Anastrozole is actually INCREASING my Estradiol. WTF?

[Bubbba]

The title basically sums up my question. Sorry for being so lengthy but, I thought I would give a full history in case it helps. The main results I'm concerned about are in the last three paragraphs. Here's the background, chronologically:

Ancient history:

I first tried HRT about 8 years ago, with some success. I stopped after about a year and I started back two years ago. I'm sorry but, I don't have the labs from 8 years ago but, I recall the Dr said I was in range for all levels, including estradiol. At that time I was on 200mg testosterone cypionate per week, no HCG and 0.5mg of Anastrozole per day. After initially starting the Test, the Dr said my estradiol was high, and after getting on the Anastrozole, he said it came to within range. So, my impression was that the Anastrozole was doing a good job lowering my estradiol. But, since I don't have the labs, I can't confirm whether it ever really worked.

Current History:

Two years ago, I started back on HRT with a different Dr. My initial baseline was (LabCorp) Total Test 221.9 ng/dl (Range 264-916), Free Test 10.2 pg/ml (Range 7.2-24). Estradiol was not tested.

I then went to a third Dr and started on 200mg test per week and 1000iu HCG per week (two 500iu shots per week). After 3 months I had a very crazy lab result which has never re-occurred: Total test 1499ng/dl (Range 264-916), free Test not tested, estradiol 61.8pg/ml (range 7.6-42.6).

I then completely stopped the test and continued only the 1000iu HCG per week. After two months I re-tested at home with a ZRT blood spot test and got 362ng/dl Test (range 400-1200) and 75pg/ml Estradiol (range 12-56). I continued the same HCG and tested at the Dr's office one month later and got (LabCorp) 213ng/dl Test (range 264-916) and Estradiol 44.1pg/ml (range 7.6-42.6)

I then stayed on the 1000iu HCG per week and started 0.25mg Anastrozole per day. I then did another ZRT blood spot test at home and got 290ng/dl Test ( and 57pg/ml estradiol. I noted that when I first went on the Anastrozole I felt kind of bad (sluggish). My impression was that the Anastrozole was lowering both my estradiol and test.

I then increased my Anastrozole to 0.75mg per day, stayed on the same 1000iu HCG per week, and after one month, re-tested at home with the ZRT blood spot and got 297ng/dl test (range 400-1200ng/dl) and 32pg/ml estradiol (range 12-56pg/ml). So, at this point, I was happy with my estradiol and thought I had found the right dosage.

So, I then went back on Test at 100mg per week, and stayed on the 1000iu HCG per week and the 0.75mg Anastrozole per day. Four months later I re-tested at home (ZRT blood spot) and got 519ng/dl Test (range 400-1200ng/dl) and 72pg/ml estradiol (range 12-56pg/ml). High again. Crap! Then two weeks later I was tested at the Dr's office and got (LabCorp) 550ng/dl Test (range 264-916) and Estradiol 55.8pg/ml (range 7.6-42.6). Still high. So, at this point, I'm wondering if the estradiol test result from 4 months ago was incorrect.

So, then I went on 200mg test per week, 1000iu HCG per week and the 0.75mg Anastrozole per day. Two months later I re-tested at home (ZRT blood spot) and got 794ng/dl Test (range 400-1200ng/dl) and 61pg/ml estradiol (range 12-56pg/ml). At this point, the estradiol was a little high but not too bad.

So far the Anastrozole I had been taking was from 8 years ago and was a generic. So I was thinking maybe it had lost some potency. So, I got a brand new prescription of actual brand name Arimidex and tried that at the same 0.75mg per day and continued the 200mg test per week, and 1000iu HCG per week. One month later I re-tested at home and got (ZRT blood spot) 545ng/dl Test (range 400-1200ng/dl) and 84pg/ml estradiol (range 12-56pg/ml). Now I'm really starting to say WTF. Lower test and higher estradiol?

So, now being confused about what's going on, I decided to go to the extreme on the Arimidex to see what would happen. I took a full 1mg per day and continued the 200mg test per week, and 1000iu HCG per week. Two months later I re-tested and got (ZRT blood spot) 671ng/dl Test (range 400-1200ng/dl) and 128pg/ml estradiol (range 12-56pg/ml). Seriouly, WTF!!! The Arimidex really seemed to be increasing my Estradiol.

So, at that point, I quit the Arimidex completely and have continued the 200mg test per week, and 1000iu HCG per week, for the last 3 months. I will re-test with ZRT blood spot in a couple of weeks and follow up at my Dr office. I assume my test will be in the 700 range and my estradiol will be around 75 or so. But, I feel OK now and am getting obvious benefit from my HRT so, maybe I'll just forget about using Anastrozole. But still, I'm not sure why I got such weird results: Are these false readings? Is there an interaction between the Arimidex and the HCG? What? maybe I could re-start taking a small dosage of the Anastrozole. Or, is there another drug I could try that might be more successful at lowering my estradiol?

Any advice y'all can provide will be greatly appreciated.

Thanks!

[Youthful55guy]

I have no experience with ZRT labs, but I'm interesting in following your experience. I'm a little Leary given the data you've posted. You've had 2 panels that were chronologically close enough to each other to compare results for Total T and for E2 between ZRT and LabCorp. The difference between the lab results (regardless of protocol) in Total T is +175% with LabCorp (213 to 550) but only +43% for ZRT (362 to 519).

For E2, (75 to 72) is essentially unchanged with ZRT while LabCorp shows a difference of 44 to 55.8. Now we have to keep in mind too that you are above the upper end of the range for both lab tests (12-56 for ZRT and 7.6-42.6 for LabCorp, so it is not surprising that they do not show much of a change. You are simply maxing out the level of detection for both test methods and they are reporting back distorted values at the high end. This is why the standard E2 lab (from any laboratory) is worse than worthless for men, the E2 levels in men are almost always below the low end of sensitivity for the standard test so it will always report back the lowest possible result it can record, which is way too high for men. So it will always tell you that you are high in E2 no matter how low your E2 may go.

My gut reaction is that, unless you live in a state where self-testing is not allowed, I'd ditch the ZRT labs and go with LabCorp self-purchased labs that you can get from at least 2 vendors that I know of. I've had a very favorable experience with https://www.discountedlabs.com/. I've done 22 separate lab panels with them over the past 4+ years and never a bad experience (all but one of the panels included E2). All the tests are conducted through LabCorp and you can specify which E2 lab method you want (again, I strongly suggest the LC/MS/MS method). I also find them to be very affordable and always get you results within 7 days. I strongly suggest the LC/MS/MS test method for E2, which is designed specifically for men.

[Youthful55guy]

He's an excerpt from a published paper from the Endocrine Society with a position statement on the challenges of measuring E2, specifically with the LC/MS, LC/MS/MS, and RIA (Radioimmunoassay) test methods. They seem to say, being diplomatic to test labs and professional opinion, that the LC/MS or LC/MS/MS test method is better.

Adult men
Normal physiology and pathophysiology
The role of target tissue aromatization of T to E2 in men is poorly understood. Estradiol levels in men are lower than in premenopausal women (53); they are at or below the sensitivity of available direct E2 assays (55). In addition, there is concern about the lack of specificity at the lower ranges of the assay, similar to issues in the measurement of levels in postmenopausal women. Comparison of the measurement of 12 steroids by GC/MS or LC/MS/MS and 6 steroids by RIA in fasting samples from 20 healthy men (aged 50–65 y) revealed significant differences. RIA showed higher E2 levels, suggesting greater cross-reactivity compared to other methods (33 ± 6 compared to 21 ± 5 pg/mL). Although each assay showed good reproducibility, the authors caution about comparing absolute levels across assays or studies (55). Thus, concordance in assays is required to define normal and abnormal E2 levels in males.

From <https://academic.oup.com/jcem/article/98/4/1376/2536715>

[Youthful55guy]

Something else to consider. Common test methods for E2 cannot distinguish between C-Reactive Protein and E2, so their results are a combination of the two. This is in contrast to LC/MS or LC/MS/MS test methods, which have zero cross-sensitivity to C-Reactive Protein.

C-Reactive Protein is a measure of inflammatory response, so when this level goes up (in response to a number of disease states), your E2 as measured by traditional E2 assays will also go up. The question is, do you have a known disease state with a large amount of inflammation? BTW, high CRP is also indicative of a high risk for coronary heart disease.

[Bubbba]

Wow, thanks for all the detail, Youthful55guy! No, I do not believe I have any type of inflammation or coronary heart disease. I will look into at home LabCorp tests through DiscountedLabs using the LC/MS/MS method. I'll also ask my current Doc about using the LC/MS/MS method for his tests. Lately he's been suggesting that I go with a lower test dosage due to the high E2 levels. I'd prefer he not lower my dosage so, it would be good to convince him everything is OK.

[Bubbba]

It's true that it's difficult to compare results between ZRT and LabCorp because the ranges are different. I take it to mean that a given number with ZRT is not equal to the same number from LabCorp.

I checked out the DiscountedLabs site and am thinking about getting the following two tests:

https://www.discountedlabs.com/testo...d-free-regular
https://www.discountedlabs.com/estra...itive-lc-ms-ms

Thanks again!

[Bubbba]

Also, would anybody have any idea why I would feel sluggish (and just bad in general) when first starting on the Anastrazole? It's very unpleasant and lasts for a couple of weeks and I gradually start feeling back to normal. Also, when I come off of Anastrazole, I feel better.

[C27H40O3]

Also, would anybody have any idea why I would feel sluggish (and just bad in general) when first starting on the Anastrazole? It's very unpleasant and lasts for a couple of weeks and I gradually start feeling back to normal. Also, when I come off of Anastrazole, I feel better.

I felt the same way, and when i told my doctor that it made me feel tired and dragging ass, he said that was impossible. I think it even made me have weaker erections. When i started the anastrazole, I stopped waking up with a tentpole under the blanket. i stopped taking it anyway. i was on 0.5 mg every three days, along with 100 mg Test-C.
I felt a little bloated without it, but i felt generally better. Alot of the brothers on this site say you dont need an AI with 200 mg test-c a week.

[Bubbba]

Thanks C27H40O3. I think I may be a "high converter" and have always had somewhat elevated E2. If possible, I would like to try to get my E2 in normal range and see how I feel. I think my challenge at this point is to get accurate test results.

I looked back at my old LabCorp results and I see that for the E2 it says: Roche ECLIA Methodology. Is this the method that's intended more for women (not the "sensitive" method"? If so, then maybe that method is the culprit.