There is a lot of success with CPA on this forum on doses between 50-25-12.5 mg i think very few failed with this drug.A lot of people consider it to have the quickest short term results within 6 months!! Imo you need to try both CPA and bica for at least 5-6 months before come to any conclusion along with e2 oral minoxidil 5-10 mg and 5ar inhibitor. Perseverance and consistency is key i think!!
I think if someone wants to use CPA, low doses are the sweet spot. I will quote a lot of posts I made in the past for this. The difference here is that CPA is a
partial agonist and not a full antagonist like Bica for the AR. Sure thing you need great/reasonable amounts of E2 when taking it.
1) https://www.hairlosstalk.com/intera...-hormonal-route-hair-life.109288/post-1905865
Could someone please explain to me, if the possibility of the partial agonist effects of SAAs like CPA/spironolactone, it is capable of making the things worse? Reading older threads, some members mentioned that is somehow fifty-fifty chance, and I believe it's making sense since Testo/DHT it will still do damage. Although, as long as I have been looking for, the majority gets very good results with CPA/spironolactone without the adverse effects of the partial agonist on the AR. So, how much should someone need to take that under consideration?
**Directly from Wikipedia:
Spironolactone, similarly to other steroidal antiandrogens such as cyproterone acetate, is actually not a pure, or silent, antagonist of the AR, but rather is a weak partial agonist with the capacity for both antagonistic and agonistic effects. However, in the presence of sufficiently high levels of potent full agonists like testosterone and DHT (the cases in which spironolactone is usually used even with regards to the "lower" relative levels present in females), spironolactone will behave more similarly to a pure antagonist. Nonetheless, there may still be a potential for spironolactone to produce androgenic effects in the body at sufficiently high dosages and/or in those with very low endogenous androgen concentrations.
Answer: https://www.hairlosstalk.com/intera...-hormonal-route-hair-life.109288/post-1905916
I don't have much information about spironolactone but if you use cpa 12.5mg/d, due to its potent antigonadotropic effect it will lower your T levels by 70% and its pretty enough to maintain a good hair, by the way, at such low doses, it wont have any antagonist or agonist effects… I have been on cpa 12.5mg/d plus finasteride 2mg/d (1mg day and 1mg night) for 20 days and its working well... And remember that you should periodically check you liver enzymes while you're on cpa.
Yes cpa at such low doses wont have any agonist or antagonist activity, as it is written in Wikipedia: "Although CPA is a potent antiandrogen, relatively high doses of CPA are nonetheless required for clinically important AR antagonism."
Even at high doses, chances are that its antagonist activity will be far more than its agonist activity. But its a weak antagonist. But look, cpa shows its antiandrogenic activity mostly by its antigonadotropic effect not by blocking the AR receptors, and since it is a very powerful antigonadotropin, it maximally lowers T levels by 70% at 12.5mg/d
https://en.m.wikipedia.org/wiki/Pharmacology_of_cyproterone_acetate
2)https://www.hairlosstalk.com/intera...-hormonal-route-hair-life.109288/post-1921208
Regarding CPA, the partial agonist effect to the AR,
still it is "troubling" me so much.. How could you "deactivate" the Partial Agonist effect from CPA? If you use Bicalutamide together, will the fully Silent Antagonist "diminish" the Partial Agonist effect of CPA? (A key property of
partial agonists is that they display both
agonistic and
antagonistic effects. In the presence of a
full agonist , a
partial agonist will act as an
antagonist, competing with the full
agonist for the same receptor and thereby reducing the ability of the full
agonist to produce its maximum effect.).
Does this means, that in a case of a full Antagonist (Bica), the partial agonist will act as full agonist ?? But still many people, are getting very good results with CPA.
It is capable of upregulating the AR receptor, or just simply the partial agonist effect, means that the AR will be still "activated" and not upregulated?? Please, if you have some free time, shed some light here.. I would totally appreciate it. Thank you very much.
Directly from Pharmacology of CPA (Wiki):
But unlike silent antagonists of the AR like nonsteroidal antiandrogens such as flutamide, bicalutamide, and enzalutamide, CPA, by virtue of its slight intrinsic activity at the AR, may be unable to fully inhibit androgenic signaling in the body, which may persist to an extent in some tissues such as the prostate gland.
Source:https://en.m.wikipedia.org/wiki/Pharmacology_of_cyproterone_acetate
Now that I read again the whole thing, I believe that this partial agonist, it means that the AR signal it will still be activated. It will get some binding though, but again it won't be fully ''binded'', like NSAAs (Bica for example). So, I believe that AR upregulation it is not very possible to happen? Please correct me if I am wrong here. Thanks.
(An escape or recovery phenomenon, in which testosterone levels increase over time, has been observed with long-term CPA monotherapy.In one study in aged men with prostate cancer, testosterone levels were initially suppressed by 70%, but increased to 50% of baseline levels between 6 and 12 months, remaining stable thereafter up to 24 months of therapy.).I believe that this has to do with the prostate cancer cells and the partial agonist effect, but this again is referring to cancer cells, instead of healthy cells for example.)
3) Another:
Cyproterone and spironolactone bind to the androgen receptor and exert mixed agonism–antagonism. In the presence of signifi cant levels of androgens, the antagonism predominates, and these agents are effective for the treatment of hirsutism. Flutamide is a nonsteroidal pure antiandrogen, effectively blocking androgenic action at target sites by competitive inhibition.
4) Discussed in the past:
Low Doses of Cyproterone Acetate Are Maximally Effective for Testosterone Suppression in Transfeminine People by Aly
transfemscience.org
Low Doses of Cyproterone Acetate Are Maximally Effective for Testosterone Suppression in Transfeminine People
5) Concerning thoughts from a Reddit post:
"CPA, as a partial agonist of the androgen receptor and not a silent antagonist like bical, 'blocks' T and DHT by binding to the receptor and weakly activating it. What I am wondering is, if T is already nuked, does more of the CPA start binding to AR's because it has no T or DHT to suppress? And could CPA by even weakly activating the ARs cause estrogen receptors to downregulate? Or keep them from upregulating, because even if it is weak there is still AR signaling going on? I heard that the breasts are particularly sensitive to any AR signaling. Is this why it is important to lower CPA dose to minimal amounts once T is nuked? Either way, I am loving a lower dose of CPA with bical."
6)
From wiki:
In accordance with its albeit weak capacity for activation of the AR, CPA has been found to stimulate androgen-sensitive
carcinoma growth in the absence of other androgens, an effect which could be blocked by co-treatment with flutamide.
[56][78][79] In one study in rodents, DHT-stimulated prostate weight remained 40% above controls with administration of CPA even at the highest dosage, while flutamide was able to completely block the stimulatory effects of DHT.
[82] In addition, CPA alone increased prostate weight by 60%, whereas flutamide had no effect.[82] As a result of its weak intrinsic androgenicity, CPA may not be as effective in the treatment of certain androgen-sensitive conditions such as prostate cancer compared to nonsteroidal antiandrogens with a silent antagonist profile at the AR.[15][83] Indeed, CPA has never been found to extend life in prostate cancer patients when added to castration relative to castration alone, unlike nonsteroidal antiandrogens.[84] As such, it is thought that the partial androgenic activity of CPA and other steroidal antiandrogens underlies the superior antiandrogenic efficacy of silent-antagonist nonsteroidal antiandrogens like flutamide.[76] However, the clinical significance of the weak androgenic activity of CPA has also been disputed.[49][85][86] In fact, some studies have found little or no stimulating effect of CPA on the prostate gland or seminal vesicles of male rats even with very high circulating concentrations of CPA.[85][86]
Nonsteroidal antiandrogens like flutamide and bicalutamide are more efficacious as antiandrogens than CPA in castrated animals due to their superior AR antagonistic activity.[72][87] Conversely, CPA is a much more potent antiandrogen than nonsteroidal antiandrogens like flutamide and bicalutamide in gonadally intact male animals, which is due to its antigonadotropic effects and consequent suppression of testosterone levels (nonsteroidal antiandrogens do not suppress testosterone levels).[72][87]
