha-DHT levels by the use of 5alpha-reductase inhibitors. We also believe that physicians prescribing 5alpha-reductase inhibitors (i.e., finasteride or dutasteride) for relief of BPH symptoms or treatment of hair loss should engage their patients in a productive discussion regarding the potential adverse side effects of these medications on their overall health and quality of life.
     
  18. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    finasteride Treatment and Male Breast Cancer

    A potential link has been suggested between dispensed finasteride and increased risk of male breast cancer (MBC). Due to the rare occurrence of MBC, it remains to be established if such a relationship exists. The purpose of this study was to combine nationwide registers in four countries to assess the potential association between dispensed finasteride and MBC.

    A cohort of all males with dispensed finasteride in Denmark, Finland, Norway, and Sweden (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males unexposed to finasteride. Individual-level register data included country, dates of dispensed finasteride, MBC diagnosis, and death. Incidence rate ratios (IRRs) were estimated using a generalized linear model with a Poisson distribution.

    An increased risk of MBC was found among finasteride users (IRR = 1.44, 95% confidence interval [95% CI] = 1.11-1.88) compared to nonusers. The IRR increased to 1.60 (95% CI = 1.20-2.13) when users in Norway and Sweden with short follow-up time were excluded. The highest IRR was seen among men with medium duration of dispensed finasteride, medium accumulated consumption of finasteride, and among men with first dispensed finasteride prescription 1-3 years prior to diagnosis. The analyses suggested possible ascertainment bias and did not support a clear relationship between dispensed finasteride and MBC.

    In conclusion, a significant association between dispensed finasteride and MBC was identified. However, due to limited data for adjustment of potential confounding and surveillance bias in the present study, further research is needed to confirm these results.

    Meijer M, Thygesen LC, Green A, et al. Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries. Cancer medicine 2017. Finasteride treatment and male breast cancer: a register‐based cohort study in four Nordic countries
     
  19. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Research Brief: Self-Reports of a Constellation of Persistent Antiandrogenic, Estrogenic, Physical, and Psychological Effects of finasteride Usage

    Our research objective is to understand more, through subjective, self-reports on discussion boards/forums, persons' experiences associated with the use of drugs that alter androgen metabolism, such as finasteride. Finasteride is an orally active, specific inhibitor of 5alpha-reductase, which is localized to many androgen-dependent tissues. Finasteride inhibits the conversion of testosterone (T) to dihydrotestosterone (DHT), and is commonly used to treat benign prostatic hypertrophy (BPH) and male pattern baldness (MPB), both disorders associated with elevated DHT levels and 5alpha-reductase activity in the prostate and hair follicles, respectively.

    It is now acknowledged that long-term use and discontinuation of finasteride has adverse effects (AEs); however, these claims have not been well documented. In this study, discussion board posts (forums) were analyzed as self-reports of what finasteride users indicate is problematic for them. Reports were categorized by the age of subjects as well as the types of AEs described: antiandrogenic, estrogenic, central, and nonspecific/severe.

    A total of 244 cases were recorded and analyzed on the discussion forum on propeciahelp.com. Among these, 74 (32%) cases reported antiandrogenic affects, 43 (19%) reported estrogenic effects, 70 (30%) reported central effects, 11 (5%) reported nonspecific/severe AEs, and 31 (14%) reported AEs in all categories. The categorization of AEs may prompt further investigation into the pathophysiology of post-finasteride syndrome (PFS). Also, subjective reports may engender greater understanding of the perceived lasting AEs of finasteride.

    Walf AA, Kaurejo S, Frye CA. Research Brief: Self-Reports of a Constellation of Persistent Antiandrogenic, Estrogenic, Physical, and Psychological Effects of Finasteride Usage Among Men. American journal of men's health. 2018. SAGE Journals: Your gateway to world-class journal research
     
  20. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Symptoms of Hypogonadism Caused By 5α-Reductase Inhibitors

    Hypogonadism causes libido loss, body hair loss, mood depression, muscle volume reduction, and hot flashes. These symptoms can be due to lack of testosterone secretion from the testes or of testosterone action in target organs. 5α-reductase inhibitors (5-ARIs), often contained in hair growth-promoting agent, are known not to cause hypogonadism because they reduce dihydrotestosterone and do not decrease total testosterone (TT).

    We here report a patient with strong cold sensation and paresthesia of lower extremities and hypogonadism caused by 5-ARIs taken orally. A 28-year-old man visited our hospital with fatigue and strong cold sensation and paresthesia of lower extremities. He was taking 2 tablet-types of 5-ARIs. The one was finasteride (1 mg/day), an imported medicine for personal use, and the other was saw palmetto (fruit extract 320 mg/day), an over-the-counter drug in Japan.

    Laboratory testing revealed TT, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels of 160 ng/dL, 2.4 mIU/mL and 8.4 mIU/mL, respectively. We diagnosed hypogonadism due to a lack of testosterone secretion. Eight days after discontinuing both drugs, TT, FSH and LH levels improved to 404 ng/dL, 2.3 mIU/mL and 5.1 mIU/mL, and his symptoms improved completely in a month.

    Physicians should consider 5-ARIs as a cause of cold sensation and paresthesia of lower extremities and carefully check every ingested drug including imported and over-the-counter drugs.

    Maita H, Kobayashi T, Osawa H, Hirano T, Kato H (2017) Symptoms of Hypogonadism Caused By 5α-Reductase Inhibitors. Int J Fam Commun Med 1(3): 00016. http://medcraveonline.com/IJFCM/IJFCM-01-00016.php
     
Tags: