Post-Finasteride Syndrome
Definition and Symptoms
Understanding PFS
DEFINITION
Post-Finasteride Syndrome (PFS) is a term used to describe a complex of symptoms with persistent sexual, neurological, mental, and physical side effects in patients who usually have taken treatment for hair loss, such as Finasteride (marketed under the brand name Propecia or generics) or for enlarged prostate (marketed under the brand name Proscar or generics).
MECHANISM
The body converts testosterone to a much more potent androgen, dihydrotestosterone (DHT). This hormone is responsible for various processes involved in physical and sexual maturation. During embryonic life, it is responsible for the sexual differentiation into the male phenotype, during puberty it is facilitating the growth of facial and pubic hair of the male phenotype [1]. In addition, DHT is involved in the genesis of neurosteroids in the brain [2].
Neurosteroids have an important function in brain protection [3], regulation of sexuality [4], [5], [6], and social behavior [6]. Low levels of certain neurosteroids have been associated with depression [7], [8] anxiety [9], and cognitive decline [10], [11].
In addition to its beneficial effects, DHT is also known to be responsible for causing male pattern baldness.
The enzyme that converts DHT into testosterone called 5 alpha-reductase (5AR). Finasteride blocks this conversion by inhibiting the 5AR [3].
Why did we choose George Barreto's research project as first research project?
It is known that finasteride could be responsible for various physical, neuronal, and sexual side effects. It is however less known that these side effects could persist after discontinuation of treatment. Multiple lines of evidence indicate that finasteride can induce a syndrome of sexual, physical and/or neuropsychiatric symptoms which may persist after discontinuation [4].
The syndrome has been reported also in association with other substances such as dutasteride, saw palmetto extract and minoxidil [5]. Due to the similarity of symptoms and disease onset, PFS is very likely to be the same disease as the post-SSRI sexual dysfunction syndrome (PSSD) and the post-accutaneous syndrome (PAS). [6]
Despite the severity of the syndrome, not enough research has been conducted to understand the underlying biomolecular mechanism of PFS that contributes to the onset and persistence of the disease.
DIAGNOSTIC & SYMPTOMS
Blood markers are usually within the normal ranges. By consequence, there are no known and valid markers for the moment to screen the disease.
In addition, the risk of getting the syndrome is impossible to predict as the incidence of the syndrome is unknown.
Reported cases are usually males between 18 and 50 years old. But older patients with PFS and even female cases have been already reported. It is also important to notice that persistent symptoms appear usually after discontinuation or re-administration. irregular drug intake – various discontinuations and/or dosage variation could be involved in the molecular mechanism. However, it cannot be taken as a general rule as cases of PFS have been reported after only one pill intake as well as after several years of use without any previous issues.
There is a wide range of symptoms that differ from patient to patient and vary in severity.
- Erectile dysfunction
- Low libido
- Reduced frequency of sexual intercourse
- Genital anaesthesia (numbness in the penis)
- Lack of nocturnal, morning and spontaneous erections
- Low semen volume
- Watery consistency of semen
- Reduced ejaculatory force
- Post-orgasm exhaustion / long refractory period
- Unfullfilling sexual intercourse
- Anxiety
- Panic attacks
- Anhedonia
- Blunted emotions
- Absent desire for social interaction
- Loss of desire for proximity
- Depersonalization/derealization
- Memory impairment
- Word finding difficulties and losing track of thoughts
- Listlessness
- Tinnitus
- Vertigo
- Lowered or complete absense of any response to alcohol and drugs
- Headache
- Gynecomastia
- Muscle weakness and atrophy
- Muscle twichting and fasciculation
- Dry, thin skin
- Dry, brittle hair
- Stop of hairloss after finasteride discontinuation
- Dry eye, dry mouth
- Joint pain
- Gum recession
- Belly pain
- Gastrointestinal complaints
- Osteoporosis
SCIENTIFIC RESEARCH
Little is known about the mechanisms. Therefore more research is urgently needed.
Indeed, it is necessary to understand the pathomechanism of the disease to develop a treatment.
It is known that there is an upregulation in androgen receptors in the penile tissue of PFS patients even years after discontinuation of finasteride [7], that there are changes in the microbiome [8], methylation of the gene that codes for the 5AR II in the cerebrospinal fluid [9], changes in neurosteroids and sex hormones in the cerebrospinal fluid [10], and penile vascular changes [11].
It is not yet proven whether the symptoms are caused by finasteride itself or by the withdrawal of the medication.
Numbers are issued and regularely updated from The World Health Organization Programme for International Drug Monitoring’s database of adverse drug reactions (ADRs).
- Kinter KJ, Anekar AA. Biochemistry, Dihydrotestosterone. [Updated 2020 Apr 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. https://www.ncbi.nlm.nih.gov/books/NBK557634/
- Melcangi RC et al, Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. The Journal of Steroid Biochemistry and Molecular Biology, Volume 171, 2017, Pages 229-235, ISSN 0960-0760. https://doi.org/10.1016/j.jsbmb.2017.04.003
- Marks LS. 5alpha-reductase: history and clinical importance. Rev Urol. 2004;6 Suppl 9(Suppl 9):S11-21. PMID: 16985920; PMCID: PMC1472916.PMCID: PMC1472916. | Pubmed
- Abdulmaged M. Traish, Post-finasteride syndrome: a surmountable challenge for clinicians, Fertility and Sterility, Volume 113, Issue 1, 2020, Pages 21-50, ISSN 0015-0282, https://doi.org/10.1016/j.fertnstert.2019.11.030.
- Propecia Help
- Finasteride FYI
- Silvia Diviccaro, Roberto Cosimo Melcangi, Silvia Giatti, Post-finasteride syndrome: An emerging clinical problem, Neurobiology of Stress, Volume 12, 2020, 100209, ISSN 2352-2895, https://doi.org/10.1016/j.ynstr.2019.100209.
- Borgo F, Macandog AD, Diviccaro S, Falvo E, Giatti S, Cavaletti G, Melcangi RC. Alterations of gut microbiota composition in post-finasteride patients: a pilot study. J Endocrinol Invest. 2020 Sep 19. doi: 10.1007/s40618-020-01424-0. Epub ahead of print. PMID: 32951160. |Pubmed
- Melcangi RC, Casarini L, Marino M, Santi D, Sperduti S, Giatti S, Diviccaro S, Grimoldi M, Caruso D, Cavaletti G, Simoni M. Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study. Endocr Connect. 2019 Aug 1;8(8):1118-1125. doi: 10.1530/EC-19-0199. PMID: 31272082; PMCID: PMC6652249. | Pubmed
- Melcangi RC, Santi D, Spezzano R, Grimoldi M, Tabacchi T, Fusco ML, Diviccaro S, Giatti S, Carrà G, Caruso D, Simoni M, Cavaletti G. Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. J Steroid Biochem Mol Biol. 2017 Jul;171:229-235. doi: 10.1016/j.jsbmb.2017.04.003. Epub 2017 Apr 10. PMID: 28408350. | Pubmed
- Khera M, Than JK, Anaissie J, Antar A, Song W, Losso B, Pastuszak A, Kohn T, Mirabal JR. Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia. Transl Androl Urol. 2020 Jun;9(3):1201-1209. doi: 10.21037/tau.2020.03.21. PMID: 32676403; PMCID: PMC7354335. | Pubmed