T Nation

Need Help with Anastrozole Dosage

Hey Guys,
Looking for some guidance. I’ve been researching on here, but I’m one of those people who don’t trust my own opinion or research on matters like this. I’ve been on TRT for about a year, and showing some effects of high E2 (anxiety, emotion swings, low libido) some time into my TRT (been on it about a year). My labs show Free T on the lower end of healthy range, and E2 on higher end of healthy range (most of the time…see below), so me and my doc were hoping to balance this out more. Here’s the details:

150mg Test Cyp/8 days. Split into a 75mg dose every 4 days, subcutaneous in belly.

Ref Ranges of lab
Total T: 264-916 ng/dL
Free T (Direct): 8.7-25.1 pg/mL
Estradiol : 7.6-42.6 pg/mL
SHBG, Serum: 16.5-55.9 nmol/L

My last two labs results…

-2 days before next injection/2 days after injection:
Total T - 751
Free T - 18.8
Estradiol - 39.8
SHBG - 36.1

-1 day before next injection/3 days after injection:
Total T - 645
Free T - 12
Estradiol - 32.4
SHBG - 34.4

I believe my Estradiol is spiking even higher the day after injection, as I have previous reports that my doctor didn’t mention noticing, like one in April (can’t recall exact timing of bloodwork in relation to injection) with the same dosage and schedule where results are:
Total - 682
Free - 12.8
Estradiol - 43.7 ***

Hoping someone like KSMan or another heavily active user can give some input on how to use the Anastrozole tablets I was just prescribed (1mg). My doc suggested half a pill twice a week. I’ve seen suggestion on here of .25mg twice a week instead, so I’m not sure.

Can some give some guidance on how much and what timing to take this to get the Estradiol lower? Also, will the subsequent effects of lowering Estradiol be higher T levels, or would I still need to inject more to get the T numbers up?

Thanks for the help guys.

EDIT**** - Appreciate the feedback guys. Would there be drawbacks of using the AI? I’ve seen the recommendations of increasing frequency of dosages to help, but if there’s not a major drawback to the AI I’d prefer to go that route, as someone who has issues with needles. Getting it down to 4 days at a time was tough enough due to phobia of sorts, and I still get vasovagal responses a lot of the time even after a year+ of TRT, so I really don’t think I’d have an easy time sticking to every other day… Thoughts?

Ideally you need to figure out why you are converting so much into e2. Are you overweight? Your SHBG is midrange, usually those people don’t have too much of an issue with e2.

Finasteride or Accutane?

Whenever you inject large infrequent doses of testosterone and estrogen peaks higher, to minimize estrogen injecting smaller doses more frequently will lower estrogen. So your estrogen is spiking higher because of the larger doses, an 20-25mg EOD protocol should lower estrogen for you.

If you do as suggested you can cut out the drugs, anastrozole should be used when lowering the dosage or changing the protocol fails to deliver results.

You’re not using the correct E2 testing methodology, Roche ECLIA methodology overstates estrogen in men when E2 levels are elevated, the LC/MS assay is more sensitive and should be used for men.

The commonly used Roche ECLIA methodology test may overestimate estradiol. That test uses immunoassay technology that cannot differentiate C-Reactive Protein (involved in inflammation) from estradiol, so it reads the combination of the two as estradiol. This sensitive estradiol test is based on liquid chromatography/mass spectrometry (LC/MS), an assay technology that does not have that limitation.

Adult Men. The use of a sensitive, LC/MS assay for serum E2 measurement in males is preferred over direct immunoassays because of its greater sensitivity and lesser interference by other steroids. In males, estradiol is present at low concentrations in blood, but it is extraordinarily high in semen. Estradiol plays an important role in epididymal function and sperm maturation and is essential for normal spermatogenesis and sperm motility.

Yea, part of the way we found the low T. Gained about 60 lbs in 2 years while maintaining my diet and workout regiment. 5"9" 225lb now

And no accutane now, but took it for a couple of years when I was in highschool. 31 now.

Yea I took it in hs too, same age also.

Aromatase in produced in the fat cells, lose weight, it will help a lot.

Not true.


However, regardless of the test used, regardless of the number, you are having high E2 symptoms. Some are very sensitive to elevated E2. I know a guy that says his nipples hurt just putting on a shirt when his E2 hits 30. Go with how you feel and not a lab number. You need to change your testosterone dosing, or add an AI, or both.

You are currently taking 75mg every four days, right? I think I would try 35mg every two days.

Simultaneous measurement of total Estradiol and Testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry.

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone related disorders in patient care and translation research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03–48.5 nM (0.75–1400 ng/dL) and estradiol 11.0–5138 pM (2.99–1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and −0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for two years with mean bias −0.7% (95%CI: −1.6% to 0.2%) for testosterone and 0.1% (95%CI: −2.2% to 2.3%) for estradiol. The method precision over a 2-year period for Quality Control pools at low, medium and high concentrations was 2.7–2.9% for testosterone and 3.3–5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies.

Keywords: CDC HoSt, Estradiol, Testosterone, Hormone, Serum, LC-MS/MS

Go to:

1. Introduction

17β-Estradiol (E2) and testosterone (TT) are sex hormones responsible for the development and maintenance of secondary sex characteristics and reproductive functions (1). They influence many physiological processes, such as growth, glucose homeostasis, bone and lipid metabolism, and cardiovascular function (25). Measurement of total circulating E2 or TT in conjunction with other biomarkers and clinical assessments is widely used for evaluation of reproductive status and function, for diagnosis of disorders such as infertility, delayed or precocious puberty, and other diseases related to altered steroid hormone metabolism. TT and E2 are also critical in monitoring therapeutic interventions such as in-vitro fertilization and antiestrogen therapy (611). Reliable and accurate measurements of these biomarkers are critical for correct diagnosis, treatment and prevention of diseases, clinical research, and public health activities.

Different technologies for measuring circulating E2 and TT are available such as radioimmunoassays (RIA), enzyme-linked immunoassays (EIA), and mass spectrometry methods (12, 13). Most of the analytical methods used in patient care and public health activities only measure either testosterone or estradiol (1417), thus requiring separate assays for each analyte. Some of these assays were found to have a high level of inaccuracy, lack of sensitivity, and problems with reproducibility. These problems were reported especially at the low concentrations commonly observed for estradiol in men and postmenopausal women (approximately below 147 pM, 40 pg/ml), and testosterone in women, children and hypogonadal men (approximately less than 3.47 nM, 100 ng/dL) (1820). Thus, new analytical methods are needed to accurately and reliably measure E2 and TT in serum.

Here we report an accurate and sensitive LC-MS/MS assay for simultaneous measurement of E2 and TT in serum without chemical derivatization. The sample preparation is automated using a liquid handling system with 96-well plates, enabling the maximal capacity of processing 146 patient samples within an 8-hour workday. Our validated method has been demonstrated to be applicable to measurements in the general population.

Very interesting. What do you think happened here?

The LC/MS/MS method has overstated E2, not the ECLIA method.

An extra y chromosome, lab error or your are genetically different in some way not common. May for some reason you have very low C-Reactive Protein. I can’t go through all the threads of the 2 years to get you the data, rinse and repeat I see a lot of the same thing over and over again, guy comes in here with the Roche ECLIA methodology and E2 comes in near the 100 mark, he is informed it’s the wrong testing and retests using the LC/MS assay and E2 is less than half.

I can’t tell you how many times this has happened, but it’s very common. Every now and again a guy comes in here from another lab company other than Labcorp and E2 levels match each other, again very common our the sensitive E2 is higher.

It’s either a mix up of regular E2 and sensitive E2, lab error or some unknown genetic mutation. The study quoted shows the majority of the time that the LC/MS assay method is more accurate on a massive study done by the CDC.

There is more skill involved when doing the LC/MS assay method, if results are unexpected, it’s most likely human error.

Would you show us one example please?

I would like to see this as well.

That is consistent with what I was told. In my case, do you think the high E2 with the LC/MS/MS method was due to human error?

Very low, like between 0-1? Like most people. Healthy people have very low CRP levels.

We don’t get many healthy people in here, the majority of men are metabolically in the gutter and have been this way for years so they’re C-reactive protein, the marker for inflammation is typically high and that makes the standard E2 testing the wrong one.

I’m going to start favoriting these particular threads of cases where E2 levels are overstated when comparing both E2 testing methodologies and make a thread to show once and for all the sensitive method is the only was to go.

The LC/MS method doesn’t have the same limitations with regard to C-reactive protein, that’s why it’s recommended for men.

Interesting, but I’m not buying that. The majority of guys using TRT are not sick, they do not have life threatening illnesses or potentially life threatening ones. Their hormones are not optimal and they feel better when optimized.

CRP is elevated in serious infections, cancer, auto-immune diseases, like RA, cardiovascular disease, morbid obesity and even birth control pills will increase CRP.

I’ve been here a while and do not recall too many, if any of the instances we reported. It would be great if you would provide some of your examples.

Let’s go back to the original poster, the guy we’re both trying to help. He comes here with his story and what appears to be side effects due to elevated E2. He provides E2 lab levels of 39.8, 32.4 and 43.7.

You respond and suggest a way to reduce E2 and therefore E2 fluctuations. Then you go on to say he had the wrong test, incorrect test, the one for women, the one overstating his E2 status. But, wait a second, if the test is invalid, overstating his E2, then what is his actual E2 level? Would LC/MS/MS have him at 28? 22? 18? If so, would you think it needs to be lowered further? At least you did not recommend an AI like previously when 1mg anastrozole was recommended for every 100mg test.

What about his symptoms? @physioLogik really got me thinking here. Of all the weightlifters, powerlifters and bodybuilders I knew taking AAS back in the day, E2 side effects were pretty uncommon. Yet, here we are, “dialing in” TRT protocols to get to the E2 “sweet spot”.

Point being, what would you say to @bladejrs if he provided these results: ECLIA 39.8 and LC/MS/MS 23.5? Would you say he is fine? I doubt it.

@physioLogik is right (wish he would come back). Yes, test E2, keep an eye on it, whatever test you use is fine. Unless you are experiencing symptoms of high E2, let it go.

By the way, sorry you have had so much trouble and bad experiences with TRT. How many protocols have you tried?

Also, on another note, thanks again to @physioLogik, no AI, my E2 is high, I still feel great, maybe better and my cholesterol just came back on the yearly with the PCP at 154. Never been below 200. Estrogen is cardioprotective.

@highpull @systemlord

Appreciate the feedback guys and the passionate discussion on the topic.

Do either of you (or anyone else who reads) think there is drawbacks of using the AI? I’ve seen the recommendations of increasing frequency of dosages to help, but if there’s not a major drawback to the AI I’d prefer to go that route, as someone who has issues with needles. Getting it down to 4 days at a time was tough enough due to phobia of sorts, and I still get vasovagal responses a lot of the time even after a year+ of TRT, so I really don’t think I’d have an easy time sticking to every other day injections.

There’s always a drawback to drugs as they aren’t natural to the body and we didn’t evolve to process chemicals.

I hope you never find out what it feels like to have estrogen at zero. If you can do TRT without an AI, excellent.

Sometimes an AI is needed, anastrozole over-responders should consider aromasin at micro dosing until tolerance is known. I benefited from 1/10 a tablet.

I agree with the above.

Some are very sensitive to aromatase inhibitors, like systemlord, and use very small dosing. If you go the AI route, start low, a low dose may be enough to remove your symptoms.

On second thought, you might look into using DIM, diindolylmethane, to manage your estrogen symptoms. Or, eat a lot of cruciferous vegetables, cauliflower, broccoli, cabbage,brussels sprouts, etc. Some have had success with DIM.