Testosterone replacement therapy is a lot more than just testosterone. We must consider the systemic effect of endogenous replacement testosterone.
Estradiol is the most potent of the three estrogens – estrone, estradiol and estriol. For this reason, it is typically the only one tested in blood and also because it is difficult to get a reliable reading and adds to the lab costs.
Although estrogen is often thought of as a female hormone, it is also important in men. Estradiol on the low range can manifest as the following symptoms:
- Depression
- Fatigue
- Joint Pain
- Limited erection sensitivity
Keeping estrogen as low as possible is not an optimal strategy. Actually, it’s a terrible one! Just like in women, estrogen helps prevent atherosclerosis, dementia and osteoporosis in men. Like all hormones, the goldilocks rule applies – not too much, not too little.
On the flipside, estrogen that is too high in men can result in the following symptoms:
- Water retention
- Excessive sweating
- Insomnia
- Hot flashes / night sweats
- Bloating
- Fatigue
Testosterone Replacement Therapy
When embarking on a testosterone replacement therapy program, it is important to have all hormones tested, including Estrogen (Estradiol). If your doctor does not test your estrogen, then you need to find another physician!
Aromatase Inhibitors
Testosterone and other precursors such as DHEA (androgens) can convert to estrogen in a process called aromatization. Aromatase inhibitors (AI) are a class of drugs that block the conversion of testosterone to estrogen and are commonly used in the treatment of breast cancer in post-menopausal women with tamoxifen as the popular drug of choice.
An off-label use of AIs is to prevent the conversion of testosterone to estrogen in men on testosterone replacement therapy (TRT). The most commonly prescribed AI is arimidex – more commonly known as anastrazole.
Are Aromatase Inhibitors Necessary?
AIs are not absolutely necessary while in TRT and recommendation should be on a case by case basis. If baseline estradiol is low and sex-hormone binding globulin high-normal then an acceptable strategy may be finding the testosterone and/or HCG dosage that results in an optimal increase to estradiol levels (through aromatization). Taking an AI in the previous example would tank the estrogen levels even lower and leave you feeling miserable.
On the flipside, if baseline estradiol is elevated then preventing the conversion of testosterone/HCG to estrogen would be a wise decision.
Alternatives to Aromatase Inhibitors
As with most drugs, there are several alternatives to taking a prescriptive AI:
- Zinc supplementation with copper in a 10:1 ratio
- More frequent testosterone injections, at a lower dose
- Injecting testosterone subcutaneous (SubQ) instead of intramuscular (IM).
The Importance of Communication
Above all, it is extremely important to communicate with your health care professional regarding your program. Finding an optimal balance is a process that takes time. Estradiol is the most difficult hormone to balance while on a testosterone replacement therapy.
To discuss your hormone replacement case with one of our qualified health care professionals, contact us today in Miami at 305.448.2600
hi thanks for the information
Your welcome
I have been doing research and came across Dr Rouzier.And tot nation.And they are saying there is a misunderstanding with Estrogen blockers.And to not take an Ai.Maybe some can watch his videos and see what they think.
Thanks Larry. Yes AIs are not required for every patient. As with everything in medicine, each patient should be treated uniquely.
Hey Ryan. My doc. does not recommend Sub shots over muscular, because he believes sub shots elevate estrogen. Do you find this to be the opposite?
Hi Christian,
Actually we do not find this. The reason is that we recommended to split the typical weekly IM injection into two smaller doses for SubQ. This in itself will decrease the chance of aromatization to estrogen. Dr. John Crisler has really popularized the SubQ method so you may want to check him out! Keep in mind we have not run any clinical trials regarding this and you should always follow the advice of your treating physician.
I’ve been taking testosterone injections for 3 months. I’m a 65 yr old male. I believe i now have gynecomastia. I’ve had it 2x in the past 5 years
Any suggestions on continuing testosterone injections?
Get your estrogen levels tested. If you have a propensity to develop Gyno you should proceed with caution and be monitored by your prescribing physician regularly.
Thanks for this advise! On test replacement and had big spike w injectable of over 500 percent from very low level w a 2.5x increase in estriodol Started on AI 2 mg per week to reduce estrogen level. Very irritated w dr that she did not tell me of alternatives to AI and inhouse pharmacy prices very high-cost of 1 pill = 8 at other pharms. I hope I can decrease estrogen level as I am concerned about strokerisk. alos will try more injection at lower mg tHanks so much Mike
Yes there are alternatives, however I’m sure your physician had good reasons. Glad you enjoyed the article.
Hi and thanks for your interest. I am currently not very active on Twitter, however my handle is @drryanbrady
Great delivery. Solid arguments. Keep up the great work.
Ryan, I am a 56 year old fitness enthusiast. I have been on clomid the past 4 years to raise my testosterone levels. I am a good clomid responder. I take 25mg EOD. My last blood test showed my total testosterone at 1372 and my E2 at 66. I seem to remember reading somewhere that for men on clomid the E2 reading will not be true? Are you familiar with this? I dont have any signs of high estrogen other than possible weight/water gain.
First of all, your total testosterone levels are great for Clomid use! I’d be curious to know your free T levels? In males, Estrogen is produced from aromatization of Testosterone. Since your levels are high and you have some possible weight/water gain then I would inclined to believe the levels are accurate. You may want to include Maca Root – a natural source of DIM, then retest in 6 weeks. I recommend discussing with your treating physician and investigate a low dose of anastrozole if levels are still elevated. Just be careful of dropping estrogen too low and the side of effects that a small percentage of people experience with anastrazole/arimidex.
I started trt therepy 3 months ago. My doctor put me on 100mg per week injections and that’s it. I after 2 months I wasnt feeling great, lots of joint pain in elbows and knees, my chest started looking different, and I had headaches. So I began serious research on trt and found out there is a lot more I can do to help the trt be more beneficial. I went to the men’s Welles’s center specialize in trt, they ran blood and my t levels were 200 range, estradiol 12.1, LH was 0.2, and FSH was 0.2. The doctor raised my t dose to 200mg per week, and gave me anastrazole, and HCG. I did more research on those medicines and found out that anastrazole lowers estrogen. My level was already low and I’m concerned about taking the anastrazole. I learned that i want my e2 levels at 20- 30. Why did he give me anastrazole with low e2 levels and what should I do?
Hi Jordan,
You are correct Anastrozole essentially lowers the estradiol (estrogen) by blocking the conversion of Testosterone to Estradiol through an enzyme called aromatase. Since your doctor doubled your Testosterone and added HCG (which can also boost T), is is prudent to include Anastrozole. Follow up in 4-6 weeks for a repeat blood test (or whatever your doctor has recommended) and go from there. You dosages may be adjusted again based on your labs.
Hello. I’m a recently retired physician on TRT using T-cyp SQ 2x/week (every 3.5 days). After extensive research and with knowledge of the half-lives of T-cyp and anastrazole, I still do not know the optimal time to dose anastrazole to lower E2 relative to the twice weekly SQ T-cyp injections. Dr. Crisler, at least in 2017, was doing the T-cyp and the AI on the same day. Sadly, he is no longer with us for me to ask for his current recommendation. Another physician recommends taking the AI 24 hours after each twice weekly T-cyp injection. Do you have any general recommendation on this matter? Thanks for any advice!
We typically recommend the same day, although each case must be monitored individually. Since you are dosing SQ the pharmacodynamics are different than IM, therefore dosing 24 hours after injection is definitely viable. Blood analysis and symptoms would be best to monitor in your case.
Hello! I have been on TRT for about 2 years now. I have been using anastrazole @ .5mg on shot day and another .5mg half way through the week, for about 6 months give or take. My last bloodwork came back total testosterone-688 ,SHBG-24, Testosterone free-180, Estradiol-16. Should I consider to stop taking anastrazole with my current estradiol level ? if so should I taper off or should I just discontinue all together
Hi Fred. We cannot give individual medical advice here, so it is best to discuss with your prescribing physician or you could give us a call for a consult.
Reference ranges of each lab are different so we cannot determine or not your levels are within range. Also remember that the timing of your dosage and blood draw also factor into this.
Typically, we prefer men to have Estradiol levels around 20-30. In general, anastrozole does come with side effects so if not needed, or a lower dose is sufficient to keep levels within range then this would be a logical approach.
Sub injections of test feels like battery acid inside your skin. Its very painful. To anyone who tries it, be ready for 3 or 4 days on intense pain in the injection area. Im no doctor but i can tell you your gonna be feeling it and might not try a second time.
Hi Dan,
It should not be painful unless you are injecting a large volume. You may want to request a higher concentration from your Doctor so you require less volume to inject. Good luck!
I am a male that has taken Testosterone Cyp. 1 1/2 ml injection about every 3 weeks for 15 years now. Someone at the dog park told me to have my doctor test my Estogen level stat and it turns out it was 130 for god knows how long. I am so mad at my doctor for never testing me because all the symptoms are exactly what I’ve experienced for years now, the sweating and so on. I started on Anastozole 1/2 mg twice a week. Is that going to help and whats to do?? Thanks for responding.
Anastrozole is an aromatase inhibitor, meaning that it will help block the conversion of Testosterone to Estrogen. Exactly how much you will need to take to achieve optimal levels is something that will need to be tested and monitored by your prescribing physician. If you’re testosterone cypionate is 200mg/ml and you are taking 1.5cc every 3 weeks this dosage of Anastrozole seems too high. Keep in mind you do not want your Estradiol (E2) to drop too low either. Please follow up with your doctor.
Thank you so much for answering. I do want to ask one more question please. Is Anastrozole the right choice to take to bring down your Estrogen or is there other drugs that might work better than that one? And when you say 1/2 mg twice a week is alot, the 1/2 pill is super tiny, and I can’t see that being near enough to take it from 130 to 30?. Thanks so much for responding.
I am 64 and just started testosterone last year the last urologist gave me a prescription for 6 months at one shot a week for ten weeks per vial. At the end of 6 months, my estrogen was 130 and I was experiencing problems that were worsening that the testosterone was supposed to help. I am low income and approaching Medicare and worried because am finding there is an undercurrent of thought in the medical community that refuses to address this problem of high estrogen and blame all of its negative effects on high testosterone. How can I find someone who will treat me properly without paying a fortune which I do not have?
I would recommend finding an experienced endocrinologist well versed in TRT that is enrolled with medicare. Unfortunately we do not work with insurance for TRT.
Is their any other drugs to take that are better than Anastrozole for lowering Estrogen in males on Testosterone?. My Estrogen was way over 100 so I am also livid at my doctor for never testing my Estrogen for the last fifteen or twenty years. I walked around with a rag at work because I sweat so much. Do you have any other suggestions for bringing it down? Can I take the DIM supplement along with the Anastrozole to speed things up a little? Thanks for answering.
Hi Jay. Sorry to hear this! DIM can help, however it may not be enough. Grape seed extract has shown some benefits, as well as Nettles, but the evidence isn’t strong. I would discuss with your physician or simply change if you’re not happy with your current one. Best wishes.
Hello Dr! Thank you for taking the time to answer people greatly appreciated. 43 yr old male got T checked after feeling down, results were 256, 5 Free, and 5 Esterdiol. My doctor injected pellots and 5 week reading was 1298 T, 20Free and 36 Esterdiol, question does 1298 seem too high? Also taking DIM do you think 36 is high for Esterdiol I know you like it around 20-30, also nuts are shrinking even in 5 weeks I wonder if your protocol is HCG ever though I am done needing kids, thanks for the thoughts
Hi there. Wow your levels were very low before! Based on what you say your labs are these levels are quite good actually. Of course the labs should also reflect alleviation of symptoms without side effects.
If kids are not not a concern then it isn’t necessary to take HCG, however if the deflation is an issue then some HCG should bring them back within a couple of days. As always please discuss with your provider.
Hi Ryan,
Great article! I have a few questions as I am currently on 133 mg of Test Cypionate per week. I have noticed that I constantly get night sweats and sometimes get foot and ankle swelling more in the afternoons and late PM. I have had everything checked and my levels are 700 for total T, 26 for estradiol, free test I cant recall but it was good and within high normal range, etc. Is this usually a common side effect or is it an indicator that something else may be underlying?
Thanks much!
Check your free testosterone and Hematocrit. Some patients swell on Cypionate. In those cases we typically investigate Enanthate or blends. Glad you enjoyed the article.
Is there a test to check your aromatase inhibitor levels!
Hi Lex, there is no specific test. It is monitored via Estradiol
Hello I just started TRT at 100 mg of cypionate per week. It’s been a total of nine weeks and everything is going well except at around 3:00 a.m. after sleeping for about 4 hours I wake to being very hot especially around my neck. I was doing subcue injections two times per week now I’m doing inner muscular injections three times per week to see if it is my estrodiol.. it’s tested at 39 peak and 20 trough.. no ai use .
When I do awake I’ve noticed also my blood pressure is higher than normal by about 20 points. Normal 125/80 ..
The only thing that I can make it stop with is using a 25 mg of Benadryl.
Didn’t have this prior to trt ..
Is this just my body trying to get adjusted to things and during my deep sleep cycles it’s showing itself.
I have a sleep study being done in case it is sleep apnea and I’m also getting my heart checked out just to make sure it’s not something happening when I’m laying down.
I was sub 300 total t for years .. 12+..
Always had bouts of hypoglycemia when my testosterone was lower.
Now it seems to be fine that I started TRT.
Renin tests are done waiting for labs..
As well as adrenal tumor test.
What’s your thoughts .. I’m 45.. and built like Arnold Schwarzenegger.
Did do past aas. Quit 12 years ago..
Do cardio . Drink 1 oz per lb of water .. no other intake of fluids but water..
Work out 5x.. no issues in gym . Other than leg day .. lol.
Hi there. Thanks for the extensive history. Unfortunately we cannot give specific medical device over the internet. If you are interested we could setup a consultation. You can call our office at 305.448.2600
Hello, I am currently a user of clomiphene citrate 50mg eod…doctor has me taking this dose and I was curious if this dose it’s mandatory to take AI with? Trying to avoid Shots for now.
Symptoms wise what would be the differences of high estrogen vs low estrogen with clomid?
It depends on what levels of Testosterone and hence Estradiol are achieved with this dosage. Some men response very well to Clomid and sometimes their levels do go supra-physiological. It is not mandatory to take with an AI, however blood tests are usually recommended to determine what is right for you.
High estrogen classically has symptoms of nipple sensitivity, decreased erection sensitivity, decreased sexual desire, increase in abdominal fat, fluid retention. This can overlap with low estrogen as well (except fluid retention / abdominal fat), therefore I prefer to test and not guess.
I found it best to take arimidex about 24 hours after my testosterone injections.
My doctor added hcg also to take. I know I have to up my dose of arimidex when taking both Hcg and test. Any suggestions as to when to take arimidex with Hcg added to the equation? What is the half life of Hcg? Getting mixed answers when looking it up. Does hcg aromatise much quicker than test cyp?
The half life of HCG injected IM is approximately 26 hours, although it can range depending on the metabolic difference of individuals (23-32 hours). HCG is usually added with Testosterone to keep the pituitary to testes cycle open (fertility, negate testicular atrophy). Since it is usually given in small doses when combined with exogenous testosterone it does not spike testosterone significantly and therefore does not aromatize to estrogen (most of the time). HCG can boost testosterone in certain low T cases, but not all. I would discuss with your doctor and check your labs to see if you are boosting to higher levels of T with HCG added then change the anastrozole dosage if necessary.
I’m currently on 120ml of cyp a week.
It is typical splitting a dose to twice a week shown to lower e2 and dht conversation?
Thanks!
Yes, splitting the dose is a strategy to keep aromatization to estrogen lower.
Hi Dr I enjoyed the article I was just wondering if you had any tips on dealing with night sweats/anxiety at night on trt. For some odd reason when I have night sweats it almost freaks me out and I start having almost mini panic attacks. Any advice would be greatly appreciated
I would have your labs rechecked. It sounds like your estrogen is off.
Hi, what are your thoughts on subq testosterone injections? Do they work for everyone? Thanks
Yes they work for everyone. The question is: should everyone be using the subq method? The dosing scheduling and volume often changes with subq as opposed to IM. Most people find this method uncomfortable in the long run as the injections tend to be more tender and leave small bumps. Some doctors recommend a combination of IM and SubQ to help reduce the roller-coaster effect of peaks and troughs. In the end you have to find a formula that works for you – with the guidance of your physician.
Could excessive armpit sweating be from my estrogen being to high?
If only the armpit region then it is unlikely, however a blood-test can help you determine whether or not your estrogen is too high.
33 years old. Test was 96ng and 229ng at 8am, 3 weeks apart when I finally convinced my doc to test. Been having fatigue, weight gain, sleep, depression, and mood problems, low libido and erection problems for a long time. Diagnosed with Secondary Hypogonadism. Doc didn’t seem knowledgeable and dismissive of TRT, etc.
I went to a men’s clinic that had me on 200mg IM Injections once a week and HCG. After a few months symptoms resolved and I was feeling normal again, I was so happy, except I felt like I would fall off the second half of the week. My testosterone was 490ng-620ng at the end of the week. After a few months I also complained of high Estradial like symptoms and their answer was the raise the testosterone dose to 220mg. Finally got full labs and my Estradiol was 71, high hematocrit, red blood cell, hemoglobin, and liver enzymes. I had crazy depression and anxiety and my blood pressure was high.
I left there cuz there APRN quit and they cut their hours way back and had all kinds of issues, not to mention I got my lab records and saw my Estradiol and other levels were climbing for months but they didn’t mention it.
I finally got on with an Endocrinologist, ordered an MRI on my pituitary (normal) and cut me back to 100mg of Testosterone a week, said she doesn’t agree with HCG or AI’s. After 5 weeks, I’ve had a return of all symptoms, lost weight and muscle although I am eating way more and exercising much less to try and offset the fatigue. Docs tested me midweek of injection and Testosterone was 467, they said that as long as it’s above 300 it’s perfect. They don’t even test for Estradiol so I’m unsure where that is.
My biggest problem has been no matter the dose, if I felt good it would only be for about 3-4 days after the injection,.and then I would crash hard the rest of the week.
I’ve mentioned twice weekly subQ injections to help with the peaks and troughs, and to help the estradiol conversion, Both of the docs are agaisnt it, In fact I had to beg them to let me go to once weekly instead of every 2 weeks injections. My PCP seems to think Testosterone is just Viagra and my Endocrinologist said she wants to wean me off of testosterone?
I have been trying to get in with other physicians but the wait times are crazy and I don’t want to keep getting ones that don’t seem to understand or believe in my condition. I am weary of the men’s clinics now. Can you guys recommend anyone in the Omaha/Lincoln Nebraska area?
Sorry for super long post.
Hi Hutch,
Well it seems like you’ve quite the yo-yo experience which is common in most men that have been to other physicians inexperienced with TRT. Sorry you have had to go through this. Without seeing your labs it is difficult to determine secondary hypogonadism, however your initial labs certainly confirm very low T. I wouldn’t be put off my “men’s clinics”. There are many good clinics out there, although as you have experience – it is very important to have labs and symptoms managed properly. Regarding your endo not “agreeing” with HCG, if you are planning to have children then HCG should be maintained for fertility? In general we do not like to use AI’s but it is necessary in some cases.
I personally don’t believe in a “perfect” number for testosterone labs. Does it seem reasonable that since you are within reference range (low side of “normal” in your case), but present with the same symptoms of low testosterone that you are perfect?
Unfortunately I do no know of anyone in Nebraska area, however here are a few things for you to consider as a general guideline that we employ in our office:
1. Regularly monitor your labs
– donate blood if your hct rises
– yes estradiol levels matter, but SHBG and other factors should be considered before taking AIs.Consider alternative to prescription AIs under the monitoring of your prescriber
2. Consider using other testosterone esters. The three primary esters include cypionate, enanthate and proprionate. There are also blends of the different types.
3. More frequent dosing (every 4 days for example), will help with the peaks and valleys symptoms you are experiencing. Dosage must be changed accordingly under guidance of your prescriber. I’m unsure as why your docs are agains SubQ other than perhaps they are not familiar with it.
As to weaning off of testosterone: this is a great goal, however the underlying cause of the low testosterone output must be investigated in detail. Failure to solve the underlying issue and not taking any replacement will leave you plagued with the same symptoms. If this is of interest to you then I suggest searching for a functional medicine physician with experience in hormones.
As always, this is not personal medical advice. You should discuss with your provider.