Benutzer:Brainbug666/PFSeng
The post-finasteride syndrome (PFS)[1][2] describes persistent sexual, neurological, and physical adverse reactions in patients who have taken finasteride, a 5-alpha reductase enzyme type I and II inhibitor[3] used to treat hair loss (under the brand name Propecia or generics) or enlarged prostate (Proscar or generics).[1][4] This presumably rare condition may persist for months to years even though the medication has been discontinued, in most cases the damage may be permanent.[1][4][5][6][7][8][9][10] The syndrome can result both after very short periods of intake or after many years of use.[11]
Symptoms
PFS include the following symptoms:
- Decrease or complete loss of libido [4][5][7]
- no reaction or decreased reaction to sexual stimuli [4][5][6][7]
- Erectile dysfunction, impotence[4][5][6][7][10][12]
- Sexual anhedonia, loss of pleasurable orgasm or complete loss of orgasm (anorgasmia)[4][5][6][7]
- Genital anesthesia[10]
- Decreased ejaculation volume, poor semen quality and infertility[5]
- Penile shrinkage[7][8][13][14]
- Curvature of penis (Peyronie‘s disease)[7]
- Testicular pain[5][6][7][10]
- Testicular shrinkage[7] and insensitivity of the scrotum
- Gynecomastia[5][8][10]
- Chronic fatigue (lethargy and listlessness)[11]
- Muscle weakness, atrophy and twitches[11]
- Dry skin
- Amnesia (disorder of short-term and long-term memory)[4][7]
- Slowed thought processes, impaired comprehension[4][7][10]
- Depression,[4][5][6][10] including suicidal depression[9][15][16][17]
- Anxiety disorder and panic attacks[11]
- Emotional flatness and anhedonia[4][6]
- Insomnia[4][11]
Often the symptomatology worsen after the discontinuation.[1][4][7]
Frequency
The frequency of PFS is not known,[4][10] but the incidence rate must be considered as low. However, due to the large number of persons using finasteride worldwide, the number of cases is at least in the thousands.[7] After previous label changes in Europe, on April 11 2012, the FDA mediated a label change in the United States which now includes libido disorders, ejaculation disorders, and orgasm disorders and possible male infertility that continue after discontinuation of the drug.[18] Further studies are demanded from science and patients.[1][4][7][10][19]
Causes
The cause of PFS is currently still unknown.[4][7][6][10] Finasteride inhibits the conversion of testosterone to DHT, but it also changes the levels of testosterone, LH and FSH. [20] The biosynthesis of DHT and various neurosteroids such as Allopregnanolone (ALLO) and Tetrahydrodeoxycorticosterone (THDOC), are dependent on known isoforms of 5α-reductase. They are positive allosteric modulators of GABAA receptors, which have the same mechanism (of action) of euphoric and anxiolytic drugs, such as Benzodiazepines. [17][21] It was shown that finasteride prevents their biosynthesis and, hence,[17][22] this effect is one of the possible causes of the emotional and sexual side effects.[15][17] However, some symptoms, such as muscle wasting, loss of body hair and the permanent side effects long after discontinuing the medication cannot fully be explained. Since some patients have normal to high testosterone levels - while at the same time presenting the clinical picture of hypogonadism - it is supposed that these patients have become resistant to androgens.[11]
Other potential consequences
The FDA has announced that finasteride may raise the chances of developing high-grade prostate cancer, a more serious form of the disease.[23][24]
Therapy
Currently, there is no effective therapy to generally treat PFS since its exact cause is still unknown.[4][7] Affected patients often do not react well to androgen supplementation. In some cases, they even show a negative reaction and worsening of symptoms. PFS patients also often do not respond well to antidepressant therapy.[7]
Public interest
In the United States media interest on regarding PFS has increased due to the coming out of affected patients and legal action taken against the manufacturer.[25][26][27][28][29] Recently, a PFS patient and the parents of Propecia suicide victim conducted a hunger strike in front of Merck headquarter.[30] Certain scientists and doctors publically have issued warnings regarding the potential of long term or permanent health damage arsing from 5AR inhibitor use.[4][7][10] To name a few:
Michael Irwig (George Washington University), AM Traish (Boston University), Irwin Goldstein (chief editor of the journal of sexual medicine), Eugene Shippen (author of the book "The Testosterone Syndrome"), M. Zitzmann (University Münster,Germany), A. Jacobs (neuroendocrinologist, New York), John Crisler, (Director, All Things Male - Center for Men's Health)
The Post-Finasteride Syndrome Foundation
In August 2012 the Post-Finasteride Syndrome Foundation (PFS Foundation), headquartered in the United States, was founded. Its objectives are to help fund research on the characterization, underlying biologic mechanisms and treatments of the post-finasteride syndrome. A secondary goal is to help increase public awareness of PFS.[31]
External links
References
- ↑ a b c d e Clinical analysis in young patient with persistent sexual dysfunctions after finasteride assumption to prevent male pattern hair loss, Author(s): Trombetta, C.; Mazzon, G.; Liguori, G.; Ollandini, G.; Cauci, S.; Toffoli, G.; Erika, E. Journal Title: European Urology - Supplements ISSN: 1569-9056
- ↑ F. La Marra, C. Di Loreto, G. Mazzon, G. Chiriacò, C. Trombetta, S. Cauci: Preliminary Evidence of a Peculiar Hormonal Profile in Men with Adverse Effects After Use of Finasteride Against Androgenetic Alopecia. In: AJP, September 2012, Vol. 181, Suppl.
- ↑ Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride, Yamana, Kazutoshi; Labrie, Fernand; Luu-The, Van, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: 10.1515/hmbci.2010.035, 8/ 2010
- ↑ a b c d e f g h i j k l m n o p q An Old Problem with a New Cause—5 Alpha Reductase Inhibitors and Persistent Sexual Dysfunction Irwin Goldstein MD Editor-in-Chief, DOI: 10.1111/j.1743-6109.2011.02368.x Referenzfehler: Ungültiges
<ref>-Tag. Der Name „An Old Problem with a New Cause—5 Alpha Reductase Inhibitors and Persistent Sexual Dysfunction“ wurde mehrere Male mit einem unterschiedlichen Inhalt definiert. - ↑ a b c d e f g h i Propecia leaflet, Merck
- ↑ a b c d e f g h Michael S. Irwig, Swapna Kolukula: Persistent Sexual Side Effects of Finasteride for Male Pattern Hair Loss. In: The Journal of Sexual Medicine
- ↑ a b c d e f g h i j k l m n o p q r Persistent Sexual Side Effects of Finasteride: Could They Be Permanent? Michael S. Irwig MD Article first published online: 12 JUL 2012
- ↑ a b c 5α-Reductases in Human Physiology: An Unfolding Story,Abdulmaged M. Traish, PhD, MBA
- ↑ a b Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride With Persistent Sexual Side Effects, Michael S. Irwig, MD
- ↑ a b c d e f g h i j k Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. fulltext
- ↑ a b c d e f The Journal of Sexual Medicine: Special Issue: PROCEEDINGS OF THE WORLD MEETING ON SEXUAL MEDICINE, CHICAGO, USA, AUGUST 26-30 2012
- ↑ Incomplete recovery of erectile function in rat after discontinuation of dual 5-alpha reductase inhibitor therapy. Oztekin CV, Gur S, Abdulkadir NA, Lokman U, Akdemir AÖ, Cetinkaya M, Hellstrom WJ.
- ↑ Effect of androgen deprivation on penile ultrastructure, Zhou-Jun SHEN1, Xie-Lai ZHOU, Ying-Li LU, Zhao-Dian CHEN
- ↑ A. M. Traish, P. Toselli u. a.: Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency. In: Journal of andrology. Band 26, Nummer 2, 2005 Mar-Apr, S. 242–248, ISSN 0196-3635. PMID 15713830.
- ↑ a b A new look at the 5alpha-reductase inhibitor finasteride. Finn DA, Beadles-Bohling AS, Beckley EH, Ford MM, Gililland KR, Gorin-Meyer RE, Wiren KM.
- ↑ Finasteride induced depression: a prospective study. Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A.
- ↑ a b c d Römer B, Gass P: Finasteride-induced depression: new insights into possible pathomechanisms. In: Journal of Cosmetic Dermatology. 9, Nr. 4, Dezember 2010, S. 331–2. doi:10.1111/j.1473-2165.2010.00533.x. PMID 21122055.
- ↑ April 2012 – FDA Mandates New Safety Labeling Changes for Propecia, Proscar
- ↑ The Effects of Chronic 5-Alpha-Reductase Inhibitor (Dutasteride) Treatment on Rat Erectile Function, Michael R. Pinsky MD, Serap Gur PhD, Anthony J. Tracey MD, Andrew Harbin MD, Wayne J.G. Hellstrom MD, FACS* DOI: 10.1111/j.1743-6109.2011.02425.x
- ↑ Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of gonadal, adrenal, and hypophyseal hormones and its clinical significance: a prospective clinical study. Uygur MC, Arik AI, Altuğ U, Erol D.
- ↑ Gunn BG, Brown AR, Lambert JJ, Belelli D: Neurosteroids and GABA(A) Receptor Interactions: A Focus on Stress. In: Frontiers in Neuroscience. 5, 2011, S. 131. doi:10.3389/fnins.2011.00131. PMID 22164129. PMC 3230140 (freier Volltext).
- ↑ Vermeulen A, Giagulli VA, De Schepper P, Buntinx A, Stoner E: Hormonal effects of an orally active 4-azasteroid inhibitor of 5 alpha-reductase in humans. In: The Prostate. 14, Nr. 1, 1989, S. 45–53. PMID 2538808.
- ↑ Finasteride (Propecia) and the Promotion of High-Grade Prostate Cancer W.R. Pitts, Jr. [Archives of Dermatology 2004;140:885–886]
- ↑ FDA Drug Safety Communication: 5-alpha-reductase-inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer, 9. Juni 2011; [1]
- ↑ Merck Propecia Side Effects Class Action Lawsuit By Matt O’Donnell
- ↑ Hair-Raising Side Effect It’s a common baldness remedy, but its side effects may be more than you—or your girlfriend—can handle: Men’s Health
- ↑ The Australian Financial Review: Looking at care with a critical eye, PUBLISHED: 26 Sep 2012
- ↑ FrenchTribune: Medication Can Cause Sexual Side-Effects, says study, 09/28/2012
- ↑ Sydney Morning Herald: Hair-loss drug a downer in the bedroom, Sept. 27, 2012
- ↑ The Australian Financial Review: Hair-loss therapy accused of link to impotence, PUBLISHED: 26 Sep 2012
- ↑ Foundation Launches Website to Fund Research into the Post-Finasteride Syndrome, Source: 26. August 2012.PFS Foundation
{{DEFAULTSORT:Post-finasteride syndrome}} [[Category:Medical terms]] [[Category:Pharmacology]] [[Category:Patient safety]] [[Category:Effects of external causes]] [[Category:Mammal reproductive system]] [[Category:Sexual disorders]] [[Category:Human sexuality|Disorders]] [[Category:Sexual health|Disorders]] [[Category:Diseases and disorders by system]] [[Category:5-alpha-reductase inhibitors]] [[Category:Depressogenics]] [[Category:Steroids]] [[Category:Medicinal chemistry]] [[Category:Enzyme inhibitors]] [[Category:Patient safety| ]] [[Category:Medical treatments]]
