Can’t use Nolva… what is next best?

[Type-IIx]

Yes this is called cross receptor activation.. think about it this way, Anadrole is a DHT drug it litteraly cant aromatize because its already reduced yet you can get estrogen/progestorene side effects such as gyno from it, i have talked with Dr.Scott stevenson and Dave Crosland about this and they think the same as me its cross receptor activation

Ask them what they think then about the data showing no detectable PR binding from the Houtman mammalian reporter bioassay (Stevenson, at least, will certainly be familiar with this data).

It's an interesting open question, from where do oxymetholone's ostensible "gynecomastic" sides arise?

I suspect it's due to one or more of the following:
- a tendency to increase 17-OHP, a "weak" progestin [41]. Note that Camerino [126] cites Junkmann and Suchowsky, 1962 that "showed no gestagenic effect" at therapeutic doses. No direct PR binding (moderately to AR, weakly to ER-alpha (weaker than oxandrolone and stanozolol) & ER-beta in mammalian reporter gene bioassay [28]
- potential for MR agonism?
- potential activation of RAAS?

References:
[41] Patt M, Beck KR, Di Marco T, Jäger MC, González-Ruiz V, Boccard J, Rudaz S, Hartmann RW, Salah M, van Koppen CJ, Grill M, Odermatt A. Profiling of anabolic androgenic steroids and selective androgen receptor modulators for interference with adrenal steroidogenesis. Biochem Pharmacol. 2020 Feb;172:113781. doi: 10.1016/j.bcp.2019.113781. Epub 2019 Dec 27.
[126] Camerino, B., & Sciaky, R. (1975). Structure and effects of anabolic steroids. Pharm
acology & Therapeutics. Part B: General and Systematic Pharmacology, 1(2), 233–275. doi:10.1016/0306-039x(75)90007-0
[28] Houtman, C. J., Sterk, S. S., van de Heijning, M. P. M., Brouwer, A., Stephany, R. W., van der Burg, B., & Sonneveld, E. (2009). Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays. Analytica Chimica Acta, 637(1-2), 247–258. doi:10.1016/j.aca.2008.09.037

 

[DrZaius7]

Ask them what they think then about the data showing no detectable PR binding from the Houtman mammalian reporter bioassay (Stevenson, at least, will certainly be familiar with this data).

It's an interesting open question, from where do oxymetholone's ostensible "gynecomastic" sides arise?

I suspect it's due to one or more of the following:
- a tendency to increase 17-OHP, a "weak" progestin [41]. Note that Camerino [126] cites Junkmann and Suchowsky, 1962 that "showed no gestagenic effect" at therapeutic doses. No direct PR binding (moderately to AR, weakly to ER-alpha (weaker than oxandrolone and stanozolol) & ER-beta in mammalian reporter gene bioassay [28]
- potential for MR agonism?
- potential activation of RAAS?

References:
[41] Patt M, Beck KR, Di Marco T, Jäger MC, González-Ruiz V, Boccard J, Rudaz S, Hartmann RW, Salah M, van Koppen CJ, Grill M, Odermatt A. Profiling of anabolic androgenic steroids and selective androgen receptor modulators for interference with adrenal steroidogenesis. Biochem Pharmacol. 2020 Feb;172:113781. doi: 10.1016/j.bcp.2019.113781. Epub 2019 Dec 27.
[126] Camerino, B., & Sciaky, R. (1975). Structure and effects of anabolic steroids. Pharm
acology & Therapeutics. Part B: General and Systematic Pharmacology, 1(2), 233–275. doi:10.1016/0306-039x(75)90007-0
[28] Houtman, C. J., Sterk, S. S., van de Heijning, M. P. M., Brouwer, A., Stephany, R. W., van der Burg, B., & Sonneveld, E. (2009). Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays. Analytica Chimica Acta, 637(1-2), 247–258. doi:10.1016/j.aca.2008.09.037

Great info. I like this discussion; according to William Llewellyn’s Anabolics
he states that oxymetholone either acts as a progestin like Deca/Tren OR that it is able to activate the estrogen receptor similar to but more strongly than the estrogenic androgen methandriol.

Since oxymetholone does not and cannot convert to estrogen an AI would be pointless and your only defense against estrogenic side effects is a SERM correct?

 

[specter]

Ask them what they think then about the data showing no detectable PR binding from the Houtman mammalian reporter bioassay (Stevenson, at least, will certainly be familiar with this data).

It's an interesting open question, from where do oxymetholone's ostensible "gynecomastic" sides arise?

I suspect it's due to one or more of the following:
- a tendency to increase 17-OHP, a "weak" progestin [41]. Note that Camerino [126] cites Junkmann and Suchowsky, 1962 that "showed no gestagenic effect" at therapeutic doses. No direct PR binding (moderately to AR, weakly to ER-alpha (weaker than oxandrolone and stanozolol) & ER-beta in mammalian reporter gene bioassay [28]
- potential for MR agonism?
- potential activation of RAAS?

References:
[41] Patt M, Beck KR, Di Marco T, Jäger MC, González-Ruiz V, Boccard J, Rudaz S, Hartmann RW, Salah M, van Koppen CJ, Grill M, Odermatt A. Profiling of anabolic androgenic steroids and selective androgen receptor modulators for interference with adrenal steroidogenesis. Biochem Pharmacol. 2020 Feb;172:113781. doi: 10.1016/j.bcp.2019.113781. Epub 2019 Dec 27.
[126] Camerino, B., & Sciaky, R. (1975). Structure and effects of anabolic steroids. Pharm
acology & Therapeutics. Part B: General and Systematic Pharmacology, 1(2), 233–275. doi:10.1016/0306-039x(75)90007-0
[28] Houtman, C. J., Sterk, S. S., van de Heijning, M. P. M., Brouwer, A., Stephany, R. W., van der Burg, B., & Sonneveld, E. (2009). Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays. Analytica Chimica Acta, 637(1-2), 247–258. doi:10.1016/j.aca.2008.09.037

Scott is in here so ill send him a message
He doesnt know who i am in here since we talked on facebook, so he knows me by my real name

 

[specter]

Talked with Scott, he says he is covering the whole Anadrole thing in the latest episode of muscleminds so he thinks we should give it a listen

 

[Type-IIx]

Talked with Scott, he says he is covering the whole Anadrole thing in the latest episode of muscleminds so he thinks we should give it a listen

Sounds great!

 

[Type-IIx]

@specter @DrZaius7 The only other plausible mechanism for oxymetholone's apparent gynecomastic effects that I can think of would be attributable to its major excreted metabolite, 17α-methyl-5α-androstane-3α,17β-diol (also a methyltestosterone metabolite).

Just at a glance:
A similar testosterone metabolite, 5α-androstane-3β,17β-diol, is a known potent activator of ER-β, and it lacks the 17α-methyl structure of this oxymetholone metabolite (which serves to prolong any anabolic effects via hepatic metabolism, and prevents aromatization of the A-ring; though of course a 17β-OH backbone would serve to increase potency dramatically, by forming a strong bond with the C-terminus/carboxy- group of the AR). Still, this does seem (speculatively) to be an active metabolite. I think I will run some modeling on it.

 

[DrZaius7]

@specter @DrZaius7 The only other plausible mechanism for oxymetholone's apparent gynecomastic effects that I can think of would be attributable to its major excreted metabolite, 17α-methyl-5α-androstane-3α,17β-diol (also a methyltestosterone metabolite).

Just at a glance:
A similar testosterone metabolite, 5α-androstane-3β,17β-diol, is a known potent activator of ER-β, and it lacks the 17α-methyl structure of this oxymetholone metabolite (which serves to prolong any anabolic effects via hepatic metabolism, and prevents aromatization of the A-ring; though of course a 17β-OH backbone would serve to increase potency dramatically, by forming a strong bond with the C-terminus/carboxy- group of the AR). Still, this does seem (speculatively) to be an active metabolite. I think I will run some modeling on it.

@Type-IIx if this was the case what is the best way to counter act it?

 

[specter]

@Type-IIx if this was the case what is the best way to counter act it?

Nolvadex

 

[OuchThatHurts]

OBJECTIVES: To assess the efficacy of the anti-estrogens tamoxifen and raloxifen in the medical management of persistent pubertal gynecomastia. STUDY DESIGN: Retrospective chart review of 38 consecutive patients with persistent pubertal gynecomastia who presented to a pediatric endocrinology clinic. Patients received reassurance alone or a 3- to 9-month course of an estrogen receptor modifier (tamoxifen or raloxifene). RESULTS: Mean (SD) age of treated subjects was 14.6 (1.5) years with gynecomastia duration of 28.3 (16.4) months. Mean reduction in breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene. Some improvement was seen in 86% of patients receiving tamoxifen and in 91% receiving raloxifene, but a greater proportion had a significant decrease (>50%) with raloxifene (86%) than tamoxifen (41%). No side effects were seen in any patients. CONCLUSION: Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia - PubMed

Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

pubmed.ncbi.nlm.nih.gov

 

[Type-IIx]

@specter I ran some modeling on this active metabolite of oxymetholone. Dr. Stevenson can contact me if he wants the full data, though he may have ran similar modeling himself.

Abbreviated results:
- Decent bioavailability (0.55)
- Druglikeness profound
- GI absorption high
- BBB permeant
- Moderately soluble
- Lipophilicity: Consensus Log Po/w 3.55

 

[Type-IIx]

@Type-IIx if this was the case what is the best way to counter act it?

A SERM like Ralox makes good sense here.

 

[DrZaius7]

OBJECTIVES: To assess the efficacy of the anti-estrogens tamoxifen and raloxifen in the medical management of persistent pubertal gynecomastia. STUDY DESIGN: Retrospective chart review of 38 consecutive patients with persistent pubertal gynecomastia who presented to a pediatric endocrinology clinic. Patients received reassurance alone or a 3- to 9-month course of an estrogen receptor modifier (tamoxifen or raloxifene). RESULTS: Mean (SD) age of treated subjects was 14.6 (1.5) years with gynecomastia duration of 28.3 (16.4) months. Mean reduction in breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene. Some improvement was seen in 86% of patients receiving tamoxifen and in 91% receiving raloxifene, but a greater proportion had a significant decrease (>50%) with raloxifene (86%) than tamoxifen (41%). No side effects were seen in any patients. CONCLUSION: Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia - PubMed

Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

pubmed.ncbi.nlm.nih.gov

@OuchThatHurts great article, thanks. What were the respective dosages?

 

[OuchThatHurts]

@OuchThatHurts great article, thanks. What were the respective dosages?

It doesn't say, unfortunately. They could have done a standard therapeutic dosage as per the clinical pharmacology but more likely these are a given dosage x/kg so that all subjects were effectively receiving the same concentration per their respective bodyweights. What I found interesting about this particular article was that not only was it done on males (albeit young males) but the gyno was hormone-related with the most important part being that raloxifene was so much more effective and selective in breast tissue than tamoxifen.

86% of subjects experienced >50% reduction. Any gyno-prone AAS user has to be loving those odds and degree of reduction. I'm not gyno-prone but in my teens, I did have a painful lump under one nipple, then months later the opposite nipple which both disappeared over 4 or 5 months (at least the pain did anyway). I had no idea what gyno even was then.

Point being that if for some reason that would ever return, I would be running to raloxifene immediately. Or at the very least, combination therapy with raloxifene and tamoxifen. The more I read though, raloxifene just seems the superior SERM and when I find articles on SERMs and AIs that are relevant to us, I try to post them up.

 

[specter]

It doesn't say, unfortunately. They could have done a standard therapeutic dosage as per the clinical pharmacology but more likely these are a given dosage x/kg so that all subjects were effectively receiving the same concentration per their respective bodyweights. What I found interesting about this particular article was that not only was it done on males (albeit young males) but the gyno was hormone-related with the most important part being that raloxifene was so much more effective and selective in breast tissue than tamoxifen.

86% of subjects experienced >50% reduction. Any gyno-prone AAS user has to be loving those odds and degree of reduction. I'm not gyno-prone but in my teens, I did have a painful lump under one nipple, then months later the opposite nipple which both disappeared over 4 or 5 months (at least the pain did anyway). I had no idea what gyno even was then.

Point being that if for some reason that would ever return, I would be running to raloxifene immediately. Or at the very least, combination therapy with raloxifene and tamoxifen. The more I read though, raloxifene just seems the superior SERM and when I find articles on SERMs and AIs that are relevant to us, I try to post them up.

Ralox def seems to better the "stronger" option as a serm, wish it would be more easily available.

 

[specter]

@specter I ran some modeling on this active metabolite of oxymetholone. Dr. Stevenson can contact me if he wants the full data, though he may have ran similar modeling himself.

Abbreviated results:
- Decent bioavailability (0.55)
- Druglikeness profound
- GI absorption high
- BBB permeant
- Moderately soluble
- Lipophilicity: Consensus Log Po/w 3.55

View attachment 156436

Ill tell him

 

[DrZaius7]

Ralox def seems to better the "stronger" option as a serm, wish it would be more easily available.

@specter definitely harder to find. Seems out of stock even if someone carries it.

 

[DrZaius7]

It doesn't say, unfortunately. They could have done a standard therapeutic dosage as per the clinical pharmacology but more likely these are a given dosage x/kg so that all subjects were effectively receiving the same concentration per their respective bodyweights. What I found interesting about this particular article was that not only was it done on males (albeit young males) but the gyno was hormone-related with the most important part being that raloxifene was so much more effective and selective in breast tissue than tamoxifen.

86% of subjects experienced >50% reduction. Any gyno-prone AAS user has to be loving those odds and degree of reduction. I'm not gyno-prone but in my teens, I did have a painful lump under one nipple, then months later the opposite nipple which both disappeared over 4 or 5 months (at least the pain did anyway). I had no idea what gyno even was then.

Point being that if for some reason that would ever return, I would be running to raloxifene immediately. Or at the very least, combination therapy with raloxifene and tamoxifen. The more I read though, raloxifene just seems the superior SERM and when I find articles on SERMs and AIs that are relevant to us, I try to post them up.

@OuchThatHurts appreciate it. I’m very sensitive unfortunately. Seems Raloxifene will be standard practice now for me if I can find it.