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Friends Remembered
- Oct 11, 2010
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Estrogen and brain aging in men and women: Depression, energy, stress
Although the incidence of Alzheimer's disease is 2 or 3 times as high among women as among men, there is a major campaign under way to convince the public that taking estrogen supplements will prevent the disease. Estrogen is now mainly promoted to prevent osteoporosis (another problem that is more common in women) and heart disease (which is more common in men).
This substance, which came into medical use as "the female hormone" for the treatment of "female problems," especially for improving fertility, and then for preventing fertility as the oral contraceptive, is now being aimed primarily at the post-reproductive population, for problems that are essentially unrelated to femininity. It is, in fact, being presented to the public as something to prevent major age-related conditions.
Brain degeneration, like osteoporosis, takes years to develop. Analysis of letters written by young women, for example, showed limited mental functioning in those who many years later developed Alzheimer's disease, and young women who have small bones are the ones most likely to develop osteoporosis later. It seems clear that the course of degenerative aging processes is set in young adulthood (or even earlier), and that it is never too early to be concerned with correcting processes that are going in the wrong direction. (See Walker, et al., 1988, and Smith, et al., 1992.)
In "The Biological Generality of Progesterone" (1979) I proposed that the life-long trajectory of energy production and longevity was strongly influenced by prenatal nutrition and progesterone. This idea was based on work by people such as Marion Diamond, who showed that prenatal progesterone enlarges the cortex of the brain, and that estrogen makes it smaller, and Leonell Strong, who showed that a treatment that lowered the estrogen function in a young mouse could produce cancer-free offspring for several generations. Strong's work was very encouraging, because it showed that biological problems that had been "bred in" over many generations could be corrected by some simple metabolic treatments.
Seeing these profoundly toxic long-range effects of estrogen, which shaped the animal's growth, development, function, and even its heredity, made it important to learn how estrogen works, because such fundamental changes covering the whole range of biology, produced by a simple little molecule, promised to reveal interesting things about the nature of life.
Aging is an energy problem, and in the brain, which has extremely high energy requirements, interference with the energy supply quickly causes cells to die.
I believe that estrogen's "principle," in all of its actions, is to interfere with the respiratory mode of energy production. This is an integrating principle that explains estrogen's immediate, direct effects on cells and organisms, which aren't explained by the idea that it acts on the genes through a specific "estrogen receptor." (It's hard to imagine, for example, how the "estrogen receptor" doctrine could explain the fact that a single injection of estrogen can kill a large portion of brain cells.) It explains why estrogen causes cells to take up water, allowing calcium to enter, activating various enzymes and cell division. On the organismic level, it explains why estrogen mimics "shock," releasing histamine and activating the nervous and glandular stress response system. The inefficiency of metabolism which doesn't use oxygen in the normal way causes glucose to be used rapidly, and this in itself is enough to trigger the release of pituitary ACTH and adrenal cortisol. The ACTH, and related hormones, liberate free fatty acids, which cells take up instead of glucose, and this (in the so-called Randall cycle) further limits the body's ability to oxidize glucose.
People have spoken of "cascades" in relation to the adrenal glucocorticoids (e.g., cortisol) and estrogen, leading to cell damage, but really both of these hormonal cascades have to be seen as part of a more general collapse of adaptive systems, as a result of both chronic and immediate inadequacies of energy production.
Estrogen activates the adrenal stress reaction by way of the hypothalamus and pituitary, by direct actions on the adrenal glands, and by a variety of indirect effects, such as the increase of free fatty acids. It activates the excitotoxic glutamic acid pathway, and interferes with protective adenosine inhibition of nerves. It has both direct and indirect ways of promoting the formation of nitric oxide and carbon monoxide. These, and other estrogen-promoted factors, quickly and seriously interfere with mitochondrial respiration. Many of these effects contribute to increased intracellular calcium and free radical production, contributing to both the excitatory excess and the energy deficit.
The biochemical details of these cascades are mainly interesting because they show how many different kinds of stress converge on a few physiological processess--mitochondrial energy production, cellular excitation, and intercellular communication--which, when damaged thousands of times, lead to the familiar states of old age. These few functions, damaged by an infinite variety of stresses, have their own complexly adaptive ways of deteriorating, producing the various degenerative diseases.
This perspective brings dementia, heart failure, autoimmunity, immunodeficiency and other diseases of aging together, in ways that allow generalized therapeutic and preventive approaches.
The antistress, antiestrogen approaches become fundamental to prevention of aging.
The pro-estrogenic nature of the unsaturated fatty acids is probably the biggest barrier to the radical elimination of degenerative diseases. Various saturated fatty acids, including butyric, octanoic, and palmitic, have protective effects on mitochondrial respiration.
Progesterone is the basic brain-protective antiestrogen. It works to protect the brain at many levels (preventing lipid peroxidation, exitotoxicity, nitric oxide damage, energy deficit, edema, etc.) and it promotes repair and recovery.
Progesterone in most cases has effects opposite to estrogen's, improving mitochondrial energy production while preventing excessive excitation. Along with pregnenolone, progesterone is recognized as a neurosteroid with anti-excitotoxic actions, with the ability to promote repair and regeneration of the nervous system. (Roof, Stein, Faden; Schumacher, et al.; Baulieu.)
The use of aspirin, which reduces inflammation and inhibits the formation of neurotoxic prostaglandins, is known to be associated with a lower incidence of Alzheimer's disease, and in other contexts, it offers protection against estrogen. Naloxone, the antiendorphin, has been found to reverse some of the cumulative effects of stress, restoring some pituitary and ovarian function, and it promotes recovery after brain injury; in a variety of ways, it corrects some of estrogen's toxic effects.
Adenosine helps to maintain brain glycogen stores, which are lost in stress and aging. Vitamin B12 protects against nitric oxide, and improves alertness.
Pyruvic acid has brain-protective effects, apparently through its decarboxylation (producing carbon dioxide) rather than through its use as an energy source, since other ketoacids are similarly protective. (The ketoacids occur in some natural foods.) The directly brain-protective effect of carbon dioxide offers many clues that should be interpreted in relation to estrogen's toxicity, since many of their effects on nerves are opposite. Estrogen blocks the production of energy while it stimulates nerve cells to use energy more rapidly, and carbon dioxide promotes the production of energy, while restraining the excitation which expends energy. The presence of carbon dioxide is an indicator of proper mitochondrial respiratory functioning.
Pharmaceutical blockers of glutamic acid transmission, and of calcium and sodium uptake, prevent some deterioration following brain injury, but the most physiological way to protect against those toxic processes is to maintain metabolic energy at a high level. Magnesium, which is protective against excitatory damage and is a calcium antagonist, tends to be retained in proportion to the activity of thyroid hormone.
As I have discussed previously, progesterone alone has brought people out of post-epileptic dementia and senile dementia, but it is reasonable to use a combined physiological approach, including thyroid.
Besides providing new insights into biological energy and aging, the recognition that estrogen activates the stresshormone system--the pituitary-adrenal system--also provides clear insights into other problems, such as the polycystic ovary syndrome, hirsutism, adrenal hyperplasia, Cushing's disease, etc.
SO it's a good idea and to use an AI with amortizable hormones and keep estrogen down!!! The Old school Idea of using an estrogen blocker only if needed is right down being stupid
REFERENCES
Although the incidence of Alzheimer's disease is 2 or 3 times as high among women as among men, there is a major campaign under way to convince the public that taking estrogen supplements will prevent the disease. Estrogen is now mainly promoted to prevent osteoporosis (another problem that is more common in women) and heart disease (which is more common in men).
This substance, which came into medical use as "the female hormone" for the treatment of "female problems," especially for improving fertility, and then for preventing fertility as the oral contraceptive, is now being aimed primarily at the post-reproductive population, for problems that are essentially unrelated to femininity. It is, in fact, being presented to the public as something to prevent major age-related conditions.
Brain degeneration, like osteoporosis, takes years to develop. Analysis of letters written by young women, for example, showed limited mental functioning in those who many years later developed Alzheimer's disease, and young women who have small bones are the ones most likely to develop osteoporosis later. It seems clear that the course of degenerative aging processes is set in young adulthood (or even earlier), and that it is never too early to be concerned with correcting processes that are going in the wrong direction. (See Walker, et al., 1988, and Smith, et al., 1992.)
In "The Biological Generality of Progesterone" (1979) I proposed that the life-long trajectory of energy production and longevity was strongly influenced by prenatal nutrition and progesterone. This idea was based on work by people such as Marion Diamond, who showed that prenatal progesterone enlarges the cortex of the brain, and that estrogen makes it smaller, and Leonell Strong, who showed that a treatment that lowered the estrogen function in a young mouse could produce cancer-free offspring for several generations. Strong's work was very encouraging, because it showed that biological problems that had been "bred in" over many generations could be corrected by some simple metabolic treatments.
Seeing these profoundly toxic long-range effects of estrogen, which shaped the animal's growth, development, function, and even its heredity, made it important to learn how estrogen works, because such fundamental changes covering the whole range of biology, produced by a simple little molecule, promised to reveal interesting things about the nature of life.
Aging is an energy problem, and in the brain, which has extremely high energy requirements, interference with the energy supply quickly causes cells to die.
I believe that estrogen's "principle," in all of its actions, is to interfere with the respiratory mode of energy production. This is an integrating principle that explains estrogen's immediate, direct effects on cells and organisms, which aren't explained by the idea that it acts on the genes through a specific "estrogen receptor." (It's hard to imagine, for example, how the "estrogen receptor" doctrine could explain the fact that a single injection of estrogen can kill a large portion of brain cells.) It explains why estrogen causes cells to take up water, allowing calcium to enter, activating various enzymes and cell division. On the organismic level, it explains why estrogen mimics "shock," releasing histamine and activating the nervous and glandular stress response system. The inefficiency of metabolism which doesn't use oxygen in the normal way causes glucose to be used rapidly, and this in itself is enough to trigger the release of pituitary ACTH and adrenal cortisol. The ACTH, and related hormones, liberate free fatty acids, which cells take up instead of glucose, and this (in the so-called Randall cycle) further limits the body's ability to oxidize glucose.
People have spoken of "cascades" in relation to the adrenal glucocorticoids (e.g., cortisol) and estrogen, leading to cell damage, but really both of these hormonal cascades have to be seen as part of a more general collapse of adaptive systems, as a result of both chronic and immediate inadequacies of energy production.
Estrogen activates the adrenal stress reaction by way of the hypothalamus and pituitary, by direct actions on the adrenal glands, and by a variety of indirect effects, such as the increase of free fatty acids. It activates the excitotoxic glutamic acid pathway, and interferes with protective adenosine inhibition of nerves. It has both direct and indirect ways of promoting the formation of nitric oxide and carbon monoxide. These, and other estrogen-promoted factors, quickly and seriously interfere with mitochondrial respiration. Many of these effects contribute to increased intracellular calcium and free radical production, contributing to both the excitatory excess and the energy deficit.
The biochemical details of these cascades are mainly interesting because they show how many different kinds of stress converge on a few physiological processess--mitochondrial energy production, cellular excitation, and intercellular communication--which, when damaged thousands of times, lead to the familiar states of old age. These few functions, damaged by an infinite variety of stresses, have their own complexly adaptive ways of deteriorating, producing the various degenerative diseases.
This perspective brings dementia, heart failure, autoimmunity, immunodeficiency and other diseases of aging together, in ways that allow generalized therapeutic and preventive approaches.
The antistress, antiestrogen approaches become fundamental to prevention of aging.
The pro-estrogenic nature of the unsaturated fatty acids is probably the biggest barrier to the radical elimination of degenerative diseases. Various saturated fatty acids, including butyric, octanoic, and palmitic, have protective effects on mitochondrial respiration.
Progesterone is the basic brain-protective antiestrogen. It works to protect the brain at many levels (preventing lipid peroxidation, exitotoxicity, nitric oxide damage, energy deficit, edema, etc.) and it promotes repair and recovery.
Progesterone in most cases has effects opposite to estrogen's, improving mitochondrial energy production while preventing excessive excitation. Along with pregnenolone, progesterone is recognized as a neurosteroid with anti-excitotoxic actions, with the ability to promote repair and regeneration of the nervous system. (Roof, Stein, Faden; Schumacher, et al.; Baulieu.)
The use of aspirin, which reduces inflammation and inhibits the formation of neurotoxic prostaglandins, is known to be associated with a lower incidence of Alzheimer's disease, and in other contexts, it offers protection against estrogen. Naloxone, the antiendorphin, has been found to reverse some of the cumulative effects of stress, restoring some pituitary and ovarian function, and it promotes recovery after brain injury; in a variety of ways, it corrects some of estrogen's toxic effects.
Adenosine helps to maintain brain glycogen stores, which are lost in stress and aging. Vitamin B12 protects against nitric oxide, and improves alertness.
Pyruvic acid has brain-protective effects, apparently through its decarboxylation (producing carbon dioxide) rather than through its use as an energy source, since other ketoacids are similarly protective. (The ketoacids occur in some natural foods.) The directly brain-protective effect of carbon dioxide offers many clues that should be interpreted in relation to estrogen's toxicity, since many of their effects on nerves are opposite. Estrogen blocks the production of energy while it stimulates nerve cells to use energy more rapidly, and carbon dioxide promotes the production of energy, while restraining the excitation which expends energy. The presence of carbon dioxide is an indicator of proper mitochondrial respiratory functioning.
Pharmaceutical blockers of glutamic acid transmission, and of calcium and sodium uptake, prevent some deterioration following brain injury, but the most physiological way to protect against those toxic processes is to maintain metabolic energy at a high level. Magnesium, which is protective against excitatory damage and is a calcium antagonist, tends to be retained in proportion to the activity of thyroid hormone.
As I have discussed previously, progesterone alone has brought people out of post-epileptic dementia and senile dementia, but it is reasonable to use a combined physiological approach, including thyroid.
Besides providing new insights into biological energy and aging, the recognition that estrogen activates the stresshormone system--the pituitary-adrenal system--also provides clear insights into other problems, such as the polycystic ovary syndrome, hirsutism, adrenal hyperplasia, Cushing's disease, etc.
SO it's a good idea and to use an AI with amortizable hormones and keep estrogen down!!! The Old school Idea of using an estrogen blocker only if needed is right down being stupid
REFERENCES
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