Finasteride is a Progestin

[MNK99]

Check page 2 and 3 as well.

https://imgur.com/a/muNDz

Lednicer, D. Antineoplastic Drugs: Organic Synthesis. 2015. "The starting material for the synthesis of finasteride is progesterone…” pp.47

I took those screenshots of Danny Roddy's video

 

[stupidfreak]

And we know that progestines have antiandrogene effects.They lower androgene receptors expression in tissiue,thus causing lowering of tissue androgene sensibility

I guess mifepristone should lower progestine level in body but how should it suppose to restore tissue androgene sensibility long term?

 

[JonnyCraig]

Does Progesterone (bio-identical progesterone) have antiandrogenic effects?

 

[stupidfreak]

Does Progesterone (bio-identical progesterone) have antiandrogenic effects?

All progestines do.Progesterone is a progestine

 

[TubZy]

All progestines do.Progesterone is a progestine

Not necessarily, for example progesterone converts to allopreg and cortisol while finasteride (a protestin) does not. So progestins don't technically act the same in the body.

 

[IHateFin]

And we know that progestines have antiandrogene effects.They lower androgene receptors expression in tissiue,thus causing lowering of tissue androgene sensibility

I guess mifepristone should lower progestine level in body but how should it suppose to restore tissue androgene sensibility long term?

I posted a study once showing ru586 upregulates androgen receptors especially in the brain. I'll see if I can find it again. It was a rat study

 

[IHateFin]

Neonatal RU-486 (mifepristone) exposure increases androgen receptor immunoreactivity and sexual behavior in male rats. - PubMed - NCBI

Here it is

 

[Ghost]

I'm curious if anyone has found literature saying that Fin acts on the Progesterone Receptor. Technically, a Progestin acts on the receptor. I personally don't believe that starting the synthesis pathway from Progesterone is enough to say that it acts on that receptor. It very well could, but sometimes only one chemical reaction is enough to mess up the binding section of the molecule, and there are 7 steps between Progesterone and Fin. The addition of the Imide group and tBu could drastically alter binding to the PR.

 

[MNK99]

Unfortunately, I have not. It seems while derived from progesterone (like any drug, it must be synthesized from somewhere), it may not be a progestin. I spent time on Google Scholar last night. I could not find much if anything on it being a progestin, maybe it's only progesterone-derived.
I do have high progesterone which makes me feel safer about trying ella/Ru.

 

[MNK99]

Anxiolytic activity of progesterone in progesterone receptor knockout mice. - PubMed - NCBI

Progesterone's anxiolytic property was blocked completely by finasteride.
"Allopregnanolone also exhibited anxiolytic effects, but the magnitude of the response was similar in both genotypes. Pretreatment of PRKO mice with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone, completely prevented the anxiolytic activity of progesterone, but had no effect on the response to allopregnanolone, demonstrating that allopregnanolone (or other 5alpha-reduced metabolites of progesterone) accounts for the response to the parent steroid hormone."

I'm not sure if this helps at all...

 

[TubZy]

I'm curious if anyone has found literature saying that Fin acts on the Progesterone Receptor. Technically, a Progestin acts on the receptor. I personally don't believe that starting the synthesis pathway from Progesterone is enough to say that it acts on that receptor. It very well could, but sometimes only one chemical reaction is enough to mess up the binding section of the molecule, and there are 7 steps between Progesterone and Fin. The addition of the Imide group and tBu could drastically alter binding to the PR.

He talks about is his opening post in this thread.

ZINC FINGER THEORY DISCUSSION for PFS - 2 cases

I don't have any studies to my knowledge on it however I don't have as much access to the research as he does.

 

[Ghost]

I've looked through my research libraries at school and haven't found it either. The other question I had on it is this:

"Progestin binds Progesterone receptors and blocks it , this increases number of Progesterone receptors"

By definition, a Progestin DOES technically block the PR, but it acts as an agonist - mimicking Progesterone. It tricks the body into thinking there is more progesterone, and not less (which would make more receptors as a homeostatic mechanism). I don't know if Fin does this or not. Doesn't appear to be many (if any) studies on it.

So maybe Fin is an Antagonist of the PR? Good study, @MNK99.

 

[Helen]

As I said, progestins can act 2 ways on the receptor. agonise or antagonize depending on current progesterone levels.

 

[IHateFin]

maybe one of the many reasons why someone may not get pfs or may actually accelorate their hairloss (which i have read happens) may be due to those whom experiance antagonistic effects on prog, but for the vast majority it probably agonizes it strongly.

i bet this has to do with the original levels of progesterone in the person taking it too similar to how Ru will act a certain way depending on circulation progesterone in the individual

 

[MNK99]

1. Transdermal delivery of bioidentical progesterone using dutasteride (A 5α-reductase inhibitor): a pilot study.

Transdermal delivery of bioidentical progesterone using dutasteride (A 5α-reductase inhibitor): a pilot study. - PubMed - NCBI

J Pharm Pharm Sci. 2010;13(4):626-36.
Transdermal delivery of bioidentical progesterone using dutasteride (A 5α-reductase inhibitor): a pilot study.
Zargar-Shoshtari S, Wahhabaghei H, Mehrsai A, Wen J, Alany R.

Abstract

PURPOSE:
Bioavailability of transdermal progesterone is low and variable. This may be attributed to transdermal metabolism by the 5α-reductase enzymes or the direct transport to the saliva. The objective of the current study was to evaluate the effect of enzyme inhibition on the bioavailability of transdermal progesterone. Serum and salivary progesterone levels were evaluated to gain a better insight into the mechanism progesterone transport across the skin.

METHOD:
Twenty postmenopausal women with a Follicle Stimulating Hormone > 40IU/L were recruited to take part in the study. The subjects were randomly allocated to either dutasteride (n=10) or placebo (n=10). Each group applied either 500 mg of non ionic cream or dutasteride cream (2mg/g) to the right arm for 2 weeks. This was followed by applying 500 mg of progesterone or progesterone dutasteride cream (equivalent to 40 mg of progesterone) for a further 2 weeks. On day 30 blood and saliva were collected for over 12 hours and progesterone concentration was measured.

RESULTS:
The baseline progesterone concentration on day zero was 0.1 ng/ml. On day 30 baseline progesterone levels increased significantly (p <0.05) to 1.40 ng/ml and 1.15 ng/ml in the progesterone and dutasteride groups, respectively. Salivary progesterone concentrations were increased by seven fold, from 0.40 ng/ml to 2.9 ng/ml. On average, salivary progesterone concentration was four times the serum levels.

CONCLUSION:
The average serum and salivary progesterone concentration, Cmax, and the AUC were slightly higher in the dutasteride group, but no significant difference could be noted. Metabolism by the 5α-reductase enzyme is unlikely to affect the bioavailability of progesterone.

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2. 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis.

5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a med... - PubMed - NCBI
-Horm Mol Biol Clin Investig. 2014 Dec;20(3):73-80. doi: 10.1515/hmbci-2014-0025.

5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis.
Traish AM, Guay AT, Zitzmann M.
PMID: 25460297 DOI: 10.1515/hmbci-2014-0025

Abstract

5α-reductases, a unique family of enzymes with a wide host of substrates and tissue distributions, play a key role in the metabolism of androgens, progestins, mineralocorticoids and glucocorticoids. These enzymes are the rate-limiting step in the synthesis of a host of neurosteroids, which are critical for central nervous system function. Androgens and glucocorticoids modulate mitochondrial function, carbohydrate, protein and lipid metabolism and energy balance. Thus, the inhibition of these regulatory enzymes results in an imbalance in steroid metabolism and clearance rates, which leads to altered physiological processes. In this report, we advance the hypothesis that inhibition of 5α-reductases by finasteride and dutasteride alters not only steroid metabolism but also interferes with the downstream actions and signaling of these hormones. We suggest that finasteride and dutasteride inhibit 5α-reductase activities and reduce the clearance of glucocorticoids and mineralocorticoids, potentiating insulin resistance, diabetes and vascular disease.

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3. Foye's Principles of Medicinal Chemistry, pp. 1381:

Foye's Principles of Medicinal Chemistry

States that Fin and Duta are 4-azasteroid progestin analogues.

https://imgur.com/a/29QNO