5-alpha syndrome (post-finasteride syndrome)

Finasteride, dutasteride, and saw palmetto have been used as treatments for hair loss and prostate conditions. Using these hormone-altering substances can lead to a wide range of health disturbances—often affecting sexuality and mental state—which may not resolve over time. If disturbances are still present three months after stopping, the individual may have a long-term condition defined here as 5-alpha syndrome. Currently, there is no effective treatment for this condition, although time and some treatments may lead to improvements.

This is a working draft. It is not medical advice.

Overview | Onset & symptoms | Risk factors & causes | Diagnosis | Treatment | Outlook / prognosis | Living with | Resources | Literature & sources

Overview

What is 5-alpha syndrome?

5-alpha syndrome is a lasting condition that can arise from taking finasteride, dutasteride, saw palmetto or other substances called 5-alpha reductase inhibitors (5ARIs). These substances partially disable an enzyme that has an important role in hormone signaling.

The syndrome often includes disturbances of male sexuality and psychological state. Sexual symptoms may include severe loss of libido and numb genitals. Psychological symptoms may include depression, anxiety, panic and suicidal thinking. Other symptoms may include slowed thought processes, insomnia, fatigue, muscle weakness, loose skin, and blurred vision.

The condition tends to unfold in phases. The months after discontinuing a 5ARI can be an erratic period when symptoms become more severe, lessen, or resolve, while new symptoms might also appear. If symptoms are still present three months after stopping the drug, and other causes are ruled out, then 5-alpha syndrome may be present.

The symptoms are clues to physiological disturbances implicating the body, mind, sexuality, behavior and identity. Medical language is not well-suited to describe “what it’s like” for the affected individual. The syndrome may bring feelings of disconnection from one’s normal self, lack of a sense of purpose, feelings of isolation, social withdrawal, and lack of interest in normal activities and relationships. These effects likely reflect the importance of the hormonal pathways that are disrupted by 5ARIs. These pathways support the function of many organs including the male reproductive system, brain, skin, eyes, kidneys and muscles.

Medical commentators have sought to reduce the syndrome to a known entity such as low testosterone, ordinary depression or a psychological disorder. It has also been called “persistent side effects,” which is not plausible if a drug is metabolized out of the system. In fact, affected systems and functions depend critically upon products of the 5-alpha reductase enzyme, the target of 5ARI drugs. Research is needed to assess whether related pathways have been permanently altered as a consequence of past exposure to 5ARIs.

Who does it affect?

The syndrome affects men who have used a 5ARI such as finasteride, dutasteride or saw palmetto. Young men appear to be at greater risk, but older men can also be affected.

The impact of the syndrome extends to partners, friends and family of the individual with the syndrome. Disabling of sexuality and loss of interest in daily life imperils relationships. Prospects for dating and new relationships may be limited. If friends and family misunderstand or disbelieve the syndrome, these relationships may be frayed.

How common is this condition?

The prevalence of 5-alpha syndrome is unknown. A study of medical records found that 0.8% of younger men who took finasteride developed erectile dysfunction that persisted after stopping the drug (Kiguradze et al., 2017).

Onset & symptoms

How do symptoms develop?

While men are taking a 5ARI or after discontinuation, changes may erratically appear in their body, mental state and capacities. Sometimes these conditions resolve within approximately three months. If they continue beyond this period, and other causes are ruled out, 5-alpha syndrome may be present. The nature and time course of the disturbances vary significantly across individuals.

Phase & durationDescription
On drug
From 1 dose to years of use
While using a 5ARI such as finasteride, the patient may experience adverse effects and decide to discontinue the drug.
Post-withdrawal
0–3 months after discontinuation
This may be an erratic period in which drug-related disturbances continue, change in severity, or resolve. New disturbances may develop after stopping the drug. See symptoms below.
Adaptation
3–12 months after discontinuation
If dysfunctions are still present—and other causes ruled out—three months after stopping the drug, 5-alpha syndrome may be present. Disturbances to physical, mental and psychological state, as well as physical symptoms, may remain, intensify, moderate, or resolve; new symptoms may develop.
Stabilization
One year after discontinuation and beyond
Dysfunctions remaining after 12 months following discontinuation may be long-lasting and resistant to treatment.
Pathways after 5ARI discontinuation. (A) After discontinuation, adverse effects may resolve uneventfully resulting in recovery. Alternatively, (B) the body may enter a dysregulated state. During an erratic period lasting weeks or months, individual symptoms may remain, increase in severity, or resolve. New symptoms may also appear. (C) If disturbances remain three months after discontinuation of a 5ARI, 5-alpha syndrome is present, with varying profile and severity. There may be a partial recovery over time. (D) Recovery from the dysregulated state may occur, avoiding the 5-alpha syndrome.
What are the symptoms?

Symptoms vary across individuals, but the following capacities are more commonly affected. A longer list of possible symptoms is in the appendix below.

Sexual

  • Loss of libido
  • Penile numbness
  • Erectile dysfunction
  • Physical changes to the penis including fibrosis (scarring), muscle loss and shrinkage
  • Altered consistency and lower volume of semen

Sleep

  • Insomnia

Energy & musculoskeletal

  • Fatigue
  • Muscle atrophy, weakness and spasms
  • Joint pain

Psychological

  • Depression
  • Anxiety
  • Panic attacks
  • Suicidal ideation
  • Anhedonia (inability to feel pleasure)

Thought processes

  • Slowed thought processes
  • Impaired memory
  • Mental cloudiness or “brain fog”

Other symptoms

  • Dry eye
  • Blurred vision
  • Tinnitus
  • Dry, thinning skin

View extended list of symptoms in appendix

Alongside these specific symptoms, the patient may experience confusion about his identity; isolation from social life; and loss of a sense of purpose. He may have lower motivation and capacity to continue work or studies.

Psychological symptoms can arise from multiple pathways. They may be directly induced by a 5ARI’s biochemical effects, but also secondary to other injuries and dysfunctions related to the drug.

Risk factors & causes

There are reports of developing the syndrome after many years of using a 5ARI, but also after one dose. The syndrome has also been reported after using finasteride in topical form.

Younger men may be at higher risk of a syndrome. Long-term use of a 5ARI may increase the risk of a syndrome. Based on anecdotal reports, stopping and restarting a 5ARI one or more times may elevate the risk of developing a syndrome.

The biomedical basis of the syndrome has not been established, but research has found an association of 5ARI treatment with altered steroid levels, altered gene expression, and injuries to the penis (see Research). 5ARIs inhibit an enzyme that supports hormone signaling in multiple organs including the male reproductive system, brain, skin, eyes and kidneys.

Diagnosis

As set out in the Medical Disclaimer, information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment.

The paradox of an unrecognized illness

5-alpha syndrome is not officially recognized as a disease. Some physicians have expressed skepticism about patient experiences, refusing to acknowledge the drug as a potential cause. They might refer the patient to a psychiatrist for treatment of a supposed mental illness. In addition, many medical specialties are focused on one physiological system, so they are not well-suited to understanding and treating a multi-system disease. For example, dermatologists, who often prescribe finasteride for hair loss, are not typically experts in sexual medicine, pharmacology or neuroendocrinology.

For men with 5-alpha syndrome, seeking health care may lead to discouraging or upsetting experiences. Weigh the costs and benefits of seeking a diagnosis. If you do seek medical care, look for physicians who are open to a complex, under-researched condition.

Planning your approach

Medical specialties focused on a single bodily system are ill-prepared to manage a disease affecting multiple systems, such as 5-alpha syndrome. Still, it may be possible to be diagnosed for specific conditions such as sexual dysfunction, insomnia and impaired thought processes. The relevant medical specialties include urology, andrology and sexual medicine; endocrinology; neurology; physiatry; psychiatry and psychotherapy; ophthalmology; and general practice. See also the approaches under Treatment pathways.

Diagnostic tests

Below is a list of diagnostic tests. Your doctor generally makes the decision as to whether the test is appropriate. Some tests are expensive or difficult to access, and may not be covered by your health plan.

A common problem is the lack of “baseline” levels, meaning test results prior to developing symptoms. Without baseline levels, it is difficult to know whether an atypical result is due to the drug or some other factor.

Other potential explanations should be explored, such as prior use of an SSRI antidepressant or isotretinoin (Accutane). Both of these drugs have been linked to long-term sexual and psychiatric dysfunctions.

With this background in mind, these tests might be relevant:

Sexuality and reproduction

A distinctive symptom of 5-alpha syndrome is genital numbness, which is not associated with depression. For more background, see Seeking a medical sign of genital numbness.

  • Erectile dysfunction questionnaire such as IIEF
  • Penile duplex Doppler ultrasound for fibrosis and other abnormalities
  • Other tests for veno-occlusive dysfunction (Hoppe & Diehm, 2020)
  • CT & MRI scans for Peyronie’s disease (Parmar et al., 2020)
  • Quantitative sensory testing for penile numbness
  • Electromyography for pudendal neuralgia
  • Semen analysis for reduced sperm count & motility
  • Hormone levels (Note: No reliable pattern of hormone abnormalities has emerged. Many physicians have interpreted 5-alpha syndrome as a low-testosterone condition, but some symptoms, such as penile fibrosis and genital numbness, cannot be explained by this diagnosis.)
Psychological state and thought processes
  • Psychiatric evaluation
  • Neuropsychological testing for cognitive dysfunction
Musculoskeletal system
  • Evaluation for muscle and joint health by physiatrist, sports medicine doctor or musculoskeletal specialist
Other systems and functions, with relevant medical specialty
  • Eyes & visual symptoms: ophthalmology
  • Tinnitus and hearing: otolaryngology (ENT)
  • Insomnia: psychiatry or general practice
  • Skin: dermatology
  • Metabolic problems: endocrinology

Treatment

As set out in the Medical Disclaimer, information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment.

Caveats & risks

In the months after discontinuing a 5ARI, there may be feelings of despair and urgency. This has led affected men to try various treatments in a short period, including drugs, hormonal treatments, supplements and experimental products. Every treatment entails risks, and could lead to a worsening of health. Also, various medications and supplements could have undesirable interactions.

Two classes of products should be viewed with particular caution: those that affect androgen levels, and psychotropic medications. These can worsen 5-alpha syndrome or cause other health problems.

If a physician is dismissive of your condition, consider seeking out a different doctor.

Treatment pathways

Since no treatment has been found to work reliably, this section offers pathways to explore. The first one is very simple, and might be best for some. Look for trusted medical professionals, friends, family members and advisors to help you navigate these pathways.

Conservative approach

This low-impact approach aims to maximize the body’s capacity to recover on its own without interference from medications or other products. It is simple and inexpensive.

  • Eat a healthy diet
  • Avoid alcohol, drugs and smoking
  • Do light exercise such as walking
  • Maintain relationships and social life as much as possible
  • Optional: seek psychotherapy
Integrative medicine

Integrative medicine focuses on the whole person and uses a combination of therapies and lifestyle changes (The Cleveland Clinic). Providers of integrative medicine include physicians, nutritionists, acupuncturists, yoga instructors and massage therapists.

Sexual and reproductive health

There is evidence that lasting post-5ARI erectile dysfunction arises from injuries to the penis including fibrosis, loss of smooth muscle, and increased connective tissue, as well as nerve damage. Diagnostic methods above may help determine whether this has occurred.

Short-term treatments for ED include vacuum erection devices, the PDE5 inhibitors tadalafil & sildenafil, and penile injections. Several therapies for penile rejuvenation are available or in development, such as shockwave therapy, platelet-rich plasma (PRP) and stem cell therapy. Finally, there are options for surgery such as penile revascularization or prosthesis.

Hormone therapies

Many men with 5-alpha syndrome have tried hormonal therapies such as testosterone injections, human chorionic gonadotropin (hCG), clomiphene, DHT gel (Andractim) and DHEA supplements. A case report described a course of high-dose hCG for a post-finasteride patient (Garreton et al., 2016). Anecdotal reports have described no effects, temporary improvements, or a worsened condition. There is currently no evidence to support hormone therapies as a treatment for 5-alpha syndrome, and there is a risk that these therapies could worsen the condition.

The following supplements also have hormonal effects: certain mushrooms (such as reishi, a 5ARI), tribulus, ashwagandha, maca root and stinging nettle.

Psychological health

Men who used 5ARIs have reported depression, anxiety, panic attacks, suicidality and lack of pleasure in normal activities, also called anhedonia. If you have these experiences, you may wish to consult with a psychiatrist. The psychiatrist may believe that these experiences are a consequence of sexual dysfunction, but evidence suggests the drug can have a direct impact on mental state.

Many psychotropic drugs can have lasting consequences after stopping, including post-SSRI sexual dysfunction (PSSD) (Healy et al., 2021). PSSD has symptoms in common with 5-alpha syndrome, and may be irreversible. Many psychiatrists are unaware of these risks. Keep these risks in mind when considering these drug classes.

Another option is psychotherapy. Here too, the therapist may initially view symptoms as psychosomatic or secondary to sexual dysfunction. Research has suggested a direct impact of 5ARIs on psychological state.

Thought processes (cognitive functioning)

Neuropsychologists evaluate and treat symptoms such as slowed thought processes and memory problems.

Outlook / prognosis

The first year after discontinuation of a 5ARI may be erratic and distressing. As time goes on, there may be stabilization or, in some cases, improvement in mental, sexual and other dysfunctions. There is currently no effective treatment for 5-alpha syndrome. Dysfunctions may remain over the long term.

Living with

5-alpha syndrome is currently unrecognized by medicine. With a biased evidence base, lack of research funding, and lack of diagnostic testing, the condition remains largely invisible to physicians. Meanwhile, no treatment has been found to fully restore lost functions. Another challenge is that men have been disbelieved and snubbed when seeking healthcare.

Even facing these headwinds, there are pathways to explore—from a conservative approach, to integrative medicine and emerging treatments. Medicine separates the body into systems, but it is important to recover one’s wholeness as an individual as much as possible. In this process, psychological support, social connections, and philosophical reflection may be of help.

Resources

Literature & sources

Medical literature

Garreton AS, Valzacchi GR, Layus O. Post-finasteride syndrome: about 2 cases and review of the literature. Andrology-Open Access. 2016. doi:10.4172/2472-1212.1000170 • Journal site

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:10.3233/JRS-210023PubMed

Khera M, Than JK, Anaissie J, et al. Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia. Transl Androl Urol. 2020. doi:10.21037/tau.2020.03.21PubMed

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:10.7717/peerj.3020PubMed

Leliefeld HHJ, Debruyne FMJ & Reisman Y. The post-finasteride syndrome: possible etiological mechanisms and symptoms. Int J Impot Res. 2023. doi:10.1038/s41443-023-00759-5 • PubMed

Schifano N, Capogrosso P, Boeri L, et al. Are finasteride-related penile curvature/Peyronie’s disease Adverse Event Reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases. Int J Impot Res. 2023. doi:10.1038/s41443-022-00568-2 • PubMed

See also: Bibliography on 5-alpha syndrome

Other sources

Adverse event data in men aged 18–40 reported 2019–2021 in FDA Federal Adverse Event Reporting System. Finasteride Watch. Undated. Accessed August 23, 2023.

Firsthand experiences of former users of 5ARIs. Finasteride Watch. Various dates.

Non-medical guidance from AVFIN (France) based on consultations with hundreds of patients.


Appendix: Extended list of symptoms

↑ back to ‘What are the symptoms?’

Sexual domain

  • General
    • Lack of libido
    • Erectile dysfunction
    • Lack of morning & spontaneous erections
    • Inability to achieve orgasm or loss of pleasurable orgasm
  • Penis
    • Penile fibrosis (scarring) & loss of smooth muscle
    • Penile shrinkage or curvature
    • Peyronie’s disease
    • Loss of sensation / numbness
  • Testicles
    • Testicular pain
    • Shrunken testicles
  • Semen
    • Reduced semen volume
    • Altered consistency of semen
    • Reduced sperm count & motility

Psychological domain

  • Anxiety
  • Depression
  • Panic attacks
  • Depersonalization / derealization
  • Anhedonia (inability to feel pleasure; lack of motivation)
  • Suicidality

Energy & musculoskeletal system

  • Fatigue
  • Muscle atrophy & weakness
  • Muscle twitching
  • Arthralgia (joint pain)

Sleep

  • Sleep disturbance / insomnia

Thought processes & memory

  • Impaired memory
  • Slowed thought processes & impaired problem solving
  • Mental cloudiness / brain fog
  • Confusion
  • Attentional difficulties

Eyes & vision

  • Dry eyes / meibomian gland dysfunction
  • Vision blurred

Hearing / vestibular system

  • Tinnitus
  • Vertigo

Skin

  • Decreased oil & sebum production
  • Dry, thinning skin
  • Gum recession

Endocrine system & metabolism

  • Changes in metabolism; increased fat deposition
  • Gynecomastia

Last revised: Oct 1, 2023