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

[ilomia]

Mine is real bad I would say debilitating. Good luck when taking the NCLEX.

Soon to be nurse.

Joint cracking isnt debilitating but it's annoying.

 

[nurselyfe]

Mine is real bad I would say debilitating. Good luck when taking the NCLEX.

Thank you I appreciate it!

 

[Vitamin_C]

I don't know why joint popping gets lumped into main low E2 symptoms. My joints popped before I went low on my E2, they popped after. My wife's joints pop and she has a lot of E2. Many people's joints pop with all sorts of E2 ranges, this is a common finding, and it seems to be correlated with years of wear and tear and exercise. Any doctor will tell you joint popping w/out pain is benign. Now, if you have accompanying pain you should be seen by a physician and get appropriate labs drawn.

 

[nurselyfe]

I don't know why joint popping gets lumped into main low E2 symptoms. My joints popped before I went low on my E2, they popped after. My wife's joints pop and she has a lot of E2. Many people's joints pop with all sorts of E2 ranges, this is a common finding, and it seems to be correlated with years of wear and tear and exercise. Any doctor will tell you joint popping w/out pain is benign. Now, if you have accompanying pain you should be seen by a physician and get appropriate labs drawn.

I don't know either. My buddy's joints do not pop when his estrogen is very low but they're definitely more achy.

Same with me, my joints pop high or low. But when it's low they are painful.

 

[madman]

I can offer you at theory, but it'd be pure speculation. Even if I was right on the mechanism, you would not find any literature on it. This is the problem at hand. Theoretically, arimidex should absolutely not cause any persistent issues; its a reversible inhibitor of aromatase. I do not think it was the arimidex itself that caused it.


I believe that there was some autoimmune negative feedback on the receptor and its post translational products. Think about it in a way that a wire has been tripped. There are ton of different co-regulators and proteins that mediate how nuclear receptors work, a lot can go wrong. I can't say I've brought my estrogen to zero and this is what caused it because I'm sure many guys have done the same and this didn't happen to them.

I believe that it is most likely epigenetic etiology. We were not born with a congenital condition and it is extremely hard to alter the genome.

This is simply speculation but I gave it the best I had. I think it's better to think about what we do know.

1. There are a vast amount of people who have used different kinds of inhibitors that now have persistent side effects after stopping the drug. E.g Finasteride, Accutane, SSRI's, and now, AI's.

2. It seems that the persistent side effects are quite specific towards what was inhibited. People who have persistent side effects from Finasteride can still get estrogenic side effects but have problems in the tissues that are androgen dependent. E.g penis shrinkage, testicular shrinkage, zero libido, impotence, loss of beard growth, bone loss, pelvic/prostatic pain, muscle wastage, loss of oil production on scalp, no energy, horrible sleep. I still have all my energy, can grow a thick beard, I have little libido, no shrinkage, but I have many low estrogen symptoms such as dry skin and unhealthy looking skin, complete loss of sebum production, scalp hair loss that is diffuse, loss of 50% hair on my arms and legs, but the hairs that still grow, grow fast, extremely flat muscles, loss of blood flow (less veins, get cold easily, lower blood pressure 128/82 to 114/65), gaining fat easily, no pumps, skin doesn't get flushed anymore like it used to do when I worked out, cold/clammy skin, slow nail growth, loss of appetite, loss of aggression, loss of nipple puffiness that accompanied high estrogen levels (no tissue growth though), loss of mild lactation, difficulty connecting to others, sometimes feel derealization, short term memory loss, and some anhedonia.

3. The severity of this was inducible. I didn't have half of these symptoms back in June/July, but every time I increased my estrogen, existing symptoms got worse, and new symptoms appeared. Guys who claim androgen insensitivity from PFS, say the exact same thing as me- increasing androgens makes their symptoms worse, and usually permanently.

4. I've used arimidex for the last 3 years. I've gone a little too low on E2 before using slightly higher doses of arimidex. Never has it gave me persistent side effects, and any side effects that I would get from low estrogen, would resolve in 4-5 days maximum. The persistent side effects that I have currently, have never occurred in my life. IT wasn't until I used large amounts of arimidex, 3-4x the amount I usually did, did this incident occur.

Over half of the symptoms you are stating are related to hypothyroidism.

 

[nurselyfe]

I agree. But that has been ruled out by a ton of blood work (posted numerous times here) 2 endocrinologists, and my TRT doc.

Was even prescribed 125mcg T4/day and it did absolutely nothing for my symptoms and made me dizzy.

Also do not have any fatigue, have regular bowel movements, and I'm still very lean. I do not have hypothyroidism lol.

Edit: I feel like no one is thinking about this logically. How would I go from being an absolute machine in the gym, eating up to 4k calories daily and not gaining fat, feeling completely healthy to randomly some kind of hypothyroid condition, when my thyroid blood work is the exact same that it's been for the last 2 years, blood work currently doesn't indicate hypothyroidism, and don't have any fatigue, sluggishness, high cholesterol, etc.

Clearly I have an estrogen receptor that does not work the way it should. At the current dosage of Test I am on right now, my nipples used to be a little puffy. Now they're extremely flat and have no puffiness.

 

[nurselyfe]

1/16/15
TSH 1.570 uIU/mL 0.450 - 4.500
Thyroxine (T4) 6.3 ug/dL 4.5 - 12.0


My Problem started on 5/23/17-5/28 area

10/24/17
TSH 1.440 uIU/mL 0.450 - 4.500
Thyroxine (T4) Free, Direct, S T4,Free(Direct) 1.26 ng/dL 0.82 - 1.77
Thyroid Antibodies Thyroid Peroxidase (TPO) Ab 9 IU/mL 0 - 34
Thyroglobulin Antibody <1.0 IU/mL 0.0 - 0.9
Triiodothyronine,Free,Serum 2.8 pg/mL 2.0 - 4.4


12/21/2017
TSH 1.940 uIU/mL 0.450 - 4.500
Thyroxine (T4) 6.6 ug/dL 4.5 - 12.0
Triiodothyronine (T3) 95 ng/dL 71 - 180

 

[nurselyfe]

Update:

All physical and sexual symptoms continue to get worse. Still on 100 milligrams of Testosterone Cypionate a week. Currently have 0 stress, almost no anxiety, still crushing school, but depressed about my situation. Sleep is still excellent and so is my energy.

Have been seeing a psychologist who has surmised that I am depressed about my situation and there is obviously something physiologically wrong, which could be contributing to the depression as well. He has suggested for me to see a psychiatrist to get this confirmed by an MD so that no one can no longer put it off to "psychosomatic symptoms", which I will be doing this Wednesday.

 

[johndoesmith]

Update:

All physical and sexual symptoms continue to get worse. Still on 100 milligrams of Testosterone Cypionate a week. Currently have 0 stress, almost no anxiety, still crushing school, but depressed about my situation. Sleep is still excellent and so is my energy.

Have been seeing a psychologist who has surmised that I am depressed about my situation and there is obviously something physiologically wrong, which could be contributing to the depression as well. He has suggested for me to see a psychiatrist to get this confirmed by an MD so that no one can no longer put it off to "psychosomatic symptoms", which I will be doing this Wednesday.

Have you had a Sensitive Estradiol test ran? I only saw one E2 test and it was a standard.

Summarize your current symptoms, looking back at some of your posts, it's not exactly very clear what they are.

 

[nurselyfe]

Have you had a Sensitive Estradiol test ran? I only saw one E2 test and it was a standard.

Summarize your current symptoms, looking back at some of your posts, it's not exactly very clear what they are.

Yes I have. I had one in the summer, which is the one below.

Protocol was 120mg T/week and 0.5mg Arimidex per week. T level 1250, E2 17 (8-35). Was having symptoms here.

Next, Endo said drop Arimidex. T level 1225, E2 36 (7-42.6) Symptoms got even worse.

Next, Endo said lower T dose to 100mg a week, and go SubQ. T level 750, E2 26 (7-42.6). Symptoms remained the same. Then I took one dose of 12.5mg clomid and symptoms got worse.

Next, Endo said go IM, because SQ was causing soreness. T level 1006, E2 35 (7-42.6). Symptoms got much worse.

All of these bloods were 8 weeks apart.

By symptoms, which were outlined in a post below, are
-Complete absence of sebum on skin
-Skin dryness
-Pale skin
-Hair loss on entire scalp that falls out at chemotherapy rates, on entire body, eye lashes, and eye brows
-Dry hair
-Dry lips
-Dry mouth
-Slow hair growth
-Skin texture changes
-Reduction in what used to be very apparent vascularity
-Reduction in blood pressure
-Slow and brittle nail growth
-Reduced strength in gym, no pump, no contraction, lose muscle much faster
-Erectile dysfunction
-Low libido, sometimes none
-No aggression
-Low appetite
-Some brain fog that I've gotten used to
-Depression (due to symptoms)
-Low mood
-Some anhedonia

 

[johndoesmith]

Yes I have. I had one in the summer, which is the one below.

Protocol was 120mg T/week and 0.5mg Arimidex per week. T level 1250, E2 17 (8-35). Was having symptoms here.

Next, Endo said drop Arimidex. T level 1225, E2 36 (7-42.6) Symptoms got even worse.

Next, Endo said lower T dose to 100mg a week, and go SubQ. T level 750, E2 26 (7-42.6). Symptoms remained the same. Then I took one dose of 12.5mg clomid and symptoms got worse.

Next, Endo said go IM, because SQ was causing soreness. T level 1006, E2 35 (7-42.6). Symptoms got much worse.

All of these bloods were 8 weeks apart.

By symptoms, which were outlined in a post below, are
-Complete absence of sebum on skin
-Skin dryness
-Pale skin
-Hair loss on entire scalp that falls out at chemotherapy rates, on entire body, eye lashes, and eye brows
-Dry hair
-Dry lips
-Dry mouth
-Slow hair growth
-Skin texture changes
-Reduction in what used to be very apparent vascularity
-Reduction in blood pressure
-Slow and brittle nail growth
-Reduced strength in gym, no pump, no contraction, lose muscle much faster
-Erectile dysfunction
-Low libido, sometimes none
-No aggression
-Low appetite
-Some brain fog that I've gotten used to
-Depression (due to symptoms)
-Low mood
-Some anhedonia

So you've only had the one Sensitive test, with all of the follow up tests being the standard assay? It's difficult to figure anything out based on the standard assay, which is probably adding to the uncertainty.

Being honest those symptoms do not seem to line up with low E2, more in line with hypothyroidism.

What is your SHBG?

 

[nurselyfe]

So you've only had the one Sensitive test, with all of the follow up tests being the standard assay? It's difficult to figure anything out based on the standard assay, which is probably adding to the uncertainty.

Being honest those symptoms do not seem to line up with low E2, more in line with hypothyroidism.

What is your SHBG?

SHGB is 31 (15-55)

I agree. My low E2 symptoms that I typically get so not resemble any of the symptoms I've stated. My low E2 symptons are good pumps, morning erections, no water retention, nipples aren't puffy, great libido, and dry mouth.

And Ive stated, the exact same protcool I am on now gives me incredible libido, fast hair growth, nipples that were a bit puffy but no gyno, great vascularity, mood etc, I do not have any of that.

My doctor already ruled out hypothyroidism and said she'd absolutely not put me anywhere need thyroid meds. And when you're hypo, you usually have low energy and high cholesterol. I have neither.

 

[johndoesmith]

SHGB is 31 (15-55)

I agree. My low E2 symptoms that I typically get so not resemble any of the symptoms I've stated. My low E2 symptons are good pumps, morning erections, no water retention, nipples aren't puffy, great libido, and dry mouth.

And Ive stated, the exact same protcool I am on now gives me incredible libido, fast hair growth, nipples that were a bit puffy but no gyno, great vascularity, mood etc, I do not have any of that.

My doctor already ruled out hypothyroidism and said she'd absolutely not put me anywhere need thyroid meds. And when you're hypo, you usually have low energy and high cholesterol. I have neither.

Then it's pretty apparent that this is not testosterone/estradiol related, as you said the same protocol has given you benefits, and now it doesn't.

Something changed since then and now.

The only thing I can see is that you have not had all of the thyroid tests ran that many claim are necessary such as RT3.

I'm almost thinking this is vascular in origin. Give us some history on you, age, race, other dxs and any changes in lifestyle around when this occurred.

 

[nurselyfe]

Then it's pretty apparent that this is not testosterone/estradiol related, as you said the same protocol has given you benefits, and now it doesn't.

Something changed since then and now.

The only thing I can see is that you have not had all of the thyroid tests ran that many claim are necessary such as RT3.

I'm almost thinking this is vascular in origin. Give us some history on you, age, race, other dxs and any changes in lifestyle around when this occurred.

Doc's won't prescribe the rT3, they don't see it of any clinical value. And based on my other labs for thyroid, it looks fine. I also do not have sleep, energy or fatigue issues. I appreciate the suggestion and interest in my case but I don't think it's vascular
in origin, but certainly causing vascular issues i.e loss of vascularity, cold extremities, ED. I'm certain it is loss of the estrogen receptor function. Medical literature states that it important in every symptom that I have. Will post studies if requested.

Age 24
Egyptian and Italian
No other dxs
No previous health concerns, illnesses, surgeries
Always maintained healthy life style
Probably around 11% body fat
No Changes in life style when this occurred, only thing I changed was overdosing badly on arimidex

 

[simeoni]

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?

 

[madman]

Yes I have. I had one in the summer, which is the one below.

Protocol was 120mg T/week and 0.5mg Arimidex per week. T level 1250, E2 17 (8-35). Was having symptoms here.

Next, Endo said drop Arimidex. T level 1225, E2 36 (7-42.6) Symptoms got even worse.

Next, Endo said lower T dose to 100mg a week, and go SubQ. T level 750, E2 26 (7-42.6). Symptoms remained the same. Then I took one dose of 12.5mg clomid and symptoms got worse.

Next, Endo said go IM, because SQ was causing soreness. T level 1006, E2 35 (7-42.6). Symptoms got much worse.

All of these bloods were 8 weeks apart.

By symptoms, which were outlined in a post below, are
-Complete absence of sebum on skin
-Skin dryness
-Pale skin
-Hair loss on entire scalp that falls out at chemotherapy rates, on entire body, eye lashes, and eye brows
-Dry hair
-Dry lips
-Dry mouth
-Slow hair growth
-Skin texture changes
-Reduction in what used to be very apparent vascularity
-Reduction in blood pressure
-Slow and brittle nail growth
-Reduced strength in gym, no pump, no contraction, lose muscle much faster
-Erectile dysfunction
-Low libido, sometimes none
-No aggression
-Low appetite
-Some brain fog that I've gotten used to
-Depression (due to symptoms)
-Low mood
-Some anhedonia

Almost seems dht related as it is responsible for stimulating the production of sebum (oily skin) from increased size/function of the oil glands (you state complete absence of sebum on skin/skin dryness/dry hair,mouth,lips,skin texture changes). People who have used/abused the horrible drug ACCUTANE commonly experience all of these symptoms.

Dht is also responsible for increased hair growth (you state slow hair growth) but you also mention hair loss on entire scalp,body,eye lashes and eye brows and slow/brittle nail growth (which can be thyroid/vascular related).

Dht also plays a role in libido/ed and mood/aggression/strength (think halotestin/test suspension).

Did you ever use dht inhibitors FINASTERIDE or DUTASTERIDE?

Aside from having healthy testosterone levels with e2 in check the main cause of ed in a majority of men is poor endothelial/vascular health.

 

[simeoni]

I found these two studies that are somewhat related to this topic. I suggest that everyone interested in this matter reads the full studies. Ill bring up few highlights from them.

1.Delayed Puberty and Estrogen Resistance in a Woman with Estrogen Receptor &#945; Variant
http://www.nejm.org/doi/10.1056/NEJMoa1303611#t=articleTop

"The patient is an 18-year-old, adopted white woman who presented at the age of 15 years with absent breast development, primary amenorrhea, and intermittent lower abdominal pain"

"At the time of presentation, laboratory studies revealed a serum estradiol level of 3500 pg per milliliter (normal follicular phase, 11 to 210 [12,848 pmol per liter; normal follicular phase, 40 to 771])"

"To determine whether exogenous estrogens would have an effect, for a total of 5 months, the patient took oral estrogen in the form of conjugated equine estrogen (at a dose of 1.25 mg for 3 months) and micronized estradiol (at doses of 3 and 4 mg per day for 1 month each)."

"Before the initiation of therapy, the patient's serum estradiol levels on immunoassay were invariably elevated, ranging from 750 to 3500 pg per milliliter (2753 to 12,848 pmol per liter) (Table 1). After isotope dilution and LC-MS, results for serum estradiol (2340 pg per milliliter [8590 pmol per liter]) and estrone (1040 pg per milliliter [3847 pmol per liter]) were 10 times the normal preovulatory levels. Serum levels of corticosteroid-binding globulin, sex-hormone&#8211;binding globulin, thyroxine-binding globulin, prolactin, and triglycerides were not increased, despite elevated estrogen levels. Gonadotropins remained mildly elevated."

"After isotope dilution and LC-MS, results for serum estradiol (2340 pg per milliliter [8590 pmol per liter]) and estrone (1040 pg per milliliter [3847 pmol per liter]) were 10 times the normal preovulatory levels. Serum levels of corticosteroid-binding globulin, sex-hormone&#8211;binding globulin, thyroxine-binding globulin, prolactin, and triglycerides were not increased, despite elevated estrogen levels. Gonadotropins remained mildly elevated."

"Untreated, the patient had a plasma estradiol level that was 10 times the normal value, similar to that of the &#945;-ERKO mouse. Her normal serum levels of sex-hormone&#8211;binding globulin, corticosteroid-binding globulin, thyroxine-binding globulin, prolactin, and triglycerides, which are known to be increased by estrogen, provide further evidence of estrogen resistance."


2.Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
http://www.nejm.org/doi/full/10.1056/NEJM199410203311604#t=articleResults

"In this report, we describe a man with estrogen resistance who had osteoporosis, unfused epiphyses, and continuing linear growth in adulthood. He also had elevated serum estrogen concentrations, abnormal gonadotropin secretion, and no target-tissue responses to estrogen therapy."

"The patient did not recall any change in facial structure, thickening or oiliness of the skin, excessive diaphoresis, skin tags, or changes in his voice. He did remember noticing increased pigment in the skin of each axilla starting at the age of 23. Though unmarried, he reported no history of gender-identity disorder. He indicated strong heterosexual interests and had normal functioning, including morning erections and nocturnal emissions."

"he patient had a full beard with early temporal hair loss. There was no thyroid enlargement or gynecomastia. The results of cardiovascular, respiratory, and abdominal examinations were normal. The patient had normal male genitalia with bilateral descended testes, each with a volume of 20 to 25 ml, and a normal-sized prostate gland."

"The serum testosterone concentration was normal, and estradiol, estrone, follicle-stimulating hormone, and luteinizing hormone concentrations were high. "


"On the basis of the hypothesis that primary estrogen resistance might explain the elevated serum estrogen and abnormal serum gonadotropin concentrations, failure of epiphyseal fusion, and possibly insulin resistance, the patient was treated with high-dose transdermal ethinyl estradiol (Estraderm patch system, Ciba, Summit, N.J.) for six months. "

"During estrogen therapy, the patient had no nausea, fluid retention, hypertension, unusual headaches, weight gain, gynecomastia, impotence, or mood alterations. In addition, there was no significant increase in the serum concentration of any estrogen-dependent protein (sex hormone-binding globulin, thyroxine-binding globulin, cortisol-binding globulin, or prolactin) or change in serum gonadotropin concentrations (Table 1). The results of tests of bone turnover were all consistent with active bone demineralization and did not decrease. Finally, total bone mineral density and bone age did not change during estrogen administration."

"The elevated serum estrogen concentrations in this man suggest a compensatory increase in aromatase activity in response to estrogen resistance, and increased aromatase activity could account for the normal concentrations of androgen despite increased secretion of luteinizing hormone. "


Ok. So we had two cases - male and a female - of genetic estrogen resistance. What is relevant to us is the fact that the resistance of the ER caused a marked increase in serum estradiol - in both cases!

If I remember correctly nurselyfe hypothesized that this would not happen in the desensitization of ER.

Another interesting point was that the male participant had a healthy libido and erection quality. Also the male did not show any worsening in his condition when he was treated with estrogen.

So again; I would like to ask from nurselyfe what do you think is the mechanism that would cause a permanent worsening of ones condition - when E2 is elevated.

 

[madman]

Androgens are the key player in hair growth, not estrogens...

https://www.ncbi.nlm.nih.gov/pubmed/18844710

I definitely agree on this one!

 

[nurselyfe]

I definitely agree on this one!

This is true. But notice the phrase, key player. So it's not the only player. Which is why I still grow a thick beard. But Estrogen Receptors are found in hair follicle cells which mediate growth as well. Just speaking about my beard as an example, my beard grows a bit more slowly,, it's very dry, and is a bit more patchy.

 

[nurselyfe]

Almost seems dht related as it is responsible for stimulating the production of sebum (oily skin) from increased size/function of the oil glands (you state complete absence of sebum on skin/skin dryness/dry hair,mouth,lips,skin texture changes). People who have used/abused the horrible drug ACCUTANE commonly experience all of these symptoms.

Dht is also responsible for increased hair growth (you state slow hair growth) but you also mention hair loss on entire scalp,body,eye lashes and eye brows and slow/brittle nail growth (which can be thyroid/vascular related).

Dht also plays a role in libido/ed and mood/aggression/strength (think halotestin/test suspension).

Did you ever use dht inhibitors FINASTERIDE or DUTASTERIDE?

Aside from having healthy testosterone levels with e2 in check the main cause of ed in a majority of men is poor endothelial/vascular health.

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.

Edit: https://www.researchgate.net/public...le_of_Estradiol_in_Male_Reproductive_Function


https://www.ncbi.nlm.nih.gov/pubmed/12619906

http://www.sciencedirect.com/science/article/pii/S0167527303004820


Estrogen and Hair: https://www.sciencedirect.com/science/article/pii/S0022202X15300403

I truly think the fact that my estrogen receptor does not function the way it should has affected my vasculature and endothelial function. 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 say there's no way I have poor vascular health. I am very vascular guy and have always had a great lipid profile, blood pressure, and my diet has been on par for 10+ years and I am only 24.