Your SlideShare is downloading. ×
  • Like
Pcos
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Now you can save presentations on your phone or tablet

Available for both IPhone and Android

Text the download link to your phone

Standard text messaging rates apply

Pcos

  • 1,088 views
Published

PCOS is an intergenerational problem having its origin in adolesence with lot of metabolic dysfunction.

PCOS is an intergenerational problem having its origin in adolesence with lot of metabolic dysfunction.

Published in Health & Medicine
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
No Downloads

Views

Total Views
1,088
On SlideShare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
113
Comments
1
Likes
2

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. PCOS Dr.Veerendrakumar C.M MD.,DNB Professor Dept of OBG,VIMS,Bellary veerendrakumarcm@gmail.com
  • 2.  1st described by Irving Stein and Michael Leventhal as a triad of amenorrhea, obesity and hirsutism (1935)  The most common endocrine disorder in women of reproductive age ~ 2%-8% of women Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 2
  • 3.  Intergenerational problem POLYCYSTIC OVARIAN SYNDROME POLYCYSTIC OVARIAN SYNDROME   Normal ovaries Polycystic ovaries  volume < 8 cm3  mildly enlarged  scattered follicles  generally > 8 cm3  peripheral distribution of follicles  increased stroma Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 3
  • 4.  EVOLVED…. From gynecological curiosity to a multi system endocrinopathy Hamburg 1996  Most common but most poorly understood condition with complex pathophysiology with considerable scientific debate. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 4
  • 5.   Oligo-ovulation or anovulation Clinical or laboratory evidence of hyperandrogenism and  Polycystic ovaries as defined by ultrasonography In addition, the definition requires the exclusion of other medical conditions that cause irregular menses and androgen excess Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 5
  • 6.  Ultrasound criteria: --- increased ovarian area/volume --- 10-15 microcyst(<10 mm diameter) organized in a peripheral rosary pattern. --- increased echogenicity of ovarian stroma. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 6
  • 7.  Increased ovarian stroma is the most valuable diagnostic factor for PCOS  Absence of it does not exclude the diagnosis. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 7
  • 8.  Transvaginal US Scan – gold standard.  Follicles of 2 -9 mm, at least 12 in number.  Bilateral or unilateral  Ovarian volume >10 cm³ prolate ellipsoid formula for volume L x B x T x 0.513 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 8
  • 9.  Use high resolution equipment  Do on day 3 -5  If dominant follicle or corpus luteum found, repeat in next cycle.  Whenever possible, use TVS  Follicle number estimated in longitudinal and cross sectional views.  Remember, all women with polycystic appearance need not have PCOS. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 9
  • 10.  should remember that 20 to 30 % of women in general population have polycystic ( multi follicular) ovaries Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 10
  • 11.  17-23% of population can have polycystic ovaries  76%-80% of these women had clinical manifestations Polson 1988,Botsis 1995 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 11
  • 12. Concept of a spectrum PCO PCOS increasing BMI Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 12
  • 13. PCO     MFO Small follicles Dense stroma Increased ovarian volume No dominant follicle     Larger follicles Lesser stroma density Normal volume Dominant follicle seen Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 13
  • 14.      Delayed normal puberty Central precocious puberty Hypothalamic anovulation Hyperprolactinemia Early normal follicular dominant phase Carefully consider clinical/biological components of consensual definition. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 14
  • 15.  Early follicular growth is excessive  Recruitment of dominant follicle do not occur Excessive AMH is involved in follicular arrest. Jonard 2004 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 15
  • 16.  3D USG – not superior to 2D USG  MRI-main role is to exclude virilizing ovarian tumor. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 16
  • 17.  increased LH pulse frequency and amplitude. secondary to increased pulse frequency of gonadotropin-releasing hormone, which selectively increases LH release,  resultant elevation of the absolute level of circulating LH Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 17
  • 18.  Androgen production by ovarian thecal cells is LH-dependent, and the elevated LH likely contributes to the excess androgens. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 18
  • 19.  FSH levels chronically remain in the midfollicular range,which is an insufficient level  Follicle growth and development is arrested and anovulation results Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 19
  • 20.  Adrenal androgen production is also increased in many PCOS patients  There may be a common defect in ovarian and adrenal biosynthesis Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 20
  • 21.  Possible theories (1) insulin resistance (2) Obesity Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 21
  • 22.  Many PCOS women, both obese and nonobese, are insulin resistant and insulin resistance is believed to play a prominent role in the pathophysiology of the syndrome Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 22
  • 23. Hyperinsulinemia 1)Increases P450c activity, which converts P to 17-OH progesterone then to androstenedione and testosterone 2) Insulin decreases hepatic synthesis of SHBG and IGF-BP1 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 23
  • 24.  Post binding defect in signalling  Insulin receptor alteration  Pancreatic beta cell dysfunction Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 24
  • 25. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 25
  • 26.  Familial clustering of PCOS common Yildiz BO et al, Journal of Clinical Endocrinology & Metabolism, 2003. “PCOS is a genetically determined ovarian disorder… Franks S et al, International Journal of Andrology, 2006. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 26
  • 27.  Believed to be ? autosomal dominant, ? ?X-linked inheritance  Dysregulation of the P450c17 gene controlling steroidogenesis,CYP11a is suspected  Insulin receptor gene defect  Follistatin gene defect Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 27
  • 28.  Adiponectin produced in adipose tissue and has anti atherogenic effect. - Lower levels in PCOS  Resistin- antagonizes insulin action -Higher levels in PCOS  Proportion of adiponectin and resistin influence cardio-metabolic risk in PCOS Seow 2004 Hum Reprod Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 28
  • 29.  Ghrelin controls food intake and energy balance  Lower levels found in PCOS Gambineri 2002 Int j obes Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 29
  • 30. emerging as a common cause of menstrual disturbances in the adolescent population Guttmann-Bauman I, Journal of Pediatric Endocrinology & Metabolism, 2005. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 30
  • 31.  >75% of women with anovulation infertility Franks et al, International Journal of Andrology, 2006.  Follicular arrest • Impaired selection of dominant follicle •Risk of multiple pregnancy with treatment Jonard S, Dewailly D, Human Reproduction Update, 2004. Prof.Veerendrakumar CM, VIMS,Bellary. 31
  • 32. 40 to 50 % of PCOS women are obese. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 32
  • 33.  Spontaneous Abortions • Increased in high BMI/PCOS patients  Wang JX et al, Human Reproduction, 2001. Impaired Glucose Tolerance Turhan NO et al, International Journal of Gynecology & Obstetrics, 2003.  Gestational Diabetes  Hypertension  Small for Gestational Age Bjercke S et al, Gynecologic and Obstetric Investigation, 2002. Weerakiet S et al, Gynecological Endocrinology, 2004. Sir-Petermann T et al, Human Reproduction, 2005. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 33
  • 34. • Racial difference exists • More in South Asians • Less in Eastern Asians Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 34
  • 35. PCOS PCOS is also associated with a characteristic metabolic syndrome that includes: insulin resistance dyslipidemia hypertension These features are linked with increased risks of type 2 diabetes and possibility of premature cardiovascular diseaseVIMS,Bellary. November 24, 2013 Prof.Veerendrakumar CM, 35
  • 36.  Endometrial Cancer • Long-term follow-up of 786 PCOS women found an increased risk of endometrial cancer Wild S et al, Human Fertility, 2000. Pillay OC et al, Human Reproduction, 2006.  Cardiovascular Disease • PCOS is characterized by endothelial dysfunction and resistance to vasodilating action of insulin Dahlgren E et al, Acta Obstetricia et Gynecologica Scandinavica, 1992. Paradisi G et al, Circulation, 2001. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 36
  • 37.  Sleep Apnea • Increased Sleep Disordered Breathing (SDB) and daytime sleepiness in PCOS vs. controls Vgontzas AN et al, Sleep Medicine Reviews, 2005.  Depression • Higher prevalence in PCOS patients, associated with higher body mass index (BMI, P=0.05) and greater insulin resistance (P=0.02) Rasgon NL et al, Journal of Affective Disorders, 2003. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 37
  • 38.  PCOS women with the metabolic syndrome had more hyperandrogenemia than PCOS women without the metabolic syndrome Apridonidze et al Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 38
  • 39. May be a severe form of PCOS  HA - Hyperandrogenism  IR - Insulin Resistance  AN - Acanthosis Nigricans May have clitoromegaly, temporal balding, deepening of voice. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 39
  • 40. Hyperprolactinemia 1. • • Prominent menstrual dysfunction Little hyperandrogenism 2. Congenital Adrenal Hyperplasia • • morning serum 17-hydroxyprogesterone concentration greater than 200 ng/dL in the early follicular phase strongly suggests the diagnosis confirmed by a high dose (250 mcg) ACTH stimulation test: post-ACTH serum 17-hydroxyprogesterone value less than 1000 ng/dL Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 40
  • 41. 3. Ovarian and adrenal tumors • serum testosterone concentrations are always higher than 150 ng/dL • adrenal tumors: serum DHEA-S concentrations higher than 800 mcg/dL • LOW serum LH concentrations 4. Cushing’s syndrome 5. Drugs: danazol; OCPs with high androgenicity Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 41
  • 42.  IRREGULAR MENSES 10 YRS  SCALP HAIR LOSS 6 YRS  EXCESSIVE HAIR GROWTH 6 YRS  AMENORRHEA 1 YR Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 42
  • 43.  Case scenario to differentiate severe form of PCOS from that of androgen secreting ovarian tumor… Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 43
  • 44.     FRONTAL BALDNESS +, HIRSUTISM + SYSTEMIC EXAMINATION – NORMAL USG – (11/12/2001) – POLYCYSTIC OVARIES DOPPLER STUDY OF OVARIAN VESSELS NORMAL SUPRARENAL AREA NORMAL Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 44
  • 45.        TESTOSTERONE 358 ng/dL (20-80) 17-OH PROGESTERONE 0.66 ng/ml (0.1-1.36) DHEA-SULPHATE 224mcg/dL (35-430) THYROID FUNCTION TESTS-NORMAL FSH- 3.8miu/ml LH - 3.6miu/ml PRL - 24ng/ml Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 45
  • 46. FINASTERIDE 5mg OD  FEMILON X 21DAYS  MINOXIDIL LOTION FOR TOPICAL APPLICATION PATIENT GOT HER MENSES BACK & SYMPTOMATICALLY IMPROVED  Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 46
  • 47.     LOW DOSE OC PILL STOPPED OI WITH CLOMIPHENE TRIED WITHOUT ANY SUCCESS USG REPEATED ON 12/5/2003 – PCOD WITH A WELL DEFINED ROUND HYPER ECHOIC MASS OF 3.5 X 3.4 X 3 cm IN RIGHT OVARY TESTOSTERONE 570 ng/dL Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 47
  • 48.     UTERUS & TUBES NORMAL POD CLEAR RT OVARY ENLARGED, EXT SURFACE NORMAL LT OVARY NORMAL Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 48
  • 49.    RT SIDED SALPINGO OVARIOTOMY DONE SPECIMEN SUBJECTED FOR HPE REPORT WAS STEROID CELL TUMOR Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 49
  • 50. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 50
  • 51. PATIENT UNDERWENT LSCS ON MAY 2004 &DELIVERED MONOZYGOTIC TWINS. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 51
  • 52.  Fasting glucose: elevated  2 hour OGTT: elevated  Fasting insulin: elevated  Free testosterone: elevated  DHEA-S: normal  17-hydroxyprogesterone: normal  Pelvic US  Lipids Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 52
  • 53.  Serum HCG  Serum prolactin  Thyroid panel  FSH: r/o ovarian failure  Serum luteinizing hormone (LH)— elevated  Serum estradiol—normal  Serum estrone—elevated Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 53
  • 54. Consume more foods  rich in complex carbohydrates  monounsaturated fat  fiber  with a decreased ratio of omega-6 to omega-3 fatty acids Reduce  Total caloric intake  Saturated fat  Cholesterol Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 54
  • 55.  Frequency of obesity in women with anovulation and PCO: 30%75% Ehrmann DA, New England Journal of Medicine, 2005.  Six month weight-loss program for overweight anovulatory women • Lost an average of 6.3 kg (13.9 lbs) • Decreased fasting insulin and testosterone levels • 92% resumed ovulation (12/13) • 85% became pregnant (11/13) Clark AM et al, Human Reproduction, 1995. Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 55
  • 56. Focus on lowering dietary fat as a means for promoting negative energy balance has led to an underestimation of the potential role of dietary composition in promoting reductions in energy intake and weight loss  Roberts SB, et al:J Am Coll Nutr 21:140S, 2002  Diets based on low-GI foods produced greater weight loss than did equivalent diets based on high-GI foods.  Low GI diet more effect than low fat in obese children Spieth LE, et al: Arch Ped Adol, 154:947, 2000 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 56
  • 57.  Hypocaloric   diets reduce insulin resistance 10-20% protein, ~50% carbohydrates < 30% total fat, < 10% saturated fat ADA nutritional recommendations: Diabetes Care 20S:14, 1997 Further improvement with 5-10kg weight reduction  Two fold increase glucose disposal rate with 16% decrease weight  Niskanen L, et al: J Obes Relat Metab Disord 20:154, 1996 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 57
  • 58.  Substitute nonhydrogenated unsaturated fats for saturated and trans-fats  increase omega-3 fatty acids from fish, fish oil supplements, or plant sources   increase fruits, vegetables, nuts, and whole grains avoid refined grain products.  Simply lowering the percentage of energy from total fat in the diet is unlikely to improve lipid profile or reduce CHD incidence. Willet WC, et al: JAMA 288:2569, 2002 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 58
  • 59.  Peripheral muscle cells metabolize 80% of glucose  Aerobic exercise 3-4x/wk 20-30 min/session Burns 100-200 kcal  40% improvement in insulin sensitivity within 48 hrs. J Appl Physiol 71:2502, 1991 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 59
  • 60.  Metformin  Pioglitazone,rosiglitazone Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 60
  • 61.  Decreases hepatic glucose production  Improves insulin sensitivity  Antilipolytic effect  Increases SHBG  Reduces leptin production  Endometrial action-IGFBP-1 increased  LH mediated action on theca cells reduced Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 61
  • 62.  Metformin • 500 mg daily • Increase by 500 mg each week until:  Normal menses  Reached max dose  Side-effects  Clomid • 50 mg days 3-7 for 3 months • 100 mg days 3-7 for 3 months Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 62
  • 63.  Metformin 500 mg b.i.d. 6 weeks, t.i.d. thereafter  Clomiphene added if anovulatory at 12 weeks  31/48 (64.5%) resumed spontaneous menses  16/31 (52%) conceived within the first six months  3/16 (19%) had spontaneous abortions Heard MJ, et al: Abstract 140, Society of Gynecologic Investigation, 2001 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 63
  • 64.  26 women received – Placebo- 1 ovulated  35 women received – Metformin- 14 ovulated  1500 mg/day Nestler et al. N Engl J Med 1998 Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 64
  • 65.  Target—1500-2500 mg per day  Clinically significant responses not regularly observed at doses less than 1000 mg per day  Extended release formulations—fewer sideeffects. Entire dose should be given with dinner Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 65
  • 66.  Diarrhea, nausea, vomiting, flatulence, indigestion, abdominal discomfort • Caused by lactic acid in the bowel wall • Minimized by slow increase in dosage  Lactic acidosis—rare • Avoid in CHF, renal insufficiency, sepsis • Discontinue for procedures using contrast (withhold X 48 hours) • Temporarily suspend for all surgical procedures that involve fluid restriction • Cimetidine causes increased metformin levels Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 66
  • 67.  Clomiphene  Aromatase citrate inhibitors e.g. Letrazol  Gonadotrophins  Risk of hyperstimulation is high Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 67
  • 68.  Wedge resection – obsolete  Laparoscopic ovarian drilling Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 68
  • 69. 4 to 5 holes on anterior surface of ovaries.  40 watts current, cutting mode  Depth of 4mm  Current passed for 4 seconds  Surface –intermittent irrigation & suction with saline Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 69
  • 70.  Weight loss—reduction in serum testosterone concentration and resumption of ovulation  Clomid: 80% will ovulate, 50% will conceive  Metformin: when added to clomid, improves ovulatory rates  FSH injections  Laparoscopic surgery: wedge resections, laparoscopic ovarian laser electrocautery  IVF Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 70
  • 71. ADVANTAGES       DISADVANTAGES High success rate Prolonged response Multiple births OHSS Dose, duration ovulation Induction        Adhesion formation Interceed not beneficial Requires surgery 1/3 require ovulation medications POF risk Less successful in smokers 25% vs 95% Prof.Veerendrakumar CM, VIMS,Bellary. November 24, 2013 71
  • 72. Learning by sharing…..