Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

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Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

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  • 1. Polycystic Ovary Syndrome Camille Andy, MD Cone Family Practice June 9, 2006
  • 2. Case Study
    • 26 yo Latina female presents with primary complaint of infertility
    • Married and sexually active with partner, but never has been pregnant
    • Never has used birth control
  • 3. You Notice…
    • Central obesity; Her BMI is 29
    • Acne on her face and upper back
    • Increased facial hair
  • 4. She Says…
    • Menstrual cycles have always been irregular, usually once every 3-8 months
    • She has been overweight since teenager; she eats the typical high carb mexican diet
    • Little exercise
    • She feels depressed and worried about not being able to conceive
    • Family history + for DMII, CAD in mother
  • 5. Does She Have PCOS? Is It Important to Know?
  • 6. Case 2
    • 34 yo with abrupt onset (<1 year) of hirsutism and pustular acne
    • History of normal menses and 2 healthy children, but now amenorrhea
    • Husband has noticed deepening of voice
    • Labs? Diagnosis?
  • 7. Case 3
    • 24 year old presents with c/o “no menses for one year”
    • Occasional galactorrhea
    • PE is significant for normal body hair patterns and clear skin, normal BMI, no striae
    • Labs? Diagnosis?
  • 8. Objectives
    • Learn to make the diagnosis of PCOS
    • Understand importance of this syndrome
    • Clarify the distinguishing hormonal patterns of PCOS
    • Discuss management goals
  • 9. PCOS
    • Most common endocrinopathy among women of reproductive age
    • Affects up to 10% of US women
    • Approx 5 million women
  • 10. Stein-Leventhal Syndrome
    • Masculinized women with amenorrhea, sterility, and enlarged ovaries with multiple cysts
    • A “gynecologic” disorder
    • Management focused on bleeding abnormalities and infertility
  • 11. New Information
    • By early 1980’s, syndrome linked to hyperinsulinemia and impaired glucose tolerance
    • 1990’s, found a defect in an insulin receptor
    • Now, much broader long-term health implications for women with PCOS
  • 12. Clinical Course
    • Young women seek medical attention
      • Irregular menses
      • Hirsutism
      • Infertility
      • Obesity
    • Peripubertal onset
    • Hormonal imbalance leads to symptoms throughout reproductive years
  • 13. Long-term Consequences
    • Infertility
    • Recurrent SAB
    • Depression/anxiety
    • Dyslipidemias
      • Elevated cholesterol, LDL, and triglycerides
      • Decreased HDL
    • Hypertension
    • Type 2 Diabetes
    • CAD
    • CVA
    • Endometrial Carcinoma
  • 14. Diagnostic Criteria
    • 2003 Consensus Meeting (European Society of Human Reproduction and Embryology/American Society of Reproductive Medicine)
    • Need 2 of 3:
      • Oligo- and/or anovulation
      • Clinical and/or biochemical signs of hyperandrogenism
      • Polycystic ovaries (by ultrasound)
    • And must exclude other endocrinopathies
  • 15. Menstrual Cycle
  • 16. Chronic Anovulation
    • Due to hormonal imbalance of gonadotropins and ovarian dysfunction
    • Reduction in ovulatory events lead to deficient progesterone secretion
    • Chronic unopposed estrogen stimulation of endometrium
      • Hyperplasia
      • Intermittent breakthrough bleeding
      • Dysfunctional uterine bleeding
  • 17. Oligo- or amenorrhea
    • Occurs in 70%
    • Typically a peripubertal onset
      • Normal or slightly delayed menarche, then irregular cycles
      • Can have normal cycles at first, then irregular after weight gain
      • Some with prolonged amenorrhea due to high androgens affecting endometrium
    • Many patients won’t think this is abnormal
  • 18. Hyperandrogenism
    • Clinical
      • Hirsutism - excess terminal (thick, pigmented) body hair in a male distribution
      • Acne
      • Android body habitus
    • Biochemical
      • 50% – 90% have elevated serum androgen levels
      • Produced by ovaries and adrenals
  • 19. Hirsutism - the Best Clinical Marker of Hyperandrogenism
  • 20. Acne – a More Variable Marker
  • 21. Other Symptoms
    • Obesity
      • > 65% have elevated BMI
      • Usually fat is abdominal/visceral
      • Strongly associated with metabolic disturbances
    • Acanthosis nigricans
      • Due to insulin stimulation of epidermis
    • Polycystic ovaries
      • 80% w/ PCOS
  • 22. Polycystic Ovaries
    • >10 follicles 2-8mm in diameter, peripheral, increased stroma
    • 80% w/ hyper-androgenism (PCOS)
    • 87% w/ oligo-menorrhea
    • 82% premenopausal w/ DM2
    • 26% amenorrhea
    • 16-23% NORMALS
  • 23. Let’s Talk Hormones
    • Too much androgen
    • Too much estrogen
    • Too much insulin
    • What about
      • LH/FSH?
      • SHBG?
      • Prolactin?
  • 24. Androgen Metabolism
    • Produced by adrenals and ovaries, and peripheral conversion
    • Testosterone most potent
      • Free form is biologically active
      • Determined by Serum Hormone Binding Globulin (SHBG)
      • Free levels tend to be elevated due to decreased SHBG (due to estrogen, androgens, and insulin)
  • 25. Androstenedione
    • Androstenedione is the immediate precursor to testosterone, produced in ovaries, stimulated by LH
    • In ovaries, it gets converted by aromatase to estrone and estradiol
    • But in PCOS, decreased activity of enzyme result in large amounts of androgen to be sent into circulation
  • 26. DHEA-S
    • Majority from adrenal glands with little peripheral conversion from DHEA
    • Therefore, good marker for adrenal androgen production
      • ie, can rule out adrenal secreting tumor if OK
    • Little intrinsic androgenic activity
  • 27. Estrogen Metabolism
    • PCOS is a slightly hyperestrogenic state due to normal to slightly elevated estradiol and estrone concentrations
      • Due to increased estrogen production from polycystic ovaries and increased peripheral conversion from fat cells
    • Therefore, at increased risk of endometrial hyperplasia, even if amenorrheic
  • 28. Control of Hormone Production
    • COMPLEX!!
    • Incompletely understood
      • Genetic predisposition
      • Hypothal-pituitary-ovarian axis dysfunction
      • Increased theca cells in ovary with increased hormonal response
      • Changes in important enzymatic pathways
  • 29. Insulin Resistance
    • Both insulin resistance and hyperinsulinemia appear to be almost universal in PCOS
    • > 50% of obese women with PCOS
    • But non-obese women with PCOS also associated with IR
    • 25-30% show impaired glucose tolerance by age 30, and 8% develop frank DM2 annually
  • 30. Role of Insulin
    • Insulin receptors are found in the ovary
    • Insulin stimulates androgen production by the ovarian theca cells
    • Plasma insulin correlates with androgen levels
    • Hyperinsulinemia induces higher androgen production by both ovary and adrenals
  • 31. Endless Cycle
    • This elevation of insulin stimulates ovarian androgen production and suppresses serum SHBG, further increasing hyperandrogenism
    • So, even though insulin resistant in adipose, muscle and liver, the ovaries are insulin sensitive
  • 32. How To Make The Diagnosis
    • Criteria suggest it is a clinical diagnosis
      • But, “must exclude other endocrinopathies”
    • Congenital adrenal hyperplasia
    • Androgen secreting tumors
    • Pituitary adenoma
    • Thyroid abnormalities
    • Cushing’s syndrome
    • Drugs
  • 33. Which Labs?
    • Check for hormonal changes that will either rule out other significant disorders that can impact the patient AND/OR those hormonal patterns that confirm an unclear clinical picture
    • Once the diagnosis is made, monitor important markers of insulin resistance or CAD
  • 34. Diagnostic Labs
    • BetaHcG
    • TSH
    • Prolactin
    • Testosterone (free or total)
    • DHEA-S
    • Androstenedione
    • 17-OHP
    • Fasting insulin
    • Fasting glucose
    • Oral glucose tolerance test
    • LH
    • FSH
    • Lipids
    • Pelvic ultrasound
  • 35. Testosterone Levels and DHEA-S
    • Can be misleading
    • Can be normal to slightly elevated
    • Free testosterone most accurate (but more expensive)
    • Order to exclude androgen-secreting neoplasm and/or to monitor therapy
  • 36. 17-hydroxyprogesterone
    • In steroid synthesis pathway, 21-hydroxylase deficiency causes nonclassical congenital adrenal hyperplasia
    • If elevated 17OHP found, order ACTH stimulation test to clarify disorder
    • RARE
  • 37. LH/FSH
    • Ratio > 2.5 (or 3) is strongly associated with PCOS
    • Dependent upon timing of sample, so not helpful if negative
  • 38. Glucose Testing
    • Oral glucose tolerance testing with insulin levels
      • Reserve for family history, morbid obesity, or symptoms
    • Ratio of fasting glucose levels to insulin
      • <4.5 correlates with insulin resistance
      • PPV 97% in obese pts with PCOS
  • 39. Summary of Diagnostic Approach to Hirsutism
    • If long-standing mild hirsutism, like family members, and normal menses, NO LABS needed
    • If mild-mod hirsutism and irregular cycles, check testosterone, prolactin, and TSH
    • If moderate-severe or rapidly progressive hirsutism or other virilizing signs, check androgens including DHEA-S
  • 40. Management Goals
    • Primary goal for all is to suppress insulin-facilitated, LH-driven androgen production
    • Must consider individual patient’s goals regarding reproductive goals and long-term risks of CAD and endometrial cancer
  • 41. First!
    • Lifestyle modification should be first-line therapy
    • 7-10% weight loss is associated with a return to normal menstrual cycles and decreased insulin resistance
  • 42. Insulin Sensitizers
    • Metformin
    • Thioglitazones
  • 43. Exercise
    • Approximately 80% of the body’s insulin mediated glucose uptake takes place in muscles, making physical activity essential for reducing insulin resistance
    • Multiple studies support benefits of exercise
  • 44. Infertility
    • Weight loss can initiate ovulation
    • Clomid (clomiphene citrate)
      • Will induce ovulation in 80%
      • Only 50% with successful fertilization
      • 50mg qd x 5d, days 5-9 after onset of spontaneous or progesterone-induced menses
      • Can add metformin 500mg tid
  • 45. Amenorrhea
    • Must protect the endometrium
      • Combined oral contraceptives with low androgenic progesterone
      • Yasmin, spironalactone analog
    • If OCPs contraindicated, should use cyclic provera, q 3 months, to withdraw endometrium
    • Can try metformin to induce ovulatory cycles
  • 46. Hirsutism/acne
    • Shaving is safe and effective
    • Bleaching, depliatory, laser, and electrolysis
    • Vaniqua cream
    • OCPs
    • Spironolactone – need to have contraception as well
    • Therapies take time to work
  • 47. Case 1
    • Latina w/ irregular menses and clinical hyperandrogenism, infertility
      • PCOS
      • weight loss, metformin and/or clomid
      • look at lipids, BP
      • discuss diagnosis/prognosis
      • address depression
  • 48. Case 2
    • 34 yo with abrupt onset (<1 year) of hirsutism and pustular acne
    • History of normal menses and 2 healthy children, but now amenorrhea
    • Husband has noticed deepening of voice
    • Labs? Diagnosis?
  • 49. Case 2
    • What’s different?
    • Labs
      • Extremely elevated DHEA-S and testosterone levels indicating an adrenal tumor
  • 50. Case 3
    • 24 year old presents with c/o “no menses for one year”
    • Occasional galactorrhea
    • PE is significant for normal body hair patterns and clear skin, normal BMI, no striae
    • Labs? Diagnosis?
  • 51. Case 3
    • Why not PCOS?
    • Labs
      • Normal LH/FSH, normal androgens, normal TSH
      • Moderately elevated prolactin
      • MRI reveals a pituitary macroadenoma
  • 52. Take Home
    • Remember brief menstrual history
    • If you notice hirsutism, think of PCOS
    • Don’t go crazy with labs, and understand which test tells you what
    • Think insulin resistance and long-term consequences