RP Email Advice Comment: Androsterone-Associated Joint Pain

haidut

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Which is, again, another steroid with very little research done on it.

Androsterone has quite a bit of research around it, but like pregnenolone it was in fashion in the first half of the 20th century so those studies are hard to dig up in full text. The drug Atromid, whose main active ingredient was androsterone, was approved by the FDA and was on the market for more than a decade until the statins came into vogue. I agree about 7-keto-DHEA - not much research around it and it is a somewhat unnatural metabolite of DHEA. But androsterone is produced in quite high amounts by healthy young people and it is one of the hormones to go down most with aging, second only to DHEA decline.
 

Drareg

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Is Sex hormone-binding globulin a possible issue here,it has a preference for DHT,we know testosterone and estrogens are also bound by it,perhaps an excess of hormone supplementation is causing it to increase?

Is there a potential that when SHBG is bound up with DHT that estrogen is left loose and concentrating somewhere?

Sex hormone-binding globulin in osteoporosis. - PubMed - NCBI
Abstract
Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that binds with high affinity to sex steroids, most notably 5alpha-dihydrotestosterone, testosterone, and 17beta-estradiol, thereby regulating their bioavailability and access to target cells. SHBG modulates the sex-steroid signaling system by binding to a specific membrane receptor (SHBG-R). Plasma SHBG levels vary in health and disease due to the effects of multiple regulation factors (age, body weight, sex steroids, insulin, and others). SHBG is involved in a number of diseases, including osteoporosis. Several studies found an inverse correlation between serum SHBG levels and bone mineral density in both males and females. SHBG levels may predict a number of macro-architectural characteristics of cortical bone. Weaker links have been reported between SHBG and bone turnover markers. Finally, high SHBG levels predict the occurrence of osteoporotic fractures of the vertebras and peripheral bones, most notably the proximal femur. Together with estradiol, SHBG plays a key role in the genesis of bone loss and osteoporotic fractures. Given that serum SHBG elevation is associated with the occurrence of multiple fractures, determination of the serum SHBG level, which can be readily performed in everyday clinical practice, may constitute a useful new marker for predicting the severity of osteoporosis.
 

Peaterpeater

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nds, but obviously without any additives. Other than that, as long as the supplement is liquid it will probably have to be DMSO because I found even in pure ethanol the thyroid powder forms large clumps and does not dissolve much. Have you tried TyroMix (the synthetic product) on your rats?

No I haven't tried TyroMix on my rat yet but I would definitely be interested in trying out a pill form of NDT for my rat. I find that the pill form is easier to use for this particular rat. Several times I have overdosed my rat on Tyromax because of the way i was rushing to dose her and squeezed the bottle just slightly too hard. Thank you for your reply. Your patience and work and is very much appreciated.
 

haidut

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No I haven't tried TyroMix on my rat yet but I would definitely be interested in trying out a pill form of NDT for my rat. I find that the pill form is easier to use for this particular rat. Several times I have overdosed my rat on Tyromax because of the way i was rushing to dose her and squeezed the bottle just slightly too hard. Thank you for your reply. Your patience and work and is very much appreciated.

OK, I will keep you posted on the NDT pills. Have almost decided on companies that can make the pills.
 

Sol Invictus

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Progesterone gave me similar joint problems when I was taking larger amounts of 3 to 9 drops. Crackling popping joints all over. I think it has to do with low estrogen as this is a common side effect with Aromatase inhibitors.
 
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goodandevil

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Progesterone gave me similar joint problems when I was taking larger amounts of 3 to 9 drops. Crackling popping joints all over. I think it has to do with low estrogen as this is a common side effect with Aromatase inhibitors.

Were you taking it in DMSO?
 

Sol Invictus

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Were you taking it in DMSO?
No, it was the progest-e. Maybe the cause could have been low cortisol caused by high progesterone (although for me DHEA never caused this and its the main hormone antogonistic to cortisol).

I have heard that with Aromatase inhibitors joints issues are common. So how can it not be caused by lowering estrogen?
 
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goodandevil

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No, it was the progest-e. Maybe the cause could have been low cortisol caused by high progesterone (although for me DHEA never caused this and its the main hormone antogonistic to cortisol).

I have heard that with Aromatase inhibitors joints issues are common. So how can it not be caused by lowering estrogen?

I remember ray talking about a persom with sever knee problems using progesterone and having the knee problems go away for a long time. Given the effects of estrogen on bones, and the efforts of the industry, having lost ground, to say that some estrogen is good, i rather doubt any claims that low estrogen causes any health problems. What is your cholesterol like? ray has said tbat progesterone causes the thyroid gland to release its hormones, and can cause temporary hyperthyroidism until it adjusts. If someone had low cholesterol then a cortisone deficiency is possible, or a vitamin deficiency, for example b6. Ray has convinced me that the claim of estrogen being necessary for anything besides breast development, or it being too low and causing problems, is dubious. Other things mimic estrogens effects, such as serotonin and i think histamine, so I in light of these facts i personally doubt the low estrogen theory. Low dose hydrocortisone, i suppose, would be a way to test it but i suspect that low cholesterol may be a culprit. My girlfriend gets bad joint pain from too much t3, her cholesterol was 145. However I had quite severe joint pain and arthropathy from androsterone (in DMSO) and my total cholesterol is over 200.

Here's a quote from him regarding low cholesterol and thyroid causing joint pain, glad i responded so I can post this in email section:

Ray: "T4 suppresses the pro-inflammatory TSH, without activating the metabolism, so probably spares the cholesterol and other antiinflammatory things."
 
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Sol Invictus

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Under normal circumstance an estrogen deficiency would unlikely occur, but if its self induced by taking too much progesterone (maybe androsterone as well) for a lengthy period of time then maybe it can occur and cause problems. I don't think a body would be able to tolerate progesterone without estrogen for too long. One of the functions of progesterone (as well as CO2) is to act as a diuretic, as it opposes aldosterone, estrogen, serotonin etc. Without estrogen wouldn't we dehydrate like prunes?

In my experience taking progest-e I felt great taking it at the beginning. Definitely gave me more testosterone. But as I continued taking it I started having problems. I began dumping a lot more water in my urine, urinating more and was always thirsty. I started developing vertical nail ridges and the palms of my hands and soles of my feet developed many lines in the skin. I also got popping and crackling joints and some spider veins, which makes me think of a copper deficiency. Isn't estrogen involved with copper absorption (when women menstruate they absorb more iron/copper due to higher estrogen)? I eat liver and oysters on a weekly basis.

The weirdest symptom was when my skin became cool all over my body even though my temp and pulse were high (Ray told me that progesterone was inhibiting Nitric Oxide and causing this.) Estrogen promotes NO.

Since stopping Progesterone my symptoms have gotten better.

To me it seems that a lot of my problems with progesterone as an AI were caused by too much Progesterone and not enough estrogen.

Doesn't the body need estrogen to stimulate the adrenals for the production of cortisol?

I guess I was using too much Progest-E.
 
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goodandevil

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I think cortisol stimulation in adrenals is from ACTH but there's probably many things that share responsibility. Do you knkw what your cholesterlol was during that time period or in general? my gf has symptoms also from progesterone but her cholesterol is very low. i really doubt the low estrogen theory because of the history of estrogen advertising, ie they said it was great now they say too much and too.little are both problems. james
 

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Glad to provide some interesting and hopefully useful input. haidut's helped me and has always answered my questions. Ray has expressed doubts on DMSO and stopped using it hinself. Perhaps it's useful acutely. i would like to see @haidut continue to succeed. i like his b vitamins very much. Ray has been very clear that there's no such thing as excessively low estrogen, and he has been very clear in his opposition to chronic or long-term use of DMSO. I feel that more attention should be paid to side effects of @haidut's supplements but that he should continue releasing new things. For example a sublingual alcohol solution may be a possibility. Personally, I'm done with DMSO.
There's no good reason to use DMSO besides the cost to my knowledge, but the cost and potentiation of steroids is an important factor.
 

chispas

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Androsterone has quite a bit of research around it, but like pregnenolone it was in fashion in the first half of the 20th century so those studies are hard to dig up in full text. The drug Atromid, whose main active ingredient was androsterone, was approved by the FDA and was on the market for more than a decade until the statins came into vogue. I agree about 7-keto-DHEA - not much research around it and it is a somewhat unnatural metabolite of DHEA. But androsterone is produced in quite high amounts by healthy young people and it is one of the hormones to go down most with aging, second only to DHEA decline.

A compound called laxogenin seems to be an antagonist of 7-keto-DHEA, and has a supposed anabolic effect while preventing lactate from rising. Supposedly, Russians have been aware of it for some time. I see it's available in Australia, which makes me assume it's probably ineffective.

Here's the link: Laxogenin and 5-hydroxy-laxogenin: natural anabolics that can enhance real anabolic steroids
 

haidut

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A compound called laxogenin seems to be an antagonist of 7-keto-DHEA, and has a supposed anabolic effect while preventing lactate from rising. Supposedly, Russians have been aware of it for some time. I see it's available in Australia, which makes me assume it's probably ineffective.

Here's the link: Laxogenin and 5-hydroxy-laxogenin: natural anabolics that can enhance real anabolic steroids

It has some structural similarity to exemestane, so it could inhibit aromatase. It is also a 5-AR derived steroidal chemical, so it could functional similarly to the 5-AR steroids. What I don't like about it is the too many hydroxyl groups. If you can find me a 3-keto-laxogenin I would be willing to try it :):
 

chispas

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It has some structural similarity to exemestane, so it could inhibit aromatase. It is also a 5-AR derived steroidal chemical, so it could functional similarly to the 5-AR steroids. What I don't like about it is the too many hydroxyl groups. If you can find me a 3-keto-laxogenin I would be willing to try it :)

What is it about the extra hydroxl groups that is undesirable? Is 3-keto-laxogenin something that exists?
 

haidut

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What is it about the extra hydroxl groups that is undesirable? Is 3-keto-laxogenin something that exists?

I don't know if 3-keto laxogenin exists but for examples on OH groups and their health effects look at the structure of progesterone/testosterone/pregnenolone (good) and estradiol/cortisol/aldosterone (bad). Also, look at the unsaturation of the A and B rings of the steroid core across the steroids. There two things are key for the effects of the steroid on health/metabolism.
 

chispas

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I don't know if 3-keto laxogenin exists but for examples on OH groups and their health effects look at the structure of progesterone/testosterone/pregnenolone (good) and estradiol/cortisol/aldosterone (bad). Also, look at the unsaturation of the A and B rings of the steroid core across the steroids. There two things are key for the effects of the steroid on health/metabolism.

Thanks for that. Good to know. Cheers.
 

grenade

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Here's an idea ...

What about adding small amounts of progesterone daily into the mix?

Whether the joint pain is occurring because cortisol is tanked or because estrogen is tanked, it still stands that progesterone is protective for the joints.

Ray Peat himself has a patent on a mixture of DHEA and progesterone used for the sole purpose of relieving chronic joint pain.

And since it seems that the anti-androgenic effects from progesterone don't occur signicantly at low doses, even males might be able to try this.

EDIT: Of course, the context in which I'm making these suggestions is for research purposes only, as the topic relates to androsterone and 11-keto DHT.
 

haidut

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Here's an idea ...

What about adding small amounts of progesterone daily into the mix?

Whether the joint pain is occurring because cortisol is tanked or because estrogen is tanked, it still stands that progesterone is protective for the joints.

Ray Peat himself has a patent on a mixture of DHEA and progesterone used for the sole purpose of relieving chronic joint pain.

And since it seems that the anti-androgenic effects from progesterone don't occur signicantly at low doses, even males might be able to try this.

EDIT: Of course, the context in which I'm making these suggestions is for research purposes only, as the topic relates to androsterone and 11-keto DHT.

I think it would be a good idea to add some progesterone when using androsterone. Progesterone has some very potent anti-cortisol effects, while androsterone's effect is mostly on estrogen. Also, like you said, proegsterone seems to help joint pain.
 

grenade

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I think it would be a good idea to add some progesterone when using androsterone. Progesterone has some very potent anti-cortisol effects, while androsterone's effect is mostly on estrogen. Also, like you said, proegsterone seems to help joint pain.

My thoughts exactly. It looks like the best of each world - lower estrogen, lower cortisol, higher androgens, and just enough progesterone.

If anyone would like to point out any downsides to combining androsterone and progesterone, I'm all ears.
 

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