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Details Title: Polycystic Ovarian Syndrome Description: 4.27.07 Total Flash Cards: 43 Created: 04/30/2007 15:31:46	To study from this set of flash cards, or to create your own your own study flash cards, register HERE. If you are already a registered user, CLICK HERE.
Cards Term What is Polycystic Ovarian Syndrome? Definition Syndrome : ovary makes too much androgen (testosterone) Linked to insulin resistance Affects 6% reproductive age women Term What are the related medical issues? Definition Most common cause anovulation, hirsutism ↑ risk for other medical issues: Diabetes, hyperlipidemia, cardiovascular disease , frontal pattern balding Term Are the ovaries too big or too small? Definition too big Term what happens in PCOS? Definition ovaries are replaced by multiple cysts. This is a horomonal condition Term Why does PCOS develop? Definition PCOS develops when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, either through the release of excessive luteinizing hormone (LH) by the anterior pituitary gland or through high levels of insulin in the blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus. This syndrome acquired its most widely used name because a common sign is multiple (poly) ovarian cysts. These form where egg follicles matured but were never released from the ovary because of abnormal hormone levels. These generally take on a 'string of pearls' appearance. Term what does insulin resistance have to do with it? Definition A majority of patients with PCOS - some investigators say all - have insulin resistance. Their elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to PCOS. Specifically, hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all these steps lead to the development of PCOS. Insulin resistance is a common finding among both normal weight and overweight PCOS patients. Term what is the stein-leventhal syndrome? Definition oligomenorrhea (irregular menstrual cycles) hirsutism obesity Term what are current PCOS diagnostic criteria? Definition 2 out of 3 required for diagnosis: 1. Oligo- or anovulation 2. Clinical and/or biochemical signs of hyperandrogenism 3. Polycystic ovaries on US, with exclusion of other etiologies Term is it genetic? Definition First degree relatives of pt with PCOS 19 / 78 mothers (24 %) affected 16 / 50 sisters (32 %) affected Incidence in general population 4% Suggests major genetic association Term what phenotypes do you find in genetic studies? Definition Phenotypes: Oligomenorrhea Polycystic ovarian morphology on U/S Hirsutism Enlarged ovaries Premature balding Insulin resistance Hyperandrogenism Term How is it genetically transmitted? Definition Autosomal dominant mode transmission Term what have we found candidate genes for? Definition Insulin secretion and action Gonadotropin secretion and action Androgen biosynthesis, secretion, transport, metabolism Term what is the pathophysiology? Definition Increased LH pulse amplitude + frequency, which will lead to ↑ androgens from theca cell. This is called hyperandrogenic. Also, Insulin resistance Alteration in post receptor signaling Term What is insulin resistance? Definition Decreased ability of insulin to act on peripheral tissues to stimulate glucose metabolism or inhibit hepatic glucose output Consequent hyperinsulinemia Term How is PCOS related to insulin resistance? Definition Insulin resistance causative feature of PCOS Not all women with PCOS manifest insulin resistance Term What is the effect of insulin sensitivity independent o fobesity? Definition Women with PCOS have insulin sensitivity independent of obesity. Term How are insulin and PCOS connected? Definition Insulin directly stimulates androgen production from ovarian stroma. Could PCOS and Insulin Resistance result from a single defect? Term how are PCOS and hyperinsulinemia related? Definition Selective insulin resistance Affected: (Glucose transport, Metabolic pathways) Preserved Ovarian steroidogenesis Term How does insulin increase androgen production? Definition via P450c17 (alpha) Term what happens with insulin resistance with ovarian sensitivity to insulin? Definition Action mediated by inositolglycan mediators Binds IGF-I receptor Up-regulates IGF-I receptor number  IGFBP-I and leads to  IGF-I Activates own receptor on ovary, adrenal, and pituitary  SHBG Term To be more specific.... Definition increased insulin affects the pituitary to stimulate increased LH , which affect both the ovary and the adrenal, to produce more androgens Term How do you diagnose PCOS? Definition Oligomenorrhea / anovulation Establish ovarian hyperandrogenism Clinical Biochemical Term What must you exclude? Definition Exclude CAH Cushings Syndrome Thyroid disease Hyperprolactinemia Tumor: ovarian, adrenal Ovarian failure Term where is xs hair growth in hirutism? Definition in the midline Term What is acne a sign of? Definition Sign of hyperandrogenemia in absence of hirsutism May be more sensitive sign in adolescent In pts 12-18 years of age with acne and no hirsutism: 88 % had at least one elevated androgen level Term what is acanthosis nigricans? Definition Raised, velvety, hyperpigmentation of skin Axilla, neck, intertrigenous areas Marker of insulin resistance Associated with PCOS Term What horomones should you evaluate? Definition TSH Prolactin FSH, E2 17 OH progesterone Total testosterone Free testosterone Term what are the characteristics of PCOS in adolscents? Definition Similar profile to that seen in adults Earlier maturation of GnRH axis – exaggerated response to puberty Persistent oligomenorrhea associated with hyperandrogenism Polycystic ovaries Insulin resistance Term What are health consequences of PCOS? Definition Diabetes; Obesity ; Heart disease ; Dyslipidemia; Hypertension; Endometrial hyperplasia; Infertility Term ↑ Risk metabolic syndrome with PCOS independent of obesity Definition Cardiovascular disease risk factors associated with: Insulin resistance Glucose intolerance Dyslipidemia Hypertension Central obesity Term CVD Definition Increased risk factors identified: Obesity, dyslipidemia, IR/DM, ↑ androgens ↑ Carotid intima-media thickness ↑ PAI-1 Increase in CV events not observed Term What are 3 mechanisms for becoming infertile? Definition Anovulation Hyperandrogenism ? Other factors ? Term tx approaches for PCOS? Definition Modalities / medications that target specific symptoms Obesity Hirsutism, acne Irregular menstrual cycles Anovulation Insulin sensitizing agents Term symptoms directed tx? Definition Obesity Diet / exercise Hirsutism Mechanical OCP Anti-androgens Menstrual irregularity Cyclic progestin OCP Anovulation / Infertility Ovarian drilling Clomiphene citrate Term How would combined oral contraceptives be helpful? Definition Effectively controls symptoms of PCOS--it helps to decrease androgens and increase SHGB Regulates menstruation Prevents endometrial hyperplasia Controls hirsutism Effect on insulin resistance Term what are 3 antiandrogens? Definition Spironolactone 100 – 200 mg/d Competitive binding at receptor Inhibitory effect on 5α-reductase  Testosterone production Flutamide 250 – 500 mg/d Androgen receptor blocker – inhibit DHT binding  adrenal 17,20 lyase activity   androgens Finasteride 5 mg/d 5-reductase inhibitor Term do antiandrogens help hirutism? Definition yes Term How does Clomiphene citrate work? Definition Anti-estrogen primarily Competes for binding sites to estrogen receptors Depletes estrogen receptors “Perceived” hypo-estrogenic state ↑ GnRH; ↑ FSH, LH Term name insulin sensitizing drugs? Definition Biguanides metformin (Glucophage) Thiazolidinedione troglitazone (Rezulin) * rosiglitazone (Avandia) pioglitazone (Actos) Term What does Metformin do? Definition Increases peripheral glucose uptake Inhibits hepatic glucose production Improves insulin sensitivity in muscle Not cause hyperinsulinemia (hypoglycemia) Approved for treatment DM Term what are metformin's tox? Definition Toxicity: GI side effects lactic acidosis dehydration renal compromise Creat >1.4 IV contrast contraindicated Monitoring prior to start & annually Renal and hepatic function Term what are metformin's proposed benefits? Definition Short term Ovulation Long term Ovulation Hirsutism Diabetes Heart disease Term what does metformin do? Definition ↓ Weight / BMI But only in combination with calorie restricted diet Variable ↓ Insulin Fasting, insulin AUC ↓ Androgen measurement Free testosterone, FAI ↑ Menstrual cyclicity, ovulation