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PCOS: PolyCystic Ovary Syndrome

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PCOS:PolyCystic Ovary Syndrome By Kimberly Dovin, PGY3 Swedish Family Medicine January 13, 2003

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PCOS:A Disorder for the Generalist or

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PCOS: Goals Identify patients with risks for or with Dx of PCOS Assess patients appropriately for PCOS and associated disease states Prescribe therapy to treat complaints and prevent sequelae

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PCOS: Objectives Define PCOS Understand pathophysiology Form an appropriate differential diagnosis Establish the work-up for PCOS Develop an array of therapies to treat complaints and prevent bad outcomes

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PCOS: Defined? I ACOG and NIH (1990): hyperandrogenism and chronic anovulation excluding other causes Stein and Levanthal (1935): association of amenorrhea with polycystic ovaries and variably: hirsutism and/or obesity

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PCOS: Epidemiology Prevalence: 4-6% females Probably same world wide No difference between blacks and whites 75% of women w/ irregularity or infertility

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PCOS: Signs and Symptoms SYMPTOMS Menstrual irregularity Infertility Hirsutism, acne, etc Obesity SIGNS Hirsutism, acne Obesity Ovarian enlargement Acanthosis nigricans

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PCOS: Signs and Symptoms II

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PCOS: Imaging and Pathology

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PCOS: PathopysiologyWhat we think we know. “Vicious cycle” Abnormal gonadotropin secretion Excess LH and low, tonic FSH Hypersecretion of androgens Disrupts follicle maturation Substrate for peripheral aromatization Negative feedback on pituitary Decreased FSH secreation Insulin resistance, Elevated insulin levels

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PCOS: Current theories of pathopysiology Autosomal Dominant Gene Insulin Resistance PCOS GnRH LH A E2 Downstream Signal Defect A=androgens, E2=estradiol

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“Could the theory of chaos contribute to the interpretation of pathogenesis of polycystic ovary syndrome?”

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PCOS: Case 1 - Hx J.D. 31yof Menstrual irregularity,LMP 5 months prior Irregular since menarche Getting longer over time Sexually active and uses condoms 40lb weight gain over past six months Previous U/S w/ ovarian cysts ROS: hair growth on her chin and chest Meds: HCTZ, Effexor, atenolol

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PCOS: Case 1 - PE BP 126/96, Weight 248lbs Skin: dark hair on chin and chest, moderate to severe acne on face and back no acanthosis nigricans Abd-obese, tender RLQ, no R/G, no abd striae Pelvic exam – nl ext genitalia no clitoromegaly, norm appearing cervix Bimanual: Uterus/adnexa not palpated U/S: Normal appearing ovaries

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PCOS: Differential Dx Androgen secreting tumor Exogenous androgens Cushing’s syndrome Nonclassical congenital adrenal hyperplasia Acromegaly Genetic defect in insulin metabolism Primary hypothalamic amenorrhea Primary ovarian failure Thyroid dz Prolactin dz

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PCOS: Case 1 Work-up Total or free testosterone +/- LH and FSH Pelvic U/S Fasting glucose Fasting lipid profile (SHBG, Insulin)

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PCOS: Work-up (cont’d) TSH Prolactin UHCG +/- 17-hydroxyprogesterone +/- Dexamethasone suppression test +/- DHEA

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PCOS: Case 1 Treatment Oligomennorhea OCPs, Progestins, insulin-sensitizing agents Hirsutism OCPs, Antiandrogens, ISAs, Eflornithine Mechanical treatments Obesity LIFESTYLE MODIFICATIONS Metformin

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PCOS: Case 1 Treatment Naturopathic options Flaxseed oil Fish oil D-chiro-inositol Chromimum Urtica Dioica (aka stinging nettle) Saw palmetto

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Case 1: Outcomes Laboratory analysis: Nl TSH and prolactin, mild elevation of testosterone, LH:FSH 3:1 Treatment: Diet and exercise counseling, metformin 850mg bid. Patient reported resumption of menses and thereafter lost to f/u

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PCOS: Case 2 - Hx R.M. 27yof Desires pregnancy w/o results X 2yrs LMP 2 wks ago/ 3 menses per yr 2 years irregularity, sometimes heavy bleeding Simlar family hx C/o facial hair which she waxes No infertility w/u

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PCOS: Case 2 – P.E. Weight 247 lbs Skin: Scant facial hair on chin, no acne Abd: obese Pelvic: norm uterus, ovaries not palpated Labs: mild elev prolactin & testosterone, elevated LH Pelvic US WNL

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PCOS: Infertility WEIGHT LOSS Clomiphene citrate 50-100mg QD +/- dexamethasone Gonadotropins Metformin Ovarian Drilling

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PCOS: Risks of Pregnancy Gestational Diabetes? Hypertension?

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PCOS: Case 2 - Outcomes Metformin 500mg bid Menses resumed q28 d X 2 Anxious to get pregnant. Advised following BBTemps Timing intercourse. If no result in 3mos start Clomid.

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PCOS: Case 3 - Hx M.P. 39yof F/u acne face and back C/o hirsutism, “like a beard” Oligomennorhea, q60day cycles G2P2 s/p BTL 14 years ago ROS: weight gain 50lbs in 3-4 years

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PCOS: Case 3 - P.E. BP 146/92 Weight 232lbs, BMI 36.3 Skin: Severe acne on face and back, evidence of shaving on face

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PCOS: Associated Disorders Diabetes Hyperlidpidemia (LDL, Triglycerides) Obesity Hypertension CAD? Incr in Risk Factors, but not mortality

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PCOS: Associated Disorders Endometrial CA Ovarian CA? +/- Breast CA NO increase in Osteoporosis Eating disorders Psychiatric dz

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PCOS: Case 3 Follow-up TSH, Prolactin, Free Testosterone, 17-OH progesterone all WNL Fasting glu = 99 LDL = 125 Referred to nutrition and prescribed exercise program Pt lost 30lbs over one year, menses more regular, hirsutism and acne slightly improved LDL dropped to 110, BP normalized

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PCOS: Conclusion PCOS: chronic anovulation/hyperandrogenism Complete a w/u to r/o other causes Advise weight loss and exercise in all patients w/ PCOS Consider medical management Use a Palm memo

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Bibliography Plycystic Ovary Syndrome. Clinical Management Guidelines. Dec 2002; ACOG Practice Bulletin No. 41. Hunter, H., MD and Sterrett, J, PharmD. Polycystic Ovary Syndrome: It’s Not Just Infertility. AFP. Sept. 1, 2000. Keri Marshall, ND Candidate 2001 Polycystic Ovary Syndrome: Clinical Considerations. Macut D, et al. Cardiovascular risk in adolescent and young adult obese females with polycystic ovary syndrome (PCOS). J Pediatr Endocrinol Metab. 2001;14 Suppl 5:1353-59; discussion 1365. Poretsky, Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis; Endocrine Reviews 20 (4): 535-582.

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Weight 247 lbs; Skin: Scant facial hair on chin, no acne; Abd: obesePt lost 30lbs over one year, me more Weight 247 lbs; Skin: Scant facial hair on chin, no acne; Abd: obesePt lost 30lbs over one year, menses more regular, hirsutism and acne slightly ... less

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