I was asked by a member to comment on some published research. I have copied some of the PM here. Note that there have been a few on this forum who have had intractable levels of E2 that anastrozole cannot manage when they are on high hCG doses as part of T+AI+hCG or on hCG monotherapy. Some men may be more prone to hCG induced E2 generation.
First, anastrozole over responders are a small fraction. The one who dropped out of the study because of libido loss may have been an anastrozole over responder as libido loss is a primary side effect for such individuals.
I have read a few like this. In this study, T and E were low, adex improved T and lowered E. But the low starting points for E did not result in large shifts in E. Why? While T-->E aromatization rates were lowered greatly, the increased T provided more substrate for T-->E. And as LH increased, testicular function increased. The intratesticular testosterone [ITT] concentrations would have increased a lot. ITT in young men can be up to 80 times higher than serum levels. ITT can feed a lot of T-->E in the testes as they have a fair amount of aromatase. And note that the testes and ovaries are sexual differentiations of the same cell clusters in embryo and one should not ever be surprised to see some female attributes in male organs. As men age, aromatase tends to increase, further contributing to increased E2 generation rates in this study of older men.
Increased E2 generation blunts the HPTA response as well as the effectiveness of the anastrozole on E2 levels.
Serum levels of anastrozole will never, as a competitive drug, be effective in the testes when ITT is much greater than serum levels.
So reduced aromatase action from the testosterone competitive anastrozole was offset by higher amounts of testosterone. This was a research study that was primarily interested in how this population of males would respond to an AI drug. The results show how they responded. The results proved to be of little interest from a clinical point of view VS what can be achieved with TRT. The poor response also shows that old men have weaknesses in their HPTA that blunt the AI effects. The testes are aged and degraded, and probably have blood circulation problems like the rest of the body and brain.
In a TRT context, T levels are very high and E levels, left to their own, are often pathologically high. Anastrozole is very effective in this context and the levels achieved trend down to the same levels as seen in this study. Perhaps these lower levels are a typical basement response. With TRT without hCG, the testes are not working and ITT levels will be close to serum levels. This small amount of tissue probably then produces very little T-->E. With T+hCG, the testes can produce a lot of E. With high ITT, anastrozole is not very effective in reducing testicular T-->E. If the testes produce a lot of E, as with high hCG doses, large anastrozole doses will simply be greatly reducing T-->E in peripheral tissues and the brain. Doing this may create problems in brain function that are expressed in varying degrees of energy, mood, depression or personality changes. Serum E2 might look optimal/healthy, but E levels in the brain can be too low and one would expect that that would reduce libido. Thus high dose hCG and anastrozole use to achieve "optimal" serum E2 levels might be producing a lower libido instead of optimizing it.
The brain does create testosterone for local needs. Too much aromatase inhibitor has some obvious problems for the brain, all the more for males who are achieving lower serum levels. Again, we see that the estrogen needs in the male brain track some of the same functional needs in females.
The above is some of the understanding that can rise above the facts in published research.