Persistent adverse effects of finasteride which may be irreversible

If you are considering taking finasteride, see: Weighing the risks of taking finasteride for hair loss

A growing body of evidence has shown that in some men, taking and discontinuing finasteride has led to impairments in sexual, mental and physical function which may persist for years after discontinuation and may be irreversible.1-5 A 2019 systematic review reported that 11 of 14 studies on reversibility described patients experiencing “irreversible adverse effects” after discontinuing finasteride.6 In 2021, an international group of doctors and researchers published diagnostic criteria for post-finasteride syndrome.7

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.8
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 be conventional “side effects,” but rather a disorder emerging from treatment and discontinuation, which does not typically respond to treatment and may be irreversible.

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 adverse events reported to US FDA, selected social media posts, private correspondence and published literature. Symptom presentation and course vary 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. In discussions among former users of finasteride, a guideline has emerged 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 has not been determined, but recent research has focused on the following interrelated hypotheses:

  1. Altered levels of neuroactive steroids, possibly resulting from altered expression of neurosteroidogenic enzymes9-11
  2. Altered function of brain receptors such as GABA and NDMA9-12
  3. Dysregulation of seritonergic and dopaminergic signaling10,12
  4. Alterations in gene expression including overexpression of androgen receptor.2

References

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

2. Howell S, Song W, Pastuszak A, Khera M. Differential Gene Expression in Post-Finasteride Syndrome Patients. J Sex Med. 2021 Sep. doi:10.1016/j.jsxm.2021.05.009PubMed

3. 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. doi:10.7717/peerj.3020 • PubMed

4. Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertility and Sterility. 2020 Jan. doi:10.1016/j.fertnstert.2019.11.030 • PubMed

5. More papers in Bibliography: Persistent adverse effects & ‘post-finasteride syndrome’

6. 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. doi:10.1016/j.jaad.2019.03.043 • PubMed

7. Healy D, Bahrick A, Bak M, et al. Diagnostic Criteria for Enduring Sexual Dysfunction after Treatment with Antidepressants, Finasteride and Isotretinoin. Int J Risk Saf Med. 2021 Oct 26. doi:10.3233/JRS-210023

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

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

10. Giatti S, Diviccaro S, Panzica G, Melcangi RC. Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin? Endocrine. 2018. doi:10.1007/s12020-018-1593-5 • PubMed

11. Giatti S, Foglio B, Romano S, et al. Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain. Neuroendocrinology. 2016. doi:10.1159/000442982 • PubMed

12. Saengmearnuparp T, Lojanapiwat B, Chattipakorn N, Chattipakorn S. The connection of 5-alpha reductase inhibitors to the development of depression. Biomed Pharmacother. 2021 Aug 31. doi:10.1016/j.biopha.2021.112100 • PubMed • Full text via ScienceDirect