Article that adds to the important health actions of progesterone reported by Dr. Mercola . A friend has Parkinson's and I will forward him this report by Dr. Mercola and these articles. Parkinson's disease (PD) is the second most common neurodegenerative disorder. Due to the aging of the world's population, its prevalence is predicted to reach 9 million people worldwide by 2030 . The disease is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra that project to the striatum, the presence of Lewy bodies and microgliosis . Current treatments aim to control motor symptoms, with no effects on the progression of the degenerative process, and lose effectiveness over time . The incidence and prevalence of PD is higher in men than in women. Several in vivo animal studies, using different experimental models of PD, have also shown that progesterone (P4) can have a neuroprotective action on dopaminergic neurons
One study showed that progesterone has a protective effect on nerve cells in the intestine. These findings raise hopes that the hormone could be used in the fight against Parkinson's disease. Nerve cells in the gastrointestinal tract communicate with those in the brain and spinal cord, suggesting that the nervous system of the digestive tract could influence the brain processes that lead to Parkinson's. Progesterone receptors were detected in nerve cells in the gastrointestinal tract and showed that progesterone protects the cells. Their findings open up prospects for the development of new neuroprotective therapeutic approaches to counteract diseases such as Parkinson's and Alzheimer's. The study was published in the journal Cells on April 21, 2023.
Progesterone, with its anti-inflammatory properties and presence in the nervous system, offers a new option for the treatment of Parkinson's disease. Its ability to enhance neuroprotection in the enteric nervous system presents interesting prospects. The review addresses the hypothesis that α-synuclein aggregates originate in the gut and can enter the brain via the vagus nerve. Gastrointestinal symptoms preceding motor symptoms support this hypothesis. Dysfunctional gut-brain signaling during intestinal dysbiosis contributes to inflammation and neurotransmitter imbalances, emphasizing the potential of microbiota-based interventions. In summary, this review uncovers the complex network of interactions between nutrition, the gut microbiome, steroid hormones, and Parkinson’s disease within the framework of the gut-brain axis. The gut-origin hypothesis sheds light on the possible initiation of α-synuclein aggregates in the gut, with subsequent transmission to the brain via the vagus nerve. Early gastrointestinal symptoms in PD patients underscore the importance of understanding gut-brain interactions. https://journals.lww.com/nrronline/fulltext/2024/10000/unraveling_the_gut_brain_axis__the_impact_of.23.aspx (2024).--
Results presented in another study show that P4 is neuroprotective in a cellular model of PD through the activation of mPRα. The intracellular mechanism underlying mPRα activity involves the ERK and PI3K-AKT signaling pathways.
I appreciate your commentary on many matters and it's clear to me that this is an important paper that shows the danger of black-and-white statement that 'estrogen replacement is good for the brain and reduces risk of Alzheimers'. However, I also think there is a danger in taking this study and forming another black-and-white conclusion that 'actually, estrogen encourages risk of Alzheimers and blocking estrogen reduces risk of Alzheimers'. To do so, we would have to ignore decades of research that supports estrogen's protective role here.
Instead, we should be asking, 'how is it that so many studies can find a protective effect of estrogen replacement on Alzheimers risk, yet estrogen blockers also show a protective effect?'. Even better, to consider what is the mechanism of estrogen / estrogen blockers and how might this explain this apparent contradiction? And does the specific population studied here provide us with clues?
To this end, I offer three statements (which I trust we can agree on) and two questions.
Statements:
- 1. estrogen has emphatically demonstrated neuroprotective effects in many types of research (through enhanced cerebral blood flow, neuroplasticity, and regulation of oxidative stress and excitotoxicity)
- 2. estrogen's effect on neuroinflammation is context-dependant (ie. some animal studies show that estrogen replacement increased susceptibility of senescent microglia to inflammation, it has been shown to reduced NkfB but enhance existing interferon signalling) and the literature indicates that it's more likely to exhibit pro-inflammatory activity in individuals with inflammatory/metabolic disorders.
- 3. this study is conducted on women who have been diagnosed with breast cancer (a condition that is, by definition, secondary to disturbed hormonal and immune activity).
Questions:
- 1. what if, like every other hormone in the body, that estrogen has both positive and negative effects, which may differ depending on the metabolic conditions of any given individual?
- 2. what if estrogen is protective in the population at large but, in certain groups that have already shown disturbed hormonal/immune activity, it increases risk?
I absolutely agree with what you have said here. We have to be careful. This is a very nuanced conversation in regards to hormone therapy and I want to say even physicians that understand it don't really understand hormone therapy! We need to have more conversations about it, but putting anything out there that is overly definitive is very premature in my opinion. We have so much to learn and we definitely need more studies in the postmenopausal group.
With all due respect, you have misinterpreted the WHI study. I respect most of what you put out there on the Internet and I'm always forever grateful for your information, but I think in this case it's really important to get with your female menopause OB/GYN's, who have extensive knowledge in this area. WHI study was done on post menopausal women that all had confounding comorbidities (advanced age, active cancers, active dementia, hypertension, active heart disease, obesity, and more) and they used synthetic hormones -notbioidentical. All of this is pivotal to outcomes. These two factors are the most important take away from the WHI study. I understand since you learned of Ray Peat you have become pro-glucose and anti-estrogen and pro-progesterone but I think this is a very sweeping superficial article about estrogen and HRT and just want to remind to be careful how you wield your power in this arena. You might be out of your depth here. There are many pro hormone clinicians out there who are menopause specialists but there is only one in particular I highly recommend to check out and that is Dr Felice Gersh. She was a practicing physician and still is I might add when the WHI study was in the works. Please look into her work and I think you will find some new information about hormones that will allow you to be able to speak about them in a more informed way. Thanks again for all you do. It is so much appreciated, but please be careful here. We don't want another WHI type story that makes everybody afraid of hormones!
You are absolutely right. But what could be the context if every earthling today undergoes a daily attack of endocrine disruptors, including among food products, which initiate estrogen surges in the body?
It’s definitely not right to divide everything into black and white, but we also can’t ignore the environmental context, right?
Article that adds to the important health actions of progesterone reported by Dr. Mercola . A friend has Parkinson's and I will forward him this report by Dr. Mercola and these articles. Parkinson's disease (PD) is the second most common neurodegenerative disorder. Due to the aging of the world's population, its prevalence is predicted to reach 9 million people worldwide by 2030 . The disease is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra that project to the striatum, the presence of Lewy bodies and microgliosis . Current treatments aim to control motor symptoms, with no effects on the progression of the degenerative process, and lose effectiveness over time . The incidence and prevalence of PD is higher in men than in women. Several in vivo animal studies, using different experimental models of PD, have also shown that progesterone (P4) can have a neuroprotective action on dopaminergic neurons
One study showed that progesterone has a protective effect on nerve cells in the intestine. These findings raise hopes that the hormone could be used in the fight against Parkinson's disease. Nerve cells in the gastrointestinal tract communicate with those in the brain and spinal cord, suggesting that the nervous system of the digestive tract could influence the brain processes that lead to Parkinson's. Progesterone receptors were detected in nerve cells in the gastrointestinal tract and showed that progesterone protects the cells. Their findings open up prospects for the development of new neuroprotective therapeutic approaches to counteract diseases such as Parkinson's and Alzheimer's. The study was published in the journal Cells on April 21, 2023.
https://www.mdpi.com/2073-4409/12/8/1206 (2023).--
https://www.news-medical.net/news/20230606/Progesterone-could-be-used-in-the-fight-against-Parkinsone28099s-disease.aspx (2023).--
Progesterone, with its anti-inflammatory properties and presence in the nervous system, offers a new option for the treatment of Parkinson's disease. Its ability to enhance neuroprotection in the enteric nervous system presents interesting prospects. The review addresses the hypothesis that α-synuclein aggregates originate in the gut and can enter the brain via the vagus nerve. Gastrointestinal symptoms preceding motor symptoms support this hypothesis. Dysfunctional gut-brain signaling during intestinal dysbiosis contributes to inflammation and neurotransmitter imbalances, emphasizing the potential of microbiota-based interventions. In summary, this review uncovers the complex network of interactions between nutrition, the gut microbiome, steroid hormones, and Parkinson’s disease within the framework of the gut-brain axis. The gut-origin hypothesis sheds light on the possible initiation of α-synuclein aggregates in the gut, with subsequent transmission to the brain via the vagus nerve. Early gastrointestinal symptoms in PD patients underscore the importance of understanding gut-brain interactions. https://journals.lww.com/nrronline/fulltext/2024/10000/unraveling_the_gut_brain_axis__the_impact_of.23.aspx (2024).--
Results presented in another study show that P4 is neuroprotective in a cellular model of PD through the activation of mPRα. The intracellular mechanism underlying mPRα activity involves the ERK and PI3K-AKT signaling pathways.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036350/ (2023).--
I appreciate your commentary on many matters and it's clear to me that this is an important paper that shows the danger of black-and-white statement that 'estrogen replacement is good for the brain and reduces risk of Alzheimers'. However, I also think there is a danger in taking this study and forming another black-and-white conclusion that 'actually, estrogen encourages risk of Alzheimers and blocking estrogen reduces risk of Alzheimers'. To do so, we would have to ignore decades of research that supports estrogen's protective role here.
Instead, we should be asking, 'how is it that so many studies can find a protective effect of estrogen replacement on Alzheimers risk, yet estrogen blockers also show a protective effect?'. Even better, to consider what is the mechanism of estrogen / estrogen blockers and how might this explain this apparent contradiction? And does the specific population studied here provide us with clues?
To this end, I offer three statements (which I trust we can agree on) and two questions.
Statements:
- 1. estrogen has emphatically demonstrated neuroprotective effects in many types of research (through enhanced cerebral blood flow, neuroplasticity, and regulation of oxidative stress and excitotoxicity)
- 2. estrogen's effect on neuroinflammation is context-dependant (ie. some animal studies show that estrogen replacement increased susceptibility of senescent microglia to inflammation, it has been shown to reduced NkfB but enhance existing interferon signalling) and the literature indicates that it's more likely to exhibit pro-inflammatory activity in individuals with inflammatory/metabolic disorders.
- 3. this study is conducted on women who have been diagnosed with breast cancer (a condition that is, by definition, secondary to disturbed hormonal and immune activity).
Questions:
- 1. what if, like every other hormone in the body, that estrogen has both positive and negative effects, which may differ depending on the metabolic conditions of any given individual?
- 2. what if estrogen is protective in the population at large but, in certain groups that have already shown disturbed hormonal/immune activity, it increases risk?
I absolutely agree with what you have said here. We have to be careful. This is a very nuanced conversation in regards to hormone therapy and I want to say even physicians that understand it don't really understand hormone therapy! We need to have more conversations about it, but putting anything out there that is overly definitive is very premature in my opinion. We have so much to learn and we definitely need more studies in the postmenopausal group.
With all due respect, you have misinterpreted the WHI study. I respect most of what you put out there on the Internet and I'm always forever grateful for your information, but I think in this case it's really important to get with your female menopause OB/GYN's, who have extensive knowledge in this area. WHI study was done on post menopausal women that all had confounding comorbidities (advanced age, active cancers, active dementia, hypertension, active heart disease, obesity, and more) and they used synthetic hormones -notbioidentical. All of this is pivotal to outcomes. These two factors are the most important take away from the WHI study. I understand since you learned of Ray Peat you have become pro-glucose and anti-estrogen and pro-progesterone but I think this is a very sweeping superficial article about estrogen and HRT and just want to remind to be careful how you wield your power in this arena. You might be out of your depth here. There are many pro hormone clinicians out there who are menopause specialists but there is only one in particular I highly recommend to check out and that is Dr Felice Gersh. She was a practicing physician and still is I might add when the WHI study was in the works. Please look into her work and I think you will find some new information about hormones that will allow you to be able to speak about them in a more informed way. Thanks again for all you do. It is so much appreciated, but please be careful here. We don't want another WHI type story that makes everybody afraid of hormones!
What might be a truer statement is 'excess estrogen in the body is problematic' ...
Estrogen and progesterone are neither angel nor devil.
They are both helpful and unhelpful depending on the context so context is everything.
You are absolutely right. But what could be the context if every earthling today undergoes a daily attack of endocrine disruptors, including among food products, which initiate estrogen surges in the body?
It’s definitely not right to divide everything into black and white, but we also can’t ignore the environmental context, right?
https://www.freedomtoffend.com/p/a-modest-proposal-to-improve-substack?r=iy2ds