MrRippedZilla
Retired
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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/
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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