Propecia Side Effects

Epigenetic = lasting damage

Why do side effects carry on long after the last tablet? Many researchers now suspect epigenetics. Here's what the word means, and what the evidence shows so far.

What “epigenetic” means

Your DNA is a set of instructions. Each gene is the recipe for a protein your body needs, such as an enzyme or a hormone receptor. Every cell carries the same recipes, but each cell only uses some of them at a time.

Epigenetics is the system that decides which genes are switched on or off. It works by attaching small chemical tags to the DNA, or to the proteins DNA is wrapped around. The tags don't change the recipe itself. They change whether the cell can read it.

The best-studied tag is a methyl group. When methyl tags build up on a gene's promoter, the stretch of DNA that acts as its on-switch, the gene is usually turned down or switched off. This is called DNA methylation.

How DNA methylation switches a gene off Top: a gene whose promoter is clear, so the enzyme is made. Bottom: the same gene with methyl tags on its promoter, so little or no enzyme is made. The DNA sequence is the same in both. Gene switched on Promoter SRD5A2 gene Enzyme made as normal Gene switched off Promoter SRD5A2 gene Methyl tags Little or no enzyme made
Methyl tags on a gene's promoter can stop the cell reading it. The gene itself is unchanged.

Epigenetic tags respond to the world around us: diet, smoking, stress, hormones and drugs can all change them. Crucially, they can be copied when cells divide, so a change can outlast whatever caused it.

Gene
A section of DNA that holds the instructions for one protein.
Promoter
The start of a gene, where the cell's machinery switches it on.
DNA methylation
Small chemical tags added to DNA that usually turn a gene down or off.
5-alpha reductase
The enzyme finasteride blocks. It is made from the SRD5A1 and SRD5A2 genes.
Androgen receptor
The protein cells use to detect testosterone and DHT.
Neurosteroids
Hormones made in the brain and nerves that affect mood, sleep and sexual function. Several depend on 5-alpha reductase.

Why it matters for Propecia

Finasteride works by blocking 5-alpha reductase, the enzyme that turns testosterone into dihydrotestosterone (DHT). Less DHT on the scalp means less hair loss. But the same enzyme is also needed to make DHT in the genitals, and to make neurosteroids in the brain and nervous system.

In theory, when you stop taking the tablets the enzyme should start working again and everything should return to normal. For most men it does. For some, the symptoms carry on for months or years, as they have for me.

One explanation researchers are investigating is that finasteride, by changing hormone levels for weeks or months, triggers epigenetic changes in some men. Those changes could then keep certain genes switched off, or turned up, after the drug itself has gone. In 2018 the researcher Abdulmaged Traish set out this idea in a paper arguing that post-finasteride syndrome may be a form of drug-induced epigenetic change.

What the research has found

  1. 2014

    More androgen receptors in penile tissue

    Researchers in Italy compared foreskin tissue from 8 men with persistent sexual side effects after finasteride with 11 men who had never taken it. The men who had taken finasteride had significantly more cells carrying androgen receptors, for example 40% of supporting cells against 23%. This could mean the tissue has adjusted to a long spell without enough DHT.

    Di Loreto C et al., PLoS One, 2014

  2. 2016

    Brain changes that outlast the drug in rats

    Rats were given finasteride for 20 days and then examined a month after the last dose. Androgen receptors were still raised in the cerebral cortex, and some neurosteroid levels in the brain and blood were still abnormal. Other changes, in oestrogen and GABA receptors in the brain, showed up a month after stopping.

    Giatti S et al., Neuroendocrinology, 2016

  3. 2019

    The first direct epigenetic evidence in patients

    Scientists at the University of Milan tested the promoter of the SRD5A2 gene, one of the genes that makes 5-alpha reductase. In the cerebrospinal fluid around the brain and spinal cord, it was methylated in 9 of 16 men with post-finasteride syndrome (56%), compared with 1 of 13 controls (8%). The same gene was not methylated in anyone's blood, which suggests the change is specific to the nervous system. The researchers suggest this could help explain the altered neurosteroid levels found in these patients in earlier studies.

    The authors were careful to say they cannot yet tell whether finasteride caused the methylation, or whether these men already had it before they took the drug.

    Melcangi RC et al., Endocrine Connections, 2019

  4. 2021

    Thousands of genes behaving differently

    A team led by Dr Mohit Khera at Baylor College of Medicine in Texas compared penile skin from 26 men with post-finasteride syndrome and 26 men who had never taken the drug. 3,764 genes were working at different levels: 1,446 turned up and 2,318 turned down. The androgen receptor gene was among those turned up, along with genes involved in stress hormones, inflammation, blood vessels and nerve health.

    This study measured gene activity, not the epigenetic tags themselves. But a pattern this wide, in men who had stopped the drug, is the kind of result an epigenetic change would produce.

    Howell S et al., The Journal of Sexual Medicine, 2021

  5. 2024

    Lasting changes in brain gene activity in rats

    The Milan group looked at every active gene in two brain areas involved in mood, memory and sleep. A month after rats stopped finasteride, groups of genes linked to inflammation, energy use and the body clock were still working differently. The authors suggest these may relate to the depression, anxiety, memory and sleep problems that patients report.

    Giatti S et al., Journal of Endocrinological Investigation, 2024

Does epigenetic mean permanent?

Not necessarily, and that is a reason for hope as well as concern.

Epigenetic changes can be remarkably stable. Because the tags are copied each time a cell divides, a change made years ago can still be shaping how a gene works today. That would explain why symptoms can persist long after the last dose, and why simply waiting doesn't help some men.

But an epigenetic change is not the same as a mutation. The DNA sequence itself is unchanged, and tags that were added can in principle be removed. The US Centers for Disease Control and Prevention gives the example of smoking: after people quit, some smoking-related methylation changes gradually move back towards normal.

The hard truth is that no one has yet shown how to reverse the changes linked to finasteride, and there is no proven treatment. Understanding the mechanism is the first step towards one.

How strong is the evidence?

It's important to be honest about what is and isn't known:

  • The human studies are small, from 8 to 26 patients each.
  • Much of the work comes from one research group in Milan, and some of it was funded by the PFS Foundation, a patient charity.
  • Rat studies show what the drug can do to an animal brain, but don't prove the same happens in people.
  • The 2019 methylation study could not show whether finasteride caused the change.

Some doctors still doubt that post-finasteride syndrome is a physical condition. A 2019 paper in Skin Appendage Disorders, for example, argued that it may be psychological. But the medicines regulators in the US and UK now formally warn that sexual side effects may persist after stopping finasteride, as set out on the homepage.

The science is not settled. What the research does show is measurable, physical differences in the tissues of men living with these symptoms. It is not “all in their heads”, as I was told.

If you are thinking about taking Propecia: no one can yet tell you who is at risk, or how to undo the changes if they happen to you.

Sources

  1. Centers for Disease Control and Prevention. Epigenetics, Health, and Disease. Reviewed 2025.
  2. Traish AM. The post-finasteride syndrome: clinical manifestation of drug-induced epigenetics due to endocrine disruption. Current Sexual Health Reports. 2018;10:88.
  3. Di Loreto C et al. Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia. PLoS One. 2014;9(6):e100237.
  4. Giatti S et al. Effects of subchronic finasteride treatment and withdrawal on neuroactive steroid levels and their receptors in the male rat brain. Neuroendocrinology. 2016;103(6):746–757.
  5. Melcangi RC et al. Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study. Endocrine Connections. 2019;8.
  6. Howell S, Song W, Pastuszak A, Khera M. Differential gene expression in post-finasteride syndrome patients. The Journal of Sexual Medicine. 2021;18(9):1479.
  7. Giatti S et al. Analysis of the finasteride treatment and its withdrawal in the rat hypothalamus and hippocampus at whole-transcriptome level. Journal of Endocrinological Investigation. 2024;47:2565–2574.
  8. Trüeb RM et al. Post-finasteride syndrome: an induced delusional disorder with the potential of a mass psychogenic illness? Skin Appendage Disorders. 2019;5(5):320–326.