Contradictions between TRT anastrozole dosing needs and high anastrozole effects in normal younger men:
We know that many guys on TRT do very well on 1.0mg anastrozole per week. We also are aware of studies where younger normal males were given 1mg or 2mg of anastrozole per day and their E2 levels averaged around 17mg/ml. [There were no significant differences between the two doses.] The result is that T levels have a strong increase, LH/FSH goes up and E2 does not drop too low levels. While technically interesting, the costs would have been extremely high.
That much anastrozole would take take E2 way too low for TRT guys and can lead to loss of libido, depression, loss of energy, ED and joint aches.
So how do we reconcile this apparent contradiction? Thankfully the needed data to resolve this is mostly already in this forum. The high dose anastrozole issue has been discussed here before, but is appropriately not in the stickies. We do have guys who find the high dose anastrozole data and they think that that is a clinical recommendation. A research paper is rarely a clinical recommendation. We have seen where doctors who go in that direction in a TRT context which is stupid and harms the patient. [Clinical research papers often are useful for determining treatment.]
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We know that higher hCG doses lead to elevated or high E2 levels that do not respond very well to anastrozole. In this context, higher TRT doses of anastrozole have often been seen to be ineffective in approaching levels near E2=22pg/ml. The high doses of hCG over stimulate the testes. The concentration of T inside the testes can be up to 80 times higher than serum levels in young virile males. High hCG doses may be increasing this concentration level even higher and some males will respond more than others. In the context of TRT, for older guys we can expect the testes of many to be blunted by age. So this effect could be expected to be stronger for younger males who have secondary hypogonadism. Because anastrozole is a competitive drug that competes with T at the aromatase enzymes, the ratio of anastrozole to free testosterone determines the outcome. A serum level of anastrozole that does a good job of managing peripheral aromatization of T–>E2 is mostly ineffective inside the testes where the T concentration levels are so much higher than serum levels. From this, you can easily see that higher doses of hCG drive intratesticular T–>E2 aromatization that cannot be managed with sane or affordable amounts anastrozole. If you drive T–>E2 down to close to zero in peripheral tissues, we can expect that there may be adverse effects in the brain and elsewhere.
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We know that SERMs increase T and E2. LH levels can go high. From this we can expect that there can be effects that are similar to high doses of hCG. [We also see a few take a SERM and hCG at the same time, totally wrong.] SERMs can easily lead to high rates of T–>E2 inside the testes and we would expect E2 levels to be unmanageable. We have seen a few hints of this effect in the forum [and in PMs sent to me].
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In one of the studies of high dose anastrozole in normal younger males, the following was postulated: The serum E2 levels do not drop as one might expect because higher T levels are creating more E2. Well we would also expect that, no brainer. But we know that peripheral T–>E2 in this context must be very very low. The only conclusion is that the testes alone are creating enough E2 to support healthy serum levels of E2. In this context, we get the same effect as a SERM and LH/FSH levels are increased, driving up intratesticular FT concentrations. [Why FT, because SHBG is only found in the blood and not in peripheral tissues; the T cannot be SHBG bound. We should expect that some would be weakly bound to other proteins, very little is known about that to my knowledge.] In light of this, these ideas really enforce the points presented in (2) above.
Summary: Low dose anastrozole works well in the TRT context of weaker or little testicular T generation. SERMs and high dose hCG can create high levels of LH/FSH that create high T levels driving high levels of T–>E inside the testes. High dose anastrozole can create the same effects as high dose SERMs or hCG, with the exception that peripheral T–>E2 is then very very low and the resulting serum E2 levels are not pathologically low, but can be healthy as a result of the testes producing enough E2 to support decent serum levels. But note that there could easily be adverse effects from blocking T–>E2 in the body where E2 is created for local utilization. The discrepancy is resolved and understood.
A danger: We know that high doses of hCG can over stimulate and down regulate the LH receptors inside the testes. Testicular LH insensitivity would be classified as testicular failure aka primary hypogonadism. I think that there is enough evidence to suspect that high levels of LH induced by SERMs or high dose anastrozole can over stimulate the testicular LH receptors and lead to the same LH receptor downregulation that one risks with higher doses of hCG. When older men with age degraded testes use higher amounts of hCG, SERMs [or high dose anastrozole] as a TRT treatment , they are at risk of damaging their testes that support those TRT methods.