Polycystic Ovary Syndrome  (PCOS) Sharon E. Moayeri, M.D., M.P.H., M.S. FACOG, Reproductive Endocrinology & ...
Objectives1. Describe PCOS and associated pathophysiology2. Identify risk factors of and conditions related to PCOS3. Di...
Polycystic Ovary SYNDROME• 1800s: polycystic ovaries – “cystic oophoritis”; “sclerocystic”• Stein & Leventhal (1953) –...
PCOS• Collection of signs and symptoms• May be difficult to diagnose – Heterogeneous presentation – Features change with...
PCOS: Clinical Presentation Signs and Symptoms PCOS 5
Epidemiology• Most common endocrine abnormality in reproductive  aged women• 5‐15% women affected – with ethnic predilect...
Polycystic Ovary Syndrome (PCOS)ETIOLOGY & PATHOPHYSIOLOGY PCOS 7
PCOS: Etiology• Neuroendocrine derangement: ↑LH relative  to FSH• Hyperinsulinemia: defect in insulin action or  secreti...
Normal Menstrual Cycle PCOS LH FSH ...
Effects of Hyperinsulinemia• Decrease binding proteins (ie., SHBG, IGFBP‐I)• Increase unbound androgens• Reduce HDL [good]...
PCOS: Androgen Excess• Worse with hyperinsulinemia• Hirsutism:  80% PCOS• Acne: 20% PCOS• Androgenic alopecia: 10% PCOS ...
PCOS Etiology: Unifying theory? PCOS 12
PCOS: Phenotypic & Genetic Variation Susceptibility  Genes Modif...
Gene Polymorphism PhenotypeIGF-2 Apal PCOSI...
PCOS 15
PCOS: Diagnostic Criteria• NIH/NICHD: USA, 1990 • ESHRE/ASRM: Rotterdam, 2004• Androgen Excess‐PCOS Intl Society: 2006 ...
PCOS CriteriaNICHD/NIH Definition, 1990 Rotterdam Definition, 2004Less inclusive ...
AE‐PCOS Society, 2006• Hyperandrogenism**: Hirsutism and/or  hyperandrogenemiaAND• Ovarian Dysfunction: Oligo‐anovulation...
Number 108, October 2009(Replaces Practice Bulletin Number 41, December 2002)
Polycystic Ovary Syndrome (PCOS)EVALUATION PCOS 20
Differential Diagnosis• Hypothalamic amenorrhea • Neoplasm: rapid onset  ...
PCOS: Menstrual Dysfunction• 25‐30% of women with oligo‐anovulation have PCOS – ≥35 day intervals or <10 bleeds per year...
Polycystic ovaries ≠ PCO syndrome• Transvaginal sono is best• Incidence decreases with age• Sonogram Morphology: ...
Assessing Hirsutism• Hirsutism vs virilization: rapidly developing virilization or certain virilizing symptoms (i.e., cli...
PCOS: Physical Exam• Blood pressure• Body mass index (kg/m2) >25 overweight >30 obese• Waist circumference > 35 in...
PCOS: Basic Work‐up• FSH & estradiol (E2) +/‐ LH:  – premature ovarian failure (low E2; high FSH) – hypothalamic ameno...
Hyperandrogenemia in PCOS • A. Huang, et al., F&S, April 2010, N= 720 (NIH criteria) • Hyperandrogenemia present 75%...
PCOS: Evaluation• DHEA‐S  – Mildly elevated in 30‐40% PCOS – adrenal tumors >700 mcg/dL  Pelvic/Adrenal contrast CT – D...
PCOS: Optional Evaluation• Total testosterone  – Ovarian tumors >200ng/dL  get imaging – PCOS: upper limit of normal f...
PCOS: Obesity• NOT part of diagnostic criteria• Common in PCOS, affects between 50 to 80%• Waist‐to‐hip ratio >0.85 predic...
PCOS: Overweight?• Screen impaired glucose tolerance or Diabetes – oral GTT: Fasting glucose  drink 75 gram glucola  ...
Metabolic Syndrome• 15% of U.S. population • 33% of PCOS!!• Adult Treatment Panel III (others exist): – Elevated blood pr...
Polycystic Ovary Syndrome (PCOS)TREATMENT: GOAL SPECIFIC PCOS 33
PCOS: Goal Specific Therapy• Screen and manage comorbidities • Hirsutism/acne/hair loss• Protect/monitor endometrium  – ...
PCOS: Co‐morbidities!• Insulin resistance, ~30%• Type‐II DM,  ~10% (3‐5x)• Gestational diabetes (2.5x)• Endometrial hyperp...
PCOS: Probable Links• Coronary artery disease• Dyslipidemia• Hypertension• Ovarian cancer (?)• Miscarriage (?)• Pregnancy ...
Prevention of CVD and DM• Lifestyle: weightloss and exercise!!• Metformin 1500‐2000 mg daily if documented  impaired gluc...
PCOS: Endometrial CA• 56 obese PCOS women (Cheung,2001) – 36% hyperplasia  2% cancer without tx – 9% atypia  23% cance...
Summary: Sequelae of  biochemical aberrationsBiochemical  Signs / Symptoms Consequen...
Treatment of HirsutismMulti‐step approach is most‐effective:• Hair removal: wax, laser, eflornithine, etc.• OCPs for at le...
Treating PCOS anovulatory infertilityIntervention Cost Risk of multiplesLifestyle/  ...
PCOS: Weight Loss• Frequency of obesity in women with anovulation and PCO:   30%‐75% ‐‐ most before puberty• 5‐10% weight...
PCOS and Infertility: Metformin?• Metformin (biguanide ): improves insulin resistance  – reduce hepatic glucose product...
PCOS and Infertility: Metformin? • MC‐RCT, 6 months • No screening for IR • Medications started concomitantly • ...
PCOS Fertility Options: Ovulation  Induction (OI)/Superovulation (SO)• Clomiphene Citrate: non‐steroidal weak estrogen r...
PCOS Fertility Options: OI/SO (2)• Gonadotropins: HMG, FSH – 60% live‐birth 12‐18 mo – Need careful monitoring (follic...
PCOS Fertility Options: ART• Assisted Reproductive Technologies (ie, IVF/ICSI)  PROS – Highly successful in PCOS: >60%...
PCOS Fertility Options: Surgery• Laparoscopic wedge resection or ovarian drilling  PROS – May avoid fertility treatmen...
PCOS: Pharmacotherapy summary PCOS 49
PCOS: Conclusions (1)• Multifaceted condition with varying presentation• No clearly accepted basis for diagnosis• Signific...
PCOS: Conclusions (2)• Treatment goals – Educate – Identify and monitor co‐morbidities • i.e., hyperlipidemia, di...
Questions? www.ocfertility.com
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Polycystic Ovary Syndrome (PCOS)

by Sharon E. Moayeri, M.D., M.P.H., M.S.
Published on: Mar 4, 2016
Published in: Health & Medicine      
Source: www.slideshare.net


Transcripts - Polycystic Ovary Syndrome (PCOS)

  • 1. Polycystic Ovary Syndrome  (PCOS) Sharon E. Moayeri, M.D., M.P.H., M.S. FACOG, Reproductive Endocrinology & Infertility www.ocfertility.com University of California, Irvine Department of Obstetrics & Gynecology34rd Annual Review Course in Clinical Obstetrics/Gynecology October 2011
  • 2. Objectives1. Describe PCOS and associated pathophysiology2. Identify risk factors of and conditions related to PCOS3. Diagnose and evaluate comorbidities relevant to PCOS4. Characterize goal specific therapy options PCOS 2
  • 3. Polycystic Ovary SYNDROME• 1800s: polycystic ovaries – “cystic oophoritis”; “sclerocystic”• Stein & Leventhal (1953) – Enlarged ovaries, hirsutism, obesity,  and chronic anovulation• “Syndrome O” – Ovarian confusion – Ovulation disruption – Over‐nourishment – Overproduction of insulin 3 PCOS
  • 4. PCOS• Collection of signs and symptoms• May be difficult to diagnose – Heterogeneous presentation – Features change with age• NO single test or feature is diagnostic PCOS 4
  • 5. PCOS: Clinical Presentation Signs and Symptoms PCOS 5
  • 6. Epidemiology• Most common endocrine abnormality in reproductive  aged women• 5‐15% women affected – with ethnic predilection – Caucasians:  4.8% – Latina/hispanics: 13% – African americans: 8.0%• Hereditary:  – Affected mother 35% – Affected sister 40% PCOS 6
  • 7. Polycystic Ovary Syndrome (PCOS)ETIOLOGY & PATHOPHYSIOLOGY PCOS 7
  • 8. PCOS: Etiology• Neuroendocrine derangement: ↑LH relative  to FSH• Hyperinsulinemia: defect in insulin action or  secretion• Androgen excess: ovarian and adrenal PCOS 8
  • 9. Normal Menstrual Cycle PCOS LH FSH Cycle day Cycle day PCOS 9
  • 10. Effects of Hyperinsulinemia• Decrease binding proteins (ie., SHBG, IGFBP‐I)• Increase unbound androgens• Reduce HDL [good] cholesterol• Risk for PCOS (Legro et al.,1999; Dunaif, et al. 1997) – Insulin resistance: ~50% – NIDDM: 8%• Acanthosis nigricans PCOS 10
  • 11. PCOS: Androgen Excess• Worse with hyperinsulinemia• Hirsutism:  80% PCOS• Acne: 20% PCOS• Androgenic alopecia: 10% PCOS PCOS 11
  • 12. PCOS Etiology: Unifying theory? PCOS 12
  • 13. PCOS: Phenotypic & Genetic Variation Susceptibility  Genes Modifier  Environment Genes PCOS 13
  • 14. Gene Polymorphism PhenotypeIGF-2 Apal PCOSIGF-IR Trinucleotide repeat Increased fasting glucose and insulin resistancePPAR-У2 Pro12Ala Body mass index Lower insulin resistance PCOS Obesity Lower insulin resistance and hirsutism scoreParaoxonase (PON-1) -108C/T PCOS Leu55Met Obesity and insulin resistanceSORBS1 Thr228Ala ObesityCalpain-10 UCSNP-43,-19,-63 PCOS and insulin levels UCSNP-43,-45 Hirsutism score and idiopathic hirsutism UCSNP-44 PCOSAdiponectin 45 T/G Androstenedione PCOS Insulin resistance 276 G/I Obesity and insulin resistance Lower adiponectin levels PCOS 14Adapted from Luque-Ramirez et al, Clinica Chimica Acta, 2006.
  • 15. PCOS 15
  • 16. PCOS: Diagnostic Criteria• NIH/NICHD: USA, 1990 • ESHRE/ASRM: Rotterdam, 2004• Androgen Excess‐PCOS Intl Society: 2006 PCOS 16
  • 17. PCOS CriteriaNICHD/NIH Definition, 1990 Rotterdam Definition, 2004Less inclusive More inclusive1 and 2 needs to be met: 2 of 3 need to be met: 1. Hyperandrogenism 1. Hyperandrogenism – clinical (hirsutism, acne,  – Clinical or biochemical frontal balding)  – biochemical (high serum  androgen concentrations) 2. Menstrual irregularity 2. Menstrual irregularity 3. **Polycystic ovaries **      – Chronic anovulation (Key difference from NIH) – Oligomenorrhea, > 35d FOR BOTH: Exclude other causes (hyperprolactinemia, NC- congenital adrenal hyperplasia, thyroid disorder, etc.) PCOS 17
  • 18. AE‐PCOS Society, 2006• Hyperandrogenism**: Hirsutism and/or  hyperandrogenemiaAND• Ovarian Dysfunction: Oligo‐anovulation  and/or polycystic ovaries• Exclusion of other androgen excess or related  disorders PCOS 18
  • 19. Number 108, October 2009(Replaces Practice Bulletin Number 41, December 2002)
  • 20. Polycystic Ovary Syndrome (PCOS)EVALUATION PCOS 20
  • 21. Differential Diagnosis• Hypothalamic amenorrhea • Neoplasm: rapid onset  symptoms? • Premature ovarian failure – Ovarian (sertoli‐leydig,  granulosa‐theca, hilus‐cell)• Idiopathic hirsutism – Adrenal – Pituitary/hypothalamic• Other endocrinopathies:  thyroid disorder,  • Drugs (i.e.,  steroids) hyperprolactinemia, NC‐CAH,  Cushing syndrome, etc.  • HAIR‐AN syndrome  – HyperAndrogenism, • Severe IR Syndromes (i.e.,  – Insulin Resistance,  Syndrome X/Metabolic  – Acanthosis Nigricans Syndrome) PCOS 21
  • 22. PCOS: Menstrual Dysfunction• 25‐30% of women with oligo‐anovulation have PCOS – ≥35 day intervals or <10 bleeds per year• 2/3 of patients with PCOS have oligo‐anovulation• PCOS patients may describe “normal” menses, but further  investigation reveals chronic anovulation in ~25% • Consequences: – Menstrual Dysfunction – Infertility – Endometrial hyperplasia/cancer PCOS 22
  • 23. Polycystic ovaries ≠ PCO syndrome• Transvaginal sono is best• Incidence decreases with age• Sonogram Morphology: – >12 follicles/ovary @ 2–9 mm diameter – Volume: >10mL – +/‐ “string of pearls”• Rule of 20%: – 20% of women with PCO have PCOS – PCO absent in ~20% with PCOS – Present ~20% without PCOS • Hypothalamic amenorrhea • Adolescents • Hyperprolactinemia PCOS 23
  • 24. Assessing Hirsutism• Hirsutism vs virilization: rapidly developing virilization or certain virilizing symptoms (i.e., clitoromegaly, voice  deepening) warrants further evaluation• Modified Ferrimen‐Gallwey – 9 body parts, scored 0‐4 each – Score >6 hirsutism PCOS 24
  • 25. PCOS: Physical Exam• Blood pressure• Body mass index (kg/m2) >25 overweight >30 obese• Waist circumference > 35 inches, abnormal• Acanthosis nigricans: insulin resistant• Acne/alopecia: androgen excess• Galactorrhea: hyperprolactinemia• Thyroid• Stigmata of Cushings? (striae, moon facies, etc…) PCOS 25
  • 26. PCOS: Basic Work‐up• FSH & estradiol (E2) +/‐ LH:  – premature ovarian failure (low E2; high FSH) – hypothalamic amenorrhea (low/normal E2; low FSH) – In [lean] PCOS, LH/FSH > 2• Free testosterone, normally <0.8% free• Prolactin & TSH  – Mild elevations of prolactin more common in PCOS – Hypothyroidsim  hyperprolactinemia – NOTE: both conditions can produce PCO morphology on sonogram• Progesterone in luteal phase to confirm ovulation  – >3 ng/mL – Can corroborate with sonogram monitoring of follicular development PCOS 26
  • 27. Hyperandrogenemia in PCOS • A. Huang, et al., F&S, April 2010, N= 720 (NIH criteria) • Hyperandrogenemia present 75%Hormone [Reference] [>88 ng/dL] [>275 mcg/dL] [0.66 ng/dL, >0.8%] PCOS 27
  • 28. PCOS: Evaluation• DHEA‐S  – Mildly elevated in 30‐40% PCOS – adrenal tumors >700 mcg/dL  Pelvic/Adrenal contrast CT – Dexamethasone suppression test• 17‐hydroxyprogesterone (17‐OHP):  – Ashkenazi Jews, Latina, Mediterraneans, Inuits, Yugoslavians – Nonclassical CAH: AR, ~5% of presumed PCOS – Measure a.m. during follicular phase – Nonclassical CAH >4 ng/mL – Borderline: 2‐4 ng/mL  Cortrosyn stimulation test  PCOS 28
  • 29. PCOS: Optional Evaluation• Total testosterone  – Ovarian tumors >200ng/dL  get imaging – PCOS: upper limit of normal female, <80ng/dL – Use to calculate free testosterone• 24‐hr urinary cortisol  – Screen Cushing’s syndrome >50mcg/24h  need  further testing PCOS 29
  • 30. PCOS: Obesity• NOT part of diagnostic criteria• Common in PCOS, affects between 50 to 80%• Waist‐to‐hip ratio >0.85 predicts insulin  resistance better than BMI• Worsens phenotype PCOS 30
  • 31. PCOS: Overweight?• Screen impaired glucose tolerance or Diabetes – oral GTT: Fasting glucose  drink 75 gram glucola  repeat 2‐hour glucose; can also test insulin • Fasting: <100 normal; 100‐125 impaired; >126 DM‐II • 2‐hour: <140 normal; 140‐199 impaired; >200 DM‐II – Fasting glucose/insulin < 4.5  (+/‐)• 20% annual risk of developing glucose intolerance• Fasting lipid panel: elevated in nearly 70% of PCOS – HDL < 50 abnormal; TG > 150 abnormal PCOS 31
  • 32. Metabolic Syndrome• 15% of U.S. population • 33% of PCOS!!• Adult Treatment Panel III (others exist): – Elevated blood pressure ≥ 130/85 – Increased waist circumference ≥ 35 in – Elevated fasting glucose ≥ 100 mg/dL – Reduced high‐density lipoprotein cholesterol  (HDL) ≤50 mg/dL – Elevated triglycerides ≥ 150 mg/dL
  • 33. Polycystic Ovary Syndrome (PCOS)TREATMENT: GOAL SPECIFIC PCOS 33
  • 34. PCOS: Goal Specific Therapy• Screen and manage comorbidities • Hirsutism/acne/hair loss• Protect/monitor endometrium  – Ultrasound +/‐ endometrial sampling – HRT/OCP (+/‐ insulin sensitizing agents) for endometrial  protection and menstrual regulation • Incidentally may reduce hyperandrogenism (hirsutism, acne, etc.)• Fertility PCOS 34
  • 35. PCOS: Co‐morbidities!• Insulin resistance, ~30%• Type‐II DM,  ~10% (3‐5x)• Gestational diabetes (2.5x)• Endometrial hyperplasia/ atypia/cancer• Metabolic syndrome/syndrome X• Sleep apnea/disordered breathing (Ehrmann, 2006) • related to IR NOT weight/BMI or androgens (30‐40x)• Depression• Sexual dysfunction PCOS 35
  • 36. PCOS: Probable Links• Coronary artery disease• Dyslipidemia• Hypertension• Ovarian cancer (?)• Miscarriage (?)• Pregnancy induced hypertension/PIH (?) PCOS 36
  • 37. Prevention of CVD and DM• Lifestyle: weightloss and exercise!!• Metformin 1500‐2000 mg daily if documented  impaired glucose tolerance or metabolic  syndrome, otherwise limited evidence for use.• Statins: beneficial in long‐term for prevention,  but must avoid pregnancy, since category X PCOS 37
  • 38. PCOS: Endometrial CA• 56 obese PCOS women (Cheung,2001) – 36% hyperplasia  2% cancer without tx – 9% atypia  23% cancer without tx• Women >50 yrs with endometrial cancer, PCOS  present in 62.5% PCOS 38
  • 39. Summary: Sequelae of  biochemical aberrationsBiochemical  Signs / Symptoms ConsequencesabnormalityHigh androgens &  Hirsutism; acne; Anovulation;Low SHBG Alopecia InfertilityChronic estrogen excess  Irregular menstrual  Endometrial  cycles, menorrhaghia,  hyperplasia/cancer; dysfunctional menstrual  Ovarian cancer (?); bleeding Breast cancer (?)Impaired glucose  Acanthosis nigricans Diabetes;tolerance/Insulin  Obesity/central  Gestational diabetes;resistance/ diabetes adiposity Hypertension; PIH/preeclampsia (?)Dyslipidemia Abnormal lipid panel CAD PCOS 39
  • 40. Treatment of HirsutismMulti‐step approach is most‐effective:• Hair removal: wax, laser, eflornithine, etc.• OCPs for at least 3 months, (>18 months is best)• Metformin (+/‐)• Continuous progestin therapy• GnRH agonist (lupron): <6m use; many side‐effects• Anti‐androgens (USE with contraceptive!):  – Spironolactone (100‐200mg/d): binds DHT intracellular  receptor; in‐utero risk: incomplete virilization of male fetus – Finasteride (2.5mg q 3 d to 5mg/d): inhibits 5‐alpha‐ reductase (blocks T  DHT); in‐utero risk: male fetus  hypospadias • Steroids: many SE, reduces androgens, ok short‐term PCOS 40
  • 41. Treating PCOS anovulatory infertilityIntervention Cost Risk of multiplesLifestyle/  Low  No increaseweight‐lossClomid/ Femara Low  Modest increase (<10%)FSH injections High Marked increase (20‐30%)Ovarian surgery High No increase, but limited efficacyIn vitro  Marked increase, but modifiable by  Highfertilization limiting the number of embryos  transferred.Modified from Barbieri, Up‐To‐Date PCOS 41
  • 42. PCOS: Weight Loss• Frequency of obesity in women with anovulation and PCO:   30%‐75% ‐‐ most before puberty• 5‐10% weight loss restores ovulation >55%  < 6months (Kiddy, 1992)• Weight‐loss program for anovulatory obese women: – Lost 6.3 kg (13.9 lbs) on average – Decreased fasting insulin and testosterone levels – Increased SHBG concentrations – 92% resumed ovulation (12/13) – 85% became pregnant (11/13) PCOS 42
  • 43. PCOS and Infertility: Metformin?• Metformin (biguanide ): improves insulin resistance  – reduce hepatic glucose production & intestinal absorption – Increase peripheral glucose uptake – increase SHBG  reduce androgen levels• Major side effect of metformin is GI (n/v/d) – Metformin 500mg qD for 1 week  2000mg daily  – Can use extend release dosing, qd @ dinner• Risks/Contraindications – Renally excreted (Cr<1.4) – Hepatotoxic ‐‐ avoid with elevated transaminase – Lactic acidosis (RARE!) – Stop 1 day before IV contrast dye study or surgery PCOS 43
  • 44. PCOS and Infertility: Metformin? • MC‐RCT, 6 months • No screening for IR • Medications started concomitantly • No difference in SAB rates N=626 CC + Plac Met + Plac CC + Met N=209 N=208 N=209 LBR, % 22.5 7.2 26.8 Preg/ovul, % 39.5 21.7 46 MGR, % 6 0 3 PCOS 44Legro et al., NEJM 2007
  • 45. PCOS Fertility Options: Ovulation  Induction (OI)/Superovulation (SO)• Clomiphene Citrate: non‐steroidal weak estrogen related  to diethystilbestrol, SERM• Clomid:  – start cycle‐day 2, 3, 4, or 5 – take for 5 days  (less common protocols exist)   – Dose 50mg/day to 200 mg/day  (take pills once per day, not  bid/tid/etc…• Ovulate ~80%  60% pregnant < 6m for OI patients• Consider letrozole/femara: aromatase inhibitor, may have  less negative impact on endometrial thickness PCOS 45
  • 46. PCOS Fertility Options: OI/SO (2)• Gonadotropins: HMG, FSH – 60% live‐birth 12‐18 mo – Need careful monitoring (follicle scans,  estradiol levels) • OHSS (~1‐2%)  • Multiple gestation risk (~20‐30%) • Risk of multiples may be hard to modify – Combine with clomid to reduce risks and  costs of treatment (i.e., start with clomid cycle day 3‐7, then add gonadotropins) PCOS 46
  • 47. PCOS Fertility Options: ART• Assisted Reproductive Technologies (ie, IVF/ICSI)  PROS – Highly successful in PCOS: >60% OPR/cycle in <35 yo – Efficient: Usually have supernumery embryos that can be  cryopreserved for future use (~70%) – Can modify risk of multiples (i.e., elective single embryo  transfer) CONS – [Relatively] expensive  (per cycle)  though increasing  evidence that this is more cost‐effective per live born…  – Risk hyperstimulation PCOS 47
  • 48. PCOS Fertility Options: Surgery• Laparoscopic wedge resection or ovarian drilling  PROS – May avoid fertility treatment risks (i.e., multiples, OHSS) – May identify and treat other comorbidities (i.e.,  endometriosis, pain, adhesions) – Intraoperative findings may alter treatment decisions CONS – Relatively invasive – Doesn’t universally restore ovulation ~50:50 – Postoperative adhesions  – Iatrogenic compromise to ovarian function/reserve – Limited data support its efficacy  – Gonadotropins likely to be successful (70% vs. 60%) PCOS 48
  • 49. PCOS: Pharmacotherapy summary PCOS 49
  • 50. PCOS: Conclusions (1)• Multifaceted condition with varying presentation• No clearly accepted basis for diagnosis• Significantly associated health consequences – Genetic and pre‐natal implications – Metabolic disorder with risk of long term health  complications: DM, cardiovascular, obesity, etc. – Reproductive repercussions: Endometrial hyperplasia   cancer;   menstrual irregularities; infertility PCOS 50
  • 51. PCOS: Conclusions (2)• Treatment goals – Educate – Identify and monitor co‐morbidities • i.e., hyperlipidemia, diabetes, endometrial hyperplasia  – Modify associated long term health risks  • i.e., diet, exercise, induce cyclic bleeding, medications – Treat patient concerns: effective therapies exist! • i.e., Hirsutism; infertility; cycle regulation PCOS 51
  • 52. Questions? www.ocfertility.com

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