Persistent adverse effects of finasteride which may be irreversible

If you are considering taking finasteride, see this page: Advice from peers on taking finasteride for hair loss

The following is from a 2019 systematic review in one of the top dermatology journals, Journal of the American Academy of Dermatology:

…[S]ome studies describe a subset of patients with persistent adverse effects after discontinuation [of finasteride]. Three studies identified in this review describe complete reversibility of sexual dysfunction in all patients, but 11 studies describe patients experiencing irreversible adverse effects.

In Zakhem GA et al. Sexual dysfunction in men taking systemic dermatologic medication: A systematic review. J Am Acad Dermatol. 2019;81(1):163-172. doi:10.1016/j.jaad.2019.03.043. PMID:30905792

A growing body of evidence suggests that taking finasteride (or discontinuing it) can result in sexual, physical and/or neuropsychiatric symptoms which may persist for years after discontinuation and may be irreversible.1 

The most common sexual symptoms are numb penis, loss of libido, low volume of semen and altered consistency of semen. Presentation of other symptoms varies considerably across individuals. (These symptoms have also been reported after taking other 5-alpha reductase inhibitors such as dutasteride and saw palmetto extract.)

Some men appear initially to tolerate finasteride, with adverse effects arising weeks, months or years after starting the drug. After discontinuation, adverse effects may remain, worsen or resolve. New adverse symptoms may also arise. There have been reports of persistent symptoms being triggered by as little as a single 0.25 mg dose of finasteride (one-quarter of the standard dose).

Patients and clinicians should distinguish between adverse symptoms observed while taking the drug, conditions immediately after discontinuation, and adverse symptoms that persist beyond three months after discontinuation. 

PhaseInterpretation of adverse effects
While taking finasterideAdverse effects of finasteride circulating in the body
0–3 months after discontinuationAcute post-withdrawal phase. Adverse symptoms reflect the body’s attempt to adapt to changes induced by the drug and withdrawal from it. The half-life of finasteride is five to six hours.2
3 months after discontinuation and beyondPost-drug syndrome. If symptoms remain after three months following discontinuation, the body has been unable to restore neuroendocrine/metabolic conditions prior to taking finasteride. Such symptoms are resistant to treatment and may be irreversible.

The syndrome does not appear to reflect “persistent side effects” of finasteride, but rather an iatrogenic disorder arising from the body’s response to disturbances in neuroendocrine and metabolic conditions, playing out long after finasteride would have been excreted.

Symptoms

Sexual function
Low libido
Genital anesthesia (numb penis)
Lack of nocturnal, morning and spontaneous erections
Low semen volume
Watery consistency of semen
Reduced ejaculatory force
Post-orgasm exhaustion / long refractory period 
Sexual anatomy
Penile fibrosis, atrophy and deformation (e.g. curvature)
Peyronie’s disease
Testicle shrinkage
Testicular pain
Gynecomastia 


Neuropsychiatric
Anxiety
Panic
Anhedonia / blunted affect
Depersonalization/derealization
Listlessness
Tinnitus
Vertigo
Lowered sensitivity to, and preference for, alcohol and drugs  
Sleep
Insomnia
Reduced duration of REM sleep
Night sweats





Dermatological
Dry, thin skin
Dry, brittle hair
Dry eye
Gum recession
Loss of skin sensitivity
Musculoskeletal
Muscle weakness and atrophy
Joint pain


Cognitive (from Ganzer et al., 2015)
Memory/recall impairment
Slowed thought processes
Impaired problem solving
Mental cloudiness or brain fog
Confusion
Attentional difficulties

Sources: Compiled from working group member experiences, critical review of social media posts, private correspondence, published literature and FDA FAERS reports. Symptom presentation varies widely across individuals.

Prognosis

The prognosis of whether adverse events following discontinuation will persist long-term is unknown. The figure shows three outcomes: recovery, partial recovery and no recovery. Patient discussions have converged on a guideline that if symptoms persist beyond three to six months, they may not resolve in the long-term.

Outcomes: recovery, partial recovery or no recovery
Figure. Outcomes after discontinuation of finasteride

Treatment

There is no effective treatment for adverse effects that persist beyond six months after stopping finasteride. There have been scattered, unverified reports of recovery from HCG injections and Proviron, along with many other reports of men who had no success with these treatments. Testosterone replacement therapy does not appear to be a successful treatment.

SSRI and SNRI-class antidepressants are not recommended because of the potential for short-term and persistent sexual adverse effects.

Pathophysiology

Pathophysiology of PFS is unknown. Studies have reported altered levels of neurosteroids and methylation of the SRD5A2 gene in patients with persistent adverse effects of finasteride (see especially work by Melcangi and colleagues in the bibliography).

References

1. See:

Diviccaro S, Melcangi RC, Giatti S. Post-finasteride syndrome: An emerging clinical problem. Neurobiol Stress. 2019;12:100209. doi:10.1016/j.ynstr.2019.100209 | PubMed

Kiguradze T, Temps WH, Yarnold PR, Cashy J, Brannigan RE, Nardone B, Micali G, West DP, Belknap SM. Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride. PeerJ. 2017;5:e3020. doi:10.7717/peerj.3020 | PubMed

Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertility and Sterility. 2020 Jan;113(1):21-50. doi:10.1016/j.fertnstert.2019.11.030 | PubMed

Zakhem GA, Goldberg JE, Motosko CC, Cohen BE, Ho RS. Sexual dysfunction in men taking systemic dermatologic medication: A systematic review. J Am Acad Dermatol. 2019;81(1):163-172. doi:10.1016/j.jaad.2019.03.043 | PubMed

See also: Bibliography: Persistent adverse effects & ‘post-finasteride syndrome’

2. Merck & Co., Inc. Prescribing information for Propecia.