Polycystic Ovarian Disease & Hyperandrogenism Evidence Based Update on Diagnosis & Consequences


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  • PCOS shows the following on U/S classically:
    Multiple, small (8-10) subcapsular cysts reflecting repeated episodes of incomplete follicular growth found adjacent to one another in a “string of Pearls” manner. There is also a dense, hyperplastic stroma reflecting an active thecal component that is over secreting androgens.
  • A ratio of less than 4.5 of fasting glucose to insulin levels correlates significantly with insulin resistance and has been studied for use as a screening test in obese patients with PCOS
  • The body recognizes the low levels of cortisol resulting in an up regulation of ACTH in an attempt to stimulate the adrenal cortex. This leads to adrenal stimulation and increased production of androgens.
  • Testosterone needed if considering treatment with antiandrogen for hisuitism as levels can then be followed.
    DHEAS not needed.
    Fasting morning 17-hydroxyprogesterone
    Levels > 800 ng/dL (8ng/ml) highly suspicious for late-onset congenital adrenal hyperplasia (CAH)
    Levels between 200-800 ng/dL (2-8ng/ml) unclear
    Levels < 200 ng/dL (2ng/ml) usually no CAH
    A ratio of less than 4.5 of fasting glucose to insulin levels correlates significantly with insulin resistance and has been studied for use as a screening test in obese patients with PCOS. Suggested only in selected patients. Information from Legro RS. Polycystic ovary syndrome: current and future treatment paradigms. Am J Obstet Gynecol 1998;179:S101-8.
  • 75% of PCOS women have IR
    Breast cancer patients found to be hyperinsulinemic and best data to support IR association.
    Prostate, colon and liver cancers also more common in obese pts with type 2 DM or pts with increased insulin levels.
    Up to 50% of all pts with essential HTN are IR.
    Metabolic syndrome is defined to capture subset of people with IR at risk for CVD so as to be a practical dx to address CVD risk but IR syndrome may be better way to describe etiology and more studies are looking at IR.
    insulin resistance is not a disease but the description of a physiologic state that greatly increases the chances of an individual developing several closely related abnormalities and associated clinical syndromes.
    PCOS pts may have IR and it is not obesity dependent.
  • The risk of endometrial cancer in this population is hard to determine because there are so few cases of endometrial cancer in women under 40 (<4% of all cases) and few studies of endometrial cancer in women with PCOS. One retrospective study of 1270 anovulatory women found the RR of endometrial cancer to be 3.1 compared to the general population.
  • Polycystic Ovarian Disease & Hyperandrogenism Evidence Based Update on Diagnosis & Consequences

    1. 1. Polycystic Ovarian Disease & Hyperandrogenism Evidence Based Update on Diagnosis & Consequences DR. SHARDA JAIN Dr. Jyoti Agarwal Dr. Jyoti Bhaskar Dr. Abhishek Parihar Directors :
    2. 2. PCOD & Hyperandrogenism There is Need to Update as Lately it is confusing The Gynaecologists !!
    3. 3. Learning Objectives • Prevalence and onset • Etiology / Pathophysiology ( Partial Story) • Update on clinical presentation • Update of diagnostic criteria for PCOD. • Short & long term consequences PCOD
    4. 4. IMPORTANCE OF PCOD • One of the MOST COMMON endocrine disorders of women • Most frequent cause of anovulatory infertility • PCOD strongly associated with Insulin Resistance which puts patients at risk for DM, CVD, HTN, OSA (sleep apnea), etc.
    5. 5. PCOD PREVALENCE • PCOD is the most common endocrine disorder affecting 4 - 12% of women of reproductive age. • PCOD appears to effect all races & nationality Incidence is definitely more in Asian Indians & seem to be increasing
    6. 6. Prevalence of PCOD In India
    7. 7. TYPES OF PCOD PATIENTS Seen in Our Practice Young adolescent Reproductive age group Women with family completed Oligo/ amenorrohoea Anovulatory infertility DUB Hirsutism / Acne Obesity Metabolic syndrome Obesity Prevention of metabolic syndrome Endometrial neoplasia/hyper plasia
    8. 8. Etiology of PCOD • Exact etiology of PCOD is still UNKNOWN – likely due to a steady state of high estrogen, androgens, luteinizing hormone (LH) and insulin levels. • High estrogen levels can cause suppression of pituitary FSH and relative increase in LH. • Increased LH stimulates the ovary, which results in anovulation, multiple cysts and theca cell hyperplasia with excess androgen output. • High insulin levels may also increase the production of testosterone by the ovaries.
    9. 9. Genetic Basis • A genetic basic that is both multifactorial and polygenic is highly suspected, as there is a well – documented aggregation of the syndrome within families (Franks, et al human reprod 12:2641,1997)) • An increased prevalence has been noted between affected individuals and their SISTERS (32 to 66 %) and MOTHER (24- 52%) (Govind et al j clin endocrinol metab 84:38,1999)
    10. 10. Autosomal Dominant Inheritance May have expression in both females and males as it is seen in first – degree male relatives of women with PCOS - have significantly higher rates of elevated circulating DHEA levels , early balding and insulin resistance compared with control males
    11. 11. INSULIN RESISTANCE A Pathopysiological Contributor in 50-80% of the PCOD Women
    12. 12. Complete Pathophysiology of PCOD
    13. 13. Newer Concepts on PCOD & its Management With Myo- Inositol Is also uploaded today By Lifecare Centre Team in slideshare.net
    14. 14. The story is still not over … Pandora Box on Myoinositol, D- Chiroinositol (40:1) & Vitamin – D In PCOD will be Uploaded soon
    15. 15. Vitamin D Deficiency is an Independent Predictor of Obesity 80% PCOS women are obese PCOS Women with vit D deficiency • Higher mean BMI • Hypertension • Hypertriglyceridemia • Lower high-density cholesterol (all p<0.05) Exp Clin Endocrinol Diabetes. 2006 Nov;114(10):577-83.) ACOG
    16. 16. PCOD Presentation • Symptom / Prevalence: – Infertility 75% –Hyperandrogenism 70% –Obesity 60-80% – Amenorrhea 50% – Abnormal uterine bleeding 30-40% – Normal menstruation 20%
    17. 17. Clinical Manifestation of PCOD AAccnnee AAccaanntthhoossisis HHirirssuuttisismm OObbeessitityy HAIR LOSS HAIR InInffeerrttiliiltityy LOSS IRREGULAR MENSES IRREGULAR MENSES
    18. 18. Common Signs and Symptoms of PCOD
    19. 19. Symptoms of PCOD
    20. 20. Challenges of PCOD in Different Age Groups But the Root Cause is The Same
    21. 21. Challenges of PCOD in Different Age Post Groups • Irregular Periods • Endometrial Cancer • Hypertension • Diabetes • Dyslipidemia • OSA •Dibetes mellitus •Endometrial cancer •Cardiovascular disease •Metabolic Syndrome Peri
    22. 22. DIAGNOSIS
    23. 23. PCOD DIAGNOSIS • No single confirmatory test for PCOS. • It is a clinical diagnosis. • Unlike past Ovarian cysts alone are not required for diagnosis. • Cysts are present on ultrasound in more than 90% of women with PCOS but also present in up to 25% of normal women.
    24. 24. Bio chemical and Diagnostic Markers of PCOD Accepted everywhere – Elevated androgen (i.e. testosterone > 60 or free testosterone >0.75) levels – Elevated LH:FSH ratio > 2:1 – Increased Insulin levels – Insulin resistance , (Clinical / Lab) – Ultrasound appearance of PCO
    25. 25. Diagnosis of Polycystic Ovarian Disease NIH (1990) 1. Oligo ovulation 2. Hyperandrogenism and / or hyperandrogenemia (with exclusion of related disorders) ESHRE /ASRM (Rotterdam) 2003 To include TWO OUT OF THREE of the following: 1. Oligo – or anovulation 2. Clinical and / or biochemical signs of hyperandrogenism 3. Polycystic ovarian (with exclusion of related disorders) AE – PCOS (2009) 1. Hyperandrogenism : hirsutism and / or hyperandrogenemia and 2. Ovarian dysfunction : oligo – anovulation and / or polycystic ovaries and 3. Exclusion of other androden – excess or related disorders
    26. 26. Our Main focus will be on Diagnosis of PCOD According to Androgen Excess & PCOS society 2009 – Hyperandrogenism • Elevated serum androgen levels or • Biological expression of hyperandrogenism (acne or hirsutism) – Ovarian Dysfunction • Anovulation or oligo-ovulation or • Polycystic ovaries – Absence of other causes of anovulation • Thyroid disorders • Hyperprolactinemia • Cushing’s syndrome • Late onset congenital adrenal hyperplasia (CAH) • Ovarian and adrenal tumors
    27. 27. Hyperandrogenism
    28. 28. Hyperandrogenism • Non-virilizing symptoms /signs include: – Hirsutism: course hair growth in androgen-dependent body areas such as sideburn area, chin, upper lip, periareolar area, chest, lower abdominal midline and thigh. – Acne – Oily skin – Abnormal menstrual cycles – Infertility
    29. 29. Hyperandrogenism Virilizing symptoms /signs include:* – Clitorimegaly – Deepening of the voice – Male pattern balding – Masculinization of body habitus – Increased libido Less commonly seen than non-virilizing S/S VIRILIZATION reflects higher androgen levels and should prompt investigations for an Androgen- producing tumor of the ovary or the adrenal gland
    30. 30. Clinical
    31. 31. Ferriman Gallway Evaluation of Hirsutism Hardly Used
    32. 32. Physical Exam – Significant Findings • SKIN – Acanthosis nigricans (darkly shaded skin in the flexures of the neck , axilla, or groin – IR/DM) Skin tags – IR/DM 10 % Acanthosis nigricans Over 50%
    33. 33. EExxcclluussiioonn ooff RReellaatteedd DDiissoorrddeerrss • Thyroid disorders SSrr..TTSSHH,,SSrr..PPrrll • Hyperprolactinemia • Cushing’s syndrome DDeexxaa ssuupprreessssiioonn tteesstt • Late onset congenital adrenal hyperplasia (CAH) • Basal morning 17-OHP,(2-3 ng/ml)) • Ovarian and adrenal tumors DHEAS • WHO I &III –FSH,LH,E2 • Syndromes of severe insulin resistance(HAIRAN syn)
    34. 34. Hyperandrogenism Differential Diagnosis
    35. 35. Screening Tests For Pcod ACOG Recommendation • ACOG recommends that all women with a suspected diagnosis of PCOD should be screened with –17-hydroxyprogesterone level to R/O late onset CAH (Level C). • PCOD and late onset CAH are distinguished from each other only by laboratory testing.
    36. 36. A word about Congenital Adrenal Hyperplasia (CAH) • Late-onset presents in early adulthood. • Autosomal Recessive. • Presents with oligomenorrhea and/or hirsutism. • 90% due to 21-hydroxylase deficiency. • Patients with 21-hydroxylase deficiency do not form cortisol in normal amounts. DIAGNOSTIC TEST is fasting 17-hydroxyprogesterone. always > 2 ng/mL . All abnormal tests should be confirmed with ACTH stimulation test. Consider endocrine referral.
    37. 37. A Lab Tests suggested for SUDDEN onset of Hyperandrogenism Test Result Total testosterone level Slightly elevated in PCOS Total testosterone > 200 ng/dL -- suspicious for adrenal or ovarian tumor therefore additional evaluation with pelvic US, CT or MRI indicated Serum DHEAS level Slightly elevated in PCOS DHEAS level > 8 ng/ml -- suspicious for adrenal tumor therefore additional evaluation should include adrenal gland imaging with CT or MRI 24 hour urine cortisol or overnight dexamethasone Urine free cortisol >20 ug/d is suggestive of Cushing’s Syndrome
    38. 38. Hyperandrogenism Hirsutism, acne, alopecia BIOCHEMICAL Testing • Free Testosterone –NO ROLE & 10 times costly • ANDROSTENADIONE-NO ROLE SUDDEN ONSET of these symptoms suggests other D/D * Cushing’s syndrome * Adrenal or ovarian tumor.
    39. 39. Summary of Suggested Lab Test by ACOG  Prolactin level  Testosterone level  LH and FSH  TSH  Fasting glucose level or 2 hr OGTT  Lipid profile, including total, LDL,HDL  17-hydroxyprogesterone level* *--Fasting level to r/o CAH
    40. 40. You Should know Prevalence of Uncommon Conditions to be Ruled Out before Making Diagnosis of PCOD • Adrenal tumors 2 per million • Cushing’s Syndrome 2 per million • Androgen secreting ovarian tumors < 1 per million PCOD 1/3 girls in India 10% global
    41. 41. AAEESS RREECCOOMMMMEENNDDAATTIIOONNSS • PPCCOOSS iiss aa HHYYPPEERRAANNDDRROOGGEENNIICC DDIISSOORRDDEERR • TThhee oovvaarriiaann mmoorrpphhoollooggyy sshhoouulldd bbee ccoonnssiiddeerreedd wwhheenn eessttaabblliisshhiinngg tthhee ddiiaaggnnoossiiss bbeeccaauussee ppoollyyccyyssttiicc oovvaarriieess aarree ffoouunndd iinn tthhee mmaajjoorriittyy,, aalltthhoouugghh nnoott aallll,, wwoommeenn wwiitthh PPCCOOSS
    43. 43. UUSSGG PPOOLLYYCCYYSSTTIICC OOVVAARRIIEESS • PPrreesseennccee ooff 1122 oorr mmoorree ffoolllliicclleess iinn eeaacchh oovvaarryy ,,22--99 mmmm iinn ddiiaammeetteerr aanndd oorr iinnccrreeaasseedd oovvaarriiaann vvoolluummee >> 1100 mmll • NNoo ssuubbjjeeccttiivvee aasssseessssmmeenntt • OOmmiitt ssttrroommaall eecchhooggeenniicciittyy aanndd vvoolluummee • WWoommeenn oonn OOCC ppiillll--??
    44. 44. PPOOLLYYCCYYSSTTIICC OOVVAARRIIEESS--UUSSGG PPRRAACCTTIICCAALL CCOONNSSIIDDEERRAATTIIOONNSS • IIff DDoommiinnaanntt FFoolllliiccllee oorr CCoorrppuuss LLuutteeuumm sseeeenn ---- ssccaann rreeppeeaatt iinn nneexxtt ccyyccllee • IIDDEEAALL--TTVVSS • iiff rreegguullaarr ccyyccllee –– DDaayy 33 -- 55 • OOlliiggoommeennoorrrrhhooeeiicc wwoommeenn----pprrooggeessttiinn wwiitthhddrraawwll bblleeeedd DDaayy 33 -- 55 oorr aannyy ddaayy • FFoolllliiccllee nnuummbbeerr && ssiizzee-- • lloonnggiittuuddiinnaall aanndd AAPP ddiiaammeetteerr aanndd ssiizzee eexxpprreesssseedd aass mmeeaann • RRuullee oouutt eennddoommeettrriiaall hhyyppeerrppllaassiiaa • AAsssseessss rriisskk ooff OOHHSSSS
    46. 46. SSccrreeeenn ffoorr MMeettaabboolliicc SSyynnddrroommee UUssiinngg tthhee RRootttteerrddaamm CCrriitteerriiaa..
    47. 47. Indian 80cm
    48. 48. IInnssuulliinn RReessiissttaannccee • IINNTTEERRPPRREETTAATTIIOONN --NNoorrmmaall ffaassttiinngg→→<<1155 mmiiccrroo IIUU//mmll AAfftteerr 22hhrr PPPP <<3300 mmiiccrroo IIUU//mmll -- IINNSSUULLIINN RREESSIISSTTAANNCCEE lliikkeellyy →→ 110000 --115500 -- IINNSSUULLIINN RREESSIISSTTAANNCCEE →→115511 –– 330000 -- sseevveerree iinnssuulliinn rreessiissttaannccee →→ >> 330000 • FFaassttiinngg gglluuccoossee ttoo ffaassttiinngg iinnssuulliinn rraattiioo iiss nnoo lloonnggeerr rreeccoommmmeennddeedd bbeeccaauussee ooff iittss vvaarriiaabbiilliittyy
    49. 49. Androgen EExxcceessss SSoocciieettyy ssccrreeeenniinngg aanndd ttrreeaattmmeenntt rreeccoommmmeennddaattiioonn ffoorr IIGGTT iinn PPCCOODD
    50. 50. f Screening foorr GGlluuccoossee IInnttoolleerraannccee-- RReeccoommmmeennddaattiioonnss ((jjcceemm--22000077) • AAAACCEE----OOGGCCTT iinn oobbeessee PPCCOOSS aanndd ffaammiillyy hh//oo • AACCOOGG——aallll PPCCOOSS--FFBBSS aanndd 22 hhrrgglluu lleevveell aafftteerr 7755gg ooff gglluuccoossee llooaadd • AADDAA---------- << 4455 YYRRSS&& BBMMII>>2255 PPCCOOSS--FFBBSS ,,iiff rraaiisseedd tthheenn OOGGTTTT • AASSRRMM &&EESSHHRREE &&EEnnddooccrriinnoollooggyy PPCCOOSS CCoonnsseennssuuss----------oobbeessee PPCCOOSS--SSccrreeeenn ffoorr mmeettaabboolliicc aanndd gglluu iinnttoolleerraannccee wwiitthh aann OOGGTTTT.. NNoonnoobbeessee PPCCOOSS iiff aaddddiittiioonnaall rriisskk ffaaccttoorrss..
    51. 51. PCOD & Ovarian Dysfunction Presentation • Initial onset in the peri-pubertal years and progressive in nature. • PCOD with OVARIAN DYSFUNCTION may have a wide range of clinical symptoms. – Menstrual irregularities, – Hirsuitism, acne, or – Infertility are the most common reasons for seeking medical care.
    52. 52. Consequences of Polycystic Ovarian disorders Short Term consequences • Obesity • Infertility • Irregular menses • Abnormal lipid levels • Hirsutism/acne/androgenic alopecia • Glucose intolerace / acanthosis nigricans Long – Term consequences • Dibetes mellitus • Endometrial cancer • Cardiovascular disease
    53. 53. Consequences of PCOD (Listed in order from most common to least common) • INFERTILITY • Recurrent spontaneous abortion • Depression/anxiety • Dyslipidemias – Total cholesterol (elevated) – LDL cholesterol (elevated) – HDL cholesterol (decreased) – Triglycerides (elevated) • Hypertension • Type 2 diabetes mellitus • Coronary atherosclerosis • Cerebrovascular accidents • Endometrial carcinoma
    54. 54. Insulin Resistance & Various Clinical Syndrome • Type 2 diabetes • Cardiovascular disease • Essential hypertension • Polycystic ovary syndrome • Non-alcoholic fatty liver disease (NASH) • Certain forms of cancer - breast,colon,liver,prostate • Sleep apnea Because all are interrelated
    55. 55. Major Consequences of PCOD • INSULIN RESISTANCE- up to 75% –Evaluate for –Hypertension –Type 2 diabetes – Dyslipidemias –OSA (Sleep apnea) –NASH, (Non-alcoholic fatty liver disease) –Metabolic Syndrome X, etc.
    56. 56. Major Consequences of PCOD • Endometrial Hyperplasia – Chronic anovulation, obesity and hyperinsulinemia are associated with endometrial hyperplasia and endometrial cancer. – This is likely due to prolonged exposure to unopposed estrogen. – Endometrial cancer risk is 3 times that of general population.
    57. 57. Major Consequences of PCOD • Dyslipidemias – 70% of women with PCOS will have abnormal lipid panels. – Elevated triglycerides and LDL and low HDL are the most common abnormalities. – All women with PCOS should be screened with fasting lipid panel ( Level A). Now endocrinologist feel that lipid profile can be done any time of the day just like TSH
    58. 58. Major Consequences of PCOD –CENTRAL OBESITY android, APPLE SHAPE Central Obesity is High Risk For Co-Morbidities / Complications – LOWER BODY OBESITY Gynecoid PEAR SHAPE 60-80% of women with PCOS are obese.
    59. 59. BMI Cutoff for INDIAN -2.5 in each category BMI Cutoff Weight Status Comments <18.5 UNDERWEIGHT Being underweight also puts you at risk for developing many health problems. 18.5 - 23.9 HEALTHY WEIGHT RANGE Your weight is within normal range. You can continue to keep a healthy weight through physical activity and healthy eating. Keep up with the good work! 24 - 26.9 OVERWEIGHT Being overweight can put you at risk for developing many chronic diseases >27 OBESE Obesity increases risks for developing many chronic diseases such as heart disease and diabetes, and decreases overall quality of life.
    60. 60. 60-80% of women with PCOS are obese. Anthropometric measurements •Waist Circumference •> 40” in males •>35” in Females •Waist HIP Ratio –>1.0 in males –>0.8 in Females
    61. 61. Target WAIST Circumference for Indians Sometimes even when BMI is within Normal range, having too much fat around the abdomen (APPLE SHAPE BODY) will still put one at risk for heart disease and diabetes. Below are the target goals for waist circumference measurements. INDIAN WOMEN Equals or less than 80cm (31.5 in)
    62. 62. Major Consequences of PCOD • Impaired Glucose Tolerance / Type 2 Diabetes – Up to 40% of women with PCOS have impaired glucose tolerance (IGT). – Risk of IGT and Type 2 Diabetes Mellitus (DM) is increased in both obese and non-obese women with PCOS. – Retrospective studies have shown 2 to 5 fold increase of type 2 diabetes in women with PCOS.
    63. 63. Summary of presentations and Consequences of PCOD The Most Common Endocrine disorder In women Symptoms may Include chronically irregular and / or Absent or delayed periods Symptoms may include facial hair , central obesity and acne Let untreated it may lead to Heart Disease Left untreated, it may lead to Uterine cancer Leading cause of Infertility P C O D
    64. 64. Left you with many Q unanswered
    65. 65. Management of Adolescent PCOD Made Easy Is also uploaded today By Lifecare centre team In slideshare.net
    66. 66. Management Guidelines of INFERTILITY an ART in PCOD Based on A ESHRE/ASSRRMM--SSppoonnssoorreedd PPCCOOSS CCoonnsseennssuuss WWoorrkksshhoopp GGrroouupp ((FFeerrtt SStteerrtt--22000088)) WWiillll bbee uuppllooaaddeedd sshhoorrttllyy
    67. 67. ADDRESS 11 Gagan Vihar, Near Karkari Morh Flyover, Delhi - 51 CONTACT US 9650588339, 011-22414049, WEBSITE : www.lifecarecentre.in www.drshardajain.com www.lifecareivf.com E-MAIL ID Sharda.lifecare@gmail.com Lifecarecentre21@gmail.com info@lifecareivf.com &