Scientists report that enzyme that alters testosterone to estrogen has big impact in healthy brain

[Nelson Vergel]

Another reason not to mess with your aromatase activity (Most of you know my opinion about how many men on TRT are overdosing anastrozole when most do not even need it)


"An enzyme that converts testosterone to estrogen appears to have significant impact in a healthy and injured brain, scientists report.


There's mounting evidence that in the healthy brain, aromatase and the estrogen it enables neurons to produce, helps keep our brains and us nimble. Now scientists are learning that with injury, aromatase and estrogen expression seem to shift to cells in the brain called astrocytes, aiding their support and nurturing of now-stressed neurons, said Dr. Darrell Brann, Regents' Professor and Vice Chairman of the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Georgia Regents University.


Several studies, including those in Brann's lab, have shown this primary shift in aromatase/estrogen expression from neurons to astrocytes following injury. In Brann's case, the studies have been in the hippocampus, a center of learning, memory, and emotions. When he used a drug to reduce astrocyte's aromatase expression in that region, increased inflammation and brain damage resulted.


Even in culture, neurons will connect and communicate, but when scientists add an aromatase inhibitor to the mix, connectivity is interrupted. Some of the first in vivo studies in zebra finches showed that aromatase levels increased following a brain injury, which also supports a protective role for the protein. More brain damage results when aromatase inhibitors are given. "There seemed to be more inflammation," Brann said.

http://www.news-medical.net/news/20...-has-big-impact-in-healthy-injured-brain.aspx

 

[KSPhD]

Trying to correlate preliminary animal and cell culture work, where the doses of AI being used would be very high, to humans on TRT is ridiculous. Beyond that, the study has no links to the primary articles being discussed and Brann himself only had a handful of pubs on pubmed concerning E2. At the moment, this is nothing more than a non-productive NIH funded project.

 

[Nelson Vergel]

I am so glad that we have a PhD on ExcelMale that can help us digest these data!

"Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [ N ‐methyl‐ 11 C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time-activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V T ) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V T in all regions, though the size of the reduction was region‐dependent, ranging from ∼70% blocking in thalamus and preoptic area to ∼10% in the cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain". Synapse 64:801–807, 2010.


Unique distribution of aromatase in the human brain: In vivo studies with PET and [N‐methyl‐11C]vorozole
by Biegon, Anat; Kim, Sung Won; Alexoff, David L;
Synapse, 11/2010, Volume 64, Issue 11

Paper attached

 

[Nelson Vergel]

"The conversion of androgens to estrogens by CYP19 (cytochrome P450AROM, aromatase) is an important step in the mechanism of androgen action in the brain. CYP19 expression has been demonstrated in the brain of various animal species and in the human temporal lobe. Studies on postnatal CYP19 expression in various other areas of the human brain are rare and carried out in a limited number of post mortem obtained tissue. Therefore, we investigated CYP19 mRNA expression in fresh human frontal and hippocampal tissues and compared them to the expression in temporal neocortex tissues. We studied biopsy materials removed at neurosurgery from 45 women and 54 men with epilepsy. Quantification of CYP19 mRNA was achieved by nested competitive reverse transcription-PCR. CYP19 mRNA concentrations were significantly higher in temporal (2.29+/-0.40 arbitrary units, AU, mean +/- SEM; n = 57) than in frontal neocortex specimens (0.92+/-0.17 AU; n = 18; P<0.04). In hippocampal tissue specimens CYP19 expression (1.41+/-0.18 AU; n = 24) was lower than in temporal neocortex specimens, but the difference did not reach statistical significance. Sex differences were not observed in any of the brain regions under investigation. In conclusion, CYP19 mRNA is expressed in the human temporal and frontal neocortex as well as in the hippocampus. Regardless of sex, CYP19 expression was significantly higher in the temporal than in the frontal neocortex."

Journal of Steroid Biochemistry and Molecular Biology, 1999, Volume 70, Issue 4

Paper attached

 

[Nelson Vergel]

I can dig up some more papers with human data, so let me know.

 

[Dr. John Crisler]

Yes, the brain thinks so much of estrogen, it makes its own. This is also another reason men need enough testosterone--to be converted into estrogen. BTW, the aromatase inhibitor anastrozole, which I use in my practice, does not cross the Blood Brain Barrier, do does not interfere with estrogen production within the brain.

 

[Nelson Vergel]

I wonder how this happened

A Case of Brain Metastases from Breast Cancer that Responded to Anastrozole Monotherapy

 

[lowe2sucks]

my 5 year trt experince tells that one should avoid messing with estrogen and inhibiting aromatase enzyme unless your doc is super professional in trt and hormones field.. when I took too much AI I felt bad negative impact on cognitive abilities.. this study is true!

 

[Nelson Vergel]

More good reading

Estradiol in Men: Libido and Brain Function

 

[Dr. John Crisler]

Yes, the brain thinks so much of estrogen, it makes its own. This is also another reason men need enough testosterone--to be converted into estrogen. BTW, the aromatase inhibitor anastrozole, which I use in my practice, does not cross the Blood Brain Barrier, do does not interfere with estrogen production within the brain.

I was wrong.

Anastrozole DOES cross the BBB, but not nearly as well as the other AI's.

 

[Nashtide]

This issue may never be settled. Guys on TRT are going to have to weigh the options and do whatever they feel is best for them. Is high estrogen levels in men for prolonged periods of time safer than tiny doses of aromatase inhibitors? I’m convinced this won’t be settled in time to help me. I’ve weighed the options and at this point, I’ve decided that a very small amount of anastrazole is better than high estrogen levels.

 

[Joey786]

I took Arimidex for a few years along with my test cyp. I never used more than 1 mg per week. After about two years on Arimidex and test cyp I started noticed I would forget what I was saying mid sentence. This would happen multiple times a day. I had a feeling my estrogen wasn’t optimal but back then it was mandatory to take ai on trt per many of the boards at the time. I continued taking Arimidex for a year after the symptoms started. Keep in mind boards like t nation were spreading estradiol demonization so I was scared to stop Arimidex. I finally stopped Arimidex and I noticed my sex drive increased, I gained body fat, and my memory problems went away. Most important I was happy. The only benefit I got from Arimidex was I was super lean. My estradiol was 24 pg/ml on the old test while I was taking Arimidex. Maybe I needed to decrease the dose a little but once I dropped it I never wanted to try it again.

 

[Systemlord]

I over-respond to anastrozole and feel terrible on micro dosing even with E2 elevated, aromasin is better tolerated and found relief at only 1/10 of a tablet. Killed it in the gym the day after I took it.

Why does anastrozole get all the attention?

 

[Nashtide]

I take 0.2mg per week in two divided doses. This keeps my E2 in the high 20’s to low 30’s, so certainly not a low level of E2 and I feel no ill effects from the anastrazole. Again, despite what the forum “experts” tell you, there is no definitive evidence that long term low dose anastrazole is detrimental. 1mg of anastrazole is a huge does. That would most likely cause E2 to be way too low for most guys. I’ve been on anastrazole for the better part of 3 years and have not experienced any of the symptoms you mentioned.

 

[S1W]

I took Arimidex for a few years along with my test cyp. I never used more than 1 mg per week. After about two years on Arimidex and test cyp I started noticed I would forget what I was saying mid sentence. This would happen multiple times a day. I had a feeling my estrogen wasn’t optimal but back then it was mandatory to take ai on trt per many of the boards at the time. I continued taking Arimidex for a year after the symptoms started. Keep in mind boards like t nation were spreading estradiol demonization so I was scared to stop Arimidex. I finally stopped Arimidex and I noticed my sex drive increased, I gained body fat, and my memory problems went away. Most important I was happy. The only benefit I got from Arimidex was I was super lean. My estradiol was 24 pg/ml on the old test while I was taking Arimidex. Maybe I needed to decrease the dose a little but once I dropped it I never wanted to try it again.

I only took a few very small doses of anastrozole (.125mg) but I would say that was the side effect I noticed the most - it just made me feel slower mentally. I was surprised by this because I had heard all about people saying it caused them joint pain, etc, but I don't think I'd ever heard anyone talk about mental effects. In fact, I thought it would make me sharper mentally.

Regardless, I didn't like the way I felt on it so decided to continue along without it.

 

[lowe2sucks]

I only took a few very small doses of anastrozole (.125mg) but I would say that was the side effect I noticed the most - it just made me feel slower mentally. I was surprised by this because I had heard all about people saying it caused them joint pain, etc, but I don't think I'd ever heard anyone talk about mental effects. In fact, I thought it would make me sharper mentally.

Regardless, I didn't like the way I felt on it so decided to continue along without it.

almost all positives of testosterone on your brain come from it's conversion to estradiol in your brain so if you block conversion you also blocks positive effects of trt on your brain that would occur if you would let it aromatase. in common thing for people to think that lower estradiol is win win for everything in trt department (erection quality, strenght, muscle gain, stamina, sharper brain) when in reality it's completely opposite
now i don't know about estradiol that comes from hcg and dhea i only can vouch for estradiol that comes from conversion from exo T solo (and too much can be bad but only if you feel like it's not doing good for you)

 

[Nashtide]

For many guys, taking a small dose of anastrazole doesn’t completely block the conversion of T to E2. So your brain isn’t deprived of estrogen. For me, my small dose of anastrazole puts my trough E2 at around 30 using the sensitive E2 test. That is by no means a low amount of E2. Anyway, this works great for me. I feel tremendous on my protocol. I wish everyone did.

 

[lowe2sucks]

Nashtide it's because you are normal responder to AI and some are over responders so whenever their using even low dose of AI their e2 gets way too low and they lose positives estrogen provides. those who are overresponders are generally in roller coaster of too high and too low estrogen which removes a lot of positives of trt. to be honest I think those who get problems with high e2 on testosterone just take too much testosterone for their needs and their body can't support that level (maybe a genetic thing some are not made for high testosterone levels) so it just converts a lot of it to e2
first people who started using testosterone were athletes, bodybuilders etc.. first protocols for man HRT were copied from bodybuilders steroid regime which would have an AI in it since dosages of T were way supraphysiological.. so whoever invented TRT thought an AI will be needed even for replacement of testosterone and trt clinics are interested in selling more drugs to you so 200mg test cyp and hcg will results for most in elevated e2 problems that will be hard to handle now you have a reason to be on AI so they sell you 3 drugs when you could just take 40-60mg twice weekly and feel great, pay much less but no you pay 2-3 times more, feel sometimes worse than with low T xD

 

[Nashtide]

Good response. I completely understand what you’re saying. I only take 100mg/week and I still do better on the micro dose of anastrazole. I am also under 15% body fat. Just goes to show that every guy is unique. I just think the AI police do a disservice to new guys here. Just because you had a bad experience doesn’t mean the next guy will. I’m not singling you out. It’s just the general tenor on this forum.

 

[lowe2sucks]

I agree.. Don't get me wrong Nashtide I had times of successful use of anastrozole myself... in beginning of trt when using low doses... but multiple e2 crashes lead to problems thats why anti AI thing.. because while it can help it also can hurt one if used incorrectly.. so unless you know what you are doing with estrogen it's better to tell guys who are new to trt that AI should be avoided (like I said unless you know what your are doing which is impossible for guys new to trt)