SAAs include cyproterone acetate, megestrol acetate, chlormadinone acetate, and spironolactone
These drugs are steroids, reducing androgenic activity in the body. In contrast to NSAAs however, they are non-selective, also binding to other steroid hormone receptors, and exhibit a variety of other activities including progestogenic and antigonadotropic. In addition, they are not silent antagonists of the AR, but are rather weak partial agonists with the capacity for both antiandrogenic and androgenic actions.
"All medically used SAAs are weak partial agonists of the AR rather than silent antagonists, and for this reason, possess inherent androgenicity in addition to their predominantly antiandrogenic actions.[75][76][77] In accordance, although CPA produces feminization of and ambiguous genitalia in male fetuses when administered to pregnant animals,[90] it has been found to produce masculinization of the genitalia of female fetuses of pregnant animals.[76] Additionally, all SAAs, including CPA and spironolactone, have been found to stimulate and significantly accelerate the growth of androgen-sensitive tumors in the absence of androgens, whereas NSAAs like flutamide have no effect and can in fact antagonize the stimulation caused by SAAs.[76][77][91] Accordingly, unlike NSAAs, the addition of CPA to castration has never been found in any controlled study to prolong survival in prostate cancer to a greater extent than castration alone.[76] In fact, a meta-analysis found that the addition of CPA to castration actually reduces the long-term effectiveness of ADT and causes an increase in mortality (mainly due to cardiovascular complications induced by CPA).[92] Also, there are two case reports of spironolactone actually accelerating progression of metastatic prostate cancer in castrated men treated with it for heart failure, and for this reason, spironolactone has been regarded as contraindicated in patients with prostate cancer.[93][94] Because of their intrinsic capacity to activate the AR, SAAs are incapable of maximally depriving the body of androgen signaling, and will always maintain at least some degree of AR activation.[77][91]"
"Due to its progestogenic (and by extension antigonadotropic) activity, CPA is able to suppress circulating testosterone levels by 70 to 80% in men at high dosages.[25][95] In contrast, NSAAs increase testosterone levels by up to 2-fold via blockade of the AR, a difference that is due to their lack of concomitant antigonadotropic action.[96] However, in spite of the combined AR antagonism and marked suppression of androgen levels by CPA (and hence a sort of CAB profile of antiandrogen action), monotherapy with an NSAA, CPA, or a GnRH analogue/castration all have about the same effectiveness in the treatment of prostate cancer,[95][19] whereas CAB in the form of the addition of bicalutamide (but not of CPA) to castration has slightly but significantly greater comparative effectiveness in slowing the progression of prostate cancer and extending life.[76][19] These differences may be related to the inherent androgenicity of CPA, which likely serves to limit its clinical efficacy as an antiandrogen in prostate cancer.[75][76][77][97"
"Flutamide is approximately 2-fold more potent than cyproterone acetate in reversing the stimulatory effect of dihydrotestosterone (DHT) on ventral prostate weight. Even at the highest dose of cyproterone acetate, prostate weight remains 40% above control while flutamide completely reverses the stimulatory action of DHT, thus suggesting some partial androgenic activity of cyproterone acetate. Megestrol acetate, on the other hand, is devoid of any antiandrogenic activity and it even increases the stimulatory effect of DHT on prostate weight. While flutamide completely reverses the inhibitory effect of DHT on plasma LH levels in castrated animals, cyproterone acetate reverses the value of this parameter by only 30% while megestrol acetate further inhibits plasma LH levels at all the doses used. Both cyproterone acetate and megestrol acetate inhibit adrenal weight to approximately 25% of control, thus indicating their glucocorticoid activity. As direct measure of androgenic activity, cyproterone acetate and megestrol acetate increased prostate weight in castrated animals by 60 and 100%, respectively (P < 0.01) while flutamide had no effect. The present data show that cyproterone acetate and megestrol acetate, in addition to their well-known progestational and glucocorticoid action, have intrinsic androgenic activity. Since it is the only compound having pure antiandrogenic activity, flutamide provides the best scientific arguments for its successful use for the treatment of androgen-sensitive diseases."
Although SAA's reduce testosterone levels drastically, they do not possess pure antiandrogenic activity due to having partial agonist proterties in relation to the Androgen Receptor. If someone was to use a steroidal anti androgen for hair loss, it would benefit them in most situations, but there is a chance that their hair loss would not become better due to the SAA's ability to still allow some androgen signaling In the body. In fact in the small minority of people with more aggressive hair loss it is possible that these SAA's could increase their hair loss since "cyproterone acetate and megestrol acetate increased prostate weight in castrated animals by 60 and 100%" the SAA's have been shown to increase prostate weigh in some which In return would mean an increase in PSA (prostate specific antigen) scores, a biological marker of androgenic activity in tissues.
This is why oncologists don't prescribe SAA's for prostate cancer anymore, if SOME ar signaling is left in the body then that will still allow for the disease to spread, same case with hair loss, another disease.
The best option would be to use a NSAA, like bicalutamide, flutamide, enzalutamide which display only pure antiandrogenic activity as their mechanism of action being selective AR antagonists despite increasing testosterone levels.
A good combination would be an NSAA with a 5ar inhibitor. Reducing DHT levels and having the NSAA only have to play the role of blocking T which has a 2-3 fold lower affinity for the AR, allowing for lower doses to be used of the NSAA, this would be better for treating aggressive hairless.
These drugs are steroids, reducing androgenic activity in the body. In contrast to NSAAs however, they are non-selective, also binding to other steroid hormone receptors, and exhibit a variety of other activities including progestogenic and antigonadotropic. In addition, they are not silent antagonists of the AR, but are rather weak partial agonists with the capacity for both antiandrogenic and androgenic actions.
"All medically used SAAs are weak partial agonists of the AR rather than silent antagonists, and for this reason, possess inherent androgenicity in addition to their predominantly antiandrogenic actions.[75][76][77] In accordance, although CPA produces feminization of and ambiguous genitalia in male fetuses when administered to pregnant animals,[90] it has been found to produce masculinization of the genitalia of female fetuses of pregnant animals.[76] Additionally, all SAAs, including CPA and spironolactone, have been found to stimulate and significantly accelerate the growth of androgen-sensitive tumors in the absence of androgens, whereas NSAAs like flutamide have no effect and can in fact antagonize the stimulation caused by SAAs.[76][77][91] Accordingly, unlike NSAAs, the addition of CPA to castration has never been found in any controlled study to prolong survival in prostate cancer to a greater extent than castration alone.[76] In fact, a meta-analysis found that the addition of CPA to castration actually reduces the long-term effectiveness of ADT and causes an increase in mortality (mainly due to cardiovascular complications induced by CPA).[92] Also, there are two case reports of spironolactone actually accelerating progression of metastatic prostate cancer in castrated men treated with it for heart failure, and for this reason, spironolactone has been regarded as contraindicated in patients with prostate cancer.[93][94] Because of their intrinsic capacity to activate the AR, SAAs are incapable of maximally depriving the body of androgen signaling, and will always maintain at least some degree of AR activation.[77][91]"
"Due to its progestogenic (and by extension antigonadotropic) activity, CPA is able to suppress circulating testosterone levels by 70 to 80% in men at high dosages.[25][95] In contrast, NSAAs increase testosterone levels by up to 2-fold via blockade of the AR, a difference that is due to their lack of concomitant antigonadotropic action.[96] However, in spite of the combined AR antagonism and marked suppression of androgen levels by CPA (and hence a sort of CAB profile of antiandrogen action), monotherapy with an NSAA, CPA, or a GnRH analogue/castration all have about the same effectiveness in the treatment of prostate cancer,[95][19] whereas CAB in the form of the addition of bicalutamide (but not of CPA) to castration has slightly but significantly greater comparative effectiveness in slowing the progression of prostate cancer and extending life.[76][19] These differences may be related to the inherent androgenicity of CPA, which likely serves to limit its clinical efficacy as an antiandrogen in prostate cancer.[75][76][77][97"
"Flutamide is approximately 2-fold more potent than cyproterone acetate in reversing the stimulatory effect of dihydrotestosterone (DHT) on ventral prostate weight. Even at the highest dose of cyproterone acetate, prostate weight remains 40% above control while flutamide completely reverses the stimulatory action of DHT, thus suggesting some partial androgenic activity of cyproterone acetate. Megestrol acetate, on the other hand, is devoid of any antiandrogenic activity and it even increases the stimulatory effect of DHT on prostate weight. While flutamide completely reverses the inhibitory effect of DHT on plasma LH levels in castrated animals, cyproterone acetate reverses the value of this parameter by only 30% while megestrol acetate further inhibits plasma LH levels at all the doses used. Both cyproterone acetate and megestrol acetate inhibit adrenal weight to approximately 25% of control, thus indicating their glucocorticoid activity. As direct measure of androgenic activity, cyproterone acetate and megestrol acetate increased prostate weight in castrated animals by 60 and 100%, respectively (P < 0.01) while flutamide had no effect. The present data show that cyproterone acetate and megestrol acetate, in addition to their well-known progestational and glucocorticoid action, have intrinsic androgenic activity. Since it is the only compound having pure antiandrogenic activity, flutamide provides the best scientific arguments for its successful use for the treatment of androgen-sensitive diseases."
Although SAA's reduce testosterone levels drastically, they do not possess pure antiandrogenic activity due to having partial agonist proterties in relation to the Androgen Receptor. If someone was to use a steroidal anti androgen for hair loss, it would benefit them in most situations, but there is a chance that their hair loss would not become better due to the SAA's ability to still allow some androgen signaling In the body. In fact in the small minority of people with more aggressive hair loss it is possible that these SAA's could increase their hair loss since "cyproterone acetate and megestrol acetate increased prostate weight in castrated animals by 60 and 100%" the SAA's have been shown to increase prostate weigh in some which In return would mean an increase in PSA (prostate specific antigen) scores, a biological marker of androgenic activity in tissues.
This is why oncologists don't prescribe SAA's for prostate cancer anymore, if SOME ar signaling is left in the body then that will still allow for the disease to spread, same case with hair loss, another disease.
The best option would be to use a NSAA, like bicalutamide, flutamide, enzalutamide which display only pure antiandrogenic activity as their mechanism of action being selective AR antagonists despite increasing testosterone levels.
A good combination would be an NSAA with a 5ar inhibitor. Reducing DHT levels and having the NSAA only have to play the role of blocking T which has a 2-3 fold lower affinity for the AR, allowing for lower doses to be used of the NSAA, this would be better for treating aggressive hairless.
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