Also see:
Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India
Childhood conditions influence adult progesterone levels
W.D. Denckla, A.V. Everitt, Hypophysectomy, & Aging
Removal of the Pituitary: Slows Aging and Hardening of Collagen
Quotes by Ray Peat, PhD:
“Besides providing new insights into biological energy and aging, the recognition that estrogen activates the stress hormone system–the pituitary-adrenal system–also provides clear insights into other problems, such as the polycystic ovary syndrome, hirsutism, adrenal hyperplasia, Cushing’s disease, etc.”
“If your thyroid is working efficiently, your pituitary doesn’t have much to do and you’re not likely to get a pituitary tumor, your adrenals don’t have much to do, and your ovaries don’t get over stimulated. The other glands have an easy job when your thyroid is working right. If your thyroid gets interfered with, you have to rev up your adrenals and your pituitary becomes commander in chief and tells everyone what to do.”
“PCOS can be produced in animals by removing the thyroid gland. The inability of ovaries to make progesterone without thyroid causes the adrenals to be overstimulated, and they are the source of increased DHEA and other androgens and estrogen.”
“Many factors, including poor nutrition, climate, emotional or physical stress (even excessive running) and toxins, can cause a progesterone deficiency. Use of estrogens, birth control pills and even IUDs can also bring about a deficiency. Animal studies and clinical experience suggests that the prenatal hormonal environment (a mother’s excess of estrogen during pregnancy) can incline a person toward a deficiency of progesterone relative to estrogen.”
“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.”
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.
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.
Endocrinology. 1993 Dec;133(6):2696-703.
Ovarian steroidal response to gonadotropins and beta-adrenergic stimulation is enhanced in polycystic ovary syndrome: role of sympathetic innervation.
Barria A, Leyton V, Ojeda SR, Lara HE.
Experimental induction of a polycystic ovarian syndrome (PCOS) in rodents by the administration of a single dose of estradiol valerate (EV) results in activation of the peripheral sympathetic neurons that innervate the ovary. This activation is evidenced by an increased capacity of ovarian nerve terminals to incorporate and release norepinephrine (NE), an increase in ovarian NE content, and a decrease in ovarian beta-adrenergic receptor number in the ovarian compartments receiving catecholaminergic innervation. The present experiments were undertaken to examine the functional consequences of this enhanced sympathetic outflow to the ovary. The steroidal responses of the gland to beta-adrenergic receptor stimulation and hCG were examined in vitro 60 days after EV administration, i.e. at the time when follicular cysts are well established. EV-treated rats exhibited a remarkable increase in ovarian progesterone and androgen responses to isoproterenol, a beta-adrenergic receptor agonist, with no changes in estradiol responsiveness. Basal estradiol release was, however, 50-fold higher than the highest levels released from normal ovaries at any phase of the estrous cycle. The ovarian progesterone and androgen responses to hCG were enhanced in EV-treated rats, as were the responses to a combination of isoproterenol and hCG. Transection of the superior ovarian nerve (SON), which carries most of the catecholaminergic fibers innervating endocrine ovarian cells, dramatically reduced the exaggerated responses of all three steroids to both beta-adrenergic and gonadotropin stimulation. SON transection also reduced the elevated levels of ovarian NE resulting from EV treatment and caused up-regulation of beta-adrenoreceptors. Most importantly, SON transection restored estrous cyclicity and ovulatory capacity. The results indicate that the increased output of ovarian steroids in PCOS is at least in part due to an enhanced responsiveness of the gland to both catecholaminergic and gonadotropin stimulation. The ability of SON transection to restore a normal response indicates that the alteration in steroid output results from a deranged activation of selective components of the noradrenergic innervation to the ovary. These findings support the concept that an alteration in the neurogenic control of the ovary contributes to the etiology of PCOS.
Br J Obstet Gynaecol. 1976 Aug;83(8):593-602.
Polycystic ovarian disease.
Duignan NM.
Sex hormone binding globulin (SHBG) capacity was reduced in 9 of 31 patients with polycystic ovarian (PCO) disease and the mean level in PCO patients was significantly less (p less than 0.001) than normal. Serum testosterone levels were elevated in 21 of 32 PCO patients and the mean level was significantly elevated (p less than 0.001). Serum androstenedione values were raised in 17 of 31 patients and the mean value was also significantly raised (p less than 0.001). Serum dehydroepiandrosterone sulphate (DHAS) concentrations were elevated in only 2 of 14 patients. Urinary 17-oxo and 17-oxogenic steroids were normal in all patients studied. Basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were normal but LH release following injection of luteinizing hormone-releasing hormone (LH-RH) was enhanced. A highly significant negative correlation (r=–0.449; p less than 0.01) was found between the logarithm of testosterone and the logarithm of LH levels. Serum prolactin concentrations were elevated in 4 of 21 PCO patients. Thyroid-stimulating hormone (TSH) values were normal. Eighteen of 20 patients ovulated following treatment with clomiphene and nine became pregnant. Five of 12 of patients treated with oestrogen/progesterone preparations noticed an improvement in their hirsutism. It is suggested that the normal cyclical release of LH is inhibited in PCO disease by a negative feedback by androgens to the hypothalamus or the pituitary, and that wedge resection should be reserved for patients in whom other forms of treatment have failed.
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.
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.
The Journal of Clinical Endocrinology & Metabolism September 1, 1996 vol. 81 no. 9 3299-3306
The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.
A Dunaif, D Scott, D Finegood, B Quintana and R Whitcomb
We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n = 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose load insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone-binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose load (r2 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydro-epiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses. We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin-sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.
