New Technologies in Reproductive Medicine, Neonatology and Gynecology : The
Proceedings of the 1st International Symposium, Folgaria, Italy by Ermelando V.
Cosmi (1999) PORTO CONTE ITALY SEPTEMBER 18-23
Polycystic ovary syndrome: metabolic challenges and new
The objective is to test the hypothesis that Polycystic Ovary Syndrome (PCOS) my be the final expression of a variety of metabolic and neuroendocrine perturbations caused by a chronic bowel inflammatory state.
Polycystic ovary syndrome is recognized as a heterogeneous syndrome, often with symptoms and signs of elevated androgen levels, menstrual irregularity, and amenorrhea in women without a well-defined underlying cause of androgen excess. In addition, hyperinsulinemia has been shown to be an important component of this syndrome, there are links between polycystic ovary syndrome and endometrial cancer, obesity, cardiovascular disease, and diabetes mellitus1.
It is clear that PCOS is a multifaceted clinical entity with both short-and long-term consequences. Long-term consequences are especially important because the problems that stem from android obesity and hyperinsulinemic conditions commence during the reproductive years and persist into the postmenopausal years. Polycystic ovary syndrome is evaluated and treated by many specialties because of its broad spectrum of clinical findings, the varied ages at which symptoms or signs of PCOS become obvious, and the metabolic disturbances that occur. The fundamental pathophysiologic defect of polycystic ovary syndrome remains unknown and is a source of controversy and ongoing study. As a gynecologist and ecography specialist, I usually perform an ecographical investigation of the main organs of all patients to gain more complete data on their state of health. These ecographies particularly focus on the abdomen, breast, and also the thyroid. In the cases of patients with PCOS, a dishomogeneous thyroid ecostructure. and colitis, a condition indicated in ecographies by intense meteorism, I find to be a common factors. The thyroid ecostructure of this patients appeared dishomogeneous in varying degrees as a result of an iodine deficiency due to unsatisfactory intestinal absorption, as a consequences and confirmation of the intestine’s chronically inflammatory state. PCOS may be the final common expression of a variety of metabolic and neuroendocrine perturbations caused by a chronic bowel inflammatory state Genetic factors determine how these are expressed.. A balanced and functional intestinal bacterial flora may easily be disturbed by various factors: infections, the wrong foods, intolerance’s to foods developed in early childhood. I excluded causes of colitis caused by parasites and occasional intestinal infections, and concentrated on colitis due to Adverse Alimentary Reaction (AAR)2.Colitis due to alimentary intolerance and/or allergy may consist of:
1) reactions of hypersensitivity with the release of chemical agents that may cause extremely variable symptomatological conditions. Various organs and apparatuses may be affected.
2) Unsatisfactory absorption by the intestine of substances or elements, the deficiency of which may contribute to imbalances and pathologies in the organs or apparatuses concerned.
A functional bacterial flora is physiologically important to a healthy organism. An intestinal disbiosis causes diarrhea, constipation and/or meteorism, and the alteration of the intestinal immune system which is the greatest defense system of an organism. Also an intestinal disbiosis may cause lesions and infections to organs and apparatuses: most likely The menstrual irregularity , although amenorrhea characteristic of anovulation is a result of an inflamed ovary trouble. Because progesterone is produced by the ovary only after ovulation, women with PCOS often have chronic estrogen exposure unopposed by progesterone. Women who have had long-standing chronic anovulation without periodic progestin exposure thus may have endometrial hyperplasia or endometrial and breast cancer.The change in the patient’s hormonal condition seems to be linked to the presence of intestinal disturbances, perhaps aggravated by a stress-provoking situation. The ovary hyperstimulated can produce, in genetic predisposed individuals, androgen excess The androgen excess of PCOS is usually manifested by varying degrees of irsutism and /or acne, such symptoms and androgen concentrations increased with the increase of the intestinal disturbances. Women with polycystic ovary syndrome are at increased risk for cardiovascular disease3. I suggest that: in the presence of a bowel chronic inflammatory state, possibly non-symptomatic, even the processes of assimilation may be jeopardized, specifically an important substance such as iodine may not be absorbed at all, or in insufficient quantities. This iodine deficiency may cause thyroid trouble and a thyroid’s characteristic dishomogeneous ecographic aspect. The thyroid function change daily related to the presence of intestinal disturbances and the degree of her dysfunction vary directly with the severity of colitis. The thyroid’s function is:
1- to regulate the lipid metabolism,
2- to prevent infections of the upper respiratory tracts.
For this reason the iodine relative deficiency related to the colitis, can cause a slow lipid metabolism and a tendency to more easily contract infections of the upper respiratory tracts and consequently rheumatic illnesses (injury heart, kidney, joints) and high prevalence of homeostatic abnormalities, than associated with alteration of lipid metabolism running to increased risk for cardiovascular disease.
From the first description of Stein-Leventhal syndrome, clinician have recognized that at least half of their patients with PCOS are obese4.Weight loss is difficult without diet which exclude foods responsible for colitis due to alimentary intolerance or allergy, which raises the possibility to have a slow metabolism.because iodine’s deficient assimilation.
Several investigators have focused on the relationship and mechanisms of insulin resistance in patients with PCOS5,6 . Most likely the chronic inflammatory state of the gastric mucous membrane caused by alimentary intolerance, can involve the pancreas and impair his function.
Women with PCOS have greater rates of gestational diabetes, impaired glucose tolerance, and frank diabetes than do age-matched control subjects6.
Women with PCOS do tend to have elevated blood pressure7. The hypothesis, still to be verified, that might explain this correlation is that foods when consumed represent a potential source of antigens . In genetically predisposed individuals recognition of alimentary antigens may cause the synthesis of specific IgE, with the resulting release of masticatory agents (histamine,tryptase,serotonin) responsible for its symptomatology. The type of immune reaction that ensues (of mediated IgE reaction or not) determines its type of expression. This is why in some cases there may only be contractions of the smooth muscles (artery,uterus,bronchial tubes), while in other cases the histamine increasing the capillary permeability may cause edema and consequently can contribute to develop higher blood pressure.
MATERIAL AND METHODS
I studied 112 women of reproductive age attending my specialized office, during the period from 1989 to 1999, with a history and signs of clinical PCOS and with ultrasonographically defined morphologic characteristics. I compared with 20 women with no history or evidences of PCOS as age-matched control subjects. Criteria for patients with PCOS, included irregularity or absence of menses, a history of oligomenorrhea or amenorrhea beginning at or near the onset of menstrual function, acne or hirsutism, no patient had virilization. As expected, patients with PCOS had significantly higher luteinizing hormone-to-follicle-stimulating hormone ratios, higher testosterone levels, higher free testosterone levels, higher dehydroepiandrosterone sulfate levels, and lower testosterone-estradiol-binding globulin binding capacity than the control group. Patients with PCOS were found to have colitis due to alimentary intolerance or allergy. A through anamnesis of this patients revealed that they had suffered from gastroenteritis since childhood, that they soon had more frequent appendicectomies or, according to the treating doctor, suffered from “irritable colon”8. Compared with the control group, more frequently the pelvic ecographies of patients with PCOS presented a common characteristic: the difficulty in performing the examination due to the intense intestinal meteorism. The thyroid ecostructure of this patients appeared dishomogeneous in varying degrees. The dishomogeneous thyroid ecostructure (DTE) ranged from a varying hypo-ecogenic aspect to a hyper-ecogenic aspect. Thyroid function is apparently normal if is analyzed the level of TSH, however 82% of this cases have a temporary or transient form of the hormonal disorder because thyroid function change daily related to the presence of intestinal disturbances. From this hypothesis it follows that patients with DTE can be considered to be affected by an Adverse Alimentary Reaction and that this reaction is caused by consuming foods to which they have an intolerance, and the frequency of this consumption. The iodine relative deficiency can cause a slow lipid metabolism and a tendency to more easily contract infections of the upper respiratory tracts.
Women with PCOS have consequently a surprisingly high prevalence of several significant metabolic abnormalities that may affect their long-term health. In my study patients with PCOS more frequently shown to have :
1- alteration of lipid metabolism with hyper-cholesterol and gall stones, grater risk running in the family of infarctus and arteriosclerosis disease; glucose intolerance and diabetes, cardiovascular diseases, obesity,
2- a tendency to more easily contract infections of the upper respiratory tracts: higher frequency of tonsillectomies and rheumatic illnesses and high prevalence of hemostatic abnormalities,
3- illnesses of the immune system including allergies,
4- increased risk for pregnancy-induced hypertension and for developing pregnancy pathologies9.
5- Bacterial vaginosis and genital tract infections10 .
The method of investigation and treatment of the patients with PCOS, in the control phase, is derived from the application of the hypothesis of possible intolerance and/or allergy to certain foods. The most logical possible solution is to identify the foods or allergic substances responsible for patients’colitis and have them follow a special diet. There are certain special aspects presented by the diagnosis of alimentary intolerance or allergy which are connected, on the one hand, with the considerable frequency of extra-immunological pathogenetic adverse food reactions and, on the other, with the unsatisfactoriny characterization of alimentary allergens used for diagnostic tests2. In some cases, from a well conducted anamnesis very indicative suspect elements may be obtained whereas cutaneous tests and serological tests for locating specific IgE often reduce specificity and sensitivity. For this reason, resorting to diets of elimination is often necessary. Preliminary diet is recommended based upon the fact that the patients should observe, especially after consuming certain foods if she shows signs of intolerance such as heartburn, a feeling of fatigue after eating, slow digestion, abdominal swelling or pain, and symptoms of dyspepsia8.In many cases the patients had drawn a connection between their intestinal disturbances and certain foods consumed, and had noticed that the same foods did not always causes the same reaction in relation whit the frequency of this consumption.This foods are identify the most responsible for alimentary intolerance or allergy: milk and cereals, fruits or vegetables like yeast, tomatoes, etc. The cereals represent the most responsible for the future appearance of PCOS condition.
RESULTS AND CONCLUSION
All of the 112 patients with PCOS, who strictly adhered to the diet had disappearance or significant reduction of symptoms reported and disappearance of clinical and diagnostic evidence of pathophysiologics defects of PCOS. When patients who were following a diet saw symptoms disappear, especially after the thirtieth week, and they began eating foods again to which they were intolerant (no longer worried about any further consequences), they often developed immediate complications and complained vaginals discharges, abdominal pain, including mestrual irregularities, hirsutisms, acne, weight gain. Many studies in patients with PCOS have shown that weight loss can improve the fundamental aspects of the endocrine syndrome of PCOS and result in lower circulating androgen levels and spontaneous resumption of menses11.Another benefit that as been reported is decreased level of circulating insulin Colitis due to alimentary intolerance or allergy is an intestinal inflammatory state, possibly non-symptomatic, that can lead to a chronic ovary disturbance and consequently PCOS. Genetic factors determine how these are expressed.
Controlled studies need to be conducted to determine whiter diet alone is sufficient to prevent such phenomena or if complementary pharmaceutical therapy is necessary to increase tolerance to foods . Perhaps everyone should consume only tolerated foods right from birth, since an alimentary intolerance might be the origin of a true pathology of the immune system and of all, or almost all, acquired pathologies and hormonal dysfunction
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