The answer to high levels of aromatase?

[dlee1234]

Hi all,

Long time reader, first time poster.

I've just come across some research which I don't believe has been discussed on here previously, and after posting in the TRT Australia group, thought certain members of this forum might find this interesting/useful.

Background:
26 yrs old
Lean, clean paleo diet, powerlifter
20mg T daily shallow IM, .25mg adex daily

.25mg adex daily keeps my estrogen at 35 on the measurements used in the US, with T sitting at 1000.

Given I'm not overweight, have no problems with my liver or health and eat a clean diet, I've been struggling to work out why I seem to produce so much aromatase, and feel like absolute garbage/struggle without an AI.

Have a read of these excerpts from Examine on caffeine:

"Most metabolism of the caffeine molecule (up to 84%) occurs through the CYP1A1/2 (Aromatase) enzyme, and other enzymes (Xanthine Oxidase, CYP2A6, NAT2) are involved in the entire metabolic cascade or quite briefly on caffeine itself. Variations in CYP1A1/2, either genetic or through supplements, can greatly affect caffeine pharmacokinetics.

Genetic variations in the CYP1A (aromatase) enzyme that degrades caffeine can alter its ergogenic (performance increasing) effects, with the AA homozygotes outperforming the C allele carriers during endurance exercise.[1]
The AA genotype, in a sample of Caucasians, affects about 46% of persons. The C allele carriers can be either 44% (heterozygous, AC) or 10% (homozygous, CC).[64] AA Genotype is known as a 'fast caffeine metabolizer' and has a higher inducability rate, and degrades caffeine at a faster rate than AC or CC.[64] A higher 'Aromatase activity' tends to be either a genotype of AA, or lifestyle factors that increase CYP1A content.
Swedish persons have higher CYP1A activity than do Korean persons when lifestyle is controlled for,[64]
Activity of the enzyme can be upregulated by smoking, increasing caffeine metabolic rate.[65][64]Heavy coffee drinking may also increase CYP1A activity[66] although perhaps only for the AA genotype.[67]

The half-life of caffeine varies widely, due to aforementioned variations in CYP1A. One study noted a range of 2.7-9.9 hours[32] with highly similar ranges in another group of persons by the same researchers.[31]

In regards to caffeine itself, a 24 hour absence from caffeine does not seem to significantly alter CYP1A2 activity and its subsequent pharmacokinetic profile[75] and intake of coffee is correlated with increased aromatase activity at an extra 1.45-fold increase per 1L of coffee consumed."


My summary and interpretations:
- Caffiene is primarily (84%) metabolised by the aromatase enzyme
- Fast metabolisers of caffeine have greater levels of aromatase
- Using an aromatase inhibitor could extend the half life of caffeine up to over 10 hours
And most importantly
- Those with the AA allele for the aromatase enzyme (high levels of aromatase naturally) will create MORE aromatase in response to consuming MORE caffeine.

I'd love to hear everyone's thoughts on this, as I know I'm not the only one struggling with out-of-control aromatase even though lifestyle/health factors/injection frequencies are in check.

I'm going to ween myself off caffeine and eliminate it for a period and see if it helps. I'll be sure to report back.

 

[CoastWatcher]

Welcome to Excelmale, and thank you for posting a thought provoking bit of research. I have linked to the full study below.

Caffeine - Scientific Review on Usage, Dosage, Side Effects

 

[dlee1234]

Thanks for that mate, I thought I included the hyperlink but clearly forgot

 

[Vince Carter]

I'd be very interested in what you come up though the times I've come off of caffeine, besides 200mg as a pre-workout aid, hasn't impacted me for improving my aromatase profile.

I, too, have taken .25mg/Daily of Anastrozole, as well as other times I've used 12.5mg/D of Aromasin, and not crashed my E because I convert so much to E.

Though the daily or EOD of those two drugs in those doses hasn't been noticeably different for me so I returned to EOD for now.

16mg/D Cyp (about to switch to Enanthate)
200iu HCG on Sunday ONLY
12.5mg EOD Aromasin (current dose)
no DHEA
no Preg

I have no other reason that I convert at this rate, to E.

 

[Vince Carter]

I didn't have enough time or an experienced Dr very early on to know about E when I had a few months on Androgel 1.62. Too, I have a bad time trying Propionate hoping that it would convert less, and again too short of an experience with that one to see if there was an effect on lowering E.

Switching to Enanthate is another attempt at getting my E to subside with a different ester.

 

[jhperez81]

I had my DNA analyzed and I'm a slow metabolizer of caffeine which makes me think I would have lower aromatase activity. Unfortunately that is not the case but I do have a higher body fat percentage which is probably the reason I have to take an AI for now.

 

[YBWV]

What about trying a faster acting ester or cream? There’s debate about aromatase based on the ester, but I’m convinced based on labs and experiences I’ve seen posted. You don’t see many people needing an ai on creams or gels.

That's the answer!
The OP raises an interesting point about caffeine/aromatase and such concepts are worthy of investigation. However, much like DIM and CDC, the effects amount to little more than rearranging the deckchairs for guys that over aromatise and under-convert (via 5a-r) to DHT on the "standard" therapy of injectable T +/- AI's.
Guys that get some, or perhaps all, of their TT from TCream will have higher levels of DHT that balance their E2 and reduce the "need" for an AI.
Injectable/transdermal doesn't need to be an either/or decision.

I made those points to Dr Crisler on his "TRT without the use of AIs" thread and was encouraged when he announced that he would look to take his patients off their AIs and offer scrotal T Cream alongside T Cyp.

There's nothing "new" about adding the transdermal T to injectable T - members here on Excelmale have reported success with such therapy. Dr Shippen offered it and I recall Jason's post on his successful treatment with Defy. It would be interesting to hear from clinicians the reason(s) why such therapy isn't more widely used.

 

[Vince Carter]

That's a characteristic that I have, too, low DHT. So I use the cream added to my injections protocol. I do think that it blunts my E a bit. I can baseline DHT test at about ~35 on a 16-79 scale. Use of 25mg (two clicks of the dispenser) two hours prior to a blood draw pushes my DHT to appx 100 on the same scale, so it works. I return to baseline within 24hrs so it's a daily application if I want to use it like that. I do tend to use it PRN (as needed), though.

I do have some fantasy of wanting to go to an exclusive cream to the scrotum delivery method, even twice per day, but I've not talked to my Dr about this. My PSA is stable @ .6

I don't mind having to use the AI, either Anastrozole, or Aromasin, but using either in these doses/frequency I don't know that that's long term sustainable.

 

[Vince Carter]

Seeing how I do on Enanthate may be my turning point, in that way, trying to convert to TD/Scrotum.