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djledda-web/raypeat-articles/processed/hot-flashes-energy-aging.html

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  1. <html>

  2.     <head><title></title></head>

  3.     <body>

  4.         <h1></h1>

  5. 

  6.         <p></p>

  7.         <blockquote>

  8.             <strong><span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  9.                             style="font-size: large"

  10.                         >Hot flashes, energy, and aging</span></span></span></strong>

  11.         </blockquote>

  12.         <blockquote></blockquote>

  13.         <blockquote>

  14.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  15.                         style="font-size: medium"

  16.                     >Around the time that menstruation and fertility are ending, certain biological problems are more

  17.                         likely to occur. Between the ages of 50 and 55, about 60% of women experience repeated episodes

  18.                         of flushing and sweating. Asthma, migraine, epilepsy, arthritis, varicose veins, aneurysms,

  19.                         urticaria, reduced lung function, hypertension, strokes, and interstitial colitis are some of

  20.                         the other problems that often begin or get worse at the menopause, but that normally aren't

  21.                         considered to be causally related to it.</span></span></span>

  22.         </blockquote>

  23.         <blockquote></blockquote>

  24.         <blockquote>

  25.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  26.                         style="font-size: medium"

  27.                     >Recently, hot flashes are being taken more seriously, because of their association with increased

  28.                         inflammation, heart disease, and risk of dementia. Around the same age, late 40s to mid-50s, men

  29.                         begin to have a sudden increase of some of the same health problems, including night sweats,

  30.                         anxiety, and insomnia. In both sexes, the high incidence of depression in this age group has

  31.                         usually been explained "psychologically," rather than biologically.</span></span></span>

  32.         </blockquote>

  33.         <blockquote></blockquote>

  34.         <blockquote>

  35.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  36.                         style="font-size: medium"

  37.                     >When the estrogen industry began concentrating on women of menopausal age (after the disastrous

  38.                         years of selling it as a fertility drug), "estrogen replacement" therapy was promoted as a cure

  39.                         for the problems associated with menopause, including hot flashes, which were explained as the

  40.                         result of a deficiency of estrogen. However, in recent years, the phrase "estrogen deficiency"

  41.                         has begun to be replaced by the phrase "estrogen withdrawal," because it has been found that

  42.                         women with hot flashes don't necessarily have less estrogen in their blood stream than women who

  43.                         don't have hot flashes.</span></span></span>

  44.         </blockquote>

  45.         <blockquote></blockquote>

  46.         <blockquote>

  47.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  48.                         style="font-size: medium"

  49.                     >Associated with this change of terminology, there has been a recognition that changes in the

  50.                         temperature regulating system in the brain, rather than changes in the amount of estrogen, are

  51.                         responsible for the hot flashes, but mainstream medicine has carefully avoided the investigation

  52.                         of this subject. The effects of estrogen on the thermoregulatory system are very clear, but the

  53.                         standard medical view is that the physiology of hot flashes simply isn't understood.</span

  54.                     ></span></span>

  55.         </blockquote>

  56.         <blockquote></blockquote>

  57.         <blockquote>

  58.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  59.                         style="font-size: medium"

  60.                     >Since the medical literature boldly describes the mechanisms of the circulatory system and the

  61.                         causes of major problems such as heart attacks, high blood pressure, and strokes, it's odd that

  62.                         it doesn't have an explanation for "hot flashes."</span></span></span>

  63.         </blockquote>

  64.         <blockquote>

  65.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  66.                         style="font-size: medium"

  67.                     >But looking at this historically, I think this selective ignorance is necessary, for the protection

  68.                         of some doctrines that have become very important for conventional medicine.</span></span></span

  69.             >

  70.         </blockquote>

  71.         <blockquote></blockquote>

  72.         <blockquote>

  73.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  74.                         style="font-size: medium"

  75.                     >When doctors are talking about diseases of the heart and circulatory system, it's common for them

  76.                         to say that estrogen is protective, because it causes blood vessels to relax and dilate,

  77.                         improving circulation and preventing hypertension. The fact that estrogen increases the

  78.                         formation of nitric oxide, a vasodilator, is often mentioned as one of its beneficial effects.

  79.                         But in the case of hot flashes, dilation of the blood vessels is exactly the problem, and

  80.                         estrogen is commonly prescribed to prevent the episodic dilation of blood vessels that

  81.                         constitutes the hot flash. Nitric oxide increases in women in association with the menopause

  82.                         (Watanabe, et al., 2000), and it is increased by inflammation, and hot flushes are associated

  83.                         with various mediators of inflammation, but, as far as I can tell, no one has measured the

  84.                         production of nitric oxide during a hot flash. Inhibitors of nitric oxide formation reduce

  85.                         vasodilation during hot flushes (Hubing, et al., 2010).</span></span></span>

  86.         </blockquote>

  87.         <blockquote></blockquote>

  88.         <blockquote>

  89.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  90.                         style="font-size: medium"

  91.                     >Starting in the 1940s, the doctrine that menopause is the result of changes in the ovaries,

  92.                         involving a depletion of eggs and an associated loss of estrogen production, was widely taught

  93.                         to medical students. By the 1970s, the taboo against discussing menopause publicly was fading,

  94.                         and the mass media began teaching the public that hot flashes are the result of an estrogen

  95.                         deficiency, and that "estrogen replacement" is the most appropriate and effective treatment, and

  96.                         in the next 20 years almost half the women in the US began taking it around the time of

  97.                         menopause. This practice became routine at a time when "evidence based medicine" was being

  98.                         promoted as a new standard, but there was no evidence that women experiencing hot flashes were

  99.                         deficient in estrogen (in fact, there was evidence that they weren't), and there was evidence

  100.                         that hot flashes began when the first menstrual period was missed, which coincided with, and

  101.                         resulted from, a failure to produce a functional corpus luteum, preventing the production of a

  102.                         normal amount of progesterone. But the silly old doctrine of deficiency is often restated by

  103.                         professors, as if there was no doubt about it (for example, Rance, 2009; Bhattacharya and

  104.                         Keating, 2012).</span></span></span>

  105.         </blockquote>

  106.         <blockquote></blockquote>

  107.         <blockquote>

  108.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  109.                         style="font-size: medium"

  110.                     >This extremely persistent disregard for important evidence about the nature of menopause and its

  111.                         symptoms was guided by the estrogen industry, which began in the 1930s to call estrogen "the

  112.                         female hormone," disregarding the facts about the biological roles of estrogen and progesterone,

  113.                         because chemicals with estrogenic effects were numerous and cheap, while progesterone was

  114.                         expensive, and had no synthetic equivalents. At the time the pharmaceutical industry began

  115.                         promoting estrogen as the female hormone to prevent miscarriage, it was already well known that

  116.                         it could produce abortion, as well as causing inflammation and cancer, and some of the most

  117.                         famous estrogen researchers were warning of its multiple dangers in the 1930s.</span></span

  118.                 ></span>

  119.         </blockquote>

  120.         <blockquote></blockquote>

  121.         <blockquote>

  122.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  123.                         style="font-size: medium"

  124.                     >Menopause is a major landmark of aging, and if its meaning is radically misunderstood, a coherent

  125.                         understanding of aging is unlikely, and without an understanding of the loss of functions with

  126.                         age, we won't really understand life. More specifically, the real causes of the many serious

  127.                         problems occurring in association with the menopause will be ignored. Finding the causes of the

  128.                         seemingly trivial hot flash will affect the way we understand aging and its diseases.</span

  129.                     ></span></span>

  130.         </blockquote>

  131.         <blockquote></blockquote>

  132.         <blockquote>

  133.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  134.                         style="font-size: medium"

  135.                     >If a common occurrence is thought to have some importance in itself, or to relate closely to

  136.                         something of importance, it will be described carefully, and its general features will become

  137.                         part of the common understanding. It's clear that our medical culture hasn't considered the hot

  138.                         flash to be important, because there are still physicians who believe that the hot flash

  139.                         represents a rise of body temperature caused by a sudden increase of heat production, which they

  140.                         sometimes explain as an upward fluctuation of thyroid gland activity. Measurement of body

  141.                         temperature before and during hot flashes has shown clearly that the internal temperature is

  142.                         lowered slightly by the hot flash, as heat is lost from the skin, as a result of vasodilation.

  143.                         Physiologists have been studying the differences in temperature regulation between men and

  144.                         women, and the effects of hormones on temperature regulation, for more than 70 years, but the

  145.                         medical profession in the United States showed almost no interest in the subject for about 50

  146.                         years.</span></span></span>

  147.         </blockquote>

  148.         <blockquote></blockquote>

  149.         <blockquote>

  150.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  151.                         style="font-size: medium"

  152.                     >August Weismann's doctrine of "mortal soma, immortal germ line," led people to postulate that

  153.                         "primordial germ" cells migrated into the ovary (consisting of "somatic" cells) during embryonic

  154.                         development, and that the baby was born with a supply of germ cells that was used up during the

  155.                         reproductive lifetime, accounting for the decline of fertility with aging. The fact that

  156.                         menstrual cycles ended around the time that fertility ended was explained by the idea that

  157.                         ovulation caused the release of estrogen, and that the absence of eggs caused a failure to

  158.                         produce estrogen, and that the absence of estrogen led to the failure of the cyclical uterine

  159.                         changes. It was all deduced from a mistaken ideology about the nature of life.&nbsp;</span

  160.                     ></span></span>

  161.         </blockquote>

  162.         <blockquote></blockquote>

  163.         <blockquote>

  164.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  165.                         style="font-size: medium"

  166.                     >Cancer of the endometrium (lining) of the uterus and breast cancer were known to be the first and

  167.                         second cancers, respectively, produced by uninterrupted exposure to estrogen (for example,

  168.                         Lipshutz, 1950). Investigation of the causes of endometrial cancer showed that women with

  169.                         anovulatory cycles, that failed to produce progesterone, or who had a reduced production of

  170.                         progesterone, developed overgrowth of the endometrium, and that these were the women who were

  171.                         later most likely to develop cancer of the endometrium. The peak incidence of endometrial cancer

  172.                         is in the postmenopausal years, resulting from prolonged exposure to estrogen, unopposed by

  173.                         progesterone. The medical belief* that "ovulation produces estrogen," and that the absence of

  174.                         menstruation means an absence of estrogen, has been very harmful to women's health.</span></span

  175.                 ></span>

  176.         </blockquote>

  177.         <blockquote></blockquote>

  178.         <blockquote>

  179.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  180.                         style="font-size: medium"

  181.                     >Several laboratories, from the 1950s through the 1980s, investigated the causes of age-related

  182.                         infertility. A.L. Soderwall, among others, demonstrated that an excess of estrogen makes it

  183.                         impossible for the uterus to maintain a pregnancy.&nbsp;</span></span></span>

  184.         </blockquote>

  185.         <blockquote>

  186.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  187.                         style="font-size: medium"

  188.                     >Subsequently, his lab showed that neither changes in the eggs nor changes in the uterus could

  189.                         explain age related infertility. Altered pituitary hormone cycles, resulting from changes in the

  190.                         brain, could account for the major changes in the ovaries and uterus.</span></span></span>

  191.         </blockquote>

  192.         <blockquote></blockquote>

  193.         <blockquote>

  194.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  195.                         style="font-size: medium"

  196.                     >Other experimenters, including P.M. Wise, V.M. Sopelak and R.L. Butcher (1982), P. Ascheim (1983),

  197.                         and D.C. Desjardins (1995) have clarified the interactions between the ovaries and the brain.

  198.                         For example, when the ovaries of an old animal are transplanted into a young animal, they are

  199.                         able to function in response to the new environment, but when the ovaries of a young animal are

  200.                         transplanted into an old animal, they fail to cycle. However, if the ovaries are removed from an

  201.                         animal when it's young, so that it lives to the normal age of infertility without being

  202.                         regularly exposed to surges of estrogen, it will then be able to support normal cycles when

  203.                         young ovaries are transplanted into it. But if it received estrogen supplements throughout its

  204.                         life, transplanted young ovaries will fail to cycle.</span></span></span>

  205.         </blockquote>

  206.         <blockquote></blockquote>

  207.         <blockquote>

  208.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  209.                         style="font-size: medium"

  210.                     >The work of Desjardins and others has demonstrated that free radicals generated by interactions of

  211.                         estrogen and iron with unsaturated fatty acids are responsible for damage to brain cells

  212.                         (Desjardins, et al., 1992). The damaged inhibitory nerve cells allow the pituitary to remain in

  213.                         a chronically active state; in old rats, this can produce a state of constant estrus. Several

  214.                         groups (Powers, et al., 2006; Everitt, et al., 1980; Telford, et al., 1986) have shown that

  215.                         removal of the pituitary gland can greatly extend lifespan, if thyroid hormone is

  216.                         supplemented.</span></span></span>

  217.         </blockquote>

  218.         <blockquote></blockquote>

  219.         <blockquote>

  220.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  221.                         style="font-size: medium"

  222.                     >One of the animal "models" used to study hot flashes is morphine withdrawal.&nbsp; The model seems

  223.                         relevant to human hot flashes, because estrogen can stop the morphine withdrawal flushing, and

  224.                         estrogen's acute and chronic effects on the brain-pituitary-ovary system involve the endorphins

  225.                         and the opioidergic nerves (Merchenthaler, et al., 1998; Holinka, et al., 2008).</span></span

  226.                 ></span>

  227.         </blockquote>

  228.         <blockquote>

  229.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  230.                         style="font-size: medium"

  231.                     >In young rats, sudden morphine withdrawal caused by injecting the anti-opiate naloxone, causes the

  232.                         tail skin to flush, with a temperature increase of a few degrees, and causes the core body

  233.                         temperature to fall slightly. However, old animals respond to the withdrawal in two different

  234.                         ways. One group responded to the naloxone with an exaggerated flushing and decrease of core

  235.                         temperature. The other group of old rats, which already had a lower body temperature, didn't

  236.                         flush at all (Simpkins, 1994). I think this provides an insight into the reason that menopausal

  237.                         treatment with estrogen can relieve some hot flashes--estrogen treatment might create a flush

  238.                         resistant state similar to that of the cooler old animals in Simpkins' experiment.</span></span

  239.                 ></span>

  240.         </blockquote>

  241.         <blockquote>

  242.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  243.                         style="font-size: medium"

  244.                     >It has been known for a long time, from studies in animals and people, that estrogen lowers body

  245.                         temperature, and that this involves a tendency to increase blood flow to the skin in response to

  246.                         a given environmental temperature, that is, the temperature "set-point" is lowered by estrogen.

  247.                         Besides increasing heat loss, estrogen decreases heat production. These physiological effects of

  248.                         estrogen can be seen in the normal menstrual cycle, with progesterone having the opposite effect

  249.                         of estrogen on metabolic rate, skin circulation, body temperature, and heat loss. This causes

  250.                         the familiar rise in temperature when ovulation occurs. Occasionally, young women will

  251.                         experience hot flashes during the luteal phase of their menstrual cycle because of insufficient

  252.                         progesterone production, or at menstruation, when the corpus luteus stops producing

  253.                         progesterone.</span></span></span>

  254.         </blockquote>

  255.         <blockquote></blockquote>

  256.         <blockquote>

  257.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  258.                         style="font-size: medium"

  259.                     >Estrogen increases the free fatty acids circulating in the blood, and this shifts metabolism away

  260.                         from oxidation of glucose to oxidation of fat, and it also reduces oxidative metabolism, for

  261.                         example by lowering thyroid function (Vandorpe and Kühn, 1989). These changes are analogous to

  262.                         those of fasting, in which metabolism shifts to the oxidation of fatty acids for energy, causes

  263.                         decreased body temperature, and in some animals leads to a state of torpor or hibernation.</span

  264.                     ></span></span>

  265.         </blockquote>

  266.         <blockquote></blockquote>

  267.         <blockquote>

  268.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  269.                         style="font-size: medium"

  270.                     >Despite decreasing oxidative metabolism, estrogen stimulates the adrenal cortex, both directly and

  271.                         indirectly through the brain and pituitary, increasing the production of cortisol. Cortisol, by

  272.                         increasing protein turnover, can increase heat production, but this effect isn't necessarily

  273.                         sufficient to maintain a normal body temperature. It increases blood glucose, mainly by blocking

  274.                         its use for energy production, but the glucose is derived from the breakdown of muscle protein.

  275.                         It allows some glucose to be stored as fat. Sudden increases in the amount of glucose can lower

  276.                         adrenaline, and chronically excessive cortisol tends to suppress adrenaline. Cushing's syndrome

  277.                         (produced by excessive cortisol) commonly involves flushing and depression, both of which are

  278.                         likely to be related to the decreased action of adrenaline.</span></span></span>

  279.         </blockquote>

  280.         <blockquote></blockquote>

  281.         <blockquote>

  282.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  283.                         style="font-size: medium"

  284.                     >While the biological changes occurring at menopause and during hot flashes are very similar to some

  285.                         of the direct actions of estrogen, and although the menopause itself is the result of prolonged

  286.                         exposure to estrogen, very large doses of estrogen can, in many women (as well as in morphine

  287.                         addicted rats), stop the flushing. In some of the published animal experiments, effective doses

  288.                         of estrogen were about 2000 times normal, and in some human studies, the dose was 30 times

  289.                         normal. By blocking the production of heat, the estrogen treatments might be creating conditions

  290.                         similar to those in Simpkin's cooler old rats, which failed to flush during morphine withdrawal.

  291.                         Menopausal estrogen treatment is known to lower temperature (Brooks, et al., 1994).</span></span

  292.                 ></span>

  293.         </blockquote>

  294.         <blockquote></blockquote>

  295.         <blockquote>

  296.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  297.                         style="font-size: medium"

  298.                     >Since the Women's Health Initiative publicized the dangers of estrogen, there has been some

  299.                         interest in alternative treatments for hot flashes. Since a reduced production of progesterone

  300.                         has been associated with hot flushes for several decades, it isn't surprising that it is now

  301.                         being tested as an alternative to estrogen. Recently, 300 mg of oral progesterone was found to

  302.                         be effective for decreasing hot flashes, and a month after discontinuing it, the hot flushes

  303.                         were still less frequent than before using it (Prior and Hitchcock, 2012). Previously,

  304.                         transdermal progesterone was found to be effective (Leonetti, et al., 1999).</span></span></span

  305.             >

  306.         </blockquote>

  307.         <blockquote></blockquote>

  308.         <blockquote>

  309.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  310.                         style="font-size: medium"

  311.                     >One of the things progesterone does is to stabilize blood sugar. In one experiment, hot flashes

  312.                         were found to be increased by lowering blood sugar, and decreased by moderately increasing blood

  313.                         sugar (Dormire and Reame, 2003).</span></span></span>

  314.         </blockquote>

  315.         <blockquote>

  316.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  317.                         style="font-size: medium"

  318.                     >Hypoglycemia increases the brain hormone, corticotropin release hormone, CRH (Widmaier, et al.,

  319.                         1988), which increases ACTH and cortisol. CRH causes vasodilation (Clifton, et al., 2005), and

  320.                         is more active in the presence of estrogen. Menopausal women are more responsive to its effects,

  321.                         and those with the most severe hot flushes are the most responsive (Yakubo, et al., 1990).</span

  322.                     ></span></span>

  323.         </blockquote>

  324.         <blockquote></blockquote>

  325.         <blockquote>

  326.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  327.                         style="font-size: medium"

  328.                     >The first reaction to a decrease of blood glucose, at least in healthy individuals, is to increase

  329.                         the activity of the sympathetic nervous system, with an increase of adrenaline, which causes the

  330.                         liver to release glucose from its glycogen stores. The effect of adrenaline on the liver is very

  331.                         quick, but adrenaline also acts on the brain, stimulating CRH, which causes the pituitary to

  332.                         secrete ACTH, which stimulates the adrenal cortex to release cortisol, which by various means

  333.                         causes blood sugar to increase, consequently causing the sympathetic nervous activity to

  334.                         decrease. Even when the liver's glycogen stores are adequate, the system cycles rhythmically,

  335.                         usually repeating about every 90 minutes throughout the day.</span></span></span>

  336.         </blockquote>

  337.         <blockquote></blockquote>

  338.         <blockquote>

  339.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  340.                         style="font-size: medium"

  341.                     >Sympathetic nervous activity typically causes vasoconstriction in the skin and extremities,

  342.                         reducing heat loss, but the small cycles in the system normally aren't noticed, except as small

  343.                         changes in alertness or appetite. With advancing age, most tissues become less sensitive to

  344.                         adrenaline and the sympathetic nervous stimulation, and the body relies increasingly on the

  345.                         production of cortisol to maintain blood glucose. Many of the changes occurring around the

  346.                         menopause, such as the rise of free fatty acids and decrease of glucose availability, increase

  347.                         the sensitivity of the CRH nerves, causing the fluctuations of the adrenergic system to cause

  348.                         larger increases of ACTH and cortisol. Estrogen is another factor that increases the sensitivity

  349.                         of the CRH nerves, and unsaturated fatty acids (Widmaier, et al. 1995) and serotonin

  350.                         (Buckingham, et al., 1982) are other factors stimulating it. Serotonin, like noradrenalin, rises

  351.                         with hypoglycemia (Vahabzadeh, et al., 1995), and estrogen contributes to hypoglycemia, by

  352.                         impairing the counterregulatory system (Cheng and Mobbs, 2009).</span></span></span>

  353.         </blockquote>

  354.         <blockquote></blockquote>

  355.         <blockquote>

  356.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  357.                         style="font-size: medium"

  358.                     >With the reduced vasoconstrictive effects of the sympathetic nerves, and the increased activity of

  359.                         CRH, cyclic vasodilation under the influence of cortisol will become more noticeable. With the

  360.                         onset of menopause, and in proportion to the number and intensity of symptoms (on the Greene

  361.                         Climacteric Scale), the daily secretion of cortisol was increased (Cagnacci, et al.,

  362.                         2011).</span></span></span>

  363.         </blockquote>

  364.         <blockquote></blockquote>

  365.         <blockquote>

  366.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  367.                         style="font-size: medium"

  368.                     >Once the ideologically based doctrine of menopause as estrogen deficiency is discarded, it's

  369.                         possible to see its features as clues to the ways in which "stress" contributes to the

  370.                         age-related degeneration of the various systems of the body--not just the reproductive system,

  371.                         but also the immune system, the nutritive, growth, and repair processes, and the motivational,

  372.                         emotional, and cognitive processes of the nervous systems. The changes around menopause aren't

  373.                         the same for all women, but the ways in which they vary can be understood in terms of the basic

  374.                         biological principles of energy and adaptation that are universal.</span></span></span>

  375.         </blockquote>

  376.         <blockquote></blockquote>

  377.         <blockquote>

  378.             <span style="color: #222222">&nbsp;<span style="font-family: georgia, times, serif"><span

  379.                         style="font-size: medium"

  380.                     ><span style="font-style: normal"><span style="font-weight: normal"

  381.                             >Each type of cell and organ is subject to injury, and in some cases these injuries are

  382.                                 cumulative. In the healthy liver, which stores glycogen, toxins can be inactivated, for

  383.                                 example by combining with glucuronic acid, derived from the stored glucose. With injury,

  384.                                 such as alcoholism combined with a diet containing polyunsaturated fats, the liver's

  385.                                 detoxifying ability is reduced. Even at an early stage, before there is a significant

  386.                                 amount of fibrosis, the reduced activity of the liver causes estrogen to accumulate in

  387.                                 the body. Estrogen's valuable actions are, in health, exerted briefly, and then the

  388.                                 synthesis of estrogen is stopped, and its excretion reduces its activity, but when the

  389.                                 liver's function is impaired, estrogen's activity continues, causing further

  390.                                 deterioration of liver function, as well as injury of nerves such as Desjardins

  391.                                 described, and the systemic energy shifts and stress activations mentioned above.</span

  392.                             ></span></span></span></span>

  393.         </blockquote>

  394.         <blockquote></blockquote>

  395.         <blockquote>

  396.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  397.                         style="font-size: medium"

  398.                     >Besides lowering the liver's detoxifying ability, stress, hypoglycemia, malnutrition,

  399.                         hypothyroidism, and aging can cause estrogen to be synthesized inappropriately and continuously.

  400.                         With aging, estrogen begins to be produced throughout the body--in fat, muscles, skin, bones,

  401.                         brain, liver, breast, uterus, etc. Polyunsaturated fats are a major factor in the induction and

  402.                         activation of the aromatase enzyme, which synthesizes estrogen.</span></span></span>

  403.         </blockquote>

  404.         <blockquote></blockquote>

  405.         <blockquote>

  406.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  407.                         style="font-size: medium"

  408.                     >Increased synthesis of estrogen, with aromatase, and decreased excretion of it, by the liver and

  409.                         kidneys, are only two of the processes that affect the influence of estrogen during aging.

  410.                         Cellular stress (chemical, mechanical, hypoxemic, hypoglycemic [Clere, et al., 2012; Aguirre, et

  411.                         al., 2007, Zaman, et al., 2006, Saxon, et al., 2007; Tamir, et al., 2002; Briski, et al., 2010])

  412.                         increases estrogen receptors (which activate CRH and the stress response). The presence of

  413.                         estrogen receptors means that estrogen will be bound inside cells, where it acts to modify those

  414.                         cells. Before estrogen can reach the liver to be inactivated, it must be released from cells.

  415.                         Ordinarily, the cyclic production of progesterone has that function, by destroying the

  416.                         estrogen-binding proteins. Progesterone also inhibits the aromatase which synthesizes estrogen,

  417.                         and shifts the activities of other enzymes, including sulfatases and dehydrogenates, in a

  418.                         comprehensive process of eliminating the presence and activity of estrogen. At menopause, when

  419.                         the ovary fails to produce the cyclic progesterone, all of these processes of estrogen

  420.                         inactivation fail. In the absence of progesterone, cortisol becomes more active, increasing

  421.                         aromatase activity, which now becomes chronic and progressive. The decrease of progesterone

  422.                         causes many other changes, including the increased conversion of polyunsaturated fatty acids to

  423.                         prostaglandins, and the formation of nitric oxide, all of which contribute to the tendency to

  424.                         flush.</span></span></span>

  425.         </blockquote>

  426.         <blockquote>

  427.             <span style="color: #222222">&nbsp; <span style="font-family: georgia, times, serif"><span

  428.                         style="font-size: medium"

  429.                     ><span style="font-style: normal"><span style="font-weight: normal"><hr /></span></span></span

  430.                     ></span></span>

  431.         </blockquote>

  432.         <blockquote>

  433.             <span style="color: #222222"><span style="font-family: georgia, times, serif"><span

  434.                         style="font-size: medium"

  435.                     >*The limits of the belief system or consciousness of US medicine are nicely defined by the topics

  436.                         included in the Index Medicus, which was published from 1879 to 2004, by the Surgeon General's

  437.                         Office of the U.S. Army, the American Medical Association, and the National Library of Medicine,

  438.                         at different times. If you look up any important topic in physiology or biochemistry in an index

  439.                         of scientific publications such as Biological Abstracts or Chemical Abstracts, and then look for

  440.                         the same subject in the Index Medicus, you will find some startling differences--long delays and

  441.                         antagonistic attitudes. At first the discrepancies seem ludicrous and hard to account for, but I

  442.                         think they can be explained by recognizing that the editors of medical journals consider science

  443.                         to be their enemy.</span></span></span>

  444.         </blockquote>

  445.         <blockquote></blockquote>

  446.         <blockquote>

  447.             <span style="color: #222222">&nbsp;&nbsp;&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; <span

  448.                     style="font-family: georgia, times, serif"

  449.                 ><span style="font-size: medium"><span style="font-style: normal"><span style="font-weight: normal"><h3>

  450.                                     REFERENCES

  451.                                 </h3></span></span></span></span></span>

  452.         </blockquote>

  453.         <blockquote>

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  455.                         style="font-size: medium"

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  458.                         Gortazar AR, Millan MM, O'Brien CA, Manolagas SC, Bellido T.</span></span></span>

  459.         </blockquote>

  460.         <blockquote></blockquote>

  461.         <blockquote>

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  464.                     >Prog Clin Biol Res. 1981;67:161-77. Metabolic adaptations to starvation, semistarvation, and

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  850.         <p>&nbsp;</p>

  851. 

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