Recap
Shortly after RxISK was launched in 2012, we began receiving reports and messages from people complaining of persistent sexual dysfunction after stopping isotretinoin, a medication used in the treatment of acne. This was interesting because it seemed to have common elements with post-SSRI sexual dysfunction (PSSD) and post-finasteride syndrome (PFS).
As a result of people bringing this to our attention and completing RxISK Reports, we were able to publish the very first peer-reviewed article in the medical literature about persistent sexual dysfunction after stopping isotretinoin. “One hundred and twenty cases of enduring sexual dysfunction following treatment” was published in 2014 and included 7 reports linked to isotretinoin, all of which were from males.
We followed this up in 2018 with “Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases“. This included 54 reports (49 male and 5 female) linked to isotretinoin – the single most reported drug in the study. We also introduced the term post-retinoid sexual dysfunction (PRSD) to describe the condition.
Sexual problems linked to isotretinoin have also been covered by the media, often alongside other reported adverse effects. Media outlets have included Cosmopolitan, Daily Mail, BBC and Channel 4 News.
The petition
In October 2018, we were contacted by an individual who had been doing some digging in regulatory databases and was unsuccessfully trying to engage with the US Food and Drug Administration (FDA) about these issues. At that time, there were no warnings at all for sexual dysfunction in the US product information for isotretinoin. A few months earlier, we had written and submitted a petition to FDA about PSSD, so this gave us the idea of adapting the petition for isotretinoin.
On 29 October 2018, we submitted the isotretinoin petition to FDA and posted an accompanying blog post. It is worth reading both of these to get a full picture of the background.
We thought there was a strong case for the addition of warnings about sexual dysfunction while on treatment, particularly given that warnings had been added in Europe and Canada in 2017. However, being realistic, we suspected that FDA would probably deny our request for a warning about post-treatment problems. The European Medicines Agency and Health Canada hadn’t included this in 2017, so it seemed unlikely that FDA would agree to it.
Following submission, we received a standard acknowledgement letter, then a further letter in 2019 advising that an outcome hadn’t yet been reached. Thirty one people supported the petition by uploading comments to FDA’s website about their own experiences or the experiences of loved ones.
Response from FDA
On 17 June 2026, we received an email from FDA with a formal response advising that our petition had been granted in part and denied in part. It is interesting that they responded to our isotretinoin petition, but not our SSRI/SNRI petition which was submitted more than 5 months earlier.
The full response is available at the above link, but a brief summary of the action to be taken by FDA is below:
- In summary, we have determined that the following adverse events listed in the Petition warrant inclusion in the ADVERSE REACTIONS section of isotretinoin product labeling: erectile dysfunction, decreased libido, and decreased vaginal lubrication.
- FDA has also determined that a fourth sexual dysfunction adverse event, vaginal dryness, which was not included in the Petition requests, should be included in all isotretinoin product labeling.
- Furthermore, we have also determined that the labeling should state in the ADVERSE REACTIONS section that certain sexual dysfunction adverse events listed in the Petition — erectile dysfunction, decreased libido, and decreased vaginal lubrication — may continue after isotretinoin is stopped.
- We note that FDA has also determined that the ADVERSE REACTIONS section of labeling should include that vaginal dryness, which was not among the adverse events listed in the Petition, may continue after isotretinoin is stopped.
FDA have agreed to not only add warnings about sexual dysfunction while taking isotretinoin, but they will also require a warning that sexual dysfunction can persist after stopping. This is a very significant development, although it creates a slightly unusual situation. There is significantly more published literature for PSSD compared to PRSD, and it first appeared in the literature much earlier. Warnings about persistent sexual dysfunction have already been added to SSRIs and SNRIs in Europe, New Zealand, Canada, Hong Kong, Australia and Malaysia. Yet despite this, SSRIs and SNRIs remain without warnings for persistent sexual dysfunction in the US, while isotretinoin is to be given them.
FDA have not agreed to the strength of warnings that we requested, particularly in relation to the enduring effects after stopping treatment. Page 16 of FDA’s response suggests that the new wording will be:
Reproductive System
Abnormal menses, sexual dysfunction that may continue after discontinuation of treatment (including erectile dysfunction, decreased libido, decreased vaginal lubrication, and vaginal dryness)
While this is better than nothing, it still doesn’t mean very much. Medical professionals are likely to read it as – adverse effects might continue for a couple of weeks after stopping the drug until it is fully out of the patient’s system, and then the person will be fine again – and if they aren’t, it’s nothing to do with the drug and must be something else. There is nothing in the wording to suggest that sexual dysfunction may continue indefinitely and have no available treatment.
Our request for genital anesthesia, anorgasmia, and decreased orgasmic sensation to be listed was also denied. This is a missed opportunity. Problems such as erectile dysfunction, decreased libido and decreased vaginal lubrication can more easily be dismissed as a mental health problem by uninterested doctors, whereas genital anesthesia, anorgasmia, and decreased orgasmic sensation are more difficult to dismiss. It is perhaps best highlighted by an anonymous comment on FDA’s website:
“My daughter took isotretinoin 2 years ago and has experienced complete loss of libido and genital anesthesia since. It is devastating. All doctors she saw for this have told her it is not listed as a side effect and offered no help. This needs to be added to the list of possible side effects. There needs to be some research done to offer these young people treatment and doctors and pharmacists should be warned.”
Although we are disappointed that FDA’s decision didn’t go far enough, the new warnings are a small step forward, and we are grateful to everyone who played their part in this achievement.
A First
Tuesday June 30.
Thanks to Peter Selley who tracked down this FDA Request.
FDA Requests Labeling Updates for Generic
Isotretinoin Products
The update on details is important for people taking Isotretinoin and for prescribers.
But it’s difficult for us linked to RxISK not to also notice the final section.
FDA’s Authority Under MODERN
This is the first time FDA has used its authority under section 324 of the Consolidated Appropriations Act, 2021—”Modernizing the Labeling of Certain Generic Drugs” (referred to as MODERN). This provision added section 503D to the Federal Food, Drug, and Cosmetic Act and established a process for FDA to order labeling updates for generic drugs when their RLD application has been withdrawn for reasons other than safety or effectiveness.
Anonymous says
Let’s hope this is the start of more global awareness around PRSD. Too late for me but hopefully young people can be spared these cruel effects in the future.
Thank you RxISK for all your efforts in pushing this subject forward!
Dr. David Healy says
Maybe not too late. We’ve recently had striking evidence that recoveries can happen even after 30 years.
The work Will Powers has been doing on PFS implicates steroid hormones, including the sexual steroids. But key to all this is cholesterol – its the originator from which our steroid hormones come. And Vitamin A – isotretinoin – increases cholesterol and steroid hormone production
There are other things that can do this also – so keep an eye on posts linked to the Isotretinoin and PSSD petitions which will feature on RxISK over the next 2 to 3 weeks
David
D
annie says
Striking evidence…
‘SSRIs and SNRIs remain without warnings for persistent sexual dysfunction in the US, while isotretinoin is to be given them.’
‘There is probably a wealth of detailed and useful information available in the reports to FDA and MHRA if they actually investigated. Unfortunately, there is little evidence that regulatory agencies do anything more than simply collect the reports.’
As David Healy, a professor of psychiatry at Bangor University, who is studying the impact of isotretinoin, explains: ‘Erectile dysfunction is psychologically devastating to young men and, without doubt, does lead to suicide.’
https://www.dailymail.com/health/article-6431453/Thousands-prescribed-Roaccutane-theres-disturbing-evidence-leave-men-suicidal.html
‘we are grateful to everyone who played their part in this achievement.’
Indeed, will ‘hollowed-out’, be trending…
Harriet Vogt says
I’ve been having a nose around the disparities between the US and UK isotretinoin labelling – respectively, sexual ‘adverse reactions’ and ‘side effects of unknown frequency’ (frequency cannot be estimated from the available data).
The MHRA have kind of delivered the missing genital anaesthesia with ‘reduced sensation in the genitals’ – (as well as the vaginal dryness FDA have agreed) – and inorgasmia. But this information is to be found on page 10 out of 11:
Unknown frequency: (frequency cannot be estimated from the available data)
V013 10
– Dark or cola-coloured urine
– Problems getting or maintaining an erection
– Lower libido
– Breast swelling with or without tenderness in males
– Vaginal dryness
– Difficulties having an orgasm
effect
https://www.medicines.org.uk/emc/files/pil.10556.pdf
Scanning through the FAERS vs MHRA vs Rxisk reports in the 2018 citizen petition –the source of the disparities seems clearly in the numbers . Whereas genital numbness came out as a high level adverse reaction in the Rxisk reports, it was barely there in FAERS (4 blokes genital hypoesthesia) nor the MHRA reports – more accurately called under-reports.
Equally both regulators have high level reporting on vulvovaginal dryness/pain/discomfort /(dyspareunia). And this ties in with commonsense/patient understanding of isotretinoin’s moa – reducing oil production by shrinking sebaceous glands – hence drying skin a common effect. Dry genitals are quite likely to feel less. Anyway, that’s how I retrofitted FDA’s manoeuvre.
What utterly freaked me out – and I’ve never seen mentioned – is the high level of gynaecomastia. Good grief – a deformed penis (that sounds like, as you say a high cholesterol/ reduced blood flow issue) and breasts is quite a price to pay. As Peter Selley noted a while ago, acne usually passes in a couple of years. It is a terrible affliction – plague of boils level horror – but what a trade off.
Curious to understand a bit more about FDA’s political/legal drivers –I asked my mate Grok – who as I’ve said before can be intelligently responsive to challenge once you get past the first tsunami of slop. Grok’s response is the legal world in which you are now far from an innocent abroad.
‘Legal dimension – you’re spot on about the liability angel in the US:
Manufacturers can face failure –to-warn lawsuits if they knew (or should have known) about risks but didn’t adequately label them. Courts often look at what was in the label at the time).
This creates a defensive incentive for companies: they may resist broad warnings without ironclad quant data to avoide admitting causality in litigation.
For regulators , updating labels too aggressively on emerging signals can be seen as valdating claims, potentially opening floodgates. Conversely, slow updates explose them (and companies to criticism for inadequate protection).
It’s a bit of a catch -22. The litigious environment pushes caution on the regulator side, which delays incorporating qualitative signals which in turn keeps patient harm stories circulating. Europe sometimes feel precautionary, partly because tort liability is lower.
Mixed methods thinking – treating rich qual data as a valid way to understand real-world causality alongside quant – would be a modern upgrade’
Grok really is a cut above your average LLM.
The theory kind of plays out in the MODERN first, Peter found. ‘for generic drugs when their RLD application has been withdrawn for reasons other than safety or effectiveness.’ Hmm, I thought, weren’t there loads of Accutane legal cases. Indeed there were – and a lot as you will know relating to IBD – but they were virtually all – even all all – dismissed or over-turned because Roche was judged to have sufficient warnings in the label.
QED.