If you are considering taking finasteride, see: Weighing the risks of taking finasteride for hair loss
KEY POINTS
Abbreviation: LD5, lasting dysfunctions after use and discontinuation of 5-alpha reductase inhibitors (finasteride, dutasteride and saw palmetto)
This is a working draft. It is not medical advice.
- LD5 is not a psychogenic condition, male hypogonadism (low testosterone) or “persistent side effects.”
- The most common dysfunctions are in these domains (roughly in order of frequency): sexual, neuropsychiatric, cognitive, energetic, musculoskeletal, sleep-related and sensory (affecting the eyes and vestibular system). Skin may also be affected.
- In the sexual domain, severe loss of libido and genital numbness are common.
- Sexual dysfunction arises, at least in part, from drug-emergent abnormalities of the penis including fibrosis and loss of smooth muscle.
- The nature, severity and course of dysfunctions are highly variable across individuals.
- LD5 has a phased course, roughly consisting of an acute phase after drug discontinuation (lasting a few months), an adjustment phase (up to one year) and a chronic phase (lasting years and possibly indefinite).
- There is no clear pattern of sex hormone abnormalities associated with LD5. Common hormone therapies have been generally ineffective. There is no known effective treatment for LD5.
A growing body of evidence has shown that in some men, taking and discontinuing 5-alpha reductase inhibitors has led to sexual, neuropsychiatric and other dysfunctions which may last for years after discontinuation and may be irreversible.1–6 A 2019 systematic review reported that 11 of 14 studies on reversibility described patients experiencing “irreversible adverse effects” after discontinuing finasteride.7 Studies have linked the use of finasteride and dutasteride to penile abnormalities. In 2021, an international group of doctors and researchers published diagnostic criteria for post-finasteride syndrome.8
Course
Some men appear initially to tolerate finasteride or dutasteride, with adverse effects arising weeks, months or years after starting the drug. After discontinuation, dysfunctions may remain, worsen or resolve. There have been reports of persistent symptoms being triggered by as little as 0.25 mg of finasteride (one-quarter of the standard dose) (see Firsthand reports).
Based on patterns in firsthand experiences, the course may be understood in terms of three phases: post-withdrawal, adaptation and stabilization:
| Phase (time frames are approximate) | Description |
| 0–3 months after discontinuation | Post-withdrawal. May be an unstable period as the body attempts to recover, with symptoms arising and changing erratically. |
| 3–12 months after discontinuation | Adaptation. During this phase, dysfunctions may remain, reduce in severity or resolve. |
| One year after discontinuation and beyond | Stabilization. Dysfunctions remaining after 12 months following discontinuation may be long-lasting and resistant to treatment. |
This figure shows three outcomes: recovery, partial recovery and no recovery:
Dysfunctions
Although this condition appears to be a post-drug disorder rather than persistent side effects, adverse events reported to FDA provide insight into dysfunctions associated with finasteride. Following are the 28 most common AEs of finasteride in men age 18–40, received by FDA 2018–2020, sorted into categories. These AEs have not been confirmed to be persistent, but likely reflect more serious cases because they were reported to FDA by healthcare providers or consumers.
| Category | AE terms | % of all AEs |
|---|---|---|
| Sexual anatomy & function | Erectile Dysfunction; Sexual Dysfunction; Organic Sexual Dysfunction; Loss Of Libido; Libido Decreased; Testicular Pain; Genital Hypoaesthesia [penile numbness]; Penile Size Reduced; Penis Disorder; Ejaculation Disorder | 21.3% |
| Neuropsychiatric | Depression; Depressed Mood; Anxiety; Suicidal Ideation; Feeling Abnormal; Panic Attack; Anhedonia | 15.7% |
| Energy & musculoskeletal | Fatigue; Asthenia; Muscle Atrophy; Arthralgia | 5.4% |
| Memory, cognition & attention | Amnesia; Cognitive Disorder; Disturbance In Attention | 3.6% |
| Sensory & vestibular | Tinnitus; Dizziness; Vision Blurred | 2.9% |
| Sleep disturbance | Insomnia | 2.7% |
Criteria: Received by FDA: 2018–2020; Sex: Male; Age: 18–40; Suspected product: Finasteride only; Reason for use: Alopecia, Androgenetic Alopecia and other hair loss conditions only (excluding Hair Transplant); Concomitant Products: None.
Treatment
There is no known effective treatment for lasting dysfunctions after discontinuing finasteride. Anecdotally, results of hormone therapies such as testosterone or human chorionic gonadotropin (hCG) have been mixed and unremarkable.
Etiopathology
Etiopathology of post-5-ARI dysfunctions has not been established, but recent research has focused on the following:
- Altered levels of neuroactive steroids2,9–10
- Altered expression of neural receptors (e.g., GABA and NDMA)9-10
- Altered gene expression3
See also a proposed explanation focusing on tissue injuries, which has not undergone peer review.
For more resources on hypotheses, see the on-ramp for researchers.
References
1. Ganzer CA, Jacobs AR, Iqbal F. Persistent sexual, emotional, and cognitive impairment post-finasteride: a survey of men reporting symptoms. Am J Mens Health. 2015. DOI • PubMed
2. Diviccaro S, Melcangi RC, Giatti S. Post-finasteride syndrome: An emerging clinical problem. Neurobiol Stress. 2019. DOI • PubMed
3. Howell S, Song W, Pastuszak A, Khera M. Differential gene expression in post-finasteride syndrome patients. J Sex Med. 2021. DOI • PubMed
4. Kiguradze T, Temps WH, Yarnold PR, et al. Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride. PeerJ. 2017. DOI • PubMed
5. Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertility and Sterility. 2020. DOI • PubMed
6. More papers in Bibliography: Persistent adverse effects & ‘post-finasteride syndrome’
7. 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 • PubMed
8. 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. DOI
9. 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 • PubMed
10. Saengmearnuparp T, Lojanapiwat B, Chattipakorn N, Chattipakorn S. The connection of 5-alpha reductase inhibitors to the development of depression. Biomed Pharmacother. 2021. DOI • PubMed
See also: Research on lasting dysfunctions after taking finasteride or dutasteride