T Nation



Well as some of you know, I decided to give to try the AI solo to increase my testosterone based on a few studies I read. Well, after 6 weeks my Testosterone came in at 638ng/dL, Free Testosterone at 94.9ng/dL and Estradiol from 62pg/dL to 24pg/dL. I was stunned because I did not feel any better!

I decided to contact the guy that ran the study and here is the conversation:

[I]Hello Hans de Boer, I had some questions regarding the long-term efficacy of aromatase inhibition for hypogonadism. I was diagnosed with hypogonadism and it appears to be secondary due to my low levels of gonadotrophins. I was about to commit to a TRT protocol of Testosterone Cypionate, HcG and Anastrazole until I saw a few studies where hypogonadism might be obesity-related. I am 5'9" and at 260 lbs. My Estradiol lab value was recorded at 62 with a range of 20-47. Six weeks on 0.5mg's of Anastrazole every-other-day brought my estradiol number down to 24. Along with this decrease, my testosterone increased to 638 (range 250-1100) up from 316. I am happy with the increase but I feel exactly the same: low mood, low energy, and low libido. Did you observe an increase in mood and libido within the participants in the study? Is this aromatase-inhibition and effective long term solution to hypogonadism? I don't know where to go from here. I have not found any doctors/endocrinologists who are up-to-date with TRT treatments and I do not know where to go from here. Any input would be greatly appreciated.

-James [/I]


[I]We have just completed a placebo controlled trial with letrozole in men with obesity related hypogonadotropic hypogonadism. Abstract is presented on Endocrine Meeting, Boston, 2011, june 4-6

Despite a marked increase in testosterone we could not detect any clinical benefit => so, aromatase inhibition is not the answer in obesity related hypogonadism.

with regards,

Hans de Boer[/I]

Wow pretty funny that they jus' finished a trial testing the very same question I had! Anyways, I looked it up and was only able to view the abstract because it's jus' being published last week:

Letrozole Normalizes Serum Testosterone but Has No Clinical Effects in Men with Obesity-Related Hypogonadotropic Hypogonadism
Sandra Loves, MD2, Jos de Jong2, Adriaan van Sorge, PhD2, Darryl Telting, PhD2, Ad Hermus, PhD, MD1 and Hans de Boer, MD, PhD2

Endocrinology (AH), Radboud University Medical Centre, Nijmegen Netherlands
Internal Medicine (SL,JDJ,AVS,DT,HDB), Rijnstate Hospital, Arnhem Netherlands

Introduction: Hypogonadotropic hypogonadism is frequently observed in morbidly obese men, due to aromatase-dependent conversion of androgens to estrogens in adipocytes. The clinical impact of this sex hormone imbalance is not known.

Aim: To evaluate the clinical effects of aromatase inhibition in obesity-related hypogonadotropic hypogonadism.

Methods: Double-blind, placebo-controlled, 6-month trial in severely obese men (BMI > 35 kg/m2) with obesity-related hypogonadism (serum total testosterone < 10 nmol/l). Predefined drug regimen (letrozole or placebo): Starting dose 1 tablet/week, subsequent dose escalation every month up to a maximum of 7 tablets/week or until a serum total testosterone of 20 nmol/L. The dose was reduced if serum estradiol decreased below 40 pmol/L.Results: 42 patients were included and 39 completed the study according to protocol: 18 on Letrozole and 21 receiving placebo. Mean age 44.6 ± 1.1 years (mean ± SE), BMI 41.1 ± 0.8 kg/m².

At baseline, both groups were well matched for all study parameters. Placebo treatment did not affect serum hormone levels, whereas Letrozole decreased serum estradiol from 119.1 ± 10.1 to 59.2 ± 6.1 pmol/L (P = 0.0001, normal range (NR) 40 - 160 pmol/L), increased serum LH from 3.3 ± 0.3 to 8.8 ± 0.9 U/L (P < 0.0001, NR: 2.0 â?? 9.0 U/L) and free testosterone from 244 ± 19 to 691 ± 39 pmol/L (P < 0.0001, NR: 225 - 625 pmol/L). Both groups demonstrated a comparable decrease in body weight of about 5 kg, and a decrease in abdominal circumference of about 4 cm. Changes in fat free mass, fat mass and bone density also did not differ between groups. Glucose metabolism, lipid profiles, physical exercise capacity and psychological characteristics did not change during treatment.

Conclusion: Despite a marked rise in serum free testosterone, low dose aromatase inhibition had no somatic or psychological effects in men with obesity-related hypogonadotropic hypogonadism. We hypothesize that, with respect to non-sexual somatic and psychological parameters, males primarily thrive on oestrogens, not testosterone.

I JUST DON'T GET IT!!!!! Why aren't these people, including me, not feeling any of the increase in testosterone? This is not a small increase, it's a substantial increase.


This is very interesting but corresponds to what I've read in feedback from other people who have tried AI only therapy. I have no idea if they were obese, but it didn't seem to work for anyone that I recall.

I did this last June and I remember having a short increase in morning woods, but still had pretty bad ED. I think I took my E2 from 49 down to 28 or so, which in turn increased my T from the mid 300's to around 500 over the course of a few months. Aside from the transient morning wood increase, I did not recognize any of the effects of the higher T/lower E2 levels.

I don't agree with the studies conclusion that the patients are thriving on estrogens instead of T. There is something else at work there, but I am not able to pinpoint it. I suspect it has more to do with the interplay with other hormones adjusting to compensate, but I'm not sure why (maybe because it is generally unhealthy to be obese and your body is still fighting that).

I wonder what the longer term benefits would be for people that lost a bunch of weight and continued the therapy...



I know AI's are notorious for decreasing libido in men. Most likely because estrogen is important in our bodies but only when there is too much are there problems...I am skeptical of TRT for secondary hypogonadism...I have the same as you and I didn't want to do TRT.


Out of curiosity. .5mg of Anastrazole EOD,affect your lipid profile?

And a rebound effect once discontinued the use?

Was Your SHBG and progesterone levels checked?


Aromasin is the only way to go when you need an AI.




T can not function without sufficient Cortisol.

too little cortisol = the body reacts by dumping T to E2.

Stopping aromataze of T to E2 via AI still leaves the body with excess T that it can not use because (the theory goes) that your body has insufficient cortisol to work along side all of that T.

hence - your numbers look great, but you still feel terrible.

now if your 8am cortisol levels come back at 15-20 AND your E2 looks good AND your Total and Free T look good AND your thyroid numbers including FT3 and RT3 are all in order, well... then you are one of the medical mystery guys like me.


I haven't checked this thread in awhile but thanks for the insight. I'm going to the doctor on the 20th and will ask to check out my adrenal glands with the saliva test.

When it comes to the thyroid, my numbers look OK. My TSH was 1.2 and my T4 numbers looked good. However they did not test free T3. I'll ask for that. When it comes to RT3, is Reverse T3 and Reuptake T3 the same thing?


i've been gone for awhile as well.

Reverse T3 is nothing like Reuptake T3.

Reuptake is an old method of estimating T3 I think.

T4 converts to T3. Too much T4, not enough cortisol, or other issues cause T4 to convert to Reverse T3. RT3 blocks Free T3 from working because RT3 binds and disables T3 receptors.


Well had my appointment with the new Endo today and it was so/so. I was referred to him through a family friend and when I went in, I was greeted by, . . . the resident. She was very nice, very thorough and I did not get a sense of egotism from her.

I showed them my labs and how I boosted my testosterone scores to 638 but felt no better through AI-monotherapy. I showed her the studies and took everything into consideration. She then spoke with the doctor and were discussing it for literally 45 minutes to an hour. NO JOKE. I'm guessing they either read the entire article or were looking up more information in the back. And no, he wasn't with another patient because I was the only one there! I asked my girlfriend who was in the waiting area if anyone else came in and no one else did. I was very happy that they were at least looking it up or taking their time.

Anyway, he ordered a bunch of tests and filled up 7 or 8 vials of blood. He was explaining to me how arimidex works and that he'll be giving it to me. (Makes me wonder if he knew this stuff beforehand though). Overall though, I'm content with him.

Now the bad stuff. I asked to test Free T3, Reverse T3, Cortisol via saliva, and DHEA-S. He said testing T3 and Reverse T3 is useless since my TSH is 1.29. He said he will be testing cortisol but not by salivia but through the blood test (I think that's what he said) and he will be testing DHEA not DHEA-S. Dammit!! One step at a time though.


DHEA tests are not a great measure because DHEA is prone to spikes and valleys. I'm not sure what exactly he will be able to infer from that - did he mention why he preferes this test over DHEA-S?

8am blood draw cortisol - while not as good as 4points saliva - is not useless. It can help.

I don't understand why he would think testing FT3/FT4 is useless. Given a 1.29 TSH, those values will probably be fine... but why deal with probability when you can have certainty? That would annoy me.


I'll ask him on Monday when I see him. As far as the cortisol, it wasn't drawn at 8am. It was done around 4PM. To be frank, I don't know much when it comes to testing DHEA-S and Cortisol, what it means, how it interferes with Testosterone and what should be done. Does anyone have a good link or maybe explain more in-depth about DHEA-S and Cortisol? Like why is DHEA-S preferred over DHEA? I'd hate to sound like an idiot on Monday.


a 4pm blood draw for cortisol is absolutely useless...you need it at 8 am to determine your adrenal function...

DHEA-S is DHEA Sulfate...it has a longer half life than DHEA itself so it is present in your body at a more consistent amount than is DHEA, which clears quickly and is subject to peaks and valleys...

The cortisol/testosterone link is a bit tricky...essentially, your body can live without many hormones...testosterone is not vital...DHEA is not vital...estrogen is not vital...meaning you will not die without them....however, cortisol IS vital...you will die without cortisol...

So when cortisol is low, your body goes into emergency mode and diverts resources to making cortisol...if there is something prohibiting this, then you are stuck in a negative feedback loop that downregulates all your other non-essential hormones in an attempt to bring cortisol online...this is why it is essential to fix cortisol issues prior to addressing other hormones

DHEA is related to testosterone as it is a testosterone precursor. So if it is low, your body is not able to produce T from it. Check out this chart for more info:


Not me I feel a lot better on AI .5 Anastrozole every 3rd day!!!!!!!!!!!!!!!!!!


I looked up your previous posts and found that in conjunction with the AI, you are taking 120mg's of Testosterone Cypionate.

My thread was in reference to those who are only taking an AI, no testosterone.


Sorry for hijacking thread... I have never found anyone to have any success with AI alone


I'm back! I've been taking a break from this whole ordeal and enjoying the rest of my summer but it's hard to when I'm in and out of doctor's offices. Anyway, long story short: Noticed decreased libido January 2010, diagnosed with low testosterone June 2010 and have been researching since then. I didn't like some of the doctors/endocrinologists I've seen before and finally decided to see this endocrinologist as referred to me by a family friend who is a doctor. I have been supplying him with my previous labs that confirm hypogonadotropic hypogonadism along with his own lab testing, an MRI of my pituitary that shows no abnormalities from my previous doctor.

My first visit we drew blood to establish some baseline numbers. He tested a lot of other stuff too like Vitamin B and Dopamine levels through a 24-hour urine test (happy to report that my Dopamine levels came back at the upper third of the range. I was always worried I was in a state of SSRI-induced down-regulation of dopamine levels from extra serotonin.) Anyways, he called me to come in and try a GnRH stimulation test. Fine. Tests came back today that my FSH and LH increased. Now he wants to try a Clomid test.

Really? Doesn't that seem redundant? Either way, if the Clomid does or doesn't work, in the end, I would be placed on TRT the way I see it. I'm getting really aggravated as weeks are passing by, I'm eager to feel better and instead of talking about a TRT plan he wants to perform another test. The nurse said he wants me to schedule a bone density scan and an ultra-sound of my kidneys later as well.

Opinions? Thoughts?


In general, I don't see how an extra test can be a bad thing... but at some point you have to start treating. There will always be another test you can run.

Any reason to suspect kidney problems?


I took me years to figure out how to fix the same issue. TRT alone will do nothing. You may get a dopamine rush at the beginning that will fix a few issues but that will then fade and leave you wondering.

What worked for me is TRT (110mg a week in every other day doses, HCG 100iu once a week one shot, .75mg Adex on T shot days. Labs are spot on.), eat a clean diet(I eat cereal, chicken, pork, fresh raw vegetables, fruit, lots of water and that's it!), and workout every day. Weights twice a week and cardio EVERY DAY. High levels of cardio made a HUGE difference for me. Depression gone. ED gone. Energy up.

I haven't been here in quite a while because I'm no longer looking for answers. I cruised through here to answer a few messages and I'm always happy to help whoever I can. The bottom line is use TRT as a base to achieve higher health. I think a lot of my health improvement has come from better blood flow and I'm now very vascular. It was a difficult puzzle because naturally I looked fit and healthy but I wasn't. Now life is much better.

I also have to add forget about analyzing labs and chasing numbers. That's a joke. Get them in the ballpark. If you think you're magically going to have a life changing experience when your E2 hits 20 or your T hits 1000 forget it. It's a lifestyle commitment that takes hard work.

TRT is great and in my opinion a very healthy choice. That said use it as a foundation to higher health. It's not magic.


Lol I agree with this... Good answer..

What symptoms are you having??

Could you please list everything.