Finasteride

links: Drugs Hair Loss reference: https://www.youtube.com/watch?v=mMgN6hYQgZ8 https://raypeatforum.com/community/threads/hair-loss-thinktank-passionate-and-or-intellectual-people.40689/post-649987 5-12-2021

Finasteride #

• (Irreversible) 5-AR inhibitor. IC50 for II = 11nM vs 313 for Type I. (or 69 vs 360)
  • According to discord guy: In rats, it inhibits all 3 isomers. Since 5-AR2 is only expressed in CNS but outside the brain, you see ED and other sides due to depletion there, rather than the brain where it is not found in large quantities.
• They attained their 1997 FDA approval by explaining how it reduces levels of DHT and so logically would increase T. They did not consider any other hormonal cascade - I guess that’s what I can thank for the whole ‘DHT blocker’ discourse. Even though in their research they knew it causes global defects in hepatic and peripheral 5-AR
• Doses are like 1-5mg/day, but over 1 is overkill. Even 0.25 is nearly as efficacious
• Lowers Interferon-γ.
• 25-50mg/kg (a shit ton, yippee) in rats downregulates Tyrosine Hydroxylase mRNA/expression in Substantia Nigra and Ventral Tegmental Area R
• Builds up Aldosterone: polyuria and inability to retain moisture.
• 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis
  • Inhibition of Cortisol conversion to 5α-dihydrocortisol can lead to its accumulation. Which of course has plenty of scares associated with it like hyperglycemia/Insulin Resistance, adiposity in body and liver, etc.
• 5α-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents
  • 5-AR knockout mice impaired liver fatty acid Beta-oxidation and gluconeogenesis. Increased liver steatosis and fibrosis in the liver.
• The Dark Side of 5α-Reductase Inhibitors’ Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression
• Follow-up of 1 mg finasteride treatment of male pattern baldness-difference between clinical trials and private office follow-up: influences on prescribing habits evaluated
  • n=1261. 68% dropout rate, and then about half of the remaining 414 felt they saw results.
• There is significant increase when levels are on the hypogonadal end, but after ~>500ng/dl, increase is minimal. No evidence to suggest de novo T biosynthesis is increased. Then it naturally follows that the Androgen Receptor expression is upregulation. After cessation, this hypersensitivity actually leads to really terrible symptoms. People take masures to downregulate it to baseline it to cure PFS with things like their old friend DHT. R
• Cholestasis; stoppage of Bile flow R.
• Taking a 5-ARi along with testosterone slowed muscle growth and did not accelerate any other measure like strength. R
• Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It’s Time to Sound the Alarm
  • Androgen deficiency reduces tear production and leads to evaporative dry eye conditions. Finasteride downregulates AR in the lacirmal gland.
  • Finasteride downregulates AR expression in the cortical region of the Kidneys.
  • Androgens increase Serine-Threonine Protein Kinase phosphorylation, expression of Pyruvate Dehydrogenase, succinate dehydrogenase and aconitase.
• The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption: Good review. There are polymorphisms in the AR gene dictating AGA risk and PFS susceptibility.
  • Part 2: Post-finasteride syndrome: a surmountable challenge for clinicians
    • Fiansteride increases HDAC
• Resnoir: “2. The issues are from hpta shutdown from e2 and desensitization of ERb, dht is the last thing I’d worry about from long term 5ari use. So get some aromatase inhibition in order, then.
• Increase in activity in the neural circuits corresponding to sexual arousal and decreasing activity in brain regions associated with higher level cognitive and motivational networks in symptomatic finasteride users in response to erotic stimuli.
• PNMT inhibitor: Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target
  • Jarvoss theorizes this is possibly more responsible for brainfog, rather than Allopregnanolone deficiency seeing as he didn’t notice much from it. Since he doesn’t get brainfog sides from dutasteride
• ~2-4 weeks of intial shedding. Fin/minox might synchronize the anagen phasn and teleogen phase of your hair alike, hence the whole “seasonal shed” stuff before anagen phases become years long.
• Sources: https://superpill.com/collections/express-ordering/products/finasteride-for-hair-loss or probably any site like alldaychemist etc. People on reddit say you can just crush them with a pill crusher (say .1mg/mL) and put it right into Kirkland minoxidil and let it sit overnight
  • BGPharm has it for $18 but $100 minimum order, lol. Could cop… Etifoxine, rapamune, oxytocin, Azelaic Acid 20% cream for $18, Edronax (Reboxetine), prucalopride, betahistine

Topical #

• Liposomal: It’s probably not as important/investigate as dutasteride, considering dut is >500 dA (528, while fin is 372)
  • Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation
    • Liposomal FNS formulations also showed more than fivefold higher deposition of drug in skin than the corresponding plain drug solution and conventional gel.
• 0.1-0.3% is what people generally use. It goes up to 1%
• Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial
  • Plasma concentrations of finasteride are way lower, but it still lowers your DHT equally.
• A novel finasteride 0.25% topical solution for androgenetic alopecia: pharmacokinetics and effects on plasma androgen levels in healthy male volunteers (Caserini et al. 2014)
  • Plasma DHT was reduced by ~ 68 - 75% with the (1ml 0.25%) topical solution and by ~ 62 - 72% with the (1mg) tablet.
  • Everything is replicated in the chart below, really:
• 100-fold lower finasteride plasma concentrations when applied topically.
• Effects of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia (Caserini et al. 2016) BEHOLD:

• Also note that 0.2 oral is enough on the response curve for the ~62-80% figure that finasteride generally tops out at, just like 5mg oral does. I’m thinking I’ll go between 0.0125% 0.025%. Assuming you have the DHT thing taking care of, I’m pretty sure there’s nothing stopping minox from losing its efficacy. In which case I’ll be really moderate. 25% drop in serum DHT is hardly anything bro. Jarvoss claims, however, that tissue accumulation/saturation will happen anyhow.