Can estrogen crash cause desensitization/knock out of the estrogen receptor - lets discuss!

[nurselyfe]

Im still interested in your hypothesis on how does the increase of serum E2 cause a permanent worsening of ones symptoms. What do you think is the mechanism behind that?

Based on my own research, epigenetics would be the only logical and plausible explanation. I am not sure through what mechanism increasing endogenous E2 makes my symptoms worse but if I had to speculate it's through epigenetic alteration i.e. methylation of a gene, which would further silence my ER in target cells. If you look at this simplified diagram, methyl groups attract more, which further represses the gene. But still, I don't know why increasing E2 worsens the signal.

I can provide breast cancer studies that show ER function on the cancer cells become insensitive to estradiol, and grow with or without estradiol. I can even provide a study that shows a paradoxical effect of estradiol on breast cancer cells, where estradiol administration causes apoptosis of cells. I've said it multiple times, when my E2 raises (via larger testosterone shot or even use of Tamoxifen or Clomid, two drugs I've used in the past with a desired effect and no ADRs), I feel like I am going through chemotherapy- severe mental agitation, severe anxiety, absolutely no appetite, severe ED, and worsening of all other symptoms. But when my E2 is stable, like it is right now, I don't have any anxiety or mental agitation, and the ED isn't as severe.

Like I said, I don't know. It's bizzare and unfair. Increasing E2 used to make me feel mentally and physical great. I'm so angry I ever used Arimidex. I am going to leave the mechanism up to doctors and researchers once this is finally investigated.



In regards to your other post with the EIS studies in the male and female. I am on TRT so my E2 would not be supraphysiological like it is in these studies. I do not have any output of LH and FSH.

Also, these patients have a congenital condition, a gene mutation in the base DNA. It's not a epigenetic matter. Based on my theory, my symptoms get worse because the receptor gets further silenced when E2 is increased. This won't happen in a DNA mutation. What's done is done and no further changes can be made in the base DNA.

Lastly, it's important to know how the libido and erectile function were evaluated. To this man, for all he could know, his erectile function could realistically be 80%, but he thinks it's 100% because he never experienced a true healthy erection. If I was born with this, I would think my erection is 100% because it still gets hard. But since I was not born with this, and I know what an incredible erection feels like, I would say my erection is 70-75% of what it was. It's all relative. Same concept with libido.

I hope this makes sense.

 

[johndoesmith]

Madman, thanks for your thoughtful reply. I have never used a DHT inhibitor.

Estradiol in men is responsible for all of those characteristics as well. There is a lot of cross talk between steroid receptors and share a lot of gene activation. I will post a great study in about 30 minutes.

I truly think the fact that my estrogen receptor does not function the way it should has affected me vascularily. E2 mediates a lot of vascular function and I will also post a study on that.

If you saw a picture of me now, let alone when I was normal, you'd definitely saw there's no way I have poor vascular health. I am very vascular guy. Always had a great lipid profile, blood pressure, and my diet has been on par for 10 years.

I found this:

[FONT=&quot]In one study acute responses of postmenopausal women to estrogen (18 hr after placement of a transdermal patch) declined with age ([/FONT]Sherwood et al., 2007[FONT=&quot]). Similarly, postmenopausal women receiving either acute estrogen (within 1 hr of sublingual administration) or chronic estrogen (3 months oral administration) all demonstrated increases in flow-mediated dilation, but this increase was significantly greater in women who were less than 5 years past menopause compared to women more than 5 years past menopause ([/FONT]Vitale et al., 2008[FONT=&quot]). Furthermore, for women more than 5 years past menopause, flow-mediated vasodilation increased significantly more in women who had received estrogen treatment in the past compared to those who had not. These findings support the idea that, in the absence of estrogen, endothelium-dependent release of NO is reduced, and the ability of estrogen to increase this response is abrogated the longer an individual is without estrogen exposure. Whether this abrogation involves epigenetic regulation of estrogen receptors (see Section II. B.1.) or other mechanisms remains to be determined.[/FONT]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637768/

That does seem to support your idea that crashing E2 can cause long lasting effects. Although the study refers to post menopausal women, which have significant differences than a 24 year old male so it may not be directly applicable.

 

[nurselyfe]

I found this:



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637768/

That does seem to support your idea that crashing E2 can cause long lasting effects. Although the study refers to post menopausal women, which have significant differences than a 24 year old male so it may not be directly applicable.

Great study. Difference is I was only without estrogen for less than a month, and I had a few 24-48 hour periods during that month where I definitely had rebounds of estrogen because I would stop the Arimidex. Another difference is that I am a male like you said.

Basically, I know something is terribly wrong with the fundamental function of my Estrogen Receptors, and it started immediately when I took way too much Arimidex.

What does not make sense to me is that I am sure there are plenty of guys who have crushed their estrogen to very low levels, like sub 3pg/mL, and this did not happen to them. I hear of guys who take 2.5mg letro every day and no aromatizing compounds before a competition. This makes me wonder if I was susceptible to this somehow? I definitely was an over responder to Arimidex. I never needed more than 0.25mg every 12-14 days.

And let's be clear- I am making estrogen at the same exact rate and quantity as I was before. I do not think my E2 is crashed whatsoever.

 

[lowe2sucks]

^we both talked how in the past when we crashed our estrogen we never got so many symptoms and so long lasting.. something definitely happened to our bodies

 

[madman]

Great study. Difference is I was only without estrogen for less than a month, and I had a few 24-48 hour periods during that month where I definitely had rebounds of estrogen because I would stop the Arimidex. Another difference is that I am a male like you said.

Basically, I know something is terribly wrong with the fundamental function of my Estrogen Receptors, and it started immediately when I took way too much Arimidex.

What does not make sense to me is that I am sure there are plenty of guys who have crushed their estrogen to very low levels, like sub 3pg/mL, and this did not happen to them. I hear of guys who take 2.5mg letro every day and no aromatizing compounds before a competition. This makes me wonder if I was susceptible to this somehow? I definitely was an over responder to Arimidex. I never needed more than 0.25mg every 12-14 days.

And let's be clear- I am making estrogen at the same exact rate and quantity as I was before. I do not think my E2 is crashed whatsoever.

Of course e2 plays a role in libido and erectile function/mood/cognition/bone health/ligament and tendon health/vascular health/lipids and any excess or lack there of can contribute to many negative issues.

Testosterones metabolites dht and estradiol both are critical and serve a purpose and are needed in healthy amounts.

It is only when they are in excess or lacking that they can have negative consequences.

I hope you can get to the bottom of this as I could not imagine anyone let alone a 24 year old having to deal with such a thing.

 

[nurselyfe]

Of course e2 plays a role in libido and erectile function/mood/cognition/bone health/ligament and tendon health/vascular health/lipids and any excess or lack there of can contribute to many negative issues.

Testosterones metabolites dht and estradiol both are critical and serve a purpose and are needed in healthy amounts.

It is only when they are in excess or lacking that they can have negative consequences.

I hope you can get to the bottom of this as I could not imagine anyone let alone a 24 year old having to deal with such a thing.

It's a nightmare and has decimated my life to say the least man, but thank you. Trying to handle this responsibly, logically, and maturely as possible.

On a positive note, Baylor College of Medicine has sent me a letter saying I should consider applying for the Undiagnosed Disease Network study. So I am working on getting a letter of referral from a healthcare provider.

 

[johndoesmith]

Great study. Difference is I was only without estrogen for less than a month, and I had a few 24-48 hour periods during that month where I definitely had rebounds of estrogen because I would stop the Arimidex. Another difference is that I am a male like you said.

Basically, I know something is terribly wrong with the fundamental function of my Estrogen Receptors, and it started immediately when I took way too much Arimidex.

What does not make sense to me is that I am sure there are plenty of guys who have crushed their estrogen to very low levels, like sub 3pg/mL, and this did not happen to them. I hear of guys who take 2.5mg letro every day and no aromatizing compounds before a competition. This makes me wonder if I was susceptible to this somehow? I definitely was an over responder to Arimidex. I never needed more than 0.25mg every 12-14 days.

And let's be clear- I am making estrogen at the same exact rate and quantity as I was before. I do not think my E2 is crashed whatsoever.

The only other thing I can think of is that somehow the low E2 triggered an autoimmune reaction and set off some latent disorder you're genetically susceptible to.

A lot of conditions function that way, as in they have a genetic component that lies dormant with a trigger setting it off.

Narcolepsy is one, look at the pandemrix vaccine. Many received it but few developed narcolepsy from it. This contributed to an advancement in the study of this disease.

 

[nurselyfe]

The only other thing I can think of is that somehow the low E2 triggered an autoimmune reaction and set off some latent disorder you're genetically susceptible to.

A lot of conditions function that way, as in they have a genetic component that lies dormant with a trigger setting it off.

Narcolepsy is one, look at the pandemrix vaccine. Many received it but few developed narcolepsy from it. This contributed to an advancement in the study of this disease.

I've also thought of this and it sounds plausible. I am hoping I can get further evaluation and rule out a latent disease.

If you look my each individual symptom, it really does make sense that it would be a hormone receptor signaling problem at play here. For example, on 100mg T Cyp per week and no AI, my nipples would get puffy albeit no gynecomastia, itchiness, tenderness, or burning. Now, I am on that same exact protocol, and my nipples are completely flat and have no puffiness. In fact, when my E2 went from 17pg/mL to 36pg/mL in August after I ceased Arimidex for good, my pre-existing gyno completely disappeared. To me, that sounds like a receptor mediated issue - specifically ER.

 

[johndoesmith]

I've also thought of this and it sounds plausible. I am hoping I can get further evaluation and rule out a latent disease.

If you look my each individual symptom, it really does make sense that it would be a hormone receptor signaling problem at play here. For example, on 100mg T Cyp per week and no AI, my nipples would get puffy albeit no gynecomastia, itchiness, tenderness, or burning. Now, I am on that same exact protocol, and my nipples are completely flat and have no puffiness. In fact, when my E2 went from 17pg/mL to 36pg/mL in August after I ceased Arimidex for good, my pre-existing gyno completely disappeared. To me, that sounds like a receptor mediated issue - specifically ER.

Yeah, see lack of nipple "puffiness" isn't really a symptom.

Honestly I was more focused on your lack of hair, hair loss and nail issues because they are quantifiable.

It's like when someone says they're "dizzy". It has no clinical meaning, and depending on their accent it can mean vertigo, lightheadedness or fatigue.

 

[nurselyfe]

Yeah, see lack of nipple "puffiness" isn't really a symptom.

Honestly I was more focused on your lack of hair, hair loss and nail issues because they are quantifiable.

It's like when someone says they're "dizzy". It has no clinical meaning, and depending on their accent it can mean vertigo, lightheadedness or fatigue.

Its not a clinical symptom. But it's something I noticed. I just know my body really well. 100mg of Testosterone would certainly would always make my nipples puffy and leaky. Now that does not happen.

The quantifable component and clinical symptoms are the hair, nails, skin, vascular, and sexual symptoms

 

[johndoesmith]

Its not a clinical symptom. But it's something I noticed. I just know my body really well. 100mg of Testosterone would certainly would always make my nipples puffy and leaky. Now that does not happen.

The quantifable component and clinical symptoms are the hair, nails, skin, vascular, and sexual symptoms

This symptoms are usually more prolactin related as opposed to E2.

If anything, that's a good thing you're not having leakiness anymore.

Keep in mind, and you may not want to hear this, sometimes you can be too aware of everything you body is doing. Some of it may just be confirmation bias or perception related.

 

[nurselyfe]

I agree, I've been a victim of this before, as I explained about my back from years ago.

Im actually bothered by the fact my nipples are no longer puffy and are leaky. This was due to poorly controlled E2. Which makes perfect sense why I would have those symptoms. Now, I don't have this at all. It's a little scary. Obviously I could live with normal looking nipples, but it's just another indicator something is wrong

I'm able to notice these little more minute symptoms because I know my body extremely well. Another example, my entire life I produced thick and moist earwax. I'd literally have to go for biyearly cleanings. Now, I produce dry and scant earwax. Once again, it's not a clinical symptom and wouldn't mention this to a doctor because has no clinical significance. It's just something I noticed because earwax used to be problematic for me.

Again, both the nipple and earwax started immediately once I crashed my E2, along with the major symptoms.

 

[johndoesmith]

I agree, I've been a victim of this before, as I explained about my back from years ago.

Im actually bothered by the fact my nipples are no longer puffy and are leaky. This was due to poorly controlled E2. Which makes perfect sense why I would have those symptoms. Now, I don't have this at all. It's a little scary. Obviously I could live with normal looking nipples, but it's just another indicator something is wrong

I'm able to notice these little more minute symptoms because I know my body extremely well. Another example, my entire life I produced thick and moist earwax. I'd literally have to go for biyearly cleanings. Now, I produce dry and scant earwax. Once again, it's not a clinical symptom and wouldn't mention this to a doctor because has no clinical significance. It's just something I noticed because earwax used to be problematic for me.

Again, both the nipple and earwax started immediately once I crashed my E2, along with the major symptoms.

Yeah, no offense man, but that is terribly difficult to not categorize as hypochondria or psychosomatic, as people shouldn't be bothered by having normal body parts and the disappearance of problems.

Now that I think of it, have you actually verified any of the quantifiable symptoms?

 

[nurselyfe]

Yeah, no offense man, but that is terribly difficult to not categorize as hypochondria or psychosomatic, as people shouldn't be bothered by having normal body parts and the disappearance of problems.

Now that I think of it, have you actually verified any of the quantifiable symptoms?

Having ear wax my entire 24 years of life (which is normal, your body produces it to trap bacteria), to not producing any is a problem. It disappearing as soon as I crashed my estradiol isn't a coincidence.

Yeah, urologist identified ED. PCP identified hair loss that isn't MPB. Going to psychiatrist this Wednesday so we can dismiss any claims of psychosomatic symptoms, because I am tired of hearing that.

You're talking to someone who never felt the need to go to the doctor over any kind of cold or seasonal sickness, I am definitely not the hypochondriac type. I can really see it from your point of view, but I can't stress enough that none of this is psychosomatic. I wish it was and I'll definitely update this thread on Wednesday after my visit.

 

[johndoesmith]

Having ear wax my entire 24 years of life (which is normal, your body produces it to trap bacteria), to not producing any is a problem. It disappearing as soon as I crashed my estradiol isn't a coincidence.

Yeah, urologist identified ED. PCP identified hair loss that isn't MPB. Going to psychiatrist this Wednesday so we can dismiss any claims of psychosomatic symptoms, because I am tired of hearing that.

You're talking to someone who never felt the need to go to the doctor over any kind of cold or seasonal sickness, I am definitely not the hypochondriac type. I can really see it from your point of view, but I can't stress enough that none of this is psychosomatic. I wish it was and I'll definitely update this thread on Wednesday after my visit.

I mean, no one admits that it's psychosomatic, and personally I believe those that are adamant they're immune to the placebo effect or psychological causes of symptoms are even more susceptible to them.

Keep in mind you're also not telling your doctors all the information you're telling us, probably because you think it's awkward to admit.

Im actually bothered by the fact my nipples are no longer puffy and are leaky

Additionally you're wanting to have symptoms, and are distressed at the fact that you do not have them.

I wouldn't be so quick to rule out psychological causes, or simply paying way too much attention to normal bodily functions.

Once again, it's not a clinical symptom and wouldn't mention this to a doctor because has no clinical significance

You mentioned this to me twice, it seems to be a concern to you, so not mentioning it will only hurt the care you're going to receive. If you're not comfortable mentioning it to your doctor, there's probably another reason you're not wanting to admit as to why.

Again I'm not doing this to say "Got you!" or anything, but the internet can lead to people paying WAY too much attention to mundane shit that doesn't need to be.

 

[nurselyfe]

I mean, no one admits that it's psychosomatic, and personally I believe those that are adamant they're immune to the placebo effect or psychological causes of symptoms are even more susceptible to them.

Keep in mind you're also not telling your doctors all the information you're telling us, probably because you think it's awkward to admit.



Additionally you're wanting to have symptoms, and are distressed at the fact that you do not have them.

I wouldn't be so quick to rule out psychological causes, or simply paying way too much attention to normal bodily functions.



You mentioned this to me twice, it seems to be a concern to you, so not mentioning it will only hurt the care you're going to receive. If you're not comfortable mentioning it to your doctor, there's probably another reason you're not wanting to admit as to why.

Again I'm not doing this to say "Got you!" or anything, but the internet can lead to people paying WAY too much attention to mundane shit that doesn't need to be.

I admitted right away I gave myself psychosomatic back pain when I was younger after my first deadlift injury.

Of course I tell my doctor everything, I know the importance of thorough past medical history, plus HIPPA, patient confidemtiality, patient to professional? To me, there's nothing to be uncomfortable about. That's like when I was in OB/GYN clinical and some women did not want a male nurse in the room. It's kind of insulting as I'm a professional and you are my patient.

What makes you think I want to have symptoms? I stated that I am having many symptoms that have decimated my life. Why on earth would I want that ...

Last but not least, the internet has not influenced me in any way. I came here after 3.5 months of dealing with symptoms. I am seeing an MD to rule out psychosomatic symptoms, though I'm positive I am not. My psychologist, who has also evaluated me believes there is something going on a physiologic level, has suggested I have an MD confirm this to further my case.

 

[lowe2sucks]

simeoni if you would rate how you feel now (post estrogen crash) and pre trt (obviously before estrogen crash) which one was better?

 

[nurselyfe]

simeoni if you would rate how you feel now (post estrogen crash) and pre trt (obviously before estrogen crash) which one was better?

Funny you ask this. Even when I came off Testosterone awhile back with a PCT of just 2 weeks of Nolvadex and Clomid, I felt much, much better than this and had none of these symptoms.

 

[simeoni]

Well it depends.

The worst months of "post estrogen crash" were definitively worse than "pre trt". Before TRT I definitively felt very bland and was somewhat apathetic but there was none of that anxious agitation that I had during the first months after overusing arimidex.

Still overall, id rate these two periods pretty much the same. For many months I was not able to feel any positive effects of testosterone even though my serum levels were much higher than before TRT.


On a side note, I would like to report that the past two weeks have been better for me. Im not entirely sure why that is. I have made a slight adjustment to my protocol. Im still taking the same amount of TE (15mg) EOD but I have added 250 IU's of HCG on the injection day. I have also stopped taking the small amount (5-8mg) of test cream on my scrotum.

Last weeks I had many days of good libido. I have not experienced a similar period in months. Hopefully things continue to improve.

simeoni if you would rate how you feel now (post estrogen crash) and pre trt (obviously before estrogen crash) which one was better?

 

[simeoni]

nurselyfe why are you on trt if you were not hypogonadal before starting testosterone replacement?

What were your pre-trt levels? If your gonads can produce a decent amount of testosterone on their own, why dont you try the natural route and see how you feel.