Prolactin: why "control your E2 and everything will be fine" is both dangerous & wrong

MrRippedZilla

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Prolactin: why "control your E2 and everything will be fine" is both dangerous & wrong

45 mins of Prolactin talk, which is why I've added cliff notes for those not able to tolerate that level of British-ness:
https://vocaroo.com/i/s0Y4qiZ0rX9L


Cliff notes

- We have multiple anecdotal examples of members, on this board, suffering with hyperprolactinemia despite normal E2 levels. These examples requires reassessing the commonly given advice of "control E2 and Prolactin will be fine".

- Prolactin is under the inhibitory control of Dopamine. To increase Prolactin, you need to inhibit Dopamine. To decrease Prolactin, you need to increase Dopamine. D2 is the key receptor of interest here.

- Pituitary Prolactin secretion is reflected by serum levels and is our main concern. Prolactin is produced locally in different tissues too but at lower levels that stay in the same vicinity and are not reflected by serum levels.

- Bf% is irrelevant for serum, pituitary secreted, Prolactin levels.

- Hyperprolactinemia causes multiple side effects including loss of libido, premature ejaculation, erectile dysfunction (very common), insulin resistance and galactorrhea (milk production). It is common to associate these negative sexual side effects with high E2 but without bloodwork, you don't really know if it's an E2 or Prolactin problem.

- Several causes for hyperprolactinemia: lack of sleep, stress, intense exercise, opiod use, antipsychotic medication, serotonin, GH, TRH (Thyrotropin-releasing hormone) chronically elevated E2, etc. All of these work primarily through dopamine depletion. Those in bold are the most relevant to us.

- Testosterone alone causes serotonin to increase, which is why it is seen as an effective anti-depressive for some folks. Insufficient data to suggest how different forms of AAS impact serotonin. Practically, an irrelevant source of Prolactin increase.

- GH has the ability to bind to the Prolactin receptor and mimic some of the actions of Prolactin. It might cause problems if GH or it's analogues are used at high doses. Bloodwork is recommended to keep an eye on it.

- The relationship between TRH, Dopamine and Prolactin is complex (though I did a ****ing great job explaining it 13mins in). Essentially, TRH in the hypothalamus is responsible for telling TSH, in the pituitary, to work harder to produce more T3/T4 if it senses a lack of T3/T4 in circulation. Dopamine normally inhibits TSH, which makes TSH's job kind of difficult so TRH inhibits Dopamine in order to allow TSH to do it's thing. Once T3/T4 numbers are good, TRH goes down, Dopamine goes back up, TSH goes down - back to homeostasis.
TRH, by inhibiting dopamine, increases Prolactin. This is seen in 1/3 of primary hypohyroid patents. Problem is fixed with T3/T4 supplementation.
It might be a good idea to add a replacement dose of T3 to your cycle depending on the anabolics being used (data is lacking to show which ones cause the biggest negative, transient, impact on thyroid numbers).

- E2 inhibits dopamine = high Prolactin. E2 is necessary to stimulate Prolactin but, at high levels, it prevents actual lactation. This means that bumping up the AI dose to deal with Prolactin can actually cause lactation, not prevent it. E2 does not need to be high for Prolactin to be high.

- Progesterone can inhibit dopamine but the impact seems to insignificant since pituitary Prolactin levels (what matters when it comes to serum Prolactin levels & the side effects we deal with) are unchanged. The data doesn't support the idea that 19-nors, which also work through progesterone activation, have a bigger impact on Prolactin levels. Anecdotal data (based on bloodwork) is mixed on the subject.

- You can deal with with high Prolactin levels in 2 ways: do nothing or take a DA (Caber being the preferred choice). Doing nothing is a valid option if you are asymptomatic. Otherwise, Caber at 0.25mg 2xweek is the way to go.

- Caber's common side effects include nausea, dizziness, headaches, constipation and sexual awesomeness.

- The risk of negative psychological side effects (lack of impulse control, psychosis, "hypersexuality", etc) is below 5% at the doses we use (below 2.5mg per week). This risk is commonly exaggerated by folks extrapolating data from Parkinson patients and other groups using much higher doses (3-11mg per week). The exception to this low risk involves patients with current mental health disorders (psychosis, depression, schizophrenia) - these individuals should avoid DAs altogether.

- The risk of cardiovascular problems (vascular/pulmonary fibrosis, heart regurgitation, etc) are non-existent for this community (dosing below 2.5mg/week, use is limited to less than 2 years straight, etc, etc).

- All side effects can be minimized by titrating down the dose of Caber. All side effects subside when Caber is discontinued. Tolerance is seen as a relative non-issue within the data.

- Skip to 39mins for answers to the questions asked in a previous thread that isn't covered above.

Summary:
- You do not need high E2 to have high Prolactin.
- Crashing your E2 levels to solve hyperprolactinemia is really stupid and causes more problems than it solves in a lot of cases.
- If you have Prolactin related side effects, get bloodwork to confirm before treating it with Caber.
- You have the option of taking Caber from the start vs waiting for sides/bloodwork. This is up to you - same story with AIs.
- If you're asymptomatic, you have the option of not doing anything.
- Data is lacking to suggest what anabolics have more/less of an impact on Prolactin.


References

Impact of prolactin receptor isoforms on reproduction
Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline - highly recommended practical guide
60 years of neuroendocrinology: the hypothalamo-prolactin axis
Prolactin (PRL) in adipose tissue: regulations and functions - focuses more on locally produced prolactin but the author, Nira Ben-Jonathan, is the best Prolactin researcher on the planet.
Prolactin and its role in human reproduction - 2019 review on the topic, highly recommended
http://www.druglib.com/druginfo/cabergoline/side-effects_adverse-reactions/
 
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Spongy

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dude. just. dude.

I just read the cliff notes at this time. But can't wait to listen to the whole thing. Great stuff.
 

Rhino99

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Zilla,
This is just awesome.
I also will read more in depth tonight but I have 1 question pertaining to this statement:
The exception to this low risk involves patients with current mental health disorders (psychosis, depression, schizophrenia) - these individuals should avoid DAs altogether.

So if you're prone to depression, anxiety, etc, and you shouldnt take a DA, how would you treat high prolactin?
 

IHI

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Gunna have to read all this later, really appreciate the time you vest into these things!
 

MrRippedZilla

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Zilla,
This is just awesome.
I also will read more in depth tonight but I have 1 question pertaining to this statement:
The exception to this low risk involves patients with current mental health disorders (psychosis, depression, schizophrenia) - these individuals should avoid DAs altogether.
So if you're prone to depression, anxiety, etc, and you shouldnt take a DA, how would you treat high prolactin?
Honestly dude, if you suffer from mental health issues then you have no business cycling in the first place.

Using patients on anti-psychotics who have hyperprolactinemia as an extreme example, here is what the data says is the correct approach to treatment:
1) Stop taking the medication that is causing the hyperprolactinemia. Unlike us, these folks may not be able to stop taking their medication for obvious reasons so...
2) Substitute something else in place of the medication causing the hyperprolactinemia. It is difficult for us to do that since we don't know how exactly different forms of AAS impact Prolactin but we could go with more mild forms in general (Anavar, Primo , etc). Most anti-psychotics deplete dopamine and increase prolactin so this may not be an option for these patients either so...
3) Take a DA anyway and monitor closely. This is controversial and is seen as a last resort for these patients. We have the option of stopping the cycle and using other, milder, forms of anabolics so it should never get to this step.
 

gymrat827

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very nice info

bet this will stir some AI discussions
 

ToolSteel

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Honestly dude, if you suffer from mental health issues then you have no business cycling in the first place.

Using patients on anti-psychotics who have hyperprolactinemia as an extreme example, here is what the data says is the correct approach to treatment:
1) Stop taking the medication that is causing the hyperprolactinemia. Unlike us, these folks may not be able to stop taking their medication for obvious reasons so...
2) Substitute something else in place of the medication causing the hyperprolactinemia. It is difficult for us to do that since we don't know how exactly different forms of AAS impact Prolactin but we could go with more mild forms in general (Anavar, Primo , etc). Most anti-psychotics deplete dopamine and increase prolactin so this may not be an option for these patients either so...
3) Take a DA anyway and monitor closely. This is controversial and is seen as a last resort for these patients. We have the option of stopping the cycle and using other, milder, forms of anabolics so it should never get to this step.
Are you aware of any data detailing the effectiveness of B6?
 

MrRippedZilla

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Are you aware of any data detailing the effectiveness of B6?
I'm aware of a couple of 24hr papers showing it to reduce prolactin but nothing more than that. It was a form of treatment many decades ago before DAs were a thing. DAs, Bromocriptine to begin with, were much better at the job and so B6 fell out of favor. It isn't mentioned once in any of the literature I referenced nor in my textbook. It also isn't used as an official form of treatment for any patients (mental health disorder or not) suffering from hyperprolactemia. Read into that what you will.

It also doesn't really get around the fact that you have to mess around with the Dopamine system in order to get Prolactin back in range - something folks with mental health disorders probably shouldn't be doing. B6 works by increasing the activity of the PLP enzyme, which converts L-DOPA into Dopamine. It's a shittier way of messing with the system but it's still messing with the system. Not something I would personally recommend over DAs under any circumstances.
 

hulksmash

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I've said all this about prolactin in posts through the years..

Well, at least people will finally read what'd been said
 
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Zilla is one of those guys that when they speak, you should listen. I read the cliff notes, will listen tonight.
 

PillarofBalance

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Ok this is starting to make better sense now... Appreciate the post Zilla.

Also sounds like prolactin should absolutely be on the blood work list no matter the cycle. Any clues as to where the notion that 19 nor was responsible for this?
 

DieYoungStrong

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Ok this is starting to make better sense now... Appreciate the post Zilla.

Also sounds like prolactin should absolutely be on the blood work list no matter the cycle. Any clues as to where the notion that 19 nor was responsible for this?

If I had to guess after reading this, I’d say they don’t armomatize traditionally but still can cause prolactin to spike, therefore 19-nors spike prolactin in bro science.
 

MrRippedZilla

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Any clues as to where the notion that 19 nor was responsible for this?
The bro-sumption of "well, they interact with the progesterone receptor so that must mean they are responsible for the prolactin increase". Or misinterpretation of in-vitro data. One of those two.

For the record, we have zero quality data on the impact of 19-nors on Prolactin, which is why I cannot say conclusively that they don't have a bigger impact on Prolactin either. What I can say conclusively is that Test alone is capable of increasing Prolactin even with normal/controlled E2. Therefore, as you said, bloodwork including Prolactin for all cycles (apart from maybe really mild stuff) with Caber on hand just in case is the way to go.
 

Bro Bundy

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does body fat have anything to do with it? Thanks for taking time to write a good piece bro..I deff notice when my body fat is high i get more E sides
 
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MrRippedZilla

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does body fat have anything to do with it? Thanks for taking time to write a good piece bro..I deff notice when my body fat is high i get more E sides
Locally, you will produce more Prolactin the fatter you are since the adipose (fat) tissue itself secretes it. But, local levels tend to stay in the same area and therefore don't play a big role in causing the bad sides (ED, lactation, etc). Local levels also don't show up on bloodwork by the way.

When it comes to Prolactin coming from the pituitary, which is the real problem since it comes in much larger amounts than what you store locally, bf% doesn't play a role.
 
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automatondan

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Thanks for posting Zilla.

I have been chewing on all this all morning and then started looking at certain compounds effects (whether inhibitory or increasing) dopamine in the body.

I found something interesting in regards to nandrolone. Increased up-regulation of DA transporters in the caudatum/putemen has been observed following administration of nandrolones (even months later), (suggesting) a reflected enhancement of DA activity. So, contrary to my original thought/theory that maybe deca/npp somehow inhibited DA activity and thus increased prolactin seems to be false. This would be a good thing in regards to our usage of ND correct? But then as I think about it more, would the positive effects of increased up-regulation only be present if there were not somehow a decrease in DA...?

It also made me wonder if amphetamine usage (ADHD meds) at low doses (especially in conjunction with ND) could help mitigate increases in prolactin due to it's increase of DA and serotonin.

Anyways, it's been many years since I studied Neuro so I am quite foggy. These were just some ideas I had....
 

MrRippedZilla

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Thanks for posting Zilla.
I found something interesting in regards to nandrolone. Increased up-regulation of DA transporters in the caudatum/putemen has been observed following administration of nandrolones (even months later), (suggesting) a reflected enhancement of DA activity. So, contrary to my original thought/theory that maybe deca/npp somehow inhibited DA activity and thus increased prolactin seems to be false. This would be a good thing in regards to our usage of ND correct? But then as I think about it more, would the positive effects of increased up-regulation only be present if there were not somehow a decrease in DA...?

It also made me wonder if amphetamine usage (ADHD meds) at low doses (especially in conjunction with ND) could help mitigate increases in prolactin due to it's increase of DA and serotonin.

Anyways, it's been many years since I studied Neuro so I am quite foggy. These were just some ideas I had....
I found the reference. It's rats. My stance on animal data is well known.
Regardless, the part in bold doesn't contradict your original thought because of the 2nd part in bold. Nandrolone increasing Dopamine makes no sense whatsoever. The MOA isn't there. It definetly inhibits it - the question is whether that level of inhibition is more/less than other forms of AAS.

Regarding amphetamine use, we don't need more serotonin in the system - AAS gives us plenty of that as it is. Considering the availability of Caber, I fail to see any reason to go with a more general form of medication to a very specific problem.
 
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