Estrogen Is Absolutely Critical For Men

[nbznj]

It’s not a myth, but it happens over 5000iu weekly. Who mentioned it here?

 

[schultz]

Interestingly, some of the latest research showing the beneficial effects of estrogen on the brain are using a specific pro drug form of estrogen which is active in the brain only. This may be something I would be interested in, since it would do away with the worries about gyno. And test alone has mixed results in terms of brain health, sleep apnea.

I guess with brain-only estrogen, you wouldn’t get the other effects on lipids, skin, joints etc... but the brain is the main thing I’m concerned with. However it’s still a research chemical at this stage I guess.

The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders. - PubMed - NCBI

Good too see the lead author has no conflicts of interest... oh, other than holding the patent on the use of DHED, and equity interests in AgyPharma.

It's also hard to take them seriously when they say stuff like this...

"In current clinical practice, chronic hormone therapies require the use of a progestin to counterbalance the detrimental impact of estrogens on the endometrium. Progestins, however, have been shown to interfere with the beneficial effect of estrogens in the brain (37)."

The citation is this paper titled -> "Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats."

In this paper they say...

"Indeed, MPA exacerbated neuronal death by glutamate-induced excitotoxicity (Nilsen, Morales, and Brinton, 2006), reduced estrogen-mediated neural protection against excitotoxicity (Nilsen and Brinton, 2002b), and completely blocked the glutamate-stimulated calcium increase produced by 17 β-estradiol, a positive mechanism by which estrogens may modulate cognitive functioning (Nilsen and Brinton, 2002a). In both clinical and preclinical studies, progesterone has been associated with detrimental cognitive effects."

The first paper in that quote - (Nilsen, Morales, and Brinton, 2006) - they say this...

"In directly comparing different progestins, we previously demonstrated that, in contrast to progesterone, medroxyprogesteroneacetate (MPA) completely antagonized the neuroprotective and memory mechanisms of estrogen [12,15]."


So according to that last paper, progesterone didn't have the same effect as medroxyprogesterone and yet in the previous quote the paper uses the word progesterone, and not progestin. The first paper about DHED knows that they shouldn't say progesterone and instead use the term 'progestin', but they sort of imply that it is progesterone by omission. They don't even mention that it's specifically medroxyprogesterone - which has shown to be much different than actual progesterone - and not regular progesterone. They don't even mention progesterone in the paper.

I will be curious to see how their research evolves. Their whole sales pitch is that estrogen has a negative effect on the body, but that DHED only turns into estrogen in the brain and doesn't affect the rest of the body.

 

[TheBeard]

It’s not a myth, but it happens over 5000iu weekly. Who mentioned it here?

Your Dr Shippen’s excerpt states « full dose: 300-500iu thrice a week »

Wanted to make sure nobody thought doses higher than that led to desensitization

 

[Goobz]

Good too see the lead author has no conflicts of interest... oh, other than holding the patent on the use of DHED, and equity interests in AgyPharma.

It's also hard to take them seriously when they say stuff like this...

"In current clinical practice, chronic hormone therapies require the use of a progestin to counterbalance the detrimental impact of estrogens on the endometrium. Progestins, however, have been shown to interfere with the beneficial effect of estrogens in the brain (37)."

The citation is this paper titled -> "Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats."

In this paper they say...

"Indeed, MPA exacerbated neuronal death by glutamate-induced excitotoxicity (Nilsen, Morales, and Brinton, 2006), reduced estrogen-mediated neural protection against excitotoxicity (Nilsen and Brinton, 2002b), and completely blocked the glutamate-stimulated calcium increase produced by 17 β-estradiol, a positive mechanism by which estrogens may modulate cognitive functioning (Nilsen and Brinton, 2002a). In both clinical and preclinical studies, progesterone has been associated with detrimental cognitive effects."

The first paper in that quote - (Nilsen, Morales, and Brinton, 2006) - they say this...

"In directly comparing different progestins, we previously demonstrated that, in contrast to progesterone, medroxyprogesteroneacetate (MPA) completely antagonized the neuroprotective and memory mechanisms of estrogen [12,15]."


So according to that last paper, progesterone didn't have the same effect as medroxyprogesterone and yet in the previous quote the paper uses the word progesterone, and not progestin. The first paper about DHED knows that they shouldn't say progesterone and instead use the term 'progestin', but they sort of imply that it is progesterone by omission. They don't even mention that it's specifically medroxyprogesterone - which has shown to be much different than actual progesterone - and not regular progesterone. They don't even mention progesterone in the paper.

I will be curious to see how their research evolves. Their whole sales pitch is that estrogen has a negative effect on the body, but that DHED only turns into estrogen in the brain and doesn't affect the rest of the body.

Thanks for the response. It’s a good point. I only read over the article briefly and found it interesting, so shared it here. Tbh I was rather skeptical myself, because apart from the gyno issue, I don’t think brain only estrogen is a good idea really - you need estrogen for much more than the brain.

However I must say that the way they conflate progestin and progesterone, rather reminds me of people demonising estrogen. In particular the WHI study, which is often quoted as proving that estrogen causes dementia. Progestin is not progesterone, so you can’t blame it’s toxic effects on progesterone. Similarly, orally administered conjugated equine estrogen is not estradiol, and has vastly different effects (it gets converted by the liver into estrone, which may actually have opposite effects in the brain and cause blood clots and cerebrovascular disease).

If memory serves, the majority of the negative effects in the WHI study came from the fake progesterone anyway, not even the fake estrogen.

 

[schultz]

Thanks for the response. It’s a good point. I only read over the article briefly and found it interesting, so shared it here. Tbh I was rather skeptical myself, because apart from the gyno issue, I don’t think brain only estrogen is a good idea really - you need estrogen for much more than the brain.

However I must say that the way they conflate progestin and progesterone, rather reminds me of people demonising estrogen. In particular the WHI study, which is often quoted as proving that estrogen causes dementia. Progestin is not progesterone, so you can’t blame it’s toxic effects on progesterone. Similarly, orally administered conjugated equine estrogen is not estradiol, and has vastly different effects (it gets converted by the liver into estrone, which may actually have opposite effects in the brain and cause blood clots and cerebrovascular disease).

If memory serves, the majority of the negative effects in the WHI study came from the fake progesterone anyway, not even the fake estrogen.

Yah I think it was medroxyprogesterone in the WHI. I was just listening to an old Politics & Science w/ Ray yesterday and he was talking about medroxyprogesterone. He says that taking it causes the body to stop producing its own progesterone. So not only does it not have the same effects entirely as progesterone, it also has some negative effects and furthermore shuts down your bodies own progesterone production. On the other hand, he said taking real progesterone for some people can actually cause their body to start producing more progesterone (sort of like a positive feedback). If this is true, regarding the MPA shutting down progesterone production, it seems like that would be the biggest problem in taking it.

 

[Nebula]

I have tried both transdermal and injections. I like injections daily protocol the best so far.

What ester have you found to work best for daily injections?

 

[tankasnowgod]

Years of using aromasin have my free Test at the top of the range, but my e2 stays in the 20s no matter what. Joints cracking, no libido, can't build muscle.

It's odd to me that anyone considers "joints cracking" a sign of low estrogen. My joints cracked a lot when I was iron loaded, as I lowered iron stores to near deficiency, most of that disappeared. I also noticed that Vitamin D and K2 seemed to help.

 

[TheBeard]

It's odd to me that anyone considers "joints cracking" a sign of low estrogen. My joints cracked a lot when I was iron loaded, as I lowered iron stores to near deficiency, most of that disappeared. I also noticed that Vitamin D and K2 seemed to help.

I observe cracking joints everytime I take Exemestane, from two days after until two weeks after like clockwork, the 20 times I have tried it on and off.
But yeah, it could be due to something else than low e2

 

[schultz]

It's odd to me that anyone considers "joints cracking" a sign of low estrogen.

Yes, it's ridiculous.

I observe cracking joints everytime I take Exemestane

That proves it!!

Or, maybe the so-called aromatase inhibitor drugs do other things in the body besides acting on the CYP19A1 enzyme? Who on this forum really believes they do one single thing in the body without any other effects? If this were the case, Ray would undoubtedly recommend them. The fact is we don't really know all the things they do because it is not worth it for drug companies to fund the research inquiring about such things.

High dose DHT brings estrogen to almost undetectable levels, yet in this study (sartorius, 2014) arthralgia was not a symptom experienced by any of the subjects. This study maintained a high dose of DHT for 2 years and the mean serum E2 was 1.7 pg/mL over the course of the study. Of interest, a few of the subjects were pulled out of the study because of secondary polycythemia, which is essentially what athletes are trying to achieve by doping with EPO.

I lay out some theories behind what the AI's could be doing in this post

The last link in that post is a very interesting case report in which a woman was taking anastrozole and had extremely high parathyroid hormone and serum calcium levels. When anastrozole was stopped the PTH and calcium returned to normal. After a month of cessation drug treatment was once again initiated and the PTH and calcium again went to very high levels and the patient had to again stop the anastrozole treatment. After cessation a second time, PTH and calcium once again fell.

According to Ray article 'Calcium and Disease':
"Interleukin-6 (IL-6), an inflammatory cytokine which increases with aging, is commonly considered to have an important role in the multiple processes of atrophy in old age. One of the things which can increase the production of IL-6 is the parathyroid hormone (PTH), which increases the amount of calcium circulating in the blood, partly by causing it to be removed from the bones; IL-6 stimulates the process of calcium removal from bones."

According to this paper:
"Chow et al recently implicated interleukin 6 (IL-6) in the persistent arthralgia that occurs in some patients following infection with chikungunya virus (CHIKV). They observed that plasma IL-6 concentrations in patients with persistent arthralgia were higher than those in fully recovered patients; the significance of this observation is supported by the known role of IL-6 in causing joint pain. A role for IL-6 in persistent arthralgia is further supported by the finding by Hoarau et al that IL-6 is specifically expressed in the affected joint during chronic chikungunya disease. Nevertheless, the plasma IL-6 concentration in patients with chronic disease is low (interquartile range, 4–40 pg/mL) and close to normal values."

 

[GreekDemiGod]

Does low estrogen turn one into Danny Roddy?

 

[schultz]

Does low estrogen turn one into Danny Roddy?

It turns you into a stud like me!

...

Who am I kidding...

 

[TheBeard]

Yes, it's ridiculous.



That proves it!!

Or, maybe the so-called aromatase inhibitor drugs do other things in the body besides acting on the CYP19A1 enzyme? Who on this forum really believes they do one single thing in the body without any other effects? If this were the case, Ray would undoubtedly recommend them. The fact is we don't really know all the things they do because it is not worth it for drug companies to fund the research inquiring about such things.

High dose DHT brings estrogen to almost undetectable levels, yet in this study (sartorius, 2014) arthralgia was not a symptom experienced by any of the subjects. This study maintained a high dose of DHT for 2 years and the mean serum E2 was 1.7 pg/mL over the course of the study. Of interest, a few of the subjects were pulled out of the study because of secondary polycythemia, which is essentially what athletes are trying to achieve by doping with EPO.

I lay out some theories behind what the AI's could be doing in this post

The last link in that post is a very interesting case report in which a woman was taking anastrozole and had extremely high parathyroid hormone and serum calcium levels. When anastrozole was stopped the PTH and calcium returned to normal. After a month of cessation drug treatment was once again initiated and the PTH and calcium again went to very high levels and the patient had to again stop the anastrozole treatment. After cessation a second time, PTH and calcium once again fell.

According to Ray article 'Calcium and Disease':
"Interleukin-6 (IL-6), an inflammatory cytokine which increases with aging, is commonly considered to have an important role in the multiple processes of atrophy in old age. One of the things which can increase the production of IL-6 is the parathyroid hormone (PTH), which increases the amount of calcium circulating in the blood, partly by causing it to be removed from the bones; IL-6 stimulates the process of calcium removal from bones."

According to this paper:
"Chow et al recently implicated interleukin 6 (IL-6) in the persistent arthralgia that occurs in some patients following infection with chikungunya virus (CHIKV). They observed that plasma IL-6 concentrations in patients with persistent arthralgia were higher than those in fully recovered patients; the significance of this observation is supported by the known role of IL-6 in causing joint pain. A role for IL-6 in persistent arthralgia is further supported by the finding by Hoarau et al that IL-6 is specifically expressed in the affected joint during chronic chikungunya disease. Nevertheless, the plasma IL-6 concentration in patients with chronic disease is low (interquartile range, 4–40 pg/mL) and close to normal values."

Glad you mention DHT: I experience the same cracking joints with stanolone powder or Proviron.
But hey, the must also be doing something else than reducing estrogen

 

[TheBeard]

Does low estrogen turn one into Danny Roddy?

No. Progesterone overdose and lack of physical labor does

 

[ilhanxx]

When I apply to scalp topical diane35, It gives a very good libido, is it because of the hyperandrogenic response or low estrogen depots? of course my sayings were in the past.

 

[Goobz]

Yes, it's ridiculous.



That proves it!!

Or, maybe the so-called aromatase inhibitor drugs do other things in the body besides acting on the CYP19A1 enzyme? Who on this forum really believes they do one single thing in the body without any other effects? If this were the case, Ray would undoubtedly recommend them. The fact is we don't really know all the things they do because it is not worth it for drug companies to fund the research inquiring about such things.

High dose DHT brings estrogen to almost undetectable levels, yet in this study (sartorius, 2014) arthralgia was not a symptom experienced by any of the subjects. This study maintained a high dose of DHT for 2 years and the mean serum E2 was 1.7 pg/mL over the course of the study. Of interest, a few of the subjects were pulled out of the study because of secondary polycythemia, which is essentially what athletes are trying to achieve by doping with EPO.

I lay out some theories behind what the AI's could be doing in this post

The last link in that post is a very interesting case report in which a woman was taking anastrozole and had extremely high parathyroid hormone and serum calcium levels. When anastrozole was stopped the PTH and calcium returned to normal. After a month of cessation drug treatment was once again initiated and the PTH and calcium again went to very high levels and the patient had to again stop the anastrozole treatment. After cessation a second time, PTH and calcium once again fell.

According to Ray article 'Calcium and Disease':
"Interleukin-6 (IL-6), an inflammatory cytokine which increases with aging, is commonly considered to have an important role in the multiple processes of atrophy in old age. One of the things which can increase the production of IL-6 is the parathyroid hormone (PTH), which increases the amount of calcium circulating in the blood, partly by causing it to be removed from the bones; IL-6 stimulates the process of calcium removal from bones."

According to this paper:
"Chow et al recently implicated interleukin 6 (IL-6) in the persistent arthralgia that occurs in some patients following infection with chikungunya virus (CHIKV). They observed that plasma IL-6 concentrations in patients with persistent arthralgia were higher than those in fully recovered patients; the significance of this observation is supported by the known role of IL-6 in causing joint pain. A role for IL-6 in persistent arthralgia is further supported by the finding by Hoarau et al that IL-6 is specifically expressed in the affected joint during chronic chikungunya disease. Nevertheless, the plasma IL-6 concentration in patients with chronic disease is low (interquartile range, 4–40 pg/mL) and close to normal values."

I actually find the opposite - this forum is full of people making creative excuses for the undesirable effects of AIs, pinning these nasty effects on anything they can other than the natural result of lowering aromatase and estrogen. For example the idea that lowering estrogen is good, but AIs are bad because they are liver toxic. Yes, they are liver toxic. But they are liver toxic partly because aromatase and estradiol are critical for overall liver health, so of course blocking them will be liver toxic.

Estradiol Accelerates Liver Regeneration in Mice

Or even in this thread - "cracking joints are due to iron overload" when estrogen plays a critical part in excreting iron.

Aromatase is such a basic and fundamental enzyme it's no wonder all these negative effects arise when it is inhibited. I don't see why it has to be some toxic side effect of these drugs, all these negative effects on joints, liver, iron, brain, mitochondria, etc. can easily be explained as the drugs simply doing their job - blocking this critically important enzyme

In regards to DHT and arthralgia - Im not sure if DHT inhibits aromatase in the tissue as well as lowering circulating estrogen, but if it doesn't then that would explain the lack of arthralgia imo. Because bringing down serum E and aromatase inhibition are two different things. Even with very low serum E, if aromatase is still functioning properly then circulating T can still exert it's normal effects by being aromatised in the tissue. Aromatase plays a far broader role than keeping circulating E levels high enough, though this is obviously also important.

Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase. - PubMed - NCBI

 

[tankasnowgod]

Or even in this thread - "cracking joints are due to iron overload" when estrogen plays a critical part in excreting iron.

False. Estrogen plays no significant role in excreting iron. Body iron stores are primarily governed by iron intake, substances in food that block and chealate iron, the iron withholding defense system, and loss of iron through sweat, and primarily, blood loss. Pre-menopausal women maintain low iron stores mainly due to menstruation, and blood loss from childbirth. This advantage disappears at menopause, and will also dissapear with an early hysterectomy, whether the ovaries are removed or not. Further, women given Estrogen as HRT do not somehow magically lower their iron stores. Men and post-menopausal women can get the same (or even better) benefits of low iron from menstruation by monitoring iron stores and donating blood. Any role estrogen plays in this process is insignificant, certainly in no way "critical."

 

[Goobz]

False. Estrogen plays no significant role in excreting iron. Body iron stores are primarily governed by iron intake, substances in food that block and chealate iron, the iron withholding defense system, and loss of iron through sweat, and primarily, blood loss. Pre-menopausal women maintain low iron stores mainly due to menstruation, and blood loss from childbirth. This advantage disappears at menopause, and will also dissapear with an early hysterectomy, whether the ovaries are removed or not. Further, women given Estrogen as HRT do not somehow magically lower their iron stores. Men and post-menopausal women can get the same (or even better) benefits of low iron from menstruation by monitoring iron stores and donating blood. Any role estrogen plays in this process is insignificant, certainly in no way "critical."

Well you may be right (since the estrogen / iron link is one I know less about than the others points I mentioned) but this study shows the sort of thing I was referring to. Low estrogen = increased tissue iron deposition.

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. - PubMed - NCBI

Edit - so yes, maybe estrogen has no role in "excreting iron" but instead has a role in reducing absorption via hepcidin (which will amount to a similar thing), and a role in preventing tissue accumulation, which is what we really care about.

 

[lampofred]

False. Estrogen plays no significant role in excreting iron. Body iron stores are primarily governed by iron intake, substances in food that block and chealate iron, the iron withholding defense system, and loss of iron through sweat, and primarily, blood loss. Pre-menopausal women maintain low iron stores mainly due to menstruation, and blood loss from childbirth. This advantage disappears at menopause, and will also dissapear with an early hysterectomy, whether the ovaries are removed or not. Further, women given Estrogen as HRT do not somehow magically lower their iron stores. Men and post-menopausal women can get the same (or even better) benefits of low iron from menstruation by monitoring iron stores and donating blood. Any role estrogen plays in this process is insignificant, certainly in no way "critical."

Estrogen doesn't play a role in excreting iron but high estrogen/oxygen deprivation (caused by high estrogen) increases iron absorption by a ridiculous amount, 10x or 20x or something along those lines.

 

[TheBeard]

I actually find the opposite - this forum is full of people making creative excuses for the undesirable effects of AIs, pinning these nasty effects on anything they can other than the natural result of lowering aromatase and estrogen. For example the idea that lowering estrogen is good, but AIs are bad because they are liver toxic. Yes, they are liver toxic. But they are liver toxic partly because aromatase and estradiol are critical for overall liver health, so of course blocking them will be liver toxic.

Estradiol Accelerates Liver Regeneration in Mice

Or even in this thread - "cracking joints are due to iron overload" when estrogen plays a critical part in excreting iron.

Aromatase is such a basic and fundamental enzyme it's no wonder all these negative effects arise when it is inhibited. I don't see why it has to be some toxic side effect of these drugs, all these negative effects on joints, liver, iron, brain, mitochondria, etc. can easily be explained as the drugs simply doing their job - blocking this critically important enzyme

In regards to DHT and arthralgia - Im not sure if DHT inhibits aromatase in the tissue as well as lowering circulating estrogen, but if it doesn't then that would explain the lack of arthralgia imo. Because bringing down serum E and aromatase inhibition are two different things. Even with very low serum E, if aromatase is still functioning properly then circulating T can still exert it's normal effects by being aromatised in the tissue. Aromatase plays a far broader role than keeping circulating E levels high enough, though this is obviously also important.

Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase. - PubMed - NCBI

Absolute common sense, thank you.

And people are still going to pick on your tony iron bit when you wrote a full page of truths

 

[schultz]

Glad you mention DHT: I experience the same cracking joints with stanolone powder or Proviron.
But hey, the must also be doing something else than reducing estrogen

And this DHT powder was purchased from a reliable source and was actually DHT? A few years back I took Arimidex for a full year as an experiment (Astra Zeneca brand) @ 1/4 tablet EOD, which is a higher dose than some people taking TRT (I don't take any T). I had zero issues with joint pain. Not once did my joints hurt. Not exactly proof of anything, but since we are exchanging anecdotes I thought I would add one.

actually find the opposite - this forum is full of people making creative excuses for the undesirable effects of AIs, pinning these nasty effects on anything they can other than the natural result of lowering aromatase and estrogen. For example the idea that lowering estrogen is good, but AIs are bad because they are liver toxic. Yes, they are liver toxic. But they are liver toxic partly because aromatase and estradiol are critical for overall liver health, so of course blocking them will be liver toxic.

Yes maybe that's true. I do enjoy playing Devil's advocate.

From what I understand, estrogen is generally toxic to the liver. Estrogen does initiate growth but any prolonged effect of estrogen would cause problems (like cancer). I doubt that blocking estradiol would be liver toxic.

Aromatase is such a basic and fundamental enzyme it's no wonder all these negative effects arise when it is inhibited. I don't see why it has to be some toxic side effect of these drugs, all these negative effects on joints, liver, iron, brain, mitochondria, etc. can easily be explained as the drugs simply doing their job - blocking this critically important enzyme

Do you follow Ray's work? He has addressed all of this stuff quite eloquently.

In regards to DHT and arthralgia - Im not sure if DHT inhibits aromatase in the tissue as well as lowering circulating estrogen, but if it doesn't then that would explain the lack of arthralgia imo. Because bringing down serum E and aromatase inhibition are two different things. Even with very low serum E, if aromatase is still functioning properly then circulating T can still exert it's normal effects by being aromatised in the tissue. Aromatase plays a far broader role than keeping circulating E levels high enough, though this is obviously also important.

Yes I think it would be different than the AI. I think DHT lowers estrogen, when taken in large amounts, simply by lowering testosterone thereby lowering the material used to make estrogen. In the study I mentioned testosterone was undetectable in the blood so testosterone wouldn't be being used to make estrogens, however as far as I understand it, estriol, which is sort of a storage form of estrogen, could be used to make estradiol still.

Or even in this thread - "cracking joints are due to iron overload" when estrogen plays a critical part in excreting iron.

Edit - so yes, maybe estrogen has no role in "excreting iron" but instead has a role in reducing absorption via hepcidin (which will amount to a similar thing), and a role in preventing tissue accumulation, which is what we really care about.

Iron's Dangers
"Women absorb iron much more efficiently than men do. From a similar meal, women will normally absorb three times as much iron as men do. When pregnant, their higher estrogen levels cause them to absorb about nine times as much as men. Every time a woman menstruates, she loses a little iron, so that by the age of 50 she is likely to have less iron stored in her tissues than a man does at the same age, but by the age of 65 women generally have as much excess iron in their tissues as men do."

Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase. - PubMed - NCBI

One of the theories on the forum is that the joint pain people experience from an AI is caused by reduced cortisol, essentially unmasking preexisting pain and/or damage. I don't know how accurate the theory is, though cortisol and estrogen raise each other so it's not that farfetched, but I did find it interesting when reading the paper you linked here that they used the AI Fadrozole to demonstrate the effects of low estrogen.

I have been trying to point out that AI's might do other things aside from lowering estrogen (like affecting other CYP enzymes). It turns out Fadrozole might actually lower the CYP11B1, the enzyme involved in the first step of cortisol synthesis. The authors even admit that there might be cross-reactivity between the so-called selective AI and other C P450 enzymes. Who knows what else they might do? They mention a drug in development meant to interfere with the CYP11B1 enzyme but that there is a problem with it also lowering the CYP11B2 (aldosterone synthase) enzyme, which plays a role in electrolyte balance. These enzymes are closely related.

https://www.ncbi.nlm.nih.gov/pubmed/30425102
"Human cytochrome P450 11B1 (CYP11B1) is responsible for the final step generating the steroid hormone cortisol, which controls stress and immune responses and glucose homeostasis. CYP11B1 is a promising drug target to manage Cushing's disease, a disorder arising from excessive cortisol production. However, the design of selective inhibitors has been hampered because structural information for CYP11B1 is unavailable and the enzyme has high amino acid sequence identity (93%) to a closely related enzyme, the aldosterone-producing CYP11B2. Here we report the X-ray crystal structure of human CYP11B1 (at 2.1 Å resolution) in complex with fadrozole, a racemic compound normally used to treat breast cancer by inhibiting estrogen-producing CYP19A1. Comparison of fadrozole-bound CYP11B1 with fadrozole-bound CYP11B2 revealed that despite conservation of the active-site residues, the overall structures and active sites had structural rearrangements consistent with distinct protein functions and inhibition. Whereas fadrozole binds to both CYP11B enzymes by coordinating the heme iron, CYP11B2 binds to the R enantiomer of fadrozole, and CYP11B1 binds to the S enantiomer, each with distinct orientations and interactions. These results provide insights into the cross-reactivity of drugs across multiple steroidogenic cytochrome P450 enzymes, provide a structural basis for understanding human steroidogenesis, and pave the way for the design of more selective inhibitors of each human CYP11B enzyme."