Post-finasteride syndrome is leaving behind a slew of victims in its trail.
Some say it’s all in the mind, a made-up myth…but those who suffer from it surely know they’re not just a hypochondriac.
It’s real alright.
Mechanisms of finasteride
So let’s discuss what the drug, finasteride, does in the first place.
Finasteride is a 5-alpha reductase inhibitor and this blocks the conversion of testosterone to DHT. What few people know is that there are 5β-R and 3 types of 5α-R enzymes and that they’re not only involved in the conversion of testosterone to DHT, but also in the:
- synthesis of bile (5β-R specifically), which is essential for the digestion of fat and absorption of fat-soluble vitamins. Bile also acts as an anti-bacterial and anti-microbial substance which keeps the gut clean and prevents SIBO and SIFO.
- conversion of:
- androstenedione → 5α-androstanedione
- progesterone → α-dihydroprogesterone (a very important neuroactive steroid and precursor to allopregnanolone)
- deoxycorticosterone → dihydrodeoxycorticosterone (DHDOC)
- cortisol → 5α-dihydrocortisol (for the deactivation of cortisol)
- aldosterone → 5α-dihydroaldosterone, which increases the excretion of salt, the opposite of aldosterone
Many of the benefits of testosterone, such as enhanced insulin sensitivity, reduced catabolism, higher dopamine, increased thyroid hormone production, are mediated by DHT, and blocking DHT production prevents those effects/benefits.
PFS isn’t fun. It scrambles your hormones, libido and cognition all over the place, right into the gutters, and leaves you feeling like an empty dysfunctional husk. Additional side effects of finasteride include:
- dry skin or thinning of the skin, weight gain, elevated glucose and lipids and worsening of insulin sensitivity (R).
- insomnia, obstructive sleep apnea (R), panic attacks, brain fog, suicidal idealization, slow cognition, anhedonia (a sign of elevated serotonin and low dopamine)
- diminished libido, erectile dysfunction, ejaculatory complaints, penile discomfort, loss of scrotal sensitivity, scrotal discomfort, loss of pubic hair, increased sperm density and gyno (R).
- involuntary muscle spasms, loss of muscle tone, increased body weight (R).
- kidney disease. DHT is highly protective to the kidney and an elevated estrogen:androgen ratio is destructive to the kidney (R).
- accumulation of fat in the liver and the progression of fatty liver (causes NAFLD) (R). Cortisol antagonist can help reverse some of these effects, which just indicate that 5-AR can prevent fatty liver by deactivating cortisol.
- reduced muscle mass gains even while on testosterone (R).
- alteration in the gut microbiota, which can lead to digestive issues, skin issues, mental issues, etc. (R)
- neuroinflammation (R). Neurosteroids such as 5α-DHP and allopregnanolone stimulate neurogenesis, neuronal survival, neuronal differentiation, synaptogenesis, glial differentiation, myelin formation, synaptic function, and synaptic plasticity (R). In addition, under pathological conditions, neuroactive steroids exert neuroprotective actions, promoting neuronal survival and re-myelination and decreasing neuroinflammation.
- anti-androgenic actions (R). Due to the structural similarity of finasteride to DHT, it is postulated that finasteride could bind to the androgen receptor. It turns out that finasteride happens to be a potent anti-androgen, independent of lowering DHT.
- Osteoporosis (R)
- Adrenal insuffeciency (R). “A putative mechanism is that elevated bile acids inhibit inactivation of cortisol in liver by 5α-reductases type 1 and type 2 and 5β-reductase, resulting in compensatory downregulation of the hypothalamic-pituitary-adrenal axis and adrenocortical atrophy.“
- Excess cortisol (R). DHT is needed to shut down the HPA axis, so blocking it increases cortisol. 5AR is also needed to deactivate cortisol, so without enough 5AR, someone can be in a hyperstressed state all the time.
- Messes with bile synthesis and excretion, creating toxic bile acids and cholestasis (R). “Due to the failure to synthesize primary bile acids in the AKR1D1 deficiency and the production instead of a spectrum of highly cholestatic and hepatotoxic 3-oxo-Δ4 bile acids, bile flow is impaired, leading to cholestasis. Since bile acids are essential for micellar solubilization of lipids, fat and fat-soluble vitamin deficiency occurs quite often.”
Hormonal and neurotransmitter alterations due to finasteride
A low DHT state can lead to low dopamine (R), high estrogen (R), high prolactin (due to reduced dopamine), high cortisol (due to reduced clearance) (R), elevated serotonin (due to elevated estrogen and lower dopamine) and hypothyroidism (R).
But always do blood tests first to see what is really going on. Do tests to see pregnenolone, progesterone, testosterone, DHT, thyroid (TSH, total and free T4 and T3, rT3), estradiol, estrone-sulfate and cortisol (both blood and 24h saliva).
In some people with PFS, DHT might be normal, but testosterone and cortisol low and estrogen and prolactin high. With proper testing you know where to focus on.
If you’ve already done blood tests and want to learn how to interpret them, check out these articles:
- How to interpret your testosterone blood results
- How to interpret your cortisol test results
- How to interpret your thyroid test results
If DHT is high, then you don’t have to focus on boosting DHT, but maybe rather allopregnanolone through increasing 5-AR type 1.
If prolactin is high, dopamine is most likely low and serotonin elevated, so then it would be good to focus on lowering prolactin.
If estrogen is high, focus on lowering that, as estrogen is a potent inducer of serotonin and prolactin.
If cortisol is low in blood tests, then you can focus on increasing that, but if cortisol is low in saliva tests but high in blood tests, focus on calming the adrenals.
Sign up for the Alpha Energy Male newsletter
Super useful research & truly life changing
I love Hans’s work and cutting edge research, and I have really benefited from Men Elite and Alpha Energy Male academy
Thank you for the amazing work, and please keep it going
Another great newsletter
Another great newsletter full of really great info.
Let’s say your DHT is low, here are the top 7 supplements you can use to increase it:
- Butea Superba
- Tribulus Terrestris
- 11-keto DHT
If you want additional methods on increasing DHT apart from supplements, check out my comprehensive article on boosting DHT:
If DHT is normal and you still feel off, mainly anxious, not confidence, shy, nervous, experiencing brain fog, etc., you might be low in allopregnanolone.
5α-R type 1, which creates the neurosteroids 5α-DHP and allopregnanolone downregulate the glutamatergic system. Low levels of these hormones increase glutamate and may account for the appearance of behavioural disorders such as anxiety, aggression, and cognitive dysfunction.
Here is how you focus specifically on increasing allopregnanolone:
- Alcohol (not a long term or good strategy really)
- Androsterone – both allopregnanolone and androsterone are potent GABA agonists, so might substitute to a degree for each other. DHEA potently increases androsterone levels, and that is how it’s thought to lower anxiety.
- Topical progesterone – the skin is rich in 5-AR, so applying progesterone to the skin should increase allopregnanolone.
- THC has been shown to increase brain pregnenolone, but this study shows that cannabis users have higher pregnanolone (a 5β-metabolite) and lower allopregnanolone (a 5α-metabolite) (R). However both are GABA agonists, weed might not be the best thing to use as it might even lower 5α-R in favour of 5β-R.
The optimal range for estrogen is around 20pg/ml and if yours is much higher, it would be best to make it a priority to lower it.
A few top supplements to lower estrogen include:
For more a comprehensive guides on lowering estrogen, check out this article:
Dopamine, testosterone and DHT go hand in hand with improving cognitive function, creativity, determination, positivity, problem-solving, euphoria, etc.
You definitely want high dopamine and low serotonin to optimize cognition and mindset.
Here are a few good ways to increase dopamine:
- Get lots of sunlight, especially in the morning
- Wake barefoot in nature
- Use Catuaba bark extract, mucuna pruriens, Tribulus Terrestris, etc.
For more a comprehensive guide on boosting dopamine, check out this article:
If dopamine is low, then prolactin will most likely be high. Prolactin is a bugger when it comes to mood and cognitive function. Keeping it low, below 7ng/ml, is absolutely key to improving.
A few of the best ways to lower prolactin include:
- Vitamin E
- Dopamine agonists, such as mucuna pruriens, huperzine A, Catuaba bark extract, etc.
- Tribulus Terrestris
- High dose vitex
- Estrogen antagonists
- Serotonin antagonists
For more a comprehensive guide on lowering prolactin, check out this article:
Serotonin is most often high in all mental and physical disorders and there is always a serotonin receptor/s gone rogue. Some might be upregulated and some downregulated, so you might experience heightened serotonin responses.
Some people actually report dramatic improvements in their symptoms after starting a certain SSRI. “How do you explain that? Huh? Punk?”
Well, SSRI drugs almost never only inhibit the reuptake of serotonin, but they often also increase allopregnanolone, decrease serotonin receptor sensitivity, block certain serotonin receptors, release dopamine and histamine, etc.
See? It’s really not the serotonin that’s so beneficial.
A few good ways to lower serotonin include:
- Increasing carbon dioxide production. CO2 keeps serotonin in check.
- Get lots of sunlight
- Vitamin B2
- Lower estrogen
For a more comprehensive guide on lowering serotonin, check out this article:
Apart from just focusing on hormones and neurotransmitters, you can also focus on diet and lifestyle. Here are a few things you can do:
- Get lots of sunlight
- Get proper sleep
- Do explosive exercises, such as uphill sprints, muscle-ups, jump squats, burpees, etc.
- Fix the liver
- Lower inflammation
- Eat truly organic
- Avoid all environmental plastics and toxins
- Be with supportive fun people
- Be active and do fun, exploratory things
- Cold and hot exposure, such as swimming in a cold river and doing sauna sessions
- Optimize thyroid. 5α-reduced steroids are significantly increased in a hyperthyroid state.
How soon can you expect to see results?
Finasteride binds to 5α-R type 2 with high affinity and dissociates very slowly with a half-life of 31 days. Furthermore, finasteride inhibits CYP3A4 (which is the enzymes that detox finasteride) and that can cause a significant buildup of finasteride in the body over time.
With that in mind, DHT can take anywhere from 4 weeks to 2 years or more to recover (R). But that does not mean you have to live with all the symptoms for that long. It just means that you might have to implement certain strategies and use certain supplements for quite some time before the enzymes normalize.
Very high levels of finasteride might then also be able to block 5βR, which will reduce bile flow. Are you sensitive to dietary fats and have greasy stool with fat floating on the surface of the water after pitching a loaf? If so you might have reduced bile flow. You might thus benefit from things that stimulate bile flow such as taurine and TUDCA. But check your bilirubin just in case.
A few additional tests you can do include:
- Bilirubin. Like mentioned above, it can help see if you have reduced bile flow
- Total cholesterol, LDL and HDL. These might be distorted by the drug, so keep an eye on them to see if they improve over time with what you’re doing.
- Vitamin D. Most people are low in vitamin D and vit D is very helpful to people with PFS.
- Liver enzymes. The buildup of the drug could cause liver damages, so have your liver enzymes tested to find out if you need to focus on your liver or not.
- Check 3adiolG for increases and 3adiol for decreases