“Women intrinsically understand human dynamics, and that makes them unstoppable. Unfortunately, the average man is less adroit at fostering such rivalries, which is why most men remain average; males are better at hating things that can’t hate them back (e.g., lawnmowers, cats, the Denver Broncos, et cetera). They don’t see the big picture.”
If I were woman I would be mad as hell.
It wouldn't be an evil-mad as much as it would be a confused-mad; like when you see someone wearing sunglasses in a mall.
Of course, some of this confused-madness would stem from anxiety surrounding the perfect time to post my #ootd (outfit of the day) on Instagram. And some from my physician's repeated attempt to ice me.
But the largest percentage, and perhaps the most infuriating, would be from the information surrounding polycystic ovarian syndrome (PCOS), which is bad. Real bad.
PCOS For People Who Don't Know WTF PCOS Is
If you ask your family physician about PCOS, he will most likely tell you that it is a hormonal imbalance with some of the following features:
- Cystic ovaries
- Elevated "male" sex hormones
- Irregular or absent menstruation
- Acne
- Low estrogen
While you sit silently waiting for more information, he will furrow his brow and tell you that PCOS has an unknown origin.
If you're still there, he will offer you birth control, Prozac, and Metformin before forcefully ejecting you from the office.
What causes PCOS?
When you get home and research PCOS on the Internet, you'll find that it is a "complex" condition that affects a lot of women.
Aggregating information from the blogosphere reveals that PCOS is supposedly caused from the following:
- Excessive dieting
- Insulin resistance
- Being overweight
- General stress
- Hypothyroidism
- Liver dysfunction
Treatment often involves: decreasing carbohydrate intake, avoiding fructose, avoiding soy (because it is estrogenic), avoiding dairy, consuming grapefruit (to increase estrogen), fasting (if you're overweight), consuming beta carotene, consuming plenty of fat, exercising, focusing on sleep, optimizing thyroid function, exploring ovarian drilling, and considering the following supplements/drugs/hormones: agnus castus, saw palmetto, milk thistle, spearmint tea, Metformin, Yaz, Yasmin, Ortho-try-cyclen, progesterone, Spironolactone and Flutamide.
PCOS & String Theory
When something is described as being as complicated as PCOS is, it's worth reviewing for contextual errors:
#1: The Idea of "Gender" Hormones
There is a strong desire to explain PCOS as an excess of the "male" hormone testosterone and the supposed deficiency of the "female" hormone estrogen.
While the above is half right, labeling hormones by gender quickly derails the conversation and gives way to tunnel vision regarding their function.
For example, testosterone can be converted into estrogen via the aromatase enzyme, which can be increased during stress. Estrogen can then act on the adrenal glands causing them to secrete hormones responsible for masculine characteristics.
Hans Selye found that estrogen, which was named for its supposed ability to produce estrous, interrupted the estrous cycle and was actually "anti-estrogenic." The function, that estrogen was named for, could not be produced unless simultaneous progesterone was given.
#2: The Role of Progesterone & Estrogen in PCOS
Confusion about estrogen not only stems from the pharmaceutical industry's tireless promotion of its "youth-promoting-feminine-re$toring-qualitie$," but also by the labeling of progesterone as "the pregnancy hormone."
As we discussed in last week's article, cholesterol, along with vitamin A, and active thyroid hormone (triiodothyronine, or T3) are needed to produce protective hormones like DHEA and progesterone from pregnenolone. In fact, high cholesterol has long been known as a marker for low thyroid.
Besides being a powerful anti-estrogen, progesterone is an anti-androgen (opposes testosterone), and reduces the effects of both aldosterone and prolactin. If progesterone production is insufficient (low thyroid as represented by low pulse and/or low body temperature, vitamin A deficiency, or low cholesterol) progesterone production will decline, increasing the ratio of estrogen to progesterone.
While I advocate lab work for the purpose of gathering evidence, what appears to be an "estrogen deficiency" in the blood, can actually be an excess of estrogen at the cellular level.
Fulfilling its role as an anti-estrogen, progesterone destroys proteins that bind estrogen inside the cell dumping it into the blood for the liver to detoxify. A deficiency of progesterone can cause the cellular accumulation of estrogen ("deficiency" in the blood), which is seen in stress, sickness, and aging.
#3: The Role of The Pituitary Hormones In PCOS
When diagnosing PCOS a physician will often look for elevated testosterone, decreased serum levels of estrogen, and an inverted ratio of the pituitary gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH).
Despite their names, both LH and FSH have estrogen-like actions, and like all pituitary hormones, are increased in stress. It's important to note that the pituitary is activated by a perceived energy deficiency (low thyroid).
Prolactin, another pituitary hormone, has been referred to as the "mothering hormone." Bromocriptine, a drug that inhibits prolactin (apparently by acting on serotonin), reduces PCOS symptoms. Similar to estrogen, prolactin decreases the cell's ability to consume oxygen and produce oxidative energy. Additionally, it has been found to inhibit the ovaries' production of progesterone.
Estrogen, Cell Division & Your Oxidative Machinery
An excess of estrogen and a deficiency of progesterone represents a much bigger problem than a simple "hormone imbalance."
The type of energy we produce sends a strong message to our cells whether to divide and grow, or differentiate and support the functional systems of the organism.
During stress, reproduction, or tissue repair, estrogen stimulates the cell's glycolytic pathway, but inhibits mitochondrial respiration, creating an anaerobic (no oxygen) environment that promotes simple cell division.
In order to achieve greater mobility, the dividing cell rids itself of its bulky oxidative machinery (partly or wholly) to produce energy through glycolysis (lactic acid instead of carbon dioxide).
If oxygen deprivation is chronic (prolonged stress), the cell may be unable to shift back to its oxidative state, even if oxygen is reintroduced.
As I have described elsewhere, the cell's ability to produce oxidative energy is representative of the metabolism of our youth, while the production of lactic acid and the cell's inability to consume oxygen is an essential characteristic of cancer (Warburg, Szent-Györgyi).
A Rational Approach To PCOS
The current "cutting-edge-alternative-evolutionary-approach" to PCOS adopts the same misguided information about estrogen that makes the traditional pharmaceutical approach so dangerous. Viewing estrogen as the "female hormone," gives way to unphysiological "therapies" including birth control and Spironolactone (an aldosterone inhibitor) that in no way treats the underlining problem.
The symptoms of increased testosterone, increased aldosterone, increased cholesterol, and abnormal or absent menstruation suggest that the production of the anti-testosterone-anti-aldosterone-made-from-cholesterol-promoter-of-regular-menstruation hormone, progesterone, has been compromised.
Restoring progesterone production may be accomplished by focusing on dietary factors that support respiration: consuming adequate protein, sugar (fruit), saturated fats, salt, b-vitamins, vitamin A (retinol, not beta carotene), vitamin D, vitamin k, calcium, copper, zinc, and magnesium.
Additional remedies for reducing estrogen levels include: thyroid hormone, natural progesterone (Progest-e is the only brand I would recommend), consuming a raw carrot a day, epsom salt/baking soda baths, vitamin E, red light, and reducing the liberation of free fatty acids with aspirin (aromatase inhibitor), niacinamide, and coffee.
References
- Am J Obstet Gynecol. 1993 Nov;169(5):1223-6. Excessive estradiol secretion in polycystic ovarian disease. Benjamin F, Toles AW, Seltzer VL, Deutsch S. Polycystic ovarian disease is both a hyperestrogenic and a hyperandrogenic syndrome, and all studies have shown that hyperestrogenemia is the result of an elevation of estrone with plasma estradiol levels in the normal follicular range. Because a literature search failed to reveal any report of polycystic ovarian disease with significantly elevated estradiol levels, we report a case in which the plasma estradiol was so massively elevated as to mimic an estrogen-producing neoplasm. This case also suggests that although polycystic ovarian disease is a very rare cause of such excessive estradiol production, it should be included in the differential diagnosis of estrogen-producing neoplasms. (Thanks Rob Turner)
- J Clin Endocrinol Metab. 1995 Feb;80(2):603-7. The impact of estrogen on adrenal androgen sensitivity and secretion in polycystic ovary syndrome. Ditkoff EC, Fruzzetti F, Chang L, Stancyzk FZ, Lobo RA. Adrenal hyperandrogenism is a common feature of patients with polycystic ovary syndrome (PCO). This may be due to enhanced adrenal sensitivity to ACTH. Because enhanced ovarian androgen secretion does not appear to explain this phenomenon, we explored the role of estrogen in inducing enhanced adrenal sensitivity, in that a state of relative hyperestrogenism exists in PCO. Eight patients with PCO and seven matched controls received ovine corticotropin-releasing hormone (oCRH; 0.1 micrograms/kg) iv before and after hypoestrogenism was induced by leuprolide acetate (LA; 1 mg, sc, each day). In patients with PCO, a third oCRH test was repeated after transdermal estradiol (E2; 0.1 mg) had been applied for a week, during which time LA was continued. At baseline, patients with PCO had increased responses of 11 beta-hydroxyandrostenedione and dehydroepiandrosterone (P < 0.03 and P < 0.02) and increased delta maximal ratios of androstenedione (A4)/ACTH and dehydroepiandrosterone/ACTH (P < 0.01) after oCRH treatment. After LA administration to patients with PCO, these ratios were significantly suppressed (P < 0.01) and returned to baseline after E2 was added. There were no changes in controls. Steroid ratio responses to oCRH suggested that 17,20-desmolase activity (delta maximum change in the ratio of A4/17-hydroxyprogesterone) was lowered with estrogen suppression and increased again after transdermal E2 administration. There was a significant positive correlation between changes in E2 levels and delta maximum change in the ratios of A4/17-OHP after oCRH treatment, signifying 17,20-desmolase activity (r = 0.58, P < 0.02). In conclusion, these data provide evidence that estrogen is at least one factor that influences adrenal androgen sensitivity in PCO and may help explain the frequent finding of adrenal hyperandrogenism in this syndrome. (Thanks Rob Turner)
- Fertil Steril. 2009 Jul;92(1):250-5. Epub 2008 Aug 3. Basal metabolic rate is decreased in women with polycystic ovary syndrome and biochemical hyperandrogenemia and is associated with insulin resistance. Georgopoulos NA, Saltamavros AD, Vervita V, Karkoulias K, Adonakis G, Decavalas G, Kourounis G, Markou KB, Kyriazopoulou V. Source Division of Reproductive Endocrinology, University of Patras Medical School, University Hospital, Patras, Greece. neoklisg@hol.gr Abstract OBJECTIVE: To evaluate basal metabolic rate (BMR) in women with PCOS and to determine its association with insulin resistance (IR). DESIGN: Prospective assessment of BMR in women with PCOS. SETTING: Outpatient clinic of the Division of Reproductive Endocrinology. PATIENT(S): The study included 91 Greek women with PCOS and biochemical hyperandrogenemia, with mean age 24.03 +/- 0.55 years and mean body mass index (BMI) 26.67 +/- 0.69 kg/m(2), and 48 matched regularly menstruating women, with mean age 26.33 +/- 0.93 years and mean BMI 23.35 +/- 0.85 kg/m(2), as control subjects. INTERVENTION(S): Assessment of BMR by indirect calorimetry, IR by HOMA and QUICKI indices, fasting insulin, and fasting glucose/insulin ratio. MAIN OUTCOME MEASURE(S): Reduced BMR in PCOS with or without IR. RESULT(S): Adjusted BMR was 1,868 +/- 41 kcal/day in the control group, 1,445.57 +/- 76 in all PCOS women, 1,590 +/- 130 in PCOS women without IR and 1,116 +/- 106 in PCOS women with IR. Adjusted BMR showed a statistically significant difference between women with PCOS and control subjects, with lowest values in the group of PCOS women with IR, even after adjusting all groups for age and BMI. CONCLUSION(S): Women with PCOS, particularly those with IR, present a significantly decreased BMR. (Thanks Vladimir)
- "The longer a woman stays on hormones, the more each cell in her body is poisoned. Does poison sound like too strong a word? A woman must decide for herself. As the years pass, her sugar metabolism may test out like a diabetic’s." -Drs. Barbara and Gideon Seaman (Thanks Rob Turner)
- Akush Ginekol (Mosk). 1990 Sep;(9):61-3. [The therapeutic effect of parlodel in the polycystic ovary syndrome]. [Article in Russian] Soboleva EL, Komarov EK, Potin VV, Svechnikova FA. Parlodel (2.5-50 mg/day) has been given for 1 to 7 days to 33 patients with the polycystic ovary syndrome (POS). The ovulatory menstrual cycle returned in 10 (30%) patients and 4 of them conceived. Pretreatment cycle disturbance persisted in 6 (18%) patients. Parlodel reduced mid-follicular mean blood LH levels to values of normal women. Some decrease in blood testosterone levels occurred only in the second phase of the cycle. Estradiol test in 6 patients showed normal positive and negative feedbacks in the hypothalamic-pituitary-ovarian axis. Parlodel treatment reduced basal and estradiol stimulated pituitary gonadotropin secretion. It is suggested that parlodel may be used in ovulation induction in a proportion of POS patients. (Thanks Rob Turner)
- Obstet Gynecol. 1980 May;55(5):579-82. Prolactin release in polycystic ovary. Falaschi P, del Pozo E, Rocco A, Toscano V, Petrangeli E, Pompei P, Frajese G. Ten normoprolactinemic and 10 hyperprolactinemic patients, all with polycystic ovary syndrome (PCO), were subjected to prolactin (PRL) stimulatory tests with thyrotropin-releasing hormone (TRH), 200 microgram intravenously, and haloperidol (a dopamine-blocking agent), 1 mg intramuscularly. The results were compared with those of 8 women with idiopathic hyperprolactinemia and 10 normal female volunteers. Distinctive features of PCO were elevated plasma concentrations of luteinizing hormone, estrone, and testosterone in the presence of normal estradiol, whereas in idiopathic hyperprolactinemia estradiol was reduced. Both groups of patients with PCO exhibited responses to TRH and haloperidol significantly higher than the controls (P less than .001), whereas only the hyperprolactinemic PCO patients reacted with an excessive PRL discharge (P less than .001). As expected, the response to both secretagogue agents was blunted in patients with idiopathic hyperprolactinemia. The present report discusses the possible implication of estrogen and the dopaminergic system in the mechanisms leading to hyperprolactinemia and enhanced PRL release in PCO. (Thanks Rob Turner)
- "Sustained high estrogen concentrations increase both insulin requirements and insulin secretion." - Constance R. Martin (Endocrine Physiology)
- Circ Shock. 1994 Aug;43(4):171-8. Sex steroid hormones in circulatory shock, sepsis syndrome, and septic shock. Fourrier F, et al. "METHODS: Estrone (E1), estradiol (E2), testosterone (T), FSH, and LH levels were daily measured during a ten day period in 50 critically ill patients (38 men, 12 post-menopausal women). Patients were separated into four groups: A) no circulatory failure, no sepsis, B) sepsis syndrome without circulatory failure, C) circulatory failure without sepsis syndrome, D) septic shock. Results of hormonal measurements were compared 1) among the 4 groups, 2) between male and female patients, 3) between septic and nonseptic patients. The potential for the infusion of the vasoactive drug dobutamine to induce sex hormonal changes was documented in ten additional septic shock patients by measuring cortisol, E1, and T at base-line and after dobutamine infusion. Changes in active renin and plasma renin activity (PRA) were used as indirect witness of the dobutamine-induced beta 2-stimulation. RESULTS: A dramatic increase in E1 and E2 levels was observed in women of groups B and D, and only in male patients of group D. In the septic patients, estrogen levels peaked at days 1 and 2 and trended to normal from day 6 after the onset of sepsis, while FSH and LH decreased. No difference was found between survivors and non-survivors. Whatever the group, male patients had low T levels throughout the study. Dobutamine induced a significant increase in active renin levels and a decrease in the regression slope between renin and PRA. Cortisol levels remained normal. No significant change in E1 and T was observed after dobutamine. CONCLUSIONS: High estrogen levels were specifically observed in patients with sepsis and septic shock, either males or females. Decreased LH and FSH levels were consistent with the negative feed-back effect of high estrogen levels on pituitary secretion. Circulating T levels were decreased in all male patients. We found no correlation between sequential estrogen levels and outcome. These levels were not modified by a dobutamine-induced beta-2 stimulation."
- Am J Obstet Gynecol. 1987 Aug;157(2):312-7. Age-related changes in the female hormonal environment during reproductive life. Musey VC, Collins DC, Musey PI, Martino-Saltzman D, Preedy JR. Previous studies have indicated that serum levels of follicle-stimulating hormone rise with age during the female reproductive life, but the effect on other hormones is not clear. We studied the effects of age, independent of pregnancy, by comparing serum hormone levels in two groups of nulliparous, premenopausal women aged 18 to 23 and 29 to 40 years. We found that increased age during reproductive life is accompanied by a significant rise in both basal and stimulated serum follicle-stimulating hormone levels. This was accompanied by an increase in the serum level of estradiol-17 beta and the urine levels of estradiol-17 beta and 17 beta-estradiol-17-glucosiduronate. The serum level of estrone sulfate decreased with age. Serum and urine levels of other estrogens were unchanged. The basal and stimulated levels of luteinizing hormone were also unchanged. There was a significant decrease in basal and stimulated serum prolactin levels. Serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate decreased with age, but serum testosterone was unchanged. It is concluded that significant age-related changes in the female hormonal environment occur during the reproductive years. (Thanks Rob Turner)
- "FSH does induce aromatase enzymes, and it increases 5-alpha reductase and 3 beta-hydroxysteroid dehydrogenase activities." - Constance R. Martin (Endocrine Physiology)
- "Apparently all steroid hormones, including the folliculoids [ESTROGENS] and luteoids, are partly inactivated in the body. Only comparatively small amounts are eliminated, through the urine or bile, in an active form. This inactivation is accomplished by: total oxidatie degradation of the nucleus itself; by reduction (e.g., progesterone to pregnanediol); and by conjugation. All these processes appear to depend on the activity of certain enzymes (e.g., "estrinase") present in various tissues, especially the liver." - Hans Selye
- "The most advisable procedure [TO REDUCE CYSTIC OVARIES] is to administer progesterone in repeated courses each consisting of four doses of 5-10 mg. given every other day, in order to substitute for the lack of endogenous corpus luteum hormone production. These progesterone treatment periods must be separated by about 18 days of rest, during which the enogenous folliculoids have time to develop a proliferative endometrium. It is true that even this therapy is merely symptomatic, since it deals only with the result of the ovarian derangement. However, for reasons which are not yet quite clear, in many instances intermittent progesteorne therapy re-establishes the normal interrelations between the ovary and the pituitary and thus results in a more or less permanent cure." -Hans Selye
- Clin Endocrinol (Oxf) 1982 Nov;17(5):495-9 Hydrotestolactone lowers serum oestradiol and PRL levels in normal men: evidence of a role of oestradiol in prl secretion. D'Agata R, Aliffi A, Maugeri G, Mongioi A, Vicari E, Gulizia S, Polosa P. The effect on serum PRL levels of lowering serum oestradiol (E2) concentration by short-term administration of an aromatase activity inhibitor, hydrotestolactone (HT), was studied in six healthy male subjects. After HT administration serum E2 levels decreased from 68 +/- 5.8 to 26 +/- 2.5 pmol/l (mean +/- SE, P less than 0.05). These E2 changes were accompanied by a significant decrease in mean 2-h PRL levels from 11.2 +/- 2.1 to 6.5 +/- 1.6 ng/ml mean +/- SE, P less than 0.05). The evaluation of individual percentage change from basal concentrations showed a varying decrease in all subjects. These findings suggest that under physiological conditions E2 may be one of the factors which control blood PRL concentrations in men.
- Estrogen Levels Increase with Age - Rob Turner
- Fat Tissue and Aging – Increased Estrogen - Rob Turner
- Plasma Estrogen Does Not Reflect Tissue Concentration of Estrogen - Rob Turner
- Estrogen and Glucose Intolerance - Rob Turner
- J Natl Cancer Inst Monogr. 2000;(27):95-112. Tissue-specific synthesis and oxidative metabolism of estrogens. Jefcoate CR, Liehr JG, Santen RJ, Sutter TR, Yager JD, Yue W, Santner SJ, Tekmal R, Demers L, Pauley R, Naftolin F, Mor G, Berstein L. Estrogen exposure represents the major known risk factor for development of breast cancer in women and is implicated in the development of prostate cancer in men. Human breast tissue has been shown to be a site of oxidative metabolism of estrogen due to the presence of specific cytochrome P450 enzymes. The oxidative metabolism of 17beta-estradiol (E2) to E2-3,4-quinone metabolites by an E2-4-hydroxylase in breast tissue provides a rational hypothesis to explain the mammary carcinogenic effects of estrogen in women because this metabolite is directly genotoxic and can undergo redox cycling to form genotoxic reactive oxygen species. In this chapter, evidence in support of this hypothesis and of the role of P4501B1 as the 4-hydroxylase expressed in human breast tissue is reviewed. However, the plausibility of this hypothesis has been questioned on the grounds that insufficient E2 is present in breast tissue to be converted to biologically significant amounts of metabolite. This critique is based on the assumption that plasma and tissue E2 levels are concordant. However, breast cancer tissue E2 levels are 10-fold to 50-fold higher in postmenopausal women than predicted from plasma levels. Consequently, factors must be present to alter breast tissue E2 levels independently of plasma concentrations. One such factor may be the local production of E2 in breast tissue through the enzyme aromatase, and the evidence supporting the expression of aromatase in breast tissue is also reviewed in this chapter. If correct, mutations or environmental factors enhancing aromatase activity might result in high tissue concentrations of E2 that would likely be sufficient to serve as substrates for CYP1B1, given its high affinity for E2. This concept, if verified experimentally, would provide plausibility to the hypothesis that sufficient E2 may be present in tissue for formation of catechol metabolites that are estrogenic and which, upon further oxidative metabolism, form genotoxic species at levels that may contribute to estrogen carcinogenesis.
- Contraception. 1981 Apr;23(4):447-55. Comparison of plasma and myometrial tissue concentrations of estradiol-17 beta and progesterone in nonpregnant women. Akerlund M, Batra S, Helm G. Plasma and myometrial tissue concentrations of estradiol (E2) and progesterone (P) were measured by radioimmunoassay techniques in samples obtained from women with regular menstrual cycles and from women in pre- or postmenopausal age. In women with regular cycles, the tissue concentration of E2 ranged from 0.13 to 1.06 ng/g wet weight, with significantly higher levels around ovulation than in follicular or luteal phases of the cycle. The tissue concentration of P ranged from 2.06 to 14.85 ng/g wet weight with significantly higher level in luteal phase than in follicular phase. The tissue/plasma ratio of E2 ranged from 1.45 to 20.36 with very high values in early follicular phase and the lowest in mid-luteal phase. The ratio for P ranged from 0.54 to 23.7 and was significantly lower in the luteal phase than in other phases of the cycle. One woman in premenopausal age with an ovarian cyst was the only case with a tissue/plasma ratio of E2 Less Than 1, since her plasma E2 levels were exceptionally high. In postmenopausal women, the tissue concentration of E2 was not significantly lower than in menstruating women in follicular phase, and the tissue concentration of P was not significantly lower than in fertile women in any of the phases. Neither in these women nor in menstruating women was there a close correlation between tissue and plasma levels. The present data indicate that the myometrial uptake capacity for ovarian steroids may be saturated, and also that a certain amount of these steroids is bound to tissue even if plasma levels are low.
- Clin Endocrinol (Oxf). 1979 Dec;11(6):603-10. Interrelations between plasma and tissue concentrations of 17 beta-oestradiol and progesterone during human pregnancy. Batra S, Bengtsson LP, Sjöberg NO. Oestradiol and progesterone concentration in plasma, decidua, myometrium and placenta obtained from women undergoing Caesarian section at term and abortion at weeks 16-22 of pregnancy were determined. There was a significant increase in oestradiol concentration (per g wet wt) both in placenta, decidua and myometrium from mid-term to term. Both at mid-term and term oestradiol concentrations in decidua and myometrium were much smaller than those in the plasma (per ml). Progesterone concentration in placenta and in myometrium did not increase from mid-term to term where it increased significantly in decidua. Decidual and myometrial progesterone concentrations at mid-term were 2-3 times higher than those in plasma, but at term the concentrations in both these tissues were lower than in plasma. The ratio progesterone/oestradiol in plasma, decidua, myometrium and placenta at mid-term was 8.7, 112.2, 61.4 and 370.0, respectively, and it decreased significantly in the myometrium and placenta but was nearly unchanged in plasma and decidua at term. The general conclusion to be drawn from the present study is the lack of correspondence between the plasma concentrations and the tissue concentrations of female sex steroids during pregnancy.
- "Estrogens in general tend to promote cell division, particularly in hormone-sensitive tissue such as the breast and uterine lining, and this is the key to why they can cause cancer." - Dr. John Lee (What Your Dr. May Not Tell You About Menopause)
- "Ovaria cysts - Fluid-filled degenerating structures often form within the ovaries when the androgen levels rise above optimum values. Cysts are common in older women, but they appear in younger ones that are fertile." - Constance R. Martin
- "…The elevation in certain blood lipid substances, such as cholesterol and free fatty acids, are comparatively simple to estimate, although they do require a chemical laboratory. Rises in STH [HGH], glucagon, insulin and prolactin are not only more difficult to determine, but also less reliable indicators of stress reactions in men." - Hans Selye (The Stress of Life - Medical Signs of Stress)
- "Estrogens are among the best known of the growth stimulants." - Constance R. Martin
- "Estrogens augment PRL secretion in several ways. They lower the sensitivities of lactotrop DA receptors, and they affect DA turnover in the brain." - Constance R. Martin
- "Estrogen tends to cause increased secretion of prolactin and the glucocorticoids, which cause bone loss, but it also promotes insulin secretion, which tends to prevent bone loss. All of these factors are associated with increased cancer risk." - Ray Peat
- "...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
- "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
- "Folliculoids [estrogens] elicit a pronounced and rather specific type of cortical hypertrophy, much greater than could be accounted for by their non-specific damaging action." - Hans Selye
- "This usually happens when a progesterone deficiency is combined with an excess of estrogen, as in the polycystic ovary syndrome and sometimes at menopause. In animals, polycystic ovaries are caused by a deficiency of the thyroid hormone, and the same regulatory mechanisms seem to operate in women. The polycystic ovary syndrome is the most common endocrine disorder in women during the reproductive years, and may occur in 10% of them. [A. Dunaif, et aI., eds. The Polycystic Ovary Syndrome. Cambridge, MA: Blackwell Scientific; 1992.] Estrogen is not an anabolic hormone, like testosterone, which builds up bone and muscle. In fact, it strongly opposes the effects of those hormones. In the polycystic ovary syndrome, an excess of estrogen stimulates the adrenal glands to produce a large amount of the androgenic steroids, probably to balance estrogen in the way progesterone does when the ovaries are functioning properly. These anabolic/androgenic hormones apparently have some of the good effects of progesterone, such as reducing the incidence of cancer, but many women are disturbed by the increased growth of body and facial hair; facial features also tend to be masculinized. In France, progesterone lotions have been in use for several years for reversing some of these effects of the adrenal hormones, and for balancing estrogen." - Ray Peat, PhD
- "Estrogen, at least when it is not opposed by a very large concentration of progesterone, creates all of the conditions known to be involved in the aging process. These effects of estrogen include interference with oxidative metabolism, formation of lipofuscin (the age-pigment), retention of iron, production of free radicals and lipid peroxides, promotion of excitotoxicity and death of nerve cells, impaired learning ability, increased tendency to form blood clots and to have vascular spasms, increased autoimmunity and atrophy of the thymus, elevated prolactin, atrophy of skin, increased susceptibility to a great variety of cancers, lowered body temperature, lower serum albumin, increased tendency toward edema, and many of the features of shock. In recent years, it has been found to be responsible even for neonatal masculinization and the masculinization of the polycystic ovary syndrome. Although the pharmaceutical industry has often referred to it as "the female hormone," I don't know of any competent scientist who has ever called it that." - Ray Peat, PhD
- "But a recent observation that a surge of estriol production precedes the onset of labor, and that its premature occurrence can identify women at risk of premature delivery (McGregor, et ai., 1995) suggests that the estriol surge might reflect the mother's increased production ofadrenal androgens during stress. (This would be analogous to the situation in the polycystic ovary syndrome, in which excessive estradiol drives the adrenals to produce androgens.)" - Ray Peat, PhD
- "Mechanisms underlying the resistance of genetic material of the animal cell to stress treatment," Genetika 30(8), 1092-1104, 1994. "...these studies prove that the formation of a mutation is a multistage process involving many cell and organism systems...which are affected by environmental factors.... They can hinder or accelerate the mutational process, in this way providing both a superadditive effect and adaptive response. Recent studies deal with a universal system of heat shock proteins, which is involved in the maintenance of resistance of genetic material and genetic processes in the cell." Gross, "Reproductive cycle biochemistry," Fertility & Sterility 12(3), 245-260, 1961. "The maintenance of an environment conducive to anaerobic metabolism--which may involve the maintenance of an adequate supply of the substances that permit anaerobiosis...seems to depend primarily upon the action of estrogen." "Glycolytic metabolism gradually increases throughout the proliferative phases of the cycle, reaching a maximum coincident with the ovulation phase, when estrogen is at a peak. Following this, glycolysis decreases, the respiratory mechanisms being more active during the secretory phase. Eschbach and Negelein showed the metabolism of the infantile mouse uterus to be less anaerobic than that of the adult. If estrogen is administered, however, there is a 98 per cent increase in glycolytic mechanisms.""The effect of the progestational steroids may be such as to interfere with the biochemical pattern required for support of this anaerobic environment." M. M. Tikhomirova, et al.
- A 1994 publication (B. Zumoff, “Hormonal profiles in women with breast cancer,” Obstet. Gynecol. Clin. North. Am. (U.S.) 21(4), 751-772) reported that there are four hormonal features in women with breast cancer: diminished androgen production, luteal inadequacy, increased 16-hydroxylation of estradiol, and increased prolactin. The 16-hydroxylation converts estradiol into estriol. -Ray Peat, PhD (via Rob Turner)
- Obstet Gynecol Clin North Am. 1994 Dec;21(4):751-72. Hormonal profiles in women with breast cancer. Zumoff B. "The literature findings on endogenous hormonal profiles in women with breast cancer are reviewed in detail. It is concluded that four sets of findings are valid: (1) diminished adrenal androgen production, probably genetic, in women with premenopausal breast cancer; (2) ovarian dysfunction (luteal inadequacy plus increased testosterone production) in breast cancer at all ages; (3) increased 16 alpha-hydroxylation of estradiol in breast cancer at all ages; and (4) evidence that prolactin is a permissive risk factor for breast cancer, and that the pregnancy-induced decrease in prolactin levels may account for the protective effect of early pregnancy against breast cancer." (via Rob Turner)
- J Natl Cancer Inst. 1986 Sep;77(3):613-6. Endogenous sex hormones, prolactin, and breast cancer in premenopausal women. Meyer F, Brown JB, Morrison AS, MacMahon B. "Forty-one women with breast cancer and 119 controls participated in a case-control study of the relation of endogenous sex hormones to breast carcinoma in premenopausal women. During the follicular phase of the menstrual cycle, one overnight urine specimen was collected. During the luteal phase, urine and blood specimens were obtained. 17 beta-Estradiol, sex hormone-binding globulin, progesterone, and prolactin were measured in plasma, whereas estrogen metabolites (estrone, estradiol, and estriol) and pregnanediol were assessed in the urine. Breast cancer was associated with high-plasma estradiol and prolactin and with low progesterone. Similar but weaker associations were observed for urinary estrogens and pregnanediol in the luteal phase." (via Rob Turner)
- "There are indications that the steroids exacerbate preexisting breast disorders, possibly by increasing prolactin levels. (Estrogens can impair B6 metabolism and therefore the synthesis of dopamine, a physiological suppressant of PRL [prolactin] secretion." - Constance R. Martin - Endocrine Physiology 1985
- "Estrogens augment PRL secretion in several ways. They lower the sensitivities of lactotrop DA receptors, and they affect DA turnover in the brain." - Constance R. Martin PhD - Endocrine Physiology 1985
- "Sustained high estrogen concentrations increase both insulin requirements and insulin secretion." - Constance R. Martin PhD - Endocrine Physiology
- "It is generally assumed that habitual abortion may be due to progesterone deficiency, hypothyroidism or vitamins-e deficiency and should be treated in theses cases with progesterone, thyroid extracts and vitamin-e respectively. In theory, thyroid therapy appears to be the least well-founded, especially when applied to women without manifest signs of hypothyroidism, yet among the measures mentioned above it is most frequently claimed to have been successful." - Hans Selye
- "In the case of chronic treatment with folliculouids, the proliferation of bone tissue may cause a severe reduction of the marrow spaces, conducive to anemia. This effect is particularly marked in birds, but also clearly demonstrable in mammals." - Hans Selye
- "Injection of folliculoids into fowl eggs during the period of incubation leads to the development of intersexual males, whose reactions may vary between perfect masculine behavior." - Hans Selye
- "Various types of stress may interfere with normal ovulation and menstruation (infectious diseases, alcoholism, dietary insufficiencies, emotional factors), and the same is true of endocrine disturbances, especially hypopituitarism, hypo- or hyperthyroidism, etc." - Hans Selye
- "Light, stress, (especially cold), dietary factors and versus stimuli are the most important non-endocrine factors which influence the production of anterior-lobe hormones [TSH, PRL, FSH, LH, GH, ACTH, etc.]." - Hans Selye
- "Folliculoids tend to increase the prolactin content of the pituitary even when given in doses sufficient to inhibit milk secretion." - Hans Selye
- "Lack of oxygen depresses sugar utilization and — as does any other alarming agent — stimulates the endogenous production of corticoids..." - Hans Selye
- "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
- "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
- Estrogen Dominance and Magnesium Deficiency - Rob Turner
- Fertil Steril. 1999 May;71(5):869-72. Serum ionized magnesium and calcium in women after menopause: inverse relation of estrogen with ionized magnesium. Muneyyirci-Delale O, Nacharaju VL, Dalloul M, Altura BM, Altura BT. OBJECTIVE: To study the serum concentrations of the sex steroid hormones and free divalent cations Mg2+ and Ca2+ in healthy women at or past menopause and to compare them with the serum concentrations of healthy, cycling women of child-bearing age at different stages of the menstrual cycle. DESIGN: Controlled clinical study. SETTING: An academic medical center. PATIENT(S): Women of varying age and duration of menopause, and healthy, cycling women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum levels of the sex steroids (estrogen, progesterone, and testosterone) and of Ca2+ and Mg2+ were measured in menopausal and postmenopausal women, and in healthy, cycling women at five different stages of the menstrual cycle. RESULT(S): The Mg2+ and total Mg levels of the postmenopausal women were inversely related to the serum level of estrogen and were similar to the levels present during the early follicular phase of healthy women of child-bearing age. The Ca2+ level was unrelated to the sex steroid hormones present, but it was increased compared with that of younger women in both the follicular phase and the luteal phase. CONCLUSION(S): Serum levels of Mg2+ and total Mg were inversely correlated with the estrogen concentration in menopausal women. Serum levels of Ca2+ were significantly elevated in menopausal women compared with younger women, but the ratio of Ca2+ to Mg2+, a measure of cardiovascular problems, was not elevated in the postmenopausal women.
- "The toxic effects of excessive intracellular calcium (decreased respiration and increased excitation) are opposed by magnesium. Both thyroid and progesterone improve magnesium retention. Estrogen dominance is often associated with magnesium deficiency, which can be an important factor in osteoporosis." -Ray Peat, PhD
- "Women's monthly cycles, in which a brief estrogen dominance is followed by sustained exposure to progesterone, are probably an important factor in the renewal of the cells of the brain and other organs, as well as those of the reproductive organs. The daily rhythms of hormones and metabolism are known to be involved in the regulation of cell renewal." - Ray Peat, PhD
- "Arachidonic acid stimulates prolactin secretion, and prolactin acts on the thyroid gland to decrease its activity, and on other tissues to increase their glycolysis (with lactate production), while decreasing oxidative metabolism (Spatling, et al., 1982; Strizhkov, 1991)." - Ray Peat
- "Eight bovine ovaries with a corpus luteum were perfused for 4 h in a haemoglobin-free semi-synthetic perfusion medium in a closed circuit. After an initial prolactin (PRL)-free perfusion phase, 4.7 ng/ml ovine PRL was added in the 1st h, followed by 47 ng/ml in the 2nd h and 470 ng/ml in the 3rd h. Glucose and oxygen consumption and the production of lactate, pyruvate and CO2 were measured, while perfusion pressure and pH-value were recorded continuously. Under the influence of PRL anaerobic glucose metabolism was stimulated by 40.5% and oxidative phosphorylation was inhibited. Energy production from aerobic glucose metabolism rose by only 0.25%. Unlike PRL, Human Menopausal Gonadotropin (hMG) and Human Chorionic Gonadotropin (hCG) stimulated aerobic metabolism. This may indicate that PRL is the "older" hormone in phylleogenetic terms." - Influence of prolactin on metabolism and energy production in perfused corpus luteum bearing bovine ovaries.
- "There are two kinds of enzyme that produce estrogen. Aromatase converts male hormones into estrogen. Beta-glucuronidase converts the inactive estrogen-glucuronides into active estrogen. The healthy liver inactivates practically all the estrogen that reaches it, mostly by combining it with the “sugar acid,” glucuronic acid. This makes the estrogen water soluble, and it is quickly eliminated in the urine. But when it passes through inflamed tissue, these tissues contain large amounts of beta-glucuronidase, which will remove the glucuronic acid, leaving the pure estrogen to accumulate in the tissue." - Ray Peat, PhD
- "Many kinds of liver impairment decrease its ability to excrete estrogen, and estrogen contributes to a variety of liver diseases. The work of the Biskinds in the 1940s showed that a dietary protein deficiency prevented the liver from detoxifying estrogen. Hypothyroidism prevents the liver from attaching glucuronic acid to estrogen, and so increases the body’s retention of estrogen, which in turn impairs the thyroid gland’s ability to secrete thyroid hormone. Hypothyroidism often results from nutritional protein deficiency." - Ray Peat, PhD
- "Although we commonly think of the ovaries as the main source of estrogen, the enzyme which makes it can be found in all parts of the body. Surprisingly, in rhesus monkeys, aromatase in the arms accounts for a very large part of estrogen production. Fat and the skin are major sources of estrogen, especially in older people. The activity of aromatase increases with aging, and under the influence of prolactin, cortisol, prostaglandin, and the pituitary hormones, FSH (follicle stimulating hormone) and growth hormone. It is inhibited by progesterone, thyroid, aspirin, and high altitude. Aromatase can produce estrogen in fat cells, fibroblasts, smooth muscle cells, breast and uterine tissue, pancreas, liver, brain, bone, skin, etc. Its action in breast cancer, endometriosis, uterine cancer, lupus, gynecomastia, and many other diseases is especially important. Aromatase in mammary tissue appears to increase estrogen receptors and cause breast neoplasia, independently of ovarian estrogen (Tekmal, et al., 1999). Women who have had their ovaries removed are usually told that they need to take estrogen, but animal experiments consistently show that removal of the gonads causes the tissue aromatases to increase. The loss of progesterone and ovarian androgens is probably responsible for this generalized increase in the formation of estrogen. In the brain, aromatase increases under the influence of estrogen treatment." - Ray Peat, PhD
- "Normal factors in the physiological control of the ovaries include an interaction between the thyroid and the gonadotrophins; the combination of hypothyroidism and stimulation by gonadotrophins can cause ovarian cysts to develop. Small amounts of estrogen can increase both FSH and LH, and large amounts of progesterone decrease both FSH and LH." - Ray Peat, PhD
- Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women. Hudson AG, Gierach GL, Modugno F, Simpson J, Wilson JW, Evans RW, Vogel VG, Weissfeld JL. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Laboratory and epidemiologic evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may be inversely related to the risk of breast cancer; however, the mechanism by which NSAIDs may protect against the development of this disease is uncertain. The objective of this observational study was to assess the relationship between current NSAID use and endogenous estradiol levels, an established breast cancer risk factor. To evaluate this aim, we conducted a cross-sectional investigation among 260 postmenopausal women who were not recently exposed to exogenous hormones. Information on current NSAID use (aspirin, cyclooxygenase-2 inhibitors, and other NSAIDs combined) was collected using a questionnaire at the time of blood draw. Estradiol was quantified in serum by radioimmunoassay. General linear models were used to evaluate the association between NSAID use and serum total estradiol. The age-adjusted and body mass index-adjusted geometric mean serum estradiol concentration among NSAID users (n = 124) was significantly lower than nonusers of NSAIDs (n = 136; 17.8 versus 21.3 pmol/L; P = 0.03). Further adjustment for additional potential confounding factors did not substantially alter estimates (17.7 versus 21.2 pmol/L; P = 0.03). To our knowledge, this report is the first to examine the relationship between NSAID use and serum estradiol in postmenopausal women. These cross-sectional findings suggest that NSAID use may be associated with lower circulating estradiol levels, potentially representing one mechanism through which NSAIDs exert protective effects on breast cancer.
- J Endocrinol. 1989 Jun;121(3):513-9. Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat. Rosental DG, Machiavelli GA, Cherñavsky AC, Speziale NS, Burdman JA. Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesterone-binding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2 alpha (PGF2 alpha), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat. (Thanks Rob Turner)
- "This change in perception of menopause can be linked, as it is in many other new “disorders” like erectile dysfunction and irritable bowel syndrome, to a marketing phenomenon by pharmaceutical companies called “if you build it, they will come.” Because pharmaceutical companies have a profound influence on the ways people define and understand diseases, the “if you build it mentality” is often successful in creating a new disease class. After all, pharmaceutical companies have tremendous resources to invent drugs where none existed before, design clinical research to position those drugs in the marketplace, fund patient and professional groups who speak through the popular media, and vigorously promote awareness of their medicines and the ailments they are designed to treat." - Carla Rothenberg - The Rise and Fall of Estrogen Therapy: The History of HRT (PDF)
- Acta Endocrinol (Copenh) 1984 Feb;105(2):167-72 Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation. Nicoletti I, Filipponi P, Fedeli L, Ambrosi F, Gregorini G, Santeusanio F. A case of a patient with hypopituitarism due to a disturbance of hypothalamo-pituitary regulation is presented, who developed high-grade hyperprolactinaemia after the initiation of substitutive therapy with testosterone esthers.The increase in serum Prl was strictly related to testosterone aromatization to oestradiol, since anti-oestrogen compounds were effective in reducing (clomiphene) or abolishing (tamoxifen) the enhanced Prl secretion. The oestrogen effect in raising Prl release was not attributable to a reduction in the dopamine inhibition of Prl-secreting cells, as the dopamine-antagonist domperidone failed to increase Prl serum levels in the same patient. This suggests that, in man, the oestrogen effect in enhancing Prl release is mainly enacted directly on the pituitary lactotrophs rather than exerted through a reduction in the hypothalamic dopamine activity
