Polycystic Ovarian Syndrome Sonia Ralli, M.D. January 18, 2007
Case <ul><li>A 40 yo female presents to you in clinic for a “physical exam”. </li></ul><ul><li>-PMH significant for HTN, o...
Case (cont’d) <ul><li>-PE significant for being mildly overweight (BMI~27), BP 140/80, HR 70. </li></ul><ul><li>-random ac...
History <ul><li>Originally described by Stein and Leventhal in 1935, first known as the “ Stein-Leventhal syndrome ” </li>...
What is PCOS? <ul><li>Disorder characterized by  2  of the following: </li></ul><ul><ul><li>Hyperandrogenism </li></ul></u...
Why is PCOS important? <ul><li>Affects 4-12% of women of reproductive age </li></ul><ul><li>Significant association betwee...
Pathogenesis <ul><li>1.  Hyperandrogenism </li></ul><ul><li>2 .  Insulin resistance </li></ul>
Ehrmann  NEJM  2005
Pathogenesis: Hyperandrogenism <ul><li>Symptoms of androgen excess </li></ul><ul><li>Reduced sex-hormone-binding globulin ...
Pathogenesis: Insulin resistance <ul><li>Favors anovulation, androgen excess, reduced SHBG </li></ul><ul><li>Metabolic syn...
Insulin resistance in PCOS:  it’s not just a theory <ul><li>Insulin resistance in PCOS is  independent  of obesity </li></...
 
Diagnosis <ul><li>Disorder characterized by  2  of the following: </li></ul><ul><ul><li>Hyperandrogenism </li></ul></ul><u...
Diagnosis <ul><li>Hyperandrogenism </li></ul><ul><ul><li>Clinical features </li></ul></ul><ul><ul><ul><ul><li>Hirsutism (g...
 
Not hirsutism!
Hirsutism
Diagnosis <ul><li>Hyperandrogenism (cont’d) </li></ul><ul><ul><li>Laboratory features </li></ul></ul><ul><ul><ul><li>Eleva...
Diagnosis <ul><li>2.  Oligoovulation or anovulation </li></ul><ul><ul><ul><li>Oligomenorrhea or amenorrhea </li></ul></ul>...
Diagnosis <ul><li>Polycystic Ovaries </li></ul><ul><ul><ul><li>Criteria by ultrasound </li></ul></ul></ul><ul><ul><ul><ul>...
Polycystic ovaries, by ultrasound
Diagnosis <ul><li>4. Absence of other disorders to account for these symptoms. </li></ul><ul><ul><li>Pregnancy    pregnan...
Diagnosis <ul><li>5. Supportive of insulin resistance </li></ul><ul><ul><li>“ Syndrome XX”:  3 or more of the following cr...
Management <ul><ul><li>Immediate/Acute issues </li></ul></ul><ul><ul><ul><ul><li>Hirsutism </li></ul></ul></ul></ul><ul><u...
Management: Immediate/Acute Issues <ul><ul><li>Control of hirsutism </li></ul></ul><ul><ul><ul><li>Medical (need a trial o...
Management: Immediate/Acute Issues <ul><ul><li>Control of hirsutism  (cont’d) </li></ul></ul><ul><ul><ul><li>Decrease test...
Management: Immediate/Acute Issues <ul><ul><li>Control of hirsutism  (cont’d) </li></ul></ul><ul><ul><ul><li>Mechanical </...
Management: Immediate/Acute Issues <ul><li>Regulation of menses </li></ul><ul><ul><ul><li>Oral contraceptives </li></ul></...
Management: Immediate/Acute Issues <ul><li>Fertility issues </li></ul><ul><ul><li>Lifestyle modification/weight loss </li>...
Management: Immediate/Acute Issues <ul><li>Fertility issues  (cont’d) </li></ul><ul><ul><li>Metformin </li></ul></ul><ul><...
Management: Long-Term Issues <ul><li>Insulin resistance </li></ul><ul><ul><ul><li>Lifestyle modification/weight loss </li>...
Management: Long-Term Issues <ul><li>Insulin resistance </li></ul><ul><ul><li>Metformin </li></ul></ul><ul><ul><ul><li>Fun...
Management: Long-Term Issues <ul><li>Insulin resistance </li></ul><ul><ul><li>Thiazolidinediones </li></ul></ul><ul><ul><u...
Management: Long-Term Issues <ul><li>Cardiovascular Risk </li></ul><ul><ul><li>Increased prevalence of HTN </li></ul></ul>...
Management: Long-Term Issues <ul><li>Obstructive Sleep Apnea </li></ul><ul><ul><li>30-fold increased risk of OSA, not expl...
Management: Long-Term Issues <ul><li>Risk for malignancy </li></ul><ul><ul><li>3X increased risk endometrial carcinoma in ...
 
Other issues Role of epilepsy? <ul><ul><li>Increased incidence of reproductive disorders in patients with epilepsy </li></...
New things on the horizon… <ul><li>Somatostatin analogs </li></ul><ul><ul><li>Function </li></ul></ul><ul><ul><ul><li>Blun...
References <ul><li>American College of Obstetricians and Gynecologists (ACOG) practice bulletin.  Polycystic ovary syndrom...
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  • Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

    1. 1. Polycystic Ovarian Syndrome Sonia Ralli, M.D. January 18, 2007
    2. 2. Case <ul><li>A 40 yo female presents to you in clinic for a “physical exam”. </li></ul><ul><li>-PMH significant for HTN, on no meds </li></ul><ul><li>-had one child at age 30, required clomiphene induction </li></ul><ul><li>-on further asking, has had to wax her upper lip and chin for many years for “stubborn hair” </li></ul>
    3. 3. Case (cont’d) <ul><li>-PE significant for being mildly overweight (BMI~27), BP 140/80, HR 70. </li></ul><ul><li>-random accucheck in office: 150 </li></ul><ul><li>Management options? </li></ul><ul><li>Screening options? </li></ul>
    4. 4. History <ul><li>Originally described by Stein and Leventhal in 1935, first known as the “ Stein-Leventhal syndrome ” </li></ul><ul><li>7 women with amenorrhea, hirsutism, and obesity, found to have a polycystic appearance to their ovaries. </li></ul>
    5. 5. What is PCOS? <ul><li>Disorder characterized by 2 of the following: </li></ul><ul><ul><li>Hyperandrogenism </li></ul></ul><ul><ul><li>Oligoovulation or chronic anovulation </li></ul></ul><ul><ul><li>Polycystic ovaries </li></ul></ul><ul><ul><li>In the absence of pituitary or adrenal disease </li></ul></ul><ul><li>It is a syndrome, ie., no single test can establish the diagnosis. </li></ul>
    6. 6. Why is PCOS important? <ul><li>Affects 4-12% of women of reproductive age </li></ul><ul><li>Significant association between obesity, insulin resistance, and PCOS. </li></ul><ul><li>Huge impact on the reproductive, metabolic, and cardiovascular health of affected women. </li></ul>
    7. 7. Pathogenesis <ul><li>1. Hyperandrogenism </li></ul><ul><li>2 . Insulin resistance </li></ul>
    8. 8. Ehrmann NEJM 2005
    9. 9. Pathogenesis: Hyperandrogenism <ul><li>Symptoms of androgen excess </li></ul><ul><li>Reduced sex-hormone-binding globulin (SHBG)  more free testosterone </li></ul><ul><li>Insulin insensitivity </li></ul><ul><li>Lipid abnormalities </li></ul><ul><li>Abdominal obesity </li></ul>
    10. 10. Pathogenesis: Insulin resistance <ul><li>Favors anovulation, androgen excess, reduced SHBG </li></ul><ul><li>Metabolic syndrome </li></ul><ul><li>Abdominal obesity </li></ul>
    11. 11. Insulin resistance in PCOS: it’s not just a theory <ul><li>Insulin resistance in PCOS is independent of obesity </li></ul><ul><ul><li>Obese women with PCOS tend to be more insulin resistant than nml-wt counterparts. </li></ul></ul><ul><ul><li>Obesity is an independent risk factor for glucose intolerance or DM in PCOS </li></ul></ul><ul><li>3-fold increased incidence of metabolic syndrome in PCOS, vs general population, independent of obesity. </li></ul><ul><li>Insulin resistance ≠ glucose intolerance </li></ul><ul><ul><li>Many insulin resistant PCOS pts have normal glucose tolerance </li></ul></ul><ul><ul><li>30-40% prevalence of glucose intolerance in PCOS women </li></ul></ul><ul><ul><li>7-10% prevalence of type 2 DM in PCOS women </li></ul></ul><ul><ul><li>Insulin resistance worsens over time </li></ul></ul><ul><ul><li>Increased risk for impaired glucose tolerance and type 2 DM </li></ul></ul>
    12. 13. Diagnosis <ul><li>Disorder characterized by 2 of the following: </li></ul><ul><ul><li>Hyperandrogenism </li></ul></ul><ul><ul><li>Oligoovulation or chronic anovulation </li></ul></ul><ul><ul><li>Polycystic ovaries </li></ul></ul><ul><li>And the absence of pituitary or adrenal disease </li></ul>
    13. 14. Diagnosis <ul><li>Hyperandrogenism </li></ul><ul><ul><li>Clinical features </li></ul></ul><ul><ul><ul><ul><li>Hirsutism (growth of coarse hair on a woman in a male pattern– upper lip, chin, chest, upper abdomen, back, etc) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Acne </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Male pattern alopecia </li></ul></ul></ul></ul><ul><ul><ul><ul><li>NOT virilization (clitoromegaly, deep voice, increased musculature, rapidly progressive hirsutism) </li></ul></ul></ul></ul>
    14. 16. Not hirsutism!
    15. 17. Hirsutism
    16. 18. Diagnosis <ul><li>Hyperandrogenism (cont’d) </li></ul><ul><ul><li>Laboratory features </li></ul></ul><ul><ul><ul><li>Elevated total testosterone </li></ul></ul></ul><ul><ul><ul><ul><li>Most values in PCOS <150 ng/dl (if >200 ng/dl, consider ovarian or adrenal tumor) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Free testosterone assays not reliable yet </li></ul></ul></ul></ul><ul><ul><ul><li>DHEA-S </li></ul></ul></ul><ul><ul><ul><ul><li>Most normal or slightly high in PCOS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>If >800 mcg/dl, consider adrenal tumor </li></ul></ul></ul></ul><ul><ul><ul><li>LH/FSH ratio </li></ul></ul></ul><ul><ul><ul><ul><li>Levels vary over menstrual cycle, released in pulsatile fashion, affected by OCPs </li></ul></ul></ul></ul><ul><ul><ul><ul><li>LH/FSH ratio >2 has little diagnostic sensitivity and need not be documented </li></ul></ul></ul></ul>
    17. 19. Diagnosis <ul><li>2. Oligoovulation or anovulation </li></ul><ul><ul><ul><li>Oligomenorrhea or amenorrhea </li></ul></ul></ul><ul><ul><ul><li>Dysfunctional uterine bleeding </li></ul></ul></ul><ul><ul><ul><li>Infertility </li></ul></ul></ul><ul><ul><ul><ul><li>30-50% 1 st trimester miscarriage rate </li></ul></ul></ul></ul><ul><ul><ul><li>3-fold increased risk endometrial carcinoma </li></ul></ul></ul>
    18. 20. Diagnosis <ul><li>Polycystic Ovaries </li></ul><ul><ul><ul><li>Criteria by ultrasound </li></ul></ul></ul><ul><ul><ul><ul><li>Increased ovarian area (>5.5 cm2) or volume (>11 ml) w/ presence of >12 follicles measuring 2-9 mm in diameter </li></ul></ul></ul></ul><ul><ul><ul><li>Polycystic ovaries not specific for PCOS </li></ul></ul></ul><ul><ul><ul><li>> 20% normal women have incidental polycystic ovaries </li></ul></ul></ul>
    19. 21. Polycystic ovaries, by ultrasound
    20. 22. Diagnosis <ul><li>4. Absence of other disorders to account for these symptoms. </li></ul><ul><ul><li>Pregnancy  pregnancy test </li></ul></ul><ul><ul><li>Hypothyroidism  TSH </li></ul></ul><ul><ul><li>Hyperprolactinemia  prolactin </li></ul></ul><ul><ul><li>Late onset congenital adrenal hyperplasia  17-hydroxyprogesterone (r/o if <200 ng/dl) </li></ul></ul><ul><ul><li>Ovarian tumor  total testosterone (esp if >200 ng/dl) </li></ul></ul><ul><ul><li>Adrenal tumor  DHEA-S (esp if > 800 mcg/dl) </li></ul></ul><ul><ul><li>Cushing’s syndrome  salivary cortisol, 24 hr urine cortisol </li></ul></ul>
    21. 23. Diagnosis <ul><li>5. Supportive of insulin resistance </li></ul><ul><ul><li>“ Syndrome XX”: 3 or more of the following criteria: </li></ul></ul><ul><ul><ul><li>Waist circumference > 88 cm </li></ul></ul></ul><ul><ul><ul><li>Triglycerides > 150 mg/dl </li></ul></ul></ul><ul><ul><ul><li>HDL <50 mg/dl </li></ul></ul></ul><ul><ul><ul><li>BP > 130/85 </li></ul></ul></ul><ul><ul><ul><li>Fasting glucose >110 mg/dl </li></ul></ul></ul><ul><ul><li>ACOG and ADA suggest screening all women w/ PCOS for glucose intolerance, type 2 DM. </li></ul></ul><ul><ul><li>Oral glucose tolerance test more sensitive than fasting glucose. </li></ul></ul><ul><ul><li>Personal or family history of DM </li></ul></ul><ul><ul><li>Acanthosis nigricans </li></ul></ul>
    22. 24. Management <ul><ul><li>Immediate/Acute issues </li></ul></ul><ul><ul><ul><ul><li>Hirsutism </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Regulation of menses </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Fertility issues </li></ul></ul></ul></ul><ul><ul><li>Long-term issues </li></ul></ul><ul><ul><ul><ul><li>Insulin resistance </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Cardiovascular risk </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Obstructive sleep apnea </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Malignancy risk </li></ul></ul></ul></ul>
    23. 25. Management: Immediate/Acute Issues <ul><ul><li>Control of hirsutism </li></ul></ul><ul><ul><ul><li>Medical (need a trial of 6-12 mos before deemed ineffective) </li></ul></ul></ul><ul><ul><ul><ul><li>Decrease testosterone production (predominantly from ovary) </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>OCPs (improvement scores 33%) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>-Increase SHBG </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Lifestyle modification/weight loss </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Metformin (improvement scores 10-13%) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Glucocorticoids? </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>-Theory: ACTH stimulates adrenal androgen synthesis. So, suppress ACTH via glucocorticoids. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>-Study by Vanky, et al- dexamethasone 0.25 mg/day vs placebo—reduction in testosterone, androstenedione, DHEA-S by 25-50%. No significant change in BMI, glucose, insulin, lipids </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>-problematic </li></ul></ul></ul></ul></ul>
    24. 26. Management: Immediate/Acute Issues <ul><ul><li>Control of hirsutism (cont’d) </li></ul></ul><ul><ul><ul><li>Decrease testosterone action </li></ul></ul></ul><ul><ul><ul><ul><li>Antiandrogens </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Spironolactone (start 50 mg bid  100 mg bid) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>-Reduction in hirsutism 45% </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>-Preferred use w/ OCPs, 75% response </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Drospirenone (analogue of spironolactone, approved in Yasmin) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>5α-reductase inhibitors (ex. Finasteride) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Lifestyle modification/weight loss </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Metformin </li></ul></ul></ul></ul>
    25. 27. Management: Immediate/Acute Issues <ul><ul><li>Control of hirsutism (cont’d) </li></ul></ul><ul><ul><ul><li>Mechanical </li></ul></ul></ul><ul><ul><ul><ul><li>Plucking/shaving/electrolysis/laser </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Vaniqa cream (eflornithine hydrochloride 13.9%) </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Mechanism: slows growth of hair by inhibiting L-ornithine decarboxylase (enzyme involved in hair growth) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>58% demonstrated some improvement in hair growth vs 32% with placebo </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Hair growth rates return to nml 8 wks off therapy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Not covered by most insurance policies </li></ul></ul></ul></ul></ul>
    26. 28. Management: Immediate/Acute Issues <ul><li>Regulation of menses </li></ul><ul><ul><ul><li>Oral contraceptives </li></ul></ul></ul><ul><ul><ul><li>Periodic progesterone withdrawal </li></ul></ul></ul><ul><ul><ul><ul><li>Medroxyprogesterone 10 mg/day x 7-10 days, every 3 months (approx 4 menses annually) </li></ul></ul></ul></ul><ul><ul><ul><li>Lifestyle modification/weight loss </li></ul></ul></ul><ul><ul><ul><li>Metformin- ie., hitting the “root cause” </li></ul></ul></ul><ul><ul><ul><ul><li>500-1000 mg bid, 6 month trial reasonable for improvement of menses </li></ul></ul></ul></ul>
    27. 29. Management: Immediate/Acute Issues <ul><li>Fertility issues </li></ul><ul><ul><li>Lifestyle modification/weight loss </li></ul></ul><ul><ul><ul><li>Loss of >5% body wt, calorie-restricted diet, and exercise associated with improvement in spontaneous pregnancy rates (7.5-15% improvement) </li></ul></ul></ul><ul><ul><li>Clomiphene citrate </li></ul></ul><ul><ul><ul><ul><li>Most women with PCOS do not respond to normal dose—20% ovulation rate! </li></ul></ul></ul></ul>
    28. 30. Management: Immediate/Acute Issues <ul><li>Fertility issues (cont’d) </li></ul><ul><ul><li>Metformin </li></ul></ul><ul><ul><ul><ul><li>OR 3.88 in achieving fertility (compared to placebo), 4.4 (for metformin+clomiphene compared to clomiphene alone) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Improved outcomes with in vitro fertilization (reduced risk of ovarian hyperstimulation when treated with FSH) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Reduction in 1st trimester spontaneous abortions </li></ul></ul></ul></ul><ul><ul><li>Thiazolidinediones </li></ul></ul><ul><ul><ul><li>Early studies w/ rosiglitazone prior to conception  30% improvement in fertility rates. </li></ul></ul></ul>
    29. 31. Management: Long-Term Issues <ul><li>Insulin resistance </li></ul><ul><ul><ul><li>Lifestyle modification/weight loss </li></ul></ul></ul>
    30. 32. Management: Long-Term Issues <ul><li>Insulin resistance </li></ul><ul><ul><li>Metformin </li></ul></ul><ul><ul><ul><li>Function </li></ul></ul></ul><ul><ul><ul><ul><li>Lowers hepatic glucose production by reducing gluconeogenesis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Increases peripheral glucose uptake by skeletal muscle and adipose tissue </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Reduces intestinal glucose absorption </li></ul></ul></ul></ul><ul><ul><ul><li>Outcomes </li></ul></ul></ul><ul><ul><ul><ul><li>Estimated 31% reduction in development of type II DM over mean period 3 years </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Taken during pregnancy, reduction in gestational diabetes and major fetal complications </li></ul></ul></ul></ul>
    31. 33. Management: Long-Term Issues <ul><li>Insulin resistance </li></ul><ul><ul><li>Thiazolidinediones </li></ul></ul><ul><ul><ul><li>Function </li></ul></ul></ul><ul><ul><ul><ul><li>Selective ligands of the nuclear transcription PPARγ, expressed in adipose tissue, pancreatic beta cells, vascular endothelium, macrophages, HPO axis. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>“ fatty acid steal” hypothesis </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Promote fatty acid uptake and storage in adipose tissue, sparing other tissues (muscle, liver) from harmful metabolic effects of free fatty acids (high levels in PCOS) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Increased expression of adiponectin (adipocytokine with an insulin sensitivity effect) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Decreased expression of 11β-hydroxysteroid dehydrogenase type 1 (enzyme converts inactive cortisone to active cortisol) </li></ul></ul></ul></ul><ul><ul><ul><li>Outcomes </li></ul></ul></ul>
    32. 34. Management: Long-Term Issues <ul><li>Cardiovascular Risk </li></ul><ul><ul><li>Increased prevalence of HTN </li></ul></ul><ul><ul><li>Dyslipidemia ( ↑ TG, ↓ HDL, ↑ LDL) </li></ul></ul><ul><ul><li>Predisposition to macrovascular disease and thrombosis </li></ul></ul><ul><ul><ul><li>Nurses’ health study: 20-60% increased risk of CAD events </li></ul></ul></ul><ul><ul><ul><li>Studies of pts undergoing coronary angiography: women with significant h/o hirsutism or polycystic ovaries more likely to have CAD, and if they had it, more extensive CAD, compared to female controls. </li></ul></ul></ul><ul><ul><li>Aggressive management…”CHAMP”? </li></ul></ul>
    33. 35. Management: Long-Term Issues <ul><li>Obstructive Sleep Apnea </li></ul><ul><ul><li>30-fold increased risk of OSA, not explained by obesity alone. </li></ul></ul><ul><ul><li>Insulin resistance strongest predictor of OSA (not BMI, age, testosterone) </li></ul></ul><ul><ul><li>Consider polysomnography if at risk </li></ul></ul>
    34. 36. Management: Long-Term Issues <ul><li>Risk for malignancy </li></ul><ul><ul><li>3X increased risk endometrial carcinoma in PCOS </li></ul></ul><ul><ul><li>Increased risk of ovarian and breast cancer </li></ul></ul><ul><ul><li>Warrants regular screening, low threshold for endometrial biopsy </li></ul></ul>
    35. 38. Other issues Role of epilepsy? <ul><ul><li>Increased incidence of reproductive disorders in patients with epilepsy </li></ul></ul><ul><ul><li>Pts on valproic acid may have higher levels of insulin, testosterone, and TG </li></ul></ul>
    36. 39. New things on the horizon… <ul><li>Somatostatin analogs </li></ul><ul><ul><li>Function </li></ul></ul><ul><ul><ul><li>Blunts LH response to GnRH </li></ul></ul></ul><ul><ul><ul><li>Decreases GH secretion by pituitary </li></ul></ul></ul><ul><ul><ul><li>Inhibits pancreatic insulin release </li></ul></ul></ul><ul><ul><li>Outcomes: limited studies </li></ul></ul><ul><ul><ul><li>7 d administration octreotide in PCOS women  decreased fasting and glucose-stimulated insulin levels </li></ul></ul></ul><ul><ul><ul><li>Reduced LH, androgen, IGF-1 levels </li></ul></ul></ul><ul><ul><ul><li>Short half-life (80-110 min) requiring multiple injections </li></ul></ul></ul><ul><ul><ul><li>Extended release octreotide (octreotide-LAR)- inject IM Q28 days- results in improvement in GH, insulin, IGF-1, hirsutism </li></ul></ul></ul><ul><ul><ul><li>Not approved yet </li></ul></ul></ul>
    37. 40. References <ul><li>American College of Obstetricians and Gynecologists (ACOG) practice bulletin. Polycystic ovary syndrome. 2002. </li></ul><ul><li>Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale H, Futterweit W, Janssen O, Legro RS, Norman RJ, Taylor AE, Witchel SF. Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. Journal of Clinical Endocrinology & Metabolism 2006;91:4237-45. </li></ul><ul><li>Barber TM, McCarthy MI, Wass JA, Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol 2006;65:137-45. </li></ul><ul><li>Ehrmann DA. Polycystic Ovary Syndrome. NEJM 2005;352:1223-36. </li></ul><ul><li>Froment P, Gizard F, Defever D, Staels B, Dupont J, Monget P. Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition. Journal of Endocrinology 2006;189:199-209. </li></ul><ul><li>Glueck CJ, Moreira A, Goldenberg N, Sieve L, Wang P. Pioglitazone and metformin in obese women with polycystic ovary syndrome not optimally responsive to metformin. Human Reproduction 2003;18:1618-25. </li></ul><ul><li>Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999;84:165-9. </li></ul><ul><li>Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. NEJM 1998;338:1876-80. </li></ul><ul><li>Norman RJ, Davies MJ, Lord J, Moran LJ. The role of lifestyle modification in polycystic ovary syndrome. Trends Endocrinol Metab 2002;13:251-7. </li></ul><ul><li>Pasquali R, Gambineri A. Insulin-sensitizing agents in polycystic ovary syndrome. European Journal of Endocrinology 2006;154:763-75. </li></ul><ul><li>Schneider JG, Tompkins C, Blumenthal RS, Mora S. The metabolic syndrome in women. Cardiol Rev 2006;14:286-91. </li></ul><ul><li>Shapiro J, Lui H. Treatments for unwanted facial hair. Skin Therapy Lett 2006;10:1-4. </li></ul><ul><li>Sheehan, MT. Polycystic ovarian syndrome: diagnosis and management. Clinical Medicine and Research 2004;2:13-27. </li></ul><ul><li>Siebert TI, Kruger TF, Steyn DW, Nosarka S. Is the addition of metformin efficacious in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome? A structured literature review. Fertil Steril 2006;86:1432-7. </li></ul><ul><li>Srikanthan P, Korenman S, Davis S. Polycystic ovarian syndrome: the next cardiovascular dilemma in women? Endocrinol Clin North Am 2006;35:611-31. </li></ul>

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