T Nation

Unintended Consequences of High hCG dosing


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.

My response:

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.


The package insert for anastrazole says that 1 mg./day can drive the estrogen levels to undetectable levels in post-menopausal women. Yet in men with some low level of testicular function the same dose only drops estrogens by about 1/3. So we men seem protected against anastrazole causing severe reductions in our estrogen levels. Usually, that is.

This could very well be from high intratesticular testosterone levels that swamp the effect of anastrazole in the testes. Makes sense to me, KSman.

There may be some low incidence of men who suffer a deep reduction in estrogens while on low doses of anastrazole (over responders). Have these been verified by seeing low serum estrogen levels or are the low estrogen levels assumed based on the reported symptoms?

It seems plausible that hCG therapy could increase intratesticular testosterone levels and therefore intratesticular T to E conversion, causing serum estrogen levels to rise, requiring increased anastrazole doses. That might have the paradoxical effect of driving down T to E conversion in the brain, where T levels are lower than in the testes. The result could be pleasing serum estradiol levels but a shortage of estrogen in the brain or in other tissues. This all seems plausible but as far as I know, data is lacking. I would imagine that lots of lab rats would have to be sacrificed to find an answer.

In sum, I wonder if we know what is the optimum serum estradiol level in men receiving TRT? It seems that we mostly have anecdotal reports.

I don’t doubt that T and E are important in the brain. One of the first things I noticed upon starting TRT (Test Cyp, 100 mg. IM/week) were vivid, colorful (alas, non-sexual) dreams. I also felt “energized” mentally. Alas, all that has faded. Is it the rising estrogen? Can it be recaptured with anastrazole?

I thought that the study cited was reassuring in that serum estrogen levels didn’t tank, adverse effects were minimal and maybe not related to the anastrazole per se, and so it seems reasonable for men to take it in low doses. What the effects might be after years or decades of use is not known, from what I could find out.

I also occurs to me that age might have to be accepted a little more gracefully. Not everything is going to be fixable. It is always something. But let’s optimize what we can. There should be no reason to go around depressed and listless because of low testosterone.


I have seen enough reports by over responders showing single digit E2, or below the particular lab test’s detectable/reportable range to not have any doubts.

I often stated that serum E2=22pg/ml is optimal for libido. Many TRT+AI guys agree. Libido is something that guys seem to be able to quantify. In my thinking, when a guy has adequate T and a good sense of well-being, libido is a result. Libido is a good barometer of one sense of well-being. And for many, when their libido is stronger, they feel better in many aspects.

Myself, if my E2 is 28 I do not feel as good as when near E2=22.

LEF.org states:
Estrogen (measured as estradiol) should be kept at 30 picograms per milliliter (pg/mL) or lower. If a manâ??s estrogen level is more than 30 pg/mL, it should be reduced.

Anastrozole does not seem to have an direct side effects that I am aware of. Reported side effects all seem to be related to E2 levels. Small dose anastrozole taken by men is a very low chemical load as well.

As for aging with “normal” decrepitude, we can alter the nature and process of aging. It is easy to block the increases of E and E:T that come with male aging. You also have to remember that not talking anastrozole and letting E and E:T run amuck is also a decision that has consequences. I guess you get to choose how you die to some extent. Others would call this a simple QOL decision.