Arimidex - Pain Caused by Crashing E2 or Another Reason?

[TLawyer]

I believe that I've seen a thread that one 1mg dose of Arimidex decreases E2 by about 70% within 24 hours, and then up to 80% when taken on regular basis thereafter. Are we able to extrapolate from that how much a single .25mg does would decrease E2? Would it be about 17.5%?

I asked because after staying of Arimidex for about 2 weeks or so, I took at .25mg dose to see whether I felt any difference. And I definitely did within about 7 hours and still am about 36 hours after that dose. Libido and sensitivity definitely improved in that 7 hours, and I feel like erection strength as well. I am low SHBG (11 at my last lab test using this protocol), and my last E2 level came in at about 55 on my current protocol (probably was higher before I took the Arimidex as I registered that 55 about 3 and half days after taking a .125 mg dose, and then stopped taking it to see how I felt, so I imagine it rose during those 2 weeks). Mentally felt better as well, although that may go along with a better libido and sensitivity. I am amazed as how quickly I felt a difference. If it is about a 17.5% decrease in E2, that would put me on the low end of about 45 (17.5% of 55). I'm just trying to get a sense of a good level for me with my E2 given that I can't run out to a lab until Tuesday, so I can't get a confirmed level (and who knows how I will feel on Tuesday). That 45 still seems like it may be on the higher end, so my thought is that perhaps .25mg is decreasing it more than 17.5%.

I will say that the only drawback is that I woke up with morning (about 24 hours after I took the .25mg dose) with my joints killing me and elbow pain, which I have suffered with since starting the smaller doses of Arimidex about 2 months ago. Physically, as far as pain, I have gradually felt better after stopping the Arimidex for those 2 weeks, including the elbow pain, but it's definitely back today after taking a dose. I had originally thought when I was experiencing that pain that I was crashing my E2, but then I came back with the 55 level, so that clearly wasn't the case. I looked up Arimidex, and I see that joint and muscle pain is a common side effect. My question is this - is that because people are crashing their E2 with Arimidex, or is it for another reason (i.e. you can experience the pain even if you don't crash E2)? Because I am not crashing it, but I definitely feel the pain almost immediately.

The pain is a little disappointing, although the libido and sensitivity increase certainly have overshadowed it.

 

[DS3]

I believe that I've seen a thread that one 1mg dose of Arimidex decreases E2 by about 70% within 24 hours, and then up to 80% when taken on regular basis thereafter. Are we able to extrapolate from that how much a single .25mg does would decrease E2? Would it be about 17.5%?

I asked because after staying of Arimidex for about 2 weeks or so, I took at .25mg dose to see whether I felt any difference. And I definitely did within about 7 hours and still am about 36 hours after that dose. Libido and sensitivity definitely improved in that 7 hours, and I feel like erection strength as well. I am low SHBG (11 at my last lab test using this protocol), and my last E2 level came in at about 55 on my current protocol (probably was higher before I took the Arimidex as I registered that 55 about 3 and half days after taking a .125 mg dose, and then stopped taking it to see how I felt, so I imagine it rose during those 2 weeks). Mentally felt better as well, although that may go along with a better libido and sensitivity. I am amazed as how quickly I felt a difference. If it is about a 17.5% decrease in E2, that would put me on the low end of about 45 (17.5% of 55). I'm just trying to get a sense of a good level for me with my E2 given that I can't run out to a lab until Tuesday, so I can't get a confirmed level (and who knows how I will feel on Tuesday). That 45 still seems like it may be on the higher end, so my thought is that perhaps .25mg is decreasing it more than 17.5%.

I will say that the only drawback is that I woke up with morning (about 24 hours after I took the .25mg dose) with my joints killing me and elbow pain, which I have suffered with since starting the smaller doses of Arimidex about 2 months ago. Physically, as far as pain, I have gradually felt better after stopping the Arimidex for those 2 weeks, including the elbow pain, but it's definitely back today after taking a dose. I had originally thought when I was experiencing that pain that I was crashing my E2, but then I came back with the 55 level, so that clearly wasn't the case. I looked up Arimidex, and I see that joint and muscle pain is a common side effect. My question is this - is that because people are crashing their E2 with Arimidex, or is it for another reason (i.e. you can experience the pain even if you don't crash E2)? Because I am not crashing it, but I definitely feel the pain almost immediately.

The pain is a little disappointing, although the libido and sensitivity increase certainly have overshadowed it.

You’ll have @Nelson Vergel and some others on here make a blanket statement that men don’t need to take Anastrozole because estrogen does not cause the negative symptoms that we believe are associated with elevated estrogen.

I can’t help but strongly believe this stance is more a reflection of inferring how they feel at higher levels of E2 (>50 pg/mL), as opposed to how most (or many) men on TRT feel at higher E2.

I can tell you my anecdote is very similar to yours. I am a low SHBG guy (for what it’s worth) and experience negative estrogenic symptoms at 50+pg/mL of estrogen. These symptoms disappear like clockwork after a 0.25 mg dose of Anastrozole. However, joint pain for me even at that dose is almost unbearable. Is this a result of crashing my E2? Nope. It tests at 40 pg/mL (from 55-60 pg/mL) within 48 hours of the dose.

My only explanation that I’ve been able to come up with that makes sense is that as you take an AI, you decrease aromatization at all Aromatase enzyme sites, including the skeletal system. Perhaps in some men the blocking of this enzyme in bone is stronger than in others and causes more joint pain. Doctors continue to blab on that this pain is only caused when men use excessive doses of an AI. This has not been the general consensus that I’ve seen on this forum, in myself, or other males I’ve talked to on TRT.

 

[Gman86]

As far as Arimidex goes, u have to factor in its half life, and how long it takes to reach steady state. I believe Arimidex has a half life of 2 days. Which means the levels of ai build up in ur system, and will level out in about 10 days. So just keep this in mind. Basically, if u feel better after 7 hours of taking a dose, the dose is way too high. Because if u keep taking that dose, say once per week, in 10 days u’ll have about double that dose in ur system. So say u take 1mg of Arimidex per week. In 10 days u’ll have about 2mg of Arimidex in ur system. So if u feel better after 7 hours, u bet ur ass ur not gonna still feel good at the 10 day mark when levels are twice as much in ur system. U can’t feel better right away, and also feel better when it reaches steady state. What u really want, is to feel better once the ai reaches steady state. Because that’s going to be the level that is in ur blood for the long haul. As long as u keep the same dosing schedule obv. It’s been a while since I went over half lives, and I think I’m getting the math correct, but anyone here feel free to correct me.

But bottom line, just remember that these drugs build up in our system, and level off eventually. How long depends on its half life. But just remember, if u feel better right away, especially within hours, ur 1000000% taking waaaaayyyy too much. Ideally, u want to start taking it, not feel anything right away, and then start to slowly feel better over the course of 10 days (with Arimidex) and feel best around the 10 day mark

 

[Blackhawk]

First, i don't think you can mathematically calculate intended effect of a quartered dose. Very little in hormone therapy is proprtional or linear in this way.

Second, I think Vince Carter who was banned from this site was potentially on to something regarding low SHBG men and E2 (N=1). He was testing Free E2 and trying to pin down the relationships between frequency and amount of T dosing, AI variables and actual E2 blood levels rather than just speculating based on symptoms. You might want to search on his posts. I don't think this is a simple topic with simple guidelines for guys with low SHBG. He also switched to Aromasin since Anastrozole caused him endless problems. One of the takeaways, is you are shooting in the dark without (very) frequent labs to pin down actual levels. Everything is a moving target.

Third, trying to adjust dosage based solely on symptoms using 0.25 doses can be an exercise in futility. 0.25 can be fine for some, but a very hefty dose for others. When I was on anastrozole, my dose was 0.07mg EOD, for a total of less than 0.25/week, and I had high SHBG. It knocked my E2 down by ~10 points.

Fourth, it seems many guys have their libido, sensitivity etc perked up by changing hormone levels, and once steady state is reached, they decrease again, so it can be a moving target that you perk up then lose it again as body adjusts to new protocol. In this sense, sometimes a bit like chasing one's own tail.

Fifth, another aspect to this is the use of transdermals as replacement or adjunct to T cyp which can convert more to DHT rather than E2, and other T esters... many cans of worms to open.

 

[Cataceous]

As far as Arimidex goes, u have to factor in its half life, and how long it takes to reach steady state. I believe Arimidex has a half life of 2 days. Which means the levels of ai build up in ur system, and will level out in about 10 days. So just keep this in mind. Basically, if u feel better after 7 hours of taking a dose, the dose is way too high. Because if u keep taking that dose, say once per week, in 10 days u’ll have about double that dose in ur system. So say u take 1mg of Arimidex per week. In 10 days u’ll have about 2mg of Arimidex in ur system. ...

The intention is ok, but the math is not. The rule of thumb is that you're close to steady-state after four to five half-lives. "Steady-state" in this case means each dosing cycle looks like the last, not that levels of the medication are constant. The problem with your example is that the dosing cycle of one week is 3.5 half-lives. With a two-day half-life the level from an initial dose has fallen to 9% of peak by the time for the second dose. Over time, contributions from doses other than the one before last are pretty negligible. So at peak you'll have 1.09 mg in your system right after each dose. If you run the math you find that 10 days after the initial dosing you'll have 0.39 mg in your system. Bottom line: if you want to see significant drug accumulation then the dose cycle length should be more like the half-life or less.

 

[Gman86]

The intention is ok, but the math is not. The rule of thumb is that you're close to steady-state after four to five half-lives. "Steady-state" in this case means each dosing cycle looks like the last, not that levels of the medication are constant. The problem with your example is that the dosing cycle of one week is 3.5 half-lives. With a two-day half-life the level from an initial dose has fallen to 9% of peak by the time for the second dose. Over time, contributions from doses other than the one before last are pretty negligible. So at peak you'll have 1.09 mg in your system right after each dose. If you run the math you find that 10 days after the initial dosing you'll have 0.39 mg in your system. Bottom line: if you want to see significant drug accumulation then the dose cycle length should be more like the half-life or less.

Ya that makes more sense. I knew my math didn’t sound right lol

 

[DS3]

The intention is ok, but the math is not. The rule of thumb is that you're close to steady-state after four to five half-lives. "Steady-state" in this case means each dosing cycle looks like the last, not that levels of the medication are constant. The problem with your example is that the dosing cycle of one week is 3.5 half-lives. With a two-day half-life the level from an initial dose has fallen to 9% of peak by the time for the second dose. Over time, contributions from doses other than the one before last are pretty negligible. So at peak you'll have 1.09 mg in your system right after each dose. If you run the math you find that 10 days after the initial dosing you'll have 0.39 mg in your system. Bottom line: if you want to see significant drug accumulation then the dose cycle length should be more like the half-life or less.

Excellent post. So this would suggest that if you want a true steady state with Anastrozole then EOD dosing would be necessary?

 

[Cataceous]

... So this would suggest that if you want a true steady state with Anastrozole then EOD dosing would be necessary?

If you're now defining "steady state" to mean fairly constant drug serum levels then even EOD is questionable. In theory, assuming rapid absorption, you get trough levels that are half of the post-dose peak levels. However, in practice I suspect that the underlying processes and their subjective results have longer time frames; I've tried both EOD and ED and can't say I noticed much difference. Even daily dosing in theory results in trough serum levels that are almost 30% lower than peaks.

 

[DS3]

If you're now defining "steady state" to mean fairly constant drug serum levels then even EOD is questionable. In theory, assuming rapid absorption, you get trough levels that are half of the post-dose peak levels. However, in practice I suspect that the underlying processes and their subjective results have longer time frames; I've tried both EOD and ED and can't say I noticed much difference. Even daily dosing in theory results in trough serum levels that are almost 30% lower than peaks.

Help me understand steady state better. Steady state, as I currently have it defined (and may be wrong so please correct me) in TRT as the maintenance of consistent hormone levels, which would require a fairly constant administration of hormones to maintain those consistent levels.

 

[TLawyer]

Help me understand steady state better. Steady state, as I currently have it defined (and may be wrong so please correct me) in TRT as the maintenance of consistent hormone levels, which would require a fairly constant administration of hormones to maintain those consistent levels.

Yes, wouldn't we be more concerned about the hormone level than the drug level? In other words, if one dose of Arimidex can keep my E2 suppressed for an extended period of time or in a very tight range before I need to take another dose, then a good amount of the actual drug may be out of my body before it would have any impact on my actual hormone level. Of course, that would assume that one dose would have that effect and the level of drug wouldn't need to remain consistent in my body to keep the consistent level of hormone.

 

[DS3]

Yes, wouldn't we be more concerned about the hormone level than the drug level? In other words, if one dose of Arimidex can keep my E2 suppressed for an extended period of time or in a very tight range before I need to take another dose, then a good amount of the actual drug may be out of my body before it would have any impact on my actual hormone level. Of course, that would assume that one dose would have that effect and the level of drug wouldn't need to remain consistent in my body to keep the consistent level of hormone.

The drug level would be directly influencing the hormone level, so the emphasis would have to be equally weighted on both variables to (1) establish the right hormone level and (2) maintain that hormone level. With a 2-day half-life, Anastrozole isn’t going to keep estrogen suppressed over the duration of a 1-week administration protocol, same as once per week Test Prop injections are not going to maintain consistent T levels.

I’m not suggesting that an AI has to or needs to be taken more than once per week, I’m just saying from a ‘steady state’ perspective (if my definition is correct) that it would need to be to maintain consistent estrogen suppression.

 

[Cataceous]

Help me understand steady state better. Steady state, as I currently have it defined (and may be wrong so please correct me) in TRT as the maintenance of consistent hormone levels, which would require a fairly constant administration of hormones to maintain those consistent levels.

There are at least a couple things we might mean by "steady state". First, there's the kind when we say we should wait four to five half-lives after starting a medication before measuring serum levels. This is due to the additive effects of consecutive doses. Each dose is modeled as making a rapid contribution to serum levels that decreases over time. The rate of decrease is modeled by an exponential decay and quantified by the half-life parameter. For any individual dose, after four half-lives the contribution is down to 1/16 of the starting amount. After five half-lives the contribution is down to 1/32. At these times we can be fairly confident that serum levels in subsequent dosing cycles should not increase by more than a few percent.

The key distinction with this kind of steady state is that it refers to variations between different dosing cycles, not variations within the dosing cycles. Unless the dosing cycle is short compared to the half-life we can expect a decrease in levels over the course of the cycle. That's why we usually measure at trough, before the next dose. The point here is that in steady state the serum levels in any cycle look the same as in any subsequent cycle, but these cycles can consist of post-dose peaks and pre-dose troughs that may be quite different.

The other steady state we're talking about means a minimal fluctuation in medication levels over the course of each dosing cycle. In other words, the serum peaks and troughs are relatively close together. We can calculate a ripple constant as the ratio of trough over peak, which is exp( -ln(2) * cycle_length / half_life). For example, if someone is injecting testosterone cypionate once a week and the half-life is five days then the ratio is 0.38, which means that serum testosterone has declined by 62% over the week, a pretty large variation. In contrast, if he injects daily then the daily decline is only 13%. In practice I think the ripple at shorter intervals is even smaller than this model predicts.

 

[Nomad]

Help me understand steady state better. Steady state, as I currently have it defined (and may be wrong so please correct me) in TRT as the maintenance of consistent hormone levels, which would require a fairly constant administration of hormones to maintain those consistent levels.

one of the things I need to keep drilling in people on other forums... for this steady state you can’t increase Armidex dosing frequency without also increasing your testosterone injection frequency.

200mg injected once a week and taking 1mg of armidex vs injecting once a week and taking .5mg armidex twice a week will yield very different results as .5mg AI peaks without your testosterone peaking near it.

always remember Armidex isnt lowering your E2 it’s preventing testosterone from converting to e2 (something shitty doctors don’t grasp)

my about perfect number is about .1mg Armidex for every 15-20mg of testosterone injected.

 

[ajax31]

I came across some interesting research about using high-dose Vitamin D (50,000 IUs a week) for the joint pain and bone loss associated with Arimidex. These studies were looking at women who use AIs for breast cancer. It was a while ago, but I seem to recall one of the studies showing that high dose Vitamin D increased aromatase activity specifically in the bones but not in the breast tissue. They didn't investigate Vitamin D's effect on aromatase levels in other organs or tissues. It raises an interesting question if high-dose Vitamin D ONLY targets aromatase in bones and joints but not elsewhere in the body.

 

[Nomad]

I came across some interesting research about using high-dose Vitamin D (50,000 IUs a week) for the joint pain and bone loss associated with Arimidex. These studies were looking at women who use AIs for breast cancer. It was a while ago, but I seem to recall one of the studies showing that high dose Vitamin D increased aromatase activity specifically in the bones but not in the breast tissue. They didn't investigate Vitamin D's effect on aromatase levels in other organs or tissues. It raises an interesting question if high-dose Vitamin D ONLY targets aromatase in bones and joints but not elsewhere in the body.

I’ve noticed no difference I’m on 50-70k iu vitamin D weekly. In the study you mentioned I wonder if the participants calcium levels were monitored since vitamin D is needed to absorb calcium amongst countless other minerals. That variable alone could drastically affect bone density.

 

[TucsonJJ]

I believe that I've seen a thread that one 1mg dose of Arimidex decreases E2 by about 70% within 24 hours, and then up to 80% when taken on regular basis thereafter. Are we able to extrapolate from that how much a single .25mg does would decrease E2? Would it be about 17.5%?

I asked because after staying of Arimidex for about 2 weeks or so, I took at .25mg dose to see whether I felt any difference. And I definitely did within about 7 hours and still am about 36 hours after that dose. Libido and sensitivity definitely improved in that 7 hours, and I feel like erection strength as well. I am low SHBG (11 at my last lab test using this protocol), and my last E2 level came in at about 55 on my current protocol (probably was higher before I took the Arimidex as I registered that 55 about 3 and half days after taking a .125 mg dose, and then stopped taking it to see how I felt, so I imagine it rose during those 2 weeks). Mentally felt better as well, although that may go along with a better libido and sensitivity. I am amazed as how quickly I felt a difference. If it is about a 17.5% decrease in E2, that would put me on the low end of about 45 (17.5% of 55). I'm just trying to get a sense of a good level for me with my E2 given that I can't run out to a lab until Tuesday, so I can't get a confirmed level (and who knows how I will feel on Tuesday). That 45 still seems like it may be on the higher end, so my thought is that perhaps .25mg is decreasing it more than 17.5%.

I will say that the only drawback is that I woke up with morning (about 24 hours after I took the .25mg dose) with my joints killing me and elbow pain, which I have suffered with since starting the smaller doses of Arimidex about 2 months ago. Physically, as far as pain, I have gradually felt better after stopping the Arimidex for those 2 weeks, including the elbow pain, but it's definitely back today after taking a dose. I had originally thought when I was experiencing that pain that I was crashing my E2, but then I came back with the 55 level, so that clearly wasn't the case. I looked up Arimidex, and I see that joint and muscle pain is a common side effect. My question is this - is that because people are crashing their E2 with Arimidex, or is it for another reason (i.e. you can experience the pain even if you don't crash E2)? Because I am not crashing it, but I definitely feel the pain almost immediately.

The pain is a little disappointing, although the libido and sensitivity increase certainly have overshadowed it.

I tried 1mg/week Arimidex when I tried TRT... was way too much too soon I think... had some really bad side effects, really felt ill... plus... had some sharp pain in my right knee and months later... I still have it! Permanent damage? Not sure... but no more of that poison for me... when I start TRT again... I'll ask for an alternative IF my E2 spikes.

 

[PhantomFear]

Most people don't understand that AI's aren't selective to solely aromatase.

The enzymes in the steroid hormone cascade all belong to the same family. As a result, any substance that inhibits one will have an effect on another, albeit to a lesser degree. You can see this in the hormones themselves. Estradiol can bind to the estrogen, androgen, progestin and glucocorticoid receptor. Testosterone can do the same, as can progesterone, as can DHEA, as can most steroid metabolites. This doesn't mean they all bind with the same affinity or elicit the same response, however. This same idea applies to aromatase inhibitors and their interaction with armomatase and the other steroid producing enzymes.

When you take an ai, you're also reducing the production of pregnenolone, progesterone, dhea and all of their associated metabolites. Most people on T are already low in these hormones due to hpta suppression, and I believe this is why very small doses can cause a large, undesired response despite little changes to serum estradiol (not that serum estradiol is a good indicator of estrogenic activity in the tissue anyway)

I personally don't subscribe to the idea that a poor response to a low dose (emphais on low; 1mg of adex a day is a different matter entirely) of ai is because of reduced estradiol when estradiol isn't significantly lowered. I find it more likely that it's due to the reduction in already low progesterone, evidenced by the complaint that even small doses can cause joint issues. Progesterone is just as important for joints as estrogen, which is why there is the current craze of everyone wanting to add nandrolone, a progestin, to their trt for the joint health benefits.

 

[Cataceous]

...
When you take an ai, you're also reducing the production of pregnenolone, progesterone, dhea and all of their associated metabolites. ...

Can you cite some credible references showing non-negligible effects? This article states that third-generation AIs such as anastrozole "block only conversion of androstenedione and testosterone to estrone and estradiol."

 

[PhantomFear]

Can you cite some credible references showing non-negligible effects? This article states that third-generation AIs such as anastrozole "block only conversion of androstenedione and testosterone to estrone and estradiol."

First generation ai's do cause more supression of upstream hormone production, mainly because they inhibit the conversion of cholesterol -> preg, and thus the entire steroid hormone cascade. Third generation ai's don't have this effect, but they do seem to effect progesterone significantly.

Here are some papers that show reduced progesterone and/or progesterone receptor (PR) expression from the use of anastrozole:

Anastrozole Reduces Progesterone and Proliferation Index in Short Term Hormone Therapy. A Prospective Placebo Double Blind Study.

Short-term Anastrozole Therapy Reduces Ki-67 and Progesterone Receptor Expression in Invasive Breast Cancer: A Prospective, Placebo-Controlled, Double-Blind Trial.

Effect of Aromatase Inhibitors versus Clomiphene Citrate for Ovulation Induction in Infertile Women with Ovulatory Dysfunction (PCO).

Also, here is a paper showing that Vitamin D alleviates aromatise inhibitor-induced bone pain:

High-Dose Vitamin D May Ease Joint Pain from Arimidex.

Vitamin D has no estrogenic activity, but does activate the androgen and progesterone receptor. This, taken with the prior studies showing anastrozole reduces progesterone and the expression of it's receptor, suggest that the bone / joint pain (and perhaps many other ai-related sides) are from reduced progestenic activity - not from low estrogen. There are a few more studies that suggest the same thing, but these are the only ones I have to hand right now.

Almost every man I've seen test their progesterone on trt are deficient. I find it more likely that ai-related sides are from reducing already low progestenic activity, rather than slightly reducing an already high estradiol.

 

[PhantomFear]

Anecdotally, I always got bone and joint pain when taking an ai.

I'm currently off TRT right now and my estradiol is rather low, yet I have zero joint pain. Here are what my last set of bloods looked like:

Testosterone: 18.2 nmol/L (500 ng/dL) (Range: 8.6 - 29 nmol/L)
Estradiol: 55 pmol/L (14 pg/ml) (Range: 45 - 159 pmol/L)
Progesterone: 1.4 nmol/L (0.44 ng/ml) (Range: < 0.474 nmol/L)

First off, the range for male progesterone is wrong.

Progesterone: the forgotten hormone in men?
"We analyzed serum samples from 1015 men aged 20–90 years and serum samples from 330 postmenopausal women aged 50–90 years by a radioimmunoassay for progesterone. We found 1.21+ 0.41 SD nmol/l (0.38+0.13 ng/ml) for men and 1.24+1.18 SD nmol/l (0.38+0.37 ng/ml) for women, i.e. there were no differences between men and women."

Despite being 3x above the 'healthy' range, my progesterone levels fall inline with most data that investigates male progesterone levels, with mine being considered high-normal.

My estradiol is objectively quite low, yet I have zero joint pain.

When I was on TRT + using an ai, I had very severe joint pain. Here are what my bloods looked like on trt, just before I came off for the second time:

Testosterone: 28.2 nmol/L (813 ng/dL) (Range: 8.6 - 29 nmol/L)
Estradiol: 150 pmol/L (40 pg/mL) (Range: 45 - 159 pmol/L)
Progesterone: < 0.141 nmol/L (Undetectable) (Range: < 0.474 nmol/L)

Higher estradiol, undetectable progesterone, and severe bone and joint pain. I'm not saying that ai alone caused my deficient progesterone, as I believe it is mostly a product of HPTA shutdown and impaired cholesterol -> preg. However, it is unsurprising that further reducing progesterone and the expression of it's receptor in a man who is already low causes undesirable effects. This is all whilst serum estraidol (not a good indicator of tissue status, I know) is at the top of the range.

Again, I understand that this is anecdotal, but it supports my previous claim and the studies I provided.