“You can’t understand the other things that I’m working on unless you know where serotonin fits in. To understand unsaturated fatty acids vs. saturated, you have to understand estrogen and serotonin, and to understand thyroid, you have to understand all of those.”
Many who earnestly seek to understand Peat's philosophy are turned off simply due to the amount of prejudice one has to shed before being able to consider the mechanisms in his framework.
Who has all of Ray Peat's ideas figured out? NOT ME, but in attempt to better understand his orientation I weblog about him incessantly.
One such aspect of Peat's philosophy that warrants more discussion is the role of Hans Selye's "shock" hormone, estrogen.
Pro Tip: Perusing these articles may enhance the readability of this one:
- The Road To Nowhere Part I: Treating The Intestine Without Addressing Endotoxin, Serotonin & Estrogen
- Orthodox Paleo, Or: How To Increase Stress, Inflammation & Bone Loss
What's Your Estrogen Orientation?
Click for a larger image.
The mainstream is estrogen-crazed. The closest women in my life have been offered estrogen in the form of birth control for acne, depression, dry skin, anxiety, digestive issues, low libido, and polycystic ovarian syndrome (PCOS).
While a case can be made that all of the above conditions involve excess levels of estrogen, sometimes I ask myself if some docs are even trying anymore.
The alternative health scene is usually a little better differentiating between estrogens, like the very potent estradiol, and the supposedly "protective" lesser estrogens, estriol and estrone. It is not uncommon for a Naturopath to prescribe the lesser estrogens or phytoestrogens (estrogen-like, plant-based supplements).
Both of these paradigms are in opposition to the extensive work of Hans Selye and Ray Peat, both of whom have detailed the harmful physiological effects of excess estrogen.
Peat and Selye's focus seems to be on "whole organism" physiology, rather than the sale of a product or "cutting-edge" research that fits some fantasy of evolution.
While the pharmaceutical industry has succeeded in training the public to refer to estrogen as "the female hormone," estrogen is as much a "male" hormone as it is a "female" hormone:
"Estrogenicity can be defined most simply as “acting the way estrogen does,” (originally, the term “estrogen” meant “producing estrus,” the female readiness to mate) and since our natural estrogen does many things, the definition is often, for practicality, based on the rapid changes produced in certain female organs by estradiol, specifically, the enlargement of the uterus by first taking up a large amount of water, and secondarily by the multiplication of cells and the production of specific proteins. A similar process occurring in the breast is also recognized as an important feature of the estrogen reaction, but as we try to define just what “estrogenicity” is, we see that there is something deeply wrong with this method of defining a hormone, because we are constantly learning more about the actions of estrogen, or of a specific form of the molecule.
Calling it “the female hormone” distracted attention from its many functions in the male, and led to great confusion about its antifertility actions and its other toxicities. Many biologists called it “folliculin,” because of the ovarian follicle's significant role in its production, but the pharmaceutical industry succeeded in naming it in relation to one of its functions, and then in extending that idea of it as “the producer of female receptivity” to the even more misleading idea that it is “the female hormone.” But when people speak about the “estrogenicity” of a substance, they mean that it has properties that parallel those of “folliculin,” the particular group of ovarian hormones that includes estradiol, estrone, and estriol." - Ray Peat, PhD
Hans Selye often referred to estrogen as "adipin" or "folliculin" and rejected the name estrogen as it did not align with its physiological function:
"...Similarly, in many animal species, the so-called "estrogens" do not in themselves cause estrus or heat without simultaneous progesterone treatment, hence the later hormone could be called "estrogenic" with almost equal justification. Furthermore, folliculoids interrupt the estrous cycle in the intact rodent so that they are actually "anti-estrogenic" under ordinary circumstances of bioassay." - Hans Selye
Additionally, Constance R. Martin explains that estrogens are involved in defeminization:
"When the effects of perinatal gonadectomy and hormone injection were first observed, it seemed reasonable to conclude that testosterone interacts with androgen receptors in the brain to bring about defeminization. However, the concept had to be revised when it was found that estrogens mimic testosterone, whereas DHT does not.
It was soon revealed that estrogen receptors begin to appear in the hypothalamus around the time of birth, and that they increase in numbers during the first few postnatal days. Moreover, neurons involved in defeminization contain aromatase enzymes that convert testosterone (but not DHT) to estrogen. The conclusion that estrogens are the defeminizing agents is supported by several findings." - Constance R. Martin
So if it's not the female hormone, what does it do?
While nailing down estrogen's specific function in the body can be confusing, Dr. Peat explains that its main physiological function is to cause the tissues to take up water to promote cell division:
"About 50 years ago, Hans Selye (known for his discovery of the stress syndrome) gave large doses of individual steroid hormones to rats to study the range of their effects. He had previously analyzed the physiology of the stress reaction, and he observed that estrogen treatment exactly duplicated the shock phase of the stress reaction.
This interferes with circulation and energy metabolism, and its physiological purpose is to cause tissue to take up water which stimulates cell division, for example in the uterus to prepare for pregnancy, and in the breasts to prepare for lactation. But none of the physiological functions of estrogen suggests that it could be beneficial in situations other than reproduction--and then only when its "shock" effect is tightly regulated by a well balanced organism--and possibly in wound healing, where its ability to stimulate cell division could be useful." - Ray Peat, PhD
"Tightly regulated" and "well balanced" are not terms I would ever use to describe those with health issues.
Progesterone, the real "feminine hormone," has an inverse relationship with estrogen and the exact opposite effects:
"It turns out that the meaning of "excess estrogen" has to be interpreted in relation to the balance of estrogen (and the multitude of factors which mimic estrogen's effects) with all of the antiestrogen factors. I have concentrated on thyroid, progesterone, and red light as the most important factors that protect against estrogen, and these all turn out to be protective against stress, shock, ionizing radiation, free radicals, lipid peroxidation, thymic atrophy, osteoporosis, arthritis, scleroderma, apoptotic cell death, and other problems that are involved in tissue degeneration or aging." - Ray Peat, PhD
Inflammation & Estrogen
While, women normally have higher levels than males, malnutrition, stress, and inflammation can greatly influence estrogen levels in both sexes:
"In good health, an animal's systems are designed so that certain tissues will be intensely but briefly stimulated by estrogen. This stimulation by estrogen doesn't produce the normal amount of carbon dioxide, so the tissue experiences oxygen deprivation, leading to swelling and cell division. (Along with the reduced carbon dioxide production, there is increased lipid peroxidation). Any similar stimulaton, whether it's produced by soot, or suffocation, or irradiation, will produce the broad range of estrogen's effects, beginning with inflammation but ending with atrophy or cancer if it is too prolonged." - Ray Peat, PhD
A chief instigator of inflammation is the release of unsaturated fats from the tissue during stress.
Encountering a stress (something that interferes with our ability to make energy; a lack of oxygen for example) causes the cells to take up glucose in an attempt to "overcome" the stressor.
When blood sugar runs low, adrenaline is released to mobilize additional glucose from the liver (glycogen). If glycogen is low or has been depleted, fuel requirements will be met by releasing free fatty acids, while glucose will be provided by cortisol.
Free fatty acids can be broken down into pro-inflammatory prostaglandins, which can activate the aromatase enzyme, creating new estrogen. One of the effects of aspirin, which can be used as an aromatase inhibitor, is to block the formation of prostaglandins by inhibiting the release of free fatty acids into the blood:
"Since the polyunsaturated fats and prostaglandins stimulate the expression of aromatase, the enzyme that synthesizes estrogen, aspirin decreases the production of estrogen. So many of aspirin's effects oppose those of estrogen, it would be tempting to suggest that its "basic action" is the suppression of estrogen. But I think it's more likely that both estrogen and aspirin are acting on some basic processes, in approximately opposite ways." - Ray Peat, PhD
Stress Promotes Estrogen & Estrogen Promotes Stress
Hans Selye found that administering estrogen to animals mimicked the first stage of "shock," as part of his famous general-adaptation-syndrome (GAS).
Peat takes Selye's work a step further suggesting that aging can be considered a "lingering" partial state of shock:
"Although Selye described shock as the first (potentially lethal) phase of stress, usually followed by the corrective adaptive processes, it’s useful to think of aging in terms of a lingering partial state of shock, in which adaptation is less than perfect." - Ray Peat, PhD
To better understand the physiological effects of the shock phase of GAS, which is synonymous with the effects of excess estrogen, I've pulled some quotes from Selye's The Textbook of Endocrinology (bolds are mine):
"The body temperature decreases during the shock phase of the alarm reaction, especially if defense is impeded by adrenalectomy or hypophysectomy. During the stage of resistance, on the other hand, there often is hyperthermia."
"The B.M.R is usually below normal during the shock-phase, but returns to normal during the stage of resistance."
This may explain why some with chronic stress are cold intolerant, while others who equally as stressed (via labs) do not exhibit this symptom.
"The blood sugar rises immediately following exposure to stress (emergency hyperglycemia); this is mainly due to the discharge of adrenaline. Later however, the blood sugar falls (often considerably below normal) and in fasting animals pronounced hypoglycemia may ensue. When the counter-shock hormones appear, the blood sugar rises again and it may reach hyperglycemic levels during the stage of resistance..."
"The liver glycogen content diminishes simultaneously with the initial hyperglycemia during the alarm reaction, presumably because the blood sugar is formed mainly at the expense of hepatic glycogen."
"Lack of oxygen depresses sugar utilization and — as does any other alarming agent — stimulates the endogenous production of corticoids..."
This aligns with Peat's focus on restoring oxidative energy in resisting various hormones of adaptation.
"The blood volume is greatly diminished in the shock-phase, but rises to or above normal during the counter-shock-phase. It tends to remain high during the stage of resistance."
"Somatic growth is inhibited during exposure to stress, especially in the alarm reaction and exhaustion stages of general-adaptation-syndrome. This has been ascribed to a "shift in pituitary-hormone formation," due to the fact that in emergencies an increased production of life-maintaining corticotrophic hormones is accomplished at the expense of other, less urgently needed, hypophyseal principles such as somatorophin, the gonadotrophins, luteotrophin, etc."
My Guts Are Leaking
As I mentioned in this article, estrogen is a factor in intestinal health.
Estrogen's ability to increase the permeability of tissue, and hinder oxidative energy, the basis for maintaining all barrier functions, suggests that it is a large factor in "leaky gut," food allergies, and conditions of "autoimmunity."
"In the hormonal environment dominated by estrogen, mild stresses such as exertion, or even restless sleep, allow toxins (and sometimes bacteria) from the intestine to enter the bloodstream, triggering a complex chain of events that create a systemic inflammatory state." - Ray Peat
The intestine is a "constant source of stress" as bacteria in the intestine produce bacterial endotoxin (lipopolysaccharide). When the intestine becomes permeable due to stress, endotoxin leaks into the serum, becoming a systemic problem:
"Bacterial toxins, whether produced in the intestine or in the manufacture of food supplements, pass through the wall of the intestine in larger amounts in stress, malnutrition, and old age. Endotoxin suppresses mitochondrial respiration, and tends to produce a shock-physiology similar to that produced by endogenous hormones. I have mentioned before that I think endotoxin can be involved in the premenstrual syndrome, and I think it might even be involved in some breast syndromes." - Ray Peat
As for the synergy between estrogen and endotoxin:
"How does estrogen enhance endotoxin toxicity? Let me count the ways." - J.J. Maher (Liver Center and Department of Medicine, University of California San Francisco) in Hepatology, 1998, 28(6):1720-1.
Orgasm-O-Meter
Lab work for estrogen can be a mixed bag.
Measuring prolactin and serotonin can help estimate estrogen levels, but sometimes so can the intensity of one's orgasm:
"High estrogen does sometimes cause insatiable sexual interest, partly because it increases adrenal androgens, and partly by inhibiting satisfying orgasms. Too much progesterone can suppress or neutralize the androgens. Thyroid is the best way to regulate the system, keeping libido up, making orgasms satisfying." - Ray Peat
Summary
I would say the whole situation earns the label of SHIT SHOW.
Without the context of Peat's thesis (structure and energy are interdependent; deranged energy production "destabilizes" the entire organism leading to the excessive utilization of emergency hormones—my words not his) I can see how one would become deeply confused about the nature of estrogen and what it actually does.
- Estrogen is not the female hormone.
- Estrogen is present in both males and females and increases during chronic stress or malnutrition.
- Inflammation increases the aromatase enzyme, producing new estrogen.
- Estrogen mimics the anti-metabolic "shock" state in the stress reaction.
- Estrogen promotes tissue permeability and is probably a factor in "leaky gut," food allergies, and "autoimmunity."
- The intensity of orgasm may be a self-diagnostic to evaluate estrogen status.
