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
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.
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.
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.