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

[simeoni]

I Used Arimidex. When I experienced my first crash I was taking 0,5 E3D. I was also using HCG at that time. After that every crash I had was with 0,25mg and never took more frequently than EOD.


As a side note: I had a decent day today. No great highs but decent. Did not feel like "dog shit". Even had a small amount of libido going. Tomorrow is injection. Interesting to see if theres a pattern with my current state.

Simeoni can you share what AI crashed your estrogen and what dose have you used?

 

[nurselyfe]

ok wow very reasonable usage. Must have been looking good after that 25 weeks 500mg. Im assuming adex didnt cause issues on these blasts just when you starting running 120mg?

I was pretty big. The best I ever looked was on 120mg weekly. I don't remember my arimidex dosage on 500mg but I was very water the entire blast. On 120-150mg weekly I would use .2mg arimidex every 1-2 weeks. Really depended, and I never thought much about it. When my pumps got worse, noticed a lot of sweating, water retention, and puffier nipples I knew it was time for that .2mg.

In march I stopped using arimidex because I had some knee issues. In april I remember I took .2mg after my girlfriends 21st birthday and responded great to it, had the most unbelievable chest pump. Then in late april I took another and had no effect. Got a new batch of fresh Teva Anastrazole, took .25mg and responded great. Within 24 hours I lost a lot of water and was happy. High E2 symtoms came back quick though. After this, this is where issues began. Took another .25mg and noticed nothing. On may 12th I took either .5 or 1mg arimidex and 1.25mg letro, responded great to it. Had pretty low E2 on May 13th. Felt tight and good mood. Started getting high E2 symptoms by the 17th. Took .25mg on 18th of arimidex and felt it that night. Felt good for 2 days then back to high E2. Think this is where I crashed it. I don't remember how much I took but this is where problems started as I was taking AIs and not getting my typical response to them. I believe I was at zero from 5/22-6/9. Because on 6/10 I got a severe migraine (never had one in my life) and woke up the next morning feeling pretty good. Almost back to normal in physical terms. I had took my last ar arimidex on 6/8.

 

[nurselyfe]

Going to be updating this post as lab work
comes in.

Edit: Cholesterol seems to be improving with diet. Lowest I've seen my LDL in 2 years, which was 97.

fT3 2.8 (2.0-4.4)
Total Cholesterol 121 (100-199)
Triglycerides 74 (0-149)
VLDL 15 (5-40)
HDL 36 (>39)
LDL 70 (0-99)

 

[simeoni]

Well thats not dreadfully low. I think we have a better picture when your fT4 and TSH values arrive. For example I had a decent fT3 few years ago but my fT4 was low. I started thyroxine shortly after that and definitively felt a clear improvement.

Going to be updating this post as lab work
comes in.

fT3 2.8 (2.0-4.4)

 

[nurselyfe]

Well thats not dreadfully low. I think we have a better picture when your fT4 and TSH values arrive. For example I had a decent fT3 few years ago but my fT4 was low. I started thyroxine shortly after that and definitively felt a clear improvement.

For sure. My TSH is usually between .85-1.5. FT4 was at 2.4 (1.2-4.9) a little over a year ago so we'll see.

 

[Vitamin_C]

Im 30. I would not call myself a bodybuilder. I do hit the gym 3-4 times a week. Never done any blast's.

One thing im wondering is the fact how the hypersensitivity of estrogen receptors would lead to a desensitization that is below baseline?

I mean when estrogen levels rise - from their deprived state - the receptor's adapt. With the majority this means a return to a normal state. How does it mean a permanent change in a very small minority? What would be the mechanism behind it?

Then men on TRT would be insensitive to FSH and LH but we don't observe this happening with anyone who does a restart. Their T-levels may still be low, but FSH and LH and respective receptors recover. We also don't observe insensitivity in human models either nor do we know how low and how long a human would have to be for this to even happen and how low you have to go, is it zero? less than 5 ng/dl? 10ng/dl? Lots of bro science... the data is scarce, and even in animal models, external validity is severely lacking. I talked to Dr. Brett Osborn about this and he's never seen this in practice and he told me receptors recover. Also, there have been men to recover from PFS by fixing their gut and making radical changes to their diet. The human body has a remarkable ability to heal itself.

 

[Vitamin_C]

"Over the next 6 months i started rapidly degenerating with numerous new physical, neurological and sexual symptoms. The connective tissue all over my body lost all tensile strength and i can no longer bend any joint without risk of injury. My small and large intestine totally lost peristalsis and i was forced to go on a liquid diet to prevent a blockage. My brainfog became so bad that i now feel like i am in a video game. My vision is now blurry and grainy with flashes and floaters. As of last week my stomach has now shut down on me and i am living off pure liquids to prevent vomitting. My **** and libido are totally gone but those are the least of my worries."

What I find interesting is that none of these symptoms can be attributed to low estrogen or estrogen insensitivity. For instance, the 5 people who were born with a genetic insensitivity to estrogen had not one of these symptoms this guy describes per the literature, and these people were absolutely, positively insensitive to estrogen. For instance, the male in the study who was insensitive to estrogen had normal sexual function and nocturnal wood/emissions.

https://en.wikipedia.org/wiki/Estrogen_insensitivity_syndrome

"I even tried estradiol creams and took my e2 over range with no effect. "

He probably started having high E2 symptoms from going over the E2 range, high E2 and low E2 symptoms can often mimic each other, particularly with mood issues and sexual function. I really hope this guy was under medical supervision while doing this, he is extremely somatic...



This dude on the PFS is trippin hard like a lot of guys do on that forum, particularly the guys who have "PFS from Rogaine". Loss of tensile strength? loss of peristalsis? huh?? Did he have a uterus? Estrogen has a role in uterine peristalsis... I do find this very fascinating, however. I have learned quite a bit from guys who recovered from PFS and they mentioned a huge psychological/anxiety aspect to their symptoms. NOT saying their symptoms aren't real, but that worrying about them perpetuated the issue.

If you want to see real deal low estrogen/Arimidex side effects, go to the breast cancer forum and there are thousands of women on there taking 1mg a day for up to 10 years. Most common symptoms are hot flashes, dry eyes/mouth, night sweats, a few mood issues, joint pain. My main symptoms of when I crashed my E2 were mild anxiety and night sweats with occasional ED. I would say the ED issues were perpetuated by performance anxiety, when I was NOT worried about getting it up, I had large erections even with low E2. I was also making great gains in the gym with E2 between 5ng/dl to 10ng/dl but I was also blasting Sustanon. When the night sweats went away, I could tell that I was back into range, after having low E2 for about 2 months, I went from 9ng/dl to 26 ng/dl on my sensitive assay. Only thing that sucks right now is the tendonitis I developed by hulking out and getting waaaay too strong on my blast, tennis elbow in both arms and golfers elbow in right arm. I am taking about a month off the gym but I am slowly introducing light weight exercises.

 

[at15]

we are apparently speaking to the 6th, 7th, and 8th documented cases in the world and the first ones ever to not have this from birth. amazing.

 

[Vitamin_C]

The dude from the PFS forums that committed suicide also didn’t even take Finasteride, but believes he gave himself PFS from saw palmetto and
Spiralactolone. Sheesh, from the Rogaine and saw palmetto causing PFS those guys on that board are toxic. Here is a study on Finasteride and saw palmetto effects on DHT


https://www.ncbi.nlm.nih.gov/m/pubmed/7805711/

 

[nurselyfe]

"Over the next 6 months i started rapidly degenerating with numerous new physical, neurological and sexual symptoms. The connective tissue all over my body lost all tensile strength and i can no longer bend any joint without risk of injury. My small and large intestine totally lost peristalsis and i was forced to go on a liquid diet to prevent a blockage. My brainfog became so bad that i now feel like i am in a video game. My vision is now blurry and grainy with flashes and floaters. As of last week my stomach has now shut down on me and i am living off pure liquids to prevent vomitting. My **** and libido are totally gone but those are the least of my worries."

What I find interesting is that none of these symptoms can be attributed to low estrogen or estrogen insensitivity. For instance, the 5 people who were born with a genetic insensitivity to estrogen had not one of these symptoms this guy describes per the literature, and these people were absolutely, positively insensitive to estrogen. For instance, the male in the study who was insensitive to estrogen had normal sexual function and nocturnal wood/emissions.

https://en.wikipedia.org/wiki/Estrogen_insensitivity_syndrome

"I even tried estradiol creams and took my e2 over range with no effect. "

He probably started having high E2 symptoms from going over the E2 range, high E2 and low E2 symptoms can often mimic each other, particularly with mood issues and sexual function. I really hope this guy was under medical supervision while doing this, he is extremely somatic...



This dude on the PFS is trippin hard like a lot of guys do on that forum, particularly the guys who have "PFS from Rogaine". Loss of tensile strength? loss of peristalsis? huh?? Did he have a uterus? Estrogen has a role in uterine peristalsis... I do find this very fascinating, however. I have learned quite a bit from guys who recovered from PFS and they mentioned a huge psychological/anxiety aspect to their symptoms. NOT saying their symptoms aren't real, but that worrying about them perpetuated the issue.

If you want to see real deal low estrogen/Arimidex side effects, go to the breast cancer forum and there are thousands of women on there taking 1mg a day for up to 10 years. Most common symptoms are hot flashes, dry eyes/mouth, night sweats, a few mood issues, joint pain. My main symptoms of when I crashed my E2 were mild anxiety and night sweats with occasional ED. I would say the ED issues were perpetuated by performance anxiety, when I was NOT worried about getting it up, I had large erections even with low E2. I was also making great gains in the gym with E2 between 5ng/dl to 10ng/dl but I was also blasting Sustanon. When the night sweats went away, I could tell that I was back into range, after having low E2 for about 2 months, I went from 9ng/dl to 26 ng/dl on my sensitive assay. Only thing that sucks right now is the tendonitis I developed by hulking out and getting waaaay too strong on my blast, tennis elbow in both arms and golfers elbow in right arm. I am taking about a month off the gym but I am slowly introducing light weight exercises.

You didn't crash your E2 like we did. I was at zero. I've probably gone as low as 9 before and recovered fine within 3 days. In fact I used to kind of like low E2 because it made me extremely dry and aggressive, never any ED or anxiety. Even when I was <5pg I could still get my **** hard and now I can't and my E2 is probably high 20's. Now, no matter how much arimidex I take I cannot get "dry" like i used to. I've demonstrated this TWICE. Used the same testosterone dose I used to while taking same amount of arimidex and had no response in physical terms. I've brought my estrogen to 17, and 18 and was still extremely watery.

You need need to stop bringing up women's breast cancer forums unless you bring blood work with it. If these women E2 readings are <3 pg/ml we can talk.

You are doing a lot of denying here. I have physical symptoms that I have never had in my 24 years of life, with no other medical problems, that all occurred during and after my E2 crashes. I don't think that's coincidence. I'm sure you know how exactly you're supposed to feel and I know for damn sure how I'm supposed to feel.

Also, we know what finasteride and SP do to DHT. We also know what arimidex does to E2 in non TRT men. Sounds bizzare, and let me repeat once more, I too would not believe this if it didn't happen to me - I used arimidex for 3.5 years with no prob, I loved the stuff. but there's some mechanism that leads to silencing of genes when using inhibitors.

 

[Vitamin_C]

//You need need to stop bringing up women's breast cancer forums unless you bring blood work with it. If these women E2 readings are <3 pg/ml we can talk.//

There are a few threads on breast cancer forum where women have posted their estrogen levels because there is a particular target number they need to be at, many are critically low for years and years, 1mg per day is no joke of a dose.

You see the Harvard study on Finasteride? There is a link between men with symptoms and anxiety/depression, postulating that when men have their first sexual side effects from Finasteride, the fear of normal body functionings returning could be perpetuating their symptoms. I recently read a study with a Finasteride group vs a Placebo group where the placebo group reported more sexual side effects than the Finasteride group off sugar pills, the mind is a powerful thing.

//Also, we know what finasteride and SP do to DHT.//

I've taken SP as part of a prostate blend, my latest DHT reading was 69 (30-85). Finasteride most definitely lowers DHT, SP's most likely lowers it at such a small rate its negligible. There were no long term sexual effects from SP after 18 months of mega dosing the herb in this study

https://www.ncbi.nlm.nih.gov/pubmed/?term=23063633

// but there's some mechanism that leads to silencing of genes when using inhibitors//

This is bro science, no such mechanism has ever been observed, this is unhealthy speculation on your part which is potentially exacerbating your symptoms.

What do you mean I didn't crash my E2 like you guys did? I mean I was as low as 5ng/dl-9ng/dl for 2 months before I rebounded back. Are you speculating you have to be less than 5 ng/dl? At zero? and for how long? What can you back this up with besides anecdotes?

 

[nurselyfe]

//You need need to stop bringing up women's breast cancer forums unless you bring blood work with it. If these women E2 readings are <3 pg/ml we can talk.//

There are a few threads on breast cancer forum where women have posted their estrogen levels because there is a particular target number they need to be at, many are critically low for years and years, 1mg per day is no joke of a dose.

You see the Harvard study on Finasteride? There is a link between men with symptoms and anxiety/depression, postulating that when men have their first sexual side effects from Finasteride, the fear of normal body functionings returning could be perpetuating their symptoms. I recently read a study with a Finasteride group vs a Placebo group where the placebo group reported more sexual side effects than the Finasteride group off sugar pills, the mind is a powerful thing.

//Also, we know what finasteride and SP do to DHT.//

I've taken SP as part of a prostate blend, my latest DHT reading was 69 (30-85). Finasteride most definitely lowers DHT, SP's most likely lowers it at such a small rate its negligible. There were no long term sexual effects from SP after 18 months of mega dosing the herb in this study

https://www.ncbi.nlm.nih.gov/pubmed/?term=23063633

// but there's some mechanism that leads to silencing of genes when using inhibitors//

This is bro science, no such mechanism has ever been observed, this is unhealthy speculation on your part which is potentially exacerbating your symptoms.

What do you mean I didn't crash my E2 like you guys did? I mean I was as low as 5ng/dl-9ng/dl for 2 months before I rebounded back. Are you speculating you have to be less than 5 ng/dl? At zero? and for how long? What can you back this up with besides anecdotes?

Ive seen the harvard study. There are plenty of men without ED and anxiety/depression before Finasteride who got it after using it. Like myself, I didn't even know what true anxiety was. Ive had some anxiety over school or girlfriends before - completely normal reactions to life, but not chronic anxiety that can absolutely cripple your mind. Never felt depression until E2 was crashed. By far the worst feeling in the world. While I was crashed I had my Mental Health Clinical rotations and I couldn't have sympathized for these people more. It made me hate that clinical because I knew exactly how they felt.
This is disturbing that practioners can completely disregard a patients symptoms, and blame their issues on psychiatric problems. As a practioner I would never tell someone who was clearly healthy before that they are manifesting symptoms psychosomatically (albeit they took a drug that causes severe side effects like Propecia), I have strong feelings for doctors like that and don't believe they should be practicing any kind of medicine.

I don't do "bro science."I hate anything that is not backed up by literature. But, here I am making an exception because it's real and tangible and no one has or can propose a mechanism yet. I'm speculating two things.

1. You have to be lower than 5pg/mL - closer to 0. For a certain period of time using inhibitors, that causes a desensitization of the receptor.

2 You have to be extremely low, not necessarily zero, but have extremely quick rebounds in E2 that go much higher in a short period of time, causing negative feedback on receptor signaling. I strongly believe that corepressor proteins have something to do with this.

I have NO literature to back this up. But I have 1000's of PFS stories and myself a few others that have on going symptoms. Not just one or two symptoms, but MANY, real, and visible symptoms.

I really do not know how much thorough I can be. I told you exactly what kind of person I was before and what I was physically before. I told you every single symtom now that are visible to the eye. I told you things that make me permanently worse when I used to use them for their desired effect. I'm providing NEW bloodwork. Why would I waste my time on here trying to explain myself if nothing was wrong with an already busy life.

 

[Vitamin_C]

//You have to be extremely low, not necessarily zero, but have extremely quick rebounds in E2 that go much higher in a short period of time, causing negative feedback on receptor signaling. I strongly believe that corepressor proteins have something to do with this. //

So you're speculating that going from too low to a large rebound over reference range in E2 can further lead to insensitivity compared to a gradual increase in estrogen?

I'm certainly not saying what you feel isn't real, its very real, but this is extremely complex. Guys have recovered from PFS, all is not loss even with PFS dudes. http://www.totalmaleoptimization.com/

What are your current symptoms?

 

[lowe2sucks]

Vitamin_C how can you explain that after my anastrozole accident my penis shrank and all of a sudden I started to have anxiety and depression 24/7, muscle loss, skin and hair went dry and a complete detachment from others? Never had these before I crashed e2 it's like a light switch turned off all of a sudden and I started to have all these weird symptoms. There has to be something that happened it can't be in my head because there are also physical symptoms. I don't know why this happened to only few of us who used an AI but it changed my whole brain and body forever.

 

[Vitamin_C]

Vitamin_C how can you explain that after my anastrozole accident my penis shrank and all of a sudden I started to have anxiety and depression 24/7, muscle loss, skin and hair went dry and a complete detachment from others? Never had these before I crashed e2 it's like a light switch turned off all of a sudden and I started to have all these weird symptoms. There has to be something that happened it can't be in my head because there are also physical symptoms. I don't know why this happened to only few of us who used an AI but it changed my whole brain and body forever.

Do you have labs to indicate you have muscle wasting/muscle loss?

//There has to be something that happened it can't be in my head because there are also physical symptoms.//

Brain/body connection is extremely strong, have you heard of phantom or referred pain?

Don't you think its odd that the male case study who had the congenital insensitivity to estrogen didn't have any symptoms you're describing?

 

[Loki]

The mind is extremely powerful and can certainly create symptoms that manifest into physical symptoms. Sometimes things happen to us that can't be explained either. I had an issue a few years ago that had me getting spinal taps, MRI's, etc... I had all the symptoms of MS. I ended up at the Mayo Clinic in MN and the explanation I was given that I was "some type of metabolic disorder" and that "something ordinary in my body was acting extraordinary". In other words they had no clue what was up... Over a six month time frame all symptoms subsided and I was back to normal....

All of this happened just after a HORRIBLE experience I had on Clomid... Was there a connection? I have no idea and nobody else could figure it out either...

 

[Vitamin_C]

The mind is extremely powerful and can certainly create symptoms that manifest into physical symptoms. Sometimes things happen to us that can't be explained either. I had an issue a few years ago that had me getting spinal taps, MRI's, etc... I had all the symptoms of MS. I ended up at the Mayo Clinic in MN and the explanation I was given that I was "some type of metabolic disorder" and that "something ordinary in my body was acting extraordinary". In other words they had no clue what was up... Over a six month time frame all symptoms subsided and I was back to normal....

All of this happened just after a HORRIBLE experience I had on Clomid... Was there a connection? I have no idea and nobody else could figure it out either...

Damn dude, that is crazy stuff. Did you do anything to change your symptoms? like lifestyle changes? what happened with you and Clomid?

 

[Loki]

Damn dude, that is crazy stuff. Did you do anything to change your symptoms? like lifestyle changes? what happened with you and Clomid?

The doctor that put me on my first TRT protocol lost his practice. He started me at a young age without even testing me. I was not educated on the process and thought I was supplementing not replacing my testosterone... When I found another clinic in my area the doctor thought I was way too young to be on TRT so he took me off my protocol and put me on 50MG of Clomid Monday - Friday and off Saturday/Sunday.

Here are the positives-

My nuts blew up to the size of small eggs
My T levels were over 1,000

Here are the negatives-

I lost my libido
Had suicidal thoughts
Experience rapid hair loss
Couldn't get out of bed
Joints hurt
Experience ED (had to get on Viagra, Stendra, Cialis, ETC)
Plus many more physical and emotional sides

I found another doctor who put me back on TRT and within days things started to resolve themselves but then I had a whole new set of issues.

I started having the following-

tingling in my extremities - arms, legs tingling and going numb
tingling sensations would wake me up in my sleep sometimes my back and face would tingle
went from bench pressing over 500lbs to less than 200lbs
had issues seeing at night, I couldn't drive early or late as it was dangerous
blurred vision
had issues with my equilibrium and balance
had to stop wearing socks and shoes during the day because the touch would almost instantly cause my shins or feet to go numb
issues with being extremely cold or hot

So I exhausted every option locally. Getting referred to specialist and finally going all the way to Rochester, MN to the Mayo Clinic.

What I did was fight everyday. Started back on bench at 135 and did the work, even if I was weak. I walked on the treadmill with numb feet almost ignoring them. I cleaned up my diet and everything very slowly subsided. I tried to take each little win and magnify it and let it carry me to the next win... I have no idea what it was but I do feel I let my mind get the best of me. Once I thought I had MS and I read more and more about it, it was somewhat self fulfilling... I am diagnosed with OCD and it was be powerful in a negative way or it can be positive too...

Last Saturday I had a great chest workout... 20 sets and on some doing over 400lbs for reps... When we finished the group wanted to do a 225 rep out.. Combine style but after 20 sets? I got 53 reps and crushed everybody .... The mind is powerful!!!!

 

[nurselyfe]

//You have to be extremely low, not necessarily zero, but have extremely quick rebounds in E2 that go much higher in a short period of time, causing negative feedback on receptor signaling. I strongly believe that corepressor proteins have something to do with this. //

So you're speculating that going from too low to a large rebound over reference range in E2 can further lead to insensitivity compared to a gradual increase in estrogen?

I'm certainly not saying what you feel isn't real, its very real, but this is extremely complex. Guys have recovered from PFS, all is not loss even with PFS dudes. http://www.totalmaleoptimization.com/

What are your current symptoms?

Not necessarily over reference range. But going from low enough where receptors are very sensitive to their ligands to a modest jump (which would happen from cessation of the reversible inhibitor). This probably wouldn't have happened if I crashed E2 on aromasin. You don't get a faster come back of E2 because new aromatase enzymes need to be synthesized.

Yes ive seen decent recoveries but they're very rare compared to the total amount of people with PFS. And some PFS suffers, exogenous compounds make them worse.

Current symptoms that Ive never had before: dry skin, no sebum production, severe diffuse hair loss, dry hair, very slow nail growth and not as thick, skin texture change, emotionally blunt, anxiety, poor circulation, feel cold with normal body temp, reduced vascularity, ED, extremely rare night time erections that are weak, low libido, nipples are much smaller and don't get puffy anymore, water retention, no aggression, can't get a pump or contraction, muscle wastage, muscle flatness, strength decrease, urine is constantly the same color - always slightly tinged yellow even when I don't drink water, haven't seen my urine yellow in 4 months, starting to get some GI issues but not sure if it's related.

 

[Vitamin_C]

The doctor that put me on my first TRT protocol lost his practice. He started me at a young age without even testing me. I was not educated on the process and thought I was supplementing not replacing my testosterone... When I found another clinic in my area the doctor thought I was way too young to be on TRT so he took me off my protocol and put me on 50MG of Clomid Monday - Friday and off Saturday/Sunday.

Here are the positives-

My nuts blew up to the size of small eggs
My T levels were over 1,000

Here are the negatives-

I lost my libido
Had suicidal thoughts
Experience rapid hair loss
Couldn't get out of bed
Joints hurt
Experience ED (had to get on Viagra, Stendra, Cialis, ETC)
Plus many more physical and emotional sides

I found another doctor who put me back on TRT and within days things started to resolve themselves but then I had a whole new set of issues.

I started having the following-

tingling in my extremities - arms, legs tingling and going numb
tingling sensations would wake me up in my sleep sometimes my back and face would tingle
went from bench pressing over 500lbs to less than 200lbs
had issues seeing at night, I couldn't drive early or late as it was dangerous
blurred vision
had issues with my equilibrium and balance
had to stop wearing socks and shoes during the day because the touch would almost instantly cause my shins or feet to go numb
issues with being extremely cold or hot

So I exhausted every option locally. Getting referred to specialist and finally going all the way to Rochester, MN to the Mayo Clinic.

What I did was fight everyday. Started back on bench at 135 and did the work, even if I was weak. I walked on the treadmill with numb feet almost ignoring them. I cleaned up my diet and everything very slowly subsided. I tried to take each little win and magnify it and let it carry me to the next win... I have no idea what it was but I do feel I let my mind get the best of me. Once I thought I had MS and I read more and more about it, it was somewhat self fulfilling... I am diagnosed with OCD and it was be powerful in a negative way or it can be positive too...

Last Saturday I had a great chest workout... 20 sets and on some doing over 400lbs for reps... When we finished the group wanted to do a 225 rep out.. Combine style but after 20 sets? I got 53 reps and crushed everybody .... The mind is powerful!!!!

Bro that is crazy stuff, OCD=anxiety, probably perpetuated your symptoms but no doubt the diet/lifestyle clean up helped you. Why at first did you have such a dramatic decrease in strength do you think?