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#Post#: 1208--------------------------------------------------
The Devasting Effects of Finasteride
DIR By: Road2HardCoreIron
Date: October 20, 2022, 4:48 am
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The Devastating Effects of Finasteride: Post-Finasteride
Syndrome (PFS)
A quick google search for ‘prevent hair loss’ often reveals
results for finasteride. A drug widely used by men and claimed
by many corners of the internet to be ‘safe’. A quick google
search for ‘finasteride side effects’ and we get a list (1):
Impotence,
Loss of interest in sex,
Trouble having an orgasm
Abnormal ejaculation
Swelling in your hands or feet
Swelling or tenderness in your breasts,
Dizziness,
Weakness
Feeling like you might pass out
Headache,
Runny nose or skin rash
But similarly all drugs carry the risk of various side effects
and yet we’re fine after using them as directed, i.e.
paracetamol. However, finasteride can be an exception & we’re
going to dive into this.
Finasteride, also known as Proscar, is used to treat hair loss
and benign prostatic hyperplasia in men. It’s a
5α-reductase inhibitor, aka an antiadrogen.
5α-reductase inhibitor is an enzyme primarily responsible
for metabolising Testosterone to Dihydrogentestosterone (DHT),
as shown below (2):
(Click for Full-Size Image)
If you look at the structure, it seems pretty similar right? All
that’s happened is we’ve reduced Testosterone (took away an
electron, which is visible from the first carbon ring at C4-5 –
that extra line indicates an extra bond [double bond] – removing
the electron turns it into a single bond). Let’s move away from
organic chemistry – DHT is considerably more potent as an
agonist of the androgen receptor. While we’re on this topic,
there’s 3 isoenzymes (subtypes) of 5α-reductase; 5-AR1,
5-AR2, & 5-AR3 (3). Finasteride inhibits only the 2nd and 3rd
isoenzyme (1st too to some extent), whereas dutasteride (another
5α-reductase inhibitor) inhibits only the 1st and 2nd
isoenzyme (4). Dutasteride has a greater potency than
finasteride for 5-AR2. Though both drugs provide some pretty
nasty adverse side effects in those predisposed to it. This is
still important as specific mutations in any of these isoenzymes
genes could therefore alter the level of response to either
dutasteride or finasteride.
DHT is involved in prostate growth, facial, axillary, pubic, and
body hair growth, having metabolites which are neurosteroids
that have antidepressant, anxiolytic, rewarding, anti-stress and
pro-cognitive effects (5, 6) and increasing force production in
fast contracting muscles (7). It’s also a selective agonist of
the beta estrogen receptor. It basically makes you feel good,
helps you grow hair, and can improve strength. Sadly it can also
increase typical male pattern balding (MPB) in those predisposed
to it (I am in this category, but I have more hair than Dr.
Stevens! I hope this trend continues).
DHT effectively miniaturizes hair follicles in the scalp in
those at risk to it. That ultimately pushes the hair out (8). In
men with an increased risk of MPB, there’s an increased
sensitivity of scalp hair follicles to normal levels of
circulating androgens, which activates genes responsible for
follicular miniaturization aka hair loss. This is unfortunately
genetic. Of course it’s clear that reducing the levels of DHT
would stop hair loss in these men, ergo the use of finasteride.
But, Post-finasteride syndrome (PFS) is no joke and affects many
men. Let’s dive into it a bit deeper.
What is Post-Finasteride Syndrome?
Post-finasteride syndrome (PFS) is a condition that exhibits
persistent sexual, neurological, physical, and mental adverse
reactions in patients that have taken finasteride to treat hair
loss.
It carries the following reported symptoms (9):
Decreased or completed loss of sex drive
Erectile dysfunction
Loss of morning and spontaneous erections
Sexual anhedonia (loss of pleasurable orgasm)
Decreased semen volume and force
Penis shrinkage and numbness
Scrotal shrinkage and numbness
Breast development and enlargement
Chronic fatigue
Myalgia, including muscle pain
Myopathy, including muscle weakness, cramps, stiffness and
twitching
Rhabdomyolysis, including muscle atrophy
Creatine kinase elevation (due to muscle breakdown)
Decreased oil & sebum production
Dry & thinning skin
Melasma (brown patches which affect parts of the face)
Lipoatrophy (localised loss of fat)
Tinnitus (ringing in the ears)
Optic neuropathy (damage of optic nerve)
Retinopathy (disease of the retina)
Increased risk of obesity
Decreased body temperature
Reduced HDL, raised fasted blood glucose and triglycerides
Elevated rheumatoid factor
Suicidal ideation
Severe memory impairment
Slowed thought process
Impaired problem solving
Depression
Anxiety
Emotional flatness
Insomnia
Obstructive sleep apnea
The list is quite exhaustive and scary. However, the condition
appears to not yet be recognized by the medical community, and
some studies suggest it may be more likely to occur in those
with a history of personality disorder (10) which brings the
quote “I think of my body as a side effect of my mind”, by
Carrie Fisher, to mind.
Given that we reduce the production of DHT when using
finasteride, we can expect side effects to occur. For one,
there’s increased GABA activity in the brain with DHT, likely
due to DHT metabolites modulating GABA-A receptors (10, 11),
which provides an anxiolytic effect (reduced anxiety). DHT may
also modify circuitry in the brain by altering the number of
excitatory spine synapses in a paracrine manner, which can
therefore affect cognitive function (in a positive manner) of
the brain (12). It’s been established that the risk of dementia
is in fact greater for patients using 5α-reductase
inhibitors (13), further demonstrating the need for DHT in the
brain for adequate cognitive function and health. In male rats,
it has been demonstrated that finasteride inhibits the brains
dopaminergic system (involved in the reward system and sense of
wellbeing) (14) which may well transfer to humans. It has even
been suggested to use testosterone supplementation (note: within
physiological levels) to improve cognition in older men, in part
due to the neuroprotective and excitatory effects of DHT (12).
Put simply, DHT is actually quite important for good mental
health. It will reduce feelings of anxiety, improve feelings of
wellbeing, and improve cognitive function.
Additionally, progesterone (another important steroid hormone)
can be converted to allopregnanolone via 5α-reductase.
Allopregnanolone is a potent ligand of the GABA-A receptor,
which in normal circumstances will reduce the risk of anxiety,
major depression, impulsive aggression, and negative symptoms in
schizophrenia (15). So, that’s another thing lost to the use of
finasteride. Though, one must bear in mind that balance is key –
excess allopregnanolone can lead to tolerance at GABA-A
receptors, leading to potentially increased risk of anxiety &
depression. Balance is always key.
The Effects Of Post-Finasteride Syndrome On The Brain
You’ve probably seen the pictures of ‘this is your brain on
drugs’, sometimes with the images of lesions present. While not
quite as bad, it should be clear that a lack of DHT is
detrimental to your brain health.
In the case of finasteride treatment, there have been observed
significant and several alterations in the hippocampus (part of
your brain), which is a part responsible for processing
long-term memory and emotional responses, leading to depressive
behaviour, reduced cognition, and neuroinflammation, plus
alterations in gut microbiota (never good) (16). We’ve also
observed finasteride inhibiting the brain’s dopaminergic system
(14). Granted, this was in male rats – we appear to note similar
clinical reports of negatively altered behaviour in humans.
Human users of finasteride who were symptomatic reported major
depression, impaired cognition/more cognitive complaints,
reduced sexual arousal and fMRIs demonstrated abnormal brain
circuitry with regard to sexual arousal (17). This appears to
persist after drug cessation. Our own UK MHRA has reported
reports of depression and suicidal ideation related to
finasteride use (18).
It’s likely that the lack of DHT has similar effects in humans
as it does in rats, ergo similar However, you may know someone
with no side effects. I’ve certainly noted such anecdotal
reports. That may be because of a difference in gene expression,
especially in important biological pathways associated with the
above adverse outcomes – in fact a recent Differential Gene
Expression study proved just this (3). How will you find out if
you have the mutant genes that increase the risk of PFS? Well
for starters I wouldn’t rely on just these few genes being
indicators as we may have epigenetic forces at play (altered
gene expression due to environmental changes, can occur via
methylation/acetylation due to a drug or some other stimuli).
Can We Resolve It?
Studies have observed that subjects still have symptoms
following as long as 16 months. The effects of PFS appear to
last for quite some time. This could be due to many reasons, oen
including epigenetic modifications in cerebral tissue of SRD5A
genes, causing downregulation of 5α-reductase in the brain
(19). Unfortunately the literature is quite sparse on recovery,
with no known treatment.
There have been anecdotal reports of recovery to near prior
finasteride use over a period of 1 to 5 years following
cessation of finasteride, but some report worsened psychological
side effects (20). All we know is that with an increased
duration spent on the drug, the worse the symptoms can be
following cessation in those prone to PFS. Just another warning,
dutaseride (Adovart) can also cause PFS as it is a
5α-reductase inhibitor.
I don’t want to scare anyone using finasteride. If you’ve not
experienced these symptoms you may well be fine as you fall into
the ‘does not get PFS’ category that some men will inevitably
fall into due to their genetic makeup. But if you have fallen
into it, you can get support from patient support forums, join
patient support groups, and talk with a medical expert on the
topic who can help you manage some of the symptoms.
For everyone else afraid of losing their hair, your best bet is
to not take 5α-reductase inhibitors. It’s a gamble that’s
not worth it. If you’re normotensive and not prone to
hypotension, not on blood pressure medication, then you could
try Minoxidil. You must always talk with your doctor first about
this, though. Anecdotally, Minoxidil is a hit or miss. But for
the hits, it works wonders to prevent further hair loss and
sometimes grow hair back. However, it can become quite
expensive, especially since you have to continue use as the hair
growth is not permanent and stops following cessation. It’s also
not side effect free, so again please consult your prescribing
clinician first before considering such a thing.
Conclusion
Post-finasteride syndrome is an awful condition that affects
many, but not every, man that uses finasteride or another
5α-reductase inhibitor. Sometimes its use is clinically
indicated, but if you’re just using it for preventing hair loss,
you are best off reconsidering. The symptoms of post-finasteride
are no joke and prevention is the best thing to do here as there
are no known ‘cures’. Means to manage some symptoms exist and
will require extensive work and support with medical experts,
groups, and more – but it’s best to not end up in that place in
the first instance. Other hair regrowth methods exist, such as
the use of Minoxidil if you are healthy and otherwise fit and
under the go-ahead of a medical professional. But bear in mind
that this is expensive and you have to continue its use to
continue new hair regrowth. Just remember that one thing that’s
more valuable than your hair and any money in the world is your
mental wellbeing. Prevention is better than cure.
References
Side Effects of Propecia (Finasteride), Warnings, Uses. RxList,
(available at
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Drug Dev. Technol. 17, 44–57 (2019)
S. Howell, W. Song, A. Pastuszak, M. Khera, J. Sex. Med. 18,
1479–1490 (2021)
Steroid 5alpha Reductase – an overview | ScienceDirect Topics,
(available at
HTML https://www.sciencedirect.com/topics/medicine-and-dentistry/steroid-5alpha-reductase)
A. S. Kohtz, C. A. Frye, Methods Mol. Biol. Clifton NJ. 829,
397–431 (2012)
P. J. Brunton, J. Steroid Biochem. Mol. Biol. 160, 160–168
(2016)
M. M. Hamdi, G. Mutungi, J. Physiol. 589, 3623–3640 (2011)
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About Post-Finasteride Syndrome – The Post-Finasteride Syndrome
Foundation, (available at
HTML https://www.pfsfoundation.org/about-pfs-post-finasteride-syndrome/)
R. M. Trüeb, A. Régnier, H. Dutra Rezende, M. F. R. Gavazzoni
Dias, Skin Appendage Disord. 5, 320–326 (2019)
GABAergic Integration of Progesterone and Androgen Feedback to
Gonadotropin-Releasing Hormone Neurons1 | Biology of
Reproduction | Oxford Academic, (available at
HTML https://academic.oup.com/biolreprod/article/72/1/33/2667017)
Z. Cai, H. Li, Front. Endocrinol. 11, 857 (2020)
B. Welk et al., J. Neurol. Sci. 379, 109–111 (2017)
L. Li et al., CNS Neurosci. Ther. 24 (2017),
doi:10.1111/cns.12781
C. Schüle, C. Nothdurfter, R. Rupprecht, Prog. Neurobiol. 113,
79–87 (2014)
S. Diviccaro et al., Psychoneuroendocrinology. 99, 206–215
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(2016)
Finasteride: rare reports of depression and suicidal thoughts.
GOV.UK, (available at
HTML https://www.gov.uk/drug-safety-update/finasteride-rare-reports-of-depression-and-suicidal-thoughts)
R. C. Melcangi et al., Endocr. Connect. 8, 1118–1125 (2019)
Frequently Asked Questions – The Post-Finasteride Syndrome
Foundation, (available at
HTML https://www.pfsfoundation.org/frequently-asked-questions/)
By Joseph Hearnshaw BSc (Hons) DPS, MSc, FRSA, MRSB, MBCS
November 16, 2021
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