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update on PCOS

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Aboubakr Elnashar

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update on PCOS

  1. 1. ABOUBAKR ELNASHAR UPDATE ON POLYCYSTIC OVARY SYNDROME Prof. Aboubakr Elnashar Benha university Hospital, Egypt CONTENTS ❑ INTRODUCTION I. DIAGNOSIS II. RISK ASSESSMENT III.TREATMENT ABOUBAKR ELNASHAR
  2. 2. PCOS ▪ Prevalence ▪ Most common disorder in women of reproductive age ▪ 8% (NIH criteria,1990) ▪ 18% (Roterdam criteria, 2003) ▪ 12% (AE, PCOS, 2009) ▪ Primary cause of anovulatory infertility. ▪Aetiology: Unknown ▪±associated with ▪ overproduction of androgens by the ovaries ▪in the majority genetic in origin. ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR
  3. 3. ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR Manifestations of PCOS across the lifespan.
  4. 4. I. DIAGNOSIS ABOUBAKR ELNASHAR DIAGNOSTIC CRITERIA 1. Irregular menstrual cycles ▪ Post menach: ▪ < 1y: Irregular cycles are normal {pubertal transition}. ▪ > 1 y: 90 days for any one cycle ▪ > 1 to < 3 y: < 21 or > 45 days. ▪ > 3 years: < 21 or > 35 days or < 8 cycles per year. ▪ Primary amenorrhea by age 15 or > 3 years post thelarche (breast development). ABOUBAKR ELNASHAR
  5. 5. ▪With irregular cycles: ▪PCOS should be considered ▪assessed according to the guidelines. ▪Ovulatory dysfunction: can still occur with regular cycles. ▪If anovulation suspected: test progesterone levels. ABOUBAKR ELNASHAR 2. Clinical hyperandrogenism ▪Comprehensive history and ▪Physical examination for clinical hyperandrogenism. ▪Adults: ▪Acne ▪Alopecia ▪Hirsutism ▪Adolescents: ▪Severe acne ▪Severe or progressive hirsutism. ABOUBAKR ELNASHAR
  6. 6. ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR ▪Assessing hirsutism: Modified Ferriman Gallway score (mFG). ▪The gold standard for evaluating hirsutism help assess response to treatment. ▪Only terminal hairs relevant in pathological hirsutism ▪untreated > 5 mm long, variable shape& pigmented ▪ 9 body areas most sensitive to androgen are assigned a score from 0 (no hair) to 4 (frankly virile), and these separate scores are summed to provide a hormonal hirsutism score ▪ A cut-off score of hirsutism, depend on ethnicity. ▪ Mild hirsutism: 8-15 ▪ Moderate: 16 - 25 ▪ Severe >25 (II-2). ABOUBAKR ELNASHAR Country Total score USA, UK 8 Mediterranean, Hispanic, and Middle Eastern 9-10 South American 6
  7. 7. ABOUBAKR ELNASHAR ▪Assessing alopecia. ▪The Ludwig visual score ABOUBAKR ELNASHAR
  8. 8. 3. Biochemical hyperandrogenism ▪Most useful when cl hyperandrogenism is unclear. ▪Assay: ▪High quality assays needed for most accurate assessment: chromatography–mass spectrometry(LCMS)/mass spectrometry& extraction/chromatography immunoassays ▪Direct free testosterone assays ▪Radiometric or enzyme-linked assays ▪Not preferred, should not be used ▪{poor sensitivity, accuracy and precision}. ABOUBAKR ELNASHAR ▪Use ▪ Free androgen index= TX 100 / SHBG if > 4.5: PCOS Not done routinely in presence of hirsutism ▪calculated bioavailable testosterone. ▪Calculated Free testosterone ▪Androstenedione & DHEAS ▪ could be considered if total or FT are not elevated ▪ However, have limited role in PCOS diagnosis. ABOUBAKR ELNASHAR
  9. 9. 4. US & polycystic ovarian morphology (PCOM) ▪US should not be used ▪< 8 years after menarche {high incidence of multi-follicular ovaries in this life stage} ▪ Irregular menstrual cycles & hyperandrogenism ▪ US is not necessary for PCOS diagnosis ▪ however US will identify PCOS phenotype. ABOUBAKR ELNASHAR Criteria of polycystic ovarian morphology ▪ 12 or more follicles, 2 - 9 mm in diameter and/or ▪ Ovarian volume >10 cm 3 . ABOUBAKR ELNASHAR
  10. 10. ▪TVS ▪Preferred if sexually active ▪With frequency 8MHz, the threshold for PCOM ▪Follicle number per ovary (FNPO) ≥ 20 &/or ▪Ovarian volume ≥ 10ml on either ovary ▪ensuring no ▪corpora lutea ▪cysts or ▪dominant follicles ▪With frequency 8 MHz: threshold for PCOM ▪ FNPO: 12 ▪ an ovarian volume ≥ 10ml on either ovary. ABOUBAKR ELNASHAR Diagnostic criteria of the polycystic ovaries morphology (PCOM) depending on examination technique 0 20 20 ABOUBAKR ELNASHAR
  11. 11. 4 different phenotypes of PCOS based on Rotterdam Criteria Phenotypes Anovulation Hyperandrogenism PCO Severe =Frank + + + Classic + + - Ovulatory - + + Non hyperandrogenic =Mild + - + ABOUBAKR ELNASHAR ❑Anti-müllerian hormone (AMH) should not yet be used as an alternative for the detection of PCOM or to diagnose PCOS. ABOUBAKR ELNASHAR
  12. 12. ▪ DIAGNOSIS of adolescent PCOS ▪ Criteria for the diagnosis differ from those used for adult ▪ Irregular menstruation plus Moderate to severe hyperandrogenism and/or hyperandrgemia ▪ Exclusion of other causes of hyperandrogenism with menstrual irregularity ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR
  13. 13. II. RISK ASSESSMENT 1. Cardiovascular disease risk ▪All with PCOS should be offered ▪Regular monitoring for wt change& excess wt ▪Monitoring could be ▪At each visit or at a minimum 6-12 monthly ▪Weight, Height ▪waist circumference ▪BMI ABOUBAKR ELNASHAR ❑All with PCOS should be assessed for ▪Individual CVD risk factors and ▪Global CVD risk. ▪ PCOS at increased risk of CVD. ▪obesity ▪cigarette smoking ▪dyslipidemia ▪hypertension ▪impaired glucose tolerance and ▪Lack of physical activity ABOUBAKR ELNASHAR
  14. 14. ▪ All women with PCOS should have blood pressure measured annually. ▪ Overweight& obese PCOS, regardless of age ▪should have a fasting lipid profile ▪total cholesterol ▪low density lipoprotein cholesterol ▪high density lipoprotein cholesterol and ▪triglyceride level at diagnosis ▪Thereafter, measurement should be guided by ▪the results and ▪global CVD risk. ABOUBAKR ELNASHAR 2. Gestational diabetes, impaired glucose tolerance & type 2 diabetes ▪5 fold in Asia ▪4 fold in the Americas ▪3 fold in Europe are increased in PCOS, with risk independent of, yet exacerbated by obesity. ▪In all with PCOS ▪Glycaemic status ▪should be assessed at baseline ▪thereafter, every one to three years, based on presence of other diabetes risk factors. ABOUBAKR ELNASHAR
  15. 15. ❑In high risk women with PCOS ▪Including ▪BMI > 25kg/m 2 or in Asians > 23kg/m 2 ▪history of abnormal glucose tolerance or ▪family history of diabetes, ▪hypertension or ▪high risk ethnicity ▪OGTT is recommended. ▪Otherwise ▪fasting glucose or ▪HbA1c should be performed. ABOUBAKR ELNASHAR ▪OGTT should be offered in all with PCOS ▪when planning pregnancy or ▪seeking fertility treatment {increased hyperglycaemia& comorbidities in pregnancy}. ▪If not performed preconception, an OGTT should be offered ▪at < 20 weeks gestation ▪all women with PCOS should be offered the test at 24-28 weeks gestation ABOUBAKR ELNASHAR
  16. 16. 3. Obstructive sleep apnea (OSA) ▪Screening should only be considered ▪to identify and alleviate related symptoms, ▪Snoring ▪Waking unrefreshed from sleep ▪Daytime sleepiness ▪the potential for fatigue to contribute to mood disorders. ABOUBAKR ELNASHAR ▪A simple screening questionnaire (Berlin tool) ▪if positive ▪referral. ▪raises the likelihood of OSA ▪does not quantify symptom burden ▪alone does not justify treatment. ▪If women with PCOS have OSA symptoms and a positive screen ▪should be referred to a specialist centre for further evaluation. ABOUBAKR ELNASHAR
  17. 17. 4. Endometrial cancer ▪Two to six fold increased risk of endometrial cancer, ▪often presents before menopause ▪however absolute risk remains relatively low. ▪low threshold for investigation of end cancer in PCOS, with ▪TVS and/or ▪Endometrial biopsy ▪recommended with ▪Persistent thickened endometrium and/or ▪Risk factors ▪prolonged amenorrhea ▪abnormal vaginal bleeding or ▪excess weight. ABOUBAKR ELNASHAR ▪Routine ultrasound screening of endometrial thickness in PCOS is not recommended. ▪Optimal prevention for endometrial hyperplasia and endometrial cancer ▪not known. ▪A pragmatic approach could include ▪COCP or ▪Progestin therapy in those with cycles longer than 90 days. ABOUBAKR ELNASHAR
  18. 18. III. TREATMENT 1. LIFE STYLE 1. Diet 2. Exercise 3. Behavioral 2. INFERTILITY 3. NON INFERTILITY ABOUBAKR ELNASHAR I. LIFESTYLE INTERVENTIONS ▪In all women with PCOS: ▪Healthy eating ▪Regular physical activity ▪Healthy lifestyle behaviours ▪In over wt & obese: Wt reduction ▪5% to 10% ▪significant clinical improvements ▪considered successful wt reduction within 6 months ABOUBAKR ELNASHAR
  19. 19. 1. Dietary intervention ▪Healthy eating principles should be followed for all women with PCOS across the life course ▪No one dietary type recommended in PCOS ▪To achieve weight loss ▪An energy deficit of ▪30% or ▪500 - 750 kcal/d ▪1,200-1,500 kcal/d could be prescribed considering individual ▪energy requirements ▪body weight ▪food preferences and ▪physical activity levels ABOUBAKR ELNASHAR 2. Exercise ❑Eencourage & advise the following for prevention of weight gain & maintenance of health: ▪ In adults from 18-64 years A minimum of ▪ 150 min/w of moderate intensity physical activity or ▪75 min/w of vigorous intensities or ▪An equivalent combination of both including muscle strengthening activities on 2 non- consecutive days/w ABOUBAKR ELNASHAR
  20. 20. ▪ In adolescents at least ▪ 60 mins of moderate to vigorous intensity physical activity/day ▪ including those that strengthen muscle& bone at least 3 times weekly. ▪ Activity be performed in at least 10 minute bouts or around 1000 steps, aiming to achieve at least 30 min daily on most days. ABOUBAKR ELNASHAR Physical activity intensity and examples. •Predicted maximal heart rate (HRmax) = 208 – (0.7 X AGE[years]);† metabolic equivalent (MET) where 1 MET is the O2/kg body weight/min required to sustain ones resting metabolic rate [3.5 mL/kg/min]) ABOUBAKR ELNASHAR
  21. 21. 3. BEHAVIOURAL STRATEGIES ▪ Cognitive behavioural interventions ▪goal-setting ▪Self-monitoring ▪stimulus control ▪Problem solving ▪assertiveness training ▪Slower eating ▪reinforcing changes and relapse prevention ▪To optimise ▪weight management ▪healthy lifestyle and ▪emotional wellbeing in women with PCOS. ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR ▪ Weight reduction in over wt and obese PCOS A. Life style B. Medication C. Bariatric surgery
  22. 22. b. Anti-obesity medications ▪ Failure to lose 10% of wt despite life style changes and diet control (Mathys, 2005) ▪ Can be considered with lifestyle, considering ▪ cost ▪ contraindications ▪ side effects ▪ availability ▪ regulatory status ▪ avoiding pregnancy when on therapy. ABOUBAKR ELNASHAR ▪ Orlistat (Rx: Orly): First drug approved by FDA ▪ Type of drug/actions: ▪ Peripherally acting pancreatic lipase inhibitor: ▪ reduces absorption of ingested fat. ▪ Dosing: ▪ 120 mg 3 times daily with meals (or over the counter alli® at half dose, 60 mg) ABOUBAKR ELNASHAR
  23. 23. ▪ Adverse effects: GIT: diarrhea, flatulence, if large amounts fat are ingested. ▪ Precautions: ▪Binds fat soluble vits. ▪Patient should ▪Take multivitamin. ▪Reduce fat and calorie diet. ▪ Contraindications: ▪Pregnancy ▪Cholestasis, chronic malabsorption syndromes, ▪Co administration with cyclosporine. ▪Can increase urinary oxalate ABOUBAKR ELNASHAR c. Bariatric Surgery ▪ 3 rd -line treatment option ▪ Indications: (NICE, 2013) 1. Morbid obese: failed to lose wt by other means 2. Moderate obesity: with significant co-morbid condition that could be improved by wt loss ▪ Should be considered an experimental therapy in women with PCOS, for the purpose of having healthy baby, with risk to benefit ratios currently too uncertain to advocate this as fertility therapy. ABOUBAKR ELNASHAR
  24. 24. ▪ Most suitable technique: laparoscopic adjustable gastric band {tightness of the band can be adjusted to accommodate for increased demands of pregnancy} ▪ Pregnancy avoidance ▪During periods of rapid weight loss ▪For at least 12 months after bariatric surgery with appropriate contraception ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR 2. TREATMENT OF INFERTILITY
  25. 25. 1 ST LINE PHARMACOLOGICAL TT ❑ Assessment of factors that may affect fertility, TT response or pregnancy outcomes 1. General Factors ▪Blood glucose, weight, blood pressure ▪Smoking, alcohol, diet, ▪Exercise, sleep and ▪Mental, emotional & sexual health ▪should be optimised ▪To improve reproductive&obstetric outcomes ABOUBAKR ELNASHAR 2. Tubal patency testing ▪Risks, benefits, costs & timing should be individualized ▪Should be considered prior to ovulation induction for women with PCOS where there is suspected tubal infertility. ABOUBAKR ELNASHAR
  26. 26. ❑ Ovulation induction principles ▪ Pregnancy should be excluded prior to ovulation induction. ▪ Unsuccessful, prolonged use of ovulation induction agents should be avoided, due to poor success rates. ABOUBAKR ELNASHAR Weight reduction letrozole Obese &overweight Normal weight &No weight loss & No ovulation LOD GnT No ovulation after 3 cycles. No pregnancy after 6 cycles. No pregnancy after 6 cycles. No pregnancy after spontaneous, CC, FSH ovulation IVF Other surgical indication Difficult follow up Less aggressive No desire for surgery Add metformin IGT &IR ABOUBAKR ELNASHAR
  27. 27. 1. Letrozole ❑Should be considered first line pharmacological TT for ovulation induction ❑Other ovulation induction agents can be used if ▪Letrozole is not available ▪Use is not permitted ▪Cost is prohibitive. ABOUBAKR ELNASHAR ▪ Advantages of letrozole over CC [Casper & Metwally, 2006]: ▪ A high rate of monofollicular development: reduce the risk of multiple pregnancies. ▪ A shorter half-life (48 hours versus two weeks for CC): lower risk of teratogenicity. ▪ No direct antiestrogenic adverse effects on the endometrium {absence of peripheral estrogen receptor blockade and the shorter half-life}. ▪ Lower serum estradiol levels – This is a particular advantage for women with breast cancer undergoing ovarian stimulation prior to gonadotoxic therapy and possibly for women with endometriosis undergoing in IVF ABOUBAKR ELNASHAR
  28. 28. ▪ ACOG 2018 ▪ While they previously suggested letrozole as first-line therapy (over CC) only for women with a BMI >30 kg/m [20], they now recommend it for all women with PCOS, regardless of BMI. ▪ They recommend lifestyle changes & weight loss for all obese women with PCOS to try to restore ovulatory cycles without the use of ovulation induction agents. ABOUBAKR ELNASHAR 2. Clomiphene citrate & Metformin ▪ CC could be used alone ▪ Metformin could be used alone: women should be informed that there are more effective ovulation induction agents. ▪ Indications: ▪ obese (BMI ≥ 30kg/m 2 ) ▪ CC-resistant PCOS ABOUBAKR ELNASHAR
  29. 29. 2 nd line pharmacological TT 1. Gonadotrophins ▪ Used as second line agents ▪ in women with PCOS who have failed first line oral ovulation induction therapy ▪ Could be considered as first line treatment ▪ in the presence of ultrasound monitoring ▪ following counseling on ▪ cost ▪ potential risk of multiple pregnancy ABOUBAKR ELNASHAR ▪ GnT, where available & affordable ▪ Should be used in preference to CC combined with metformin in CC-resistance PCOS ▪ GnT with the addition of metformin ▪ could be used rather than GnT alone, in ▪ CC-resistance PCOS ▪ Either GnT or LOD ▪ could be used in, CC-resistance PCOS, following counseling on benefits and risks of each therapy. ABOUBAKR ELNASHAR
  30. 30. ❑Where GnT are prescribed, the following should be considered: ▪ Cost & availability ▪ Expertise required for use in ovulation induction ▪ Degree of intensive US monitoring required ▪ No difference in clinical efficacy of GnT preparations ▪ low dose GnT protocols optimise monofollicular development ▪ Risk & implications of potential multiple pregnancy ABOUBAKR ELNASHAR ▪ GnT induced ovulation ▪Should only be triggered when there are fewer than 3 mature follicles ▪should be cancelled if ▪there are more than 2 mature follicles ▪the patient advised to avoid unprotected intercourse. ABOUBAKR ELNASHAR
  31. 31. ▪ GnT regimens: 50-75 IU 14 days 7 days Chronic low dose step-up: ▪ Start with 50 – 75 IU/day for 14 days. ▪ Increase by 25–37.5 every 7 days until follicular development is observed. ▪ Maintained until follicular selection is achieved. ▪ Recommended in PCOS (low OHSS). ABOUBAKR ELNASHAR 2. Laparoscopic ovarian surgery ▪ Could be second line therapy for CC resistant PCOS , ▪ Could potentially be offered as first line treatment if laparoscopy is indicated for another reason ▪ Risks ▪ should be explained to all women ABOUBAKR ELNASHAR
  32. 32. ❑Where LOD is to be recommended, the following should be considered: ▪ Comparative cost ▪ Expertise required for use in ovulation induction ▪ Risks: ▪ Intra-operative and post-operative risks are higher in overweight& obese ▪ ±a small risk of lower ovarian reserve or loss of ovarian function ▪ Periadnexal adhesion ABOUBAKR ELNASHAR ❑Restricted Indications of LOD 1. Failure of ovulation of 1st line pharmacological TT. in ▪ Absence of other causes of infertility ▪ Normal BMI ▪ {often unsuccessful in obese women} (Amer et al, 2004). 2. ±Prophylaxis against re-development of OHSS: Rare (Eftehar et al, 2016; Seyam, Hefzy, 2018) ABOUBAKR ELNASHAR
  33. 33. ❑ LOD ▪ Not treatment of ▪ Hirsuitism. ▪ No clear evidence that LOD improves menstrual regularity or the androgenic symptoms of PCOS, compared to most of the medical treatments used in the included studies (Cochrane SR, 2017) ▪ Failure to get pregnant ▪ Not repeated ABOUBAKR ELNASHAR 3 RD LINE TT ▪ IVF third line ▪ Where other ovulation induction therapies have failed. ▪ IVF is effective ▪ when elective single embryo transfer is used, multiple pregnancies can be minimised. ▪ Counseling prior to starting TT, including on: ▪ availability, cost and convenience ▪ increased risk of OHSS ▪ options to reduce the risk of OHSS ABOUBAKR ELNASHAR
  34. 34. ▪ Urinary or recombinant follicle stimulation ▪ Can be used ▪ Insufficient evidence to recommend specific FSH preparations. ▪ Exogenous recombinant LH ▪ Should not be routinely used in combination with FSH ▪ GnRH antagonist protocol ▪ preferred over GnRH agonist long protocol ▪ Reduce ▪ duration of stimulation ▪ total gonadotrophin dose ▪ incidence of OHSS ABOUBAKR ELNASHAR ▪ HCG ▪ should be used at the lowest doses to trigger final oocyte maturation ▪To reduce the incidence of OHSS. ▪Triggering with a GnRHa and freezing all suitable embryos ▪ could be considered ▪ With a GnRH antagonist protocol ▪ At an increased risk of developing OHSS or ▪ Where fresh embryo transfer is not planned. ABOUBAKR ELNASHAR
  35. 35. ❑Adjunct metformin ▪In Agonist Protocol: ▪ No effect on CPR or LBR ▪ Reduces the risk of OHSS (Cochrane SR, 2014, ESHRE,2018) ▪ Improves the rates of miscarriage and implantation (Palomba et al, 2013). ▪In antagonist protocol: not recommended ▪No decrease in OHSS ▪Decrease in CPR (Jacob et al, 2016; RCT) ▪Metformin before and/or during OS is not recommended with the GnRH antagonist protocol for women with PCOS (ESHRE, 2019) ABOUBAKR ELNASHAR ❑In agonist protocol with adjunct metformin therapy ▪Dose: 1000-2550mg daily 850mg twice daily for 16 d (short term) ▪Start: at the start of GnRha treatment ▪Cessation at the time of the pregnancy test or menses (unless the metformin therapy is otherwise indicated) ▪Side-effects ABOUBAKR ELNASHAR
  36. 36. 3. TREATMENT OF NON-FERTILITY • Hyperandrogenism • Irregular cycles ABOUBAKR ELNASHAR LINES OF TREATMENT ❑Life style: 1. Diet 2. Exercise 3. Behavioral I. 1 st line therapy: COCP alone II. 2 nd line therapy 1. COCP plus Metformin 2. COCP plus Antiandrogen 3. Metformin ABOUBAKR ELNASHAR
  37. 37. I. FIRST LINE THERAPY COCP alone ❑ Indications: 1. Adult women with PCOS for management of hyperandrogenism and/or irregular menstrual cycles. 2. Should be considered in adolescents 1. with a clear diagnosis of PCOS for management of clinical hyperandrogenism and/or irregular menstrual cycles. 2. who are deemed “at risk” but not yet diagnosed with PCOS, for management of cl hyperandrogenism&irregular menstrual cycles. ABOUBAKR ELNASHAR ▪ Absolute contraindications for COCP 1. history of migraine with aura 2. DVT/pulmonary emboli (PE) 3. Known thrombogenic mutation 4. Multiple risk factors for arterial CVD 5. History of ischemic heart disease or stroke 6. Complicated valvular heart disease, 7. Breast cancer 8. Neuropathy 9. Severe cirrhosis ABOUBAKR ELNASHAR
  38. 38. ▪ Other risk factors for DVT need consideration 1. Smoking. 2. BMI > 30 kg/m 2 ▪ Consider additional PCOS related risk factors 1. high BMI 2. hyperlipidemia 3. Hypertension ▪ For Hirsutism ▪COCP and ▪additional cosmetic therapy for at least 6 months ABOUBAKR ELNASHAR ❑BMI: ▪≤35 kg/m 2 with no specific metabolic and/ or CV abnormalities ▪Any type ▪Choice acc to: ▪ preferences of the physician and patient ▪ specific clinical characteristics of the patient (Italian society of endocrinology, 2015) ▪≥35 kg/m 2 : ▪COC should be prescribed with caution ▪≥40 kg/m 2 : ▪Not used(RCOG, 2011). ▪If contraception is needed: alternative measures, such as progestin-only methods (Italian society of endocrinology, 2015) ABOUBAKR ELNASHAR
  39. 39. ▪ Type: ▪ Androgenic activity: ▪ Anti-androgenic: Drospirenone, CPA, Dienogest ▪ Minimal androgenic: norgestimate and desogestrel ▪ Most androgenic: Levonorgestrel, norethisterone ▪ Lowest risk of DVT: Levonorgestrel, Norethisterone Norgestimate ABOUBAKR ELNASHAR ▪ No COCP preparation is superior ▪ Use ▪ lowest effective estrogen dose: 20-30 ug EE or equivalent ▪ Antiandrogenic or minimally androgenic ▪ 35 ug EE plus cyproterone acetate ▪ Not first line in PCOS (higher DVT risk) ▪ Should only be used when treating ▪ Moderate to severe hirsutism or ▪ Acne ABOUBAKR ELNASHAR
  40. 40. ▪ Other lower risk preparations ▪ recommended first line ▪ Contraception ▪ irregular menstrual cycles ▪ mild to moderate hirsutism ABOUBAKR ELNASHAR II. Second line pharmacological therapies 1. COCP + Metformin ▪Should be considered in women with PCOS for ▪management of metabolic features, ▪where COCP + lifestyle does not achieve goals. ▪Could be considered in ▪Adolescent PCOS ▪BMI ≥ 25kg/m 2 ▪ Most beneficial in high metabolic risk groups ▪those with diabetes risk factors ▪impaired glucose tolerance ▪high-risk ethnic groups. ABOUBAKR ELNASHAR
  41. 41. 2. COCP + Anti-androgens ▪Evidence in PCOS ▪relatively limited. ▪Anti-androgens must be used with contraception {prevent male fetal virilisation}. ▪Can be considered ▪after 6/12 cosmetic treatment + COCP ▪if they fail to reach hirsutism goals. ▪with androgenic alopecia. ABOUBAKR ELNASHAR Spironolactone (Aldactone) ❑Dose: 100-200 mg/d remission: decrease dose to 25-50 mg 100-200 mg/d from D1-D21 ❑Mechanism : on receptor ovary & adrenals Liver kidney ABOUBAKR ELNASHAR
  42. 42. 3. Metformin ▪should be considered in ▪Adults for ▪weight, hormonal and metabolic outcomes ▪Adolescents. with a ▪clear diagnosis of PCOS or ▪symptoms of PCOS before diagnosis is made. ▪Most useful with ▪BMI ≥ 25kg/m 2 ▪High risk ethnic groups. ABOUBAKR ELNASHAR ▪ Metformin appears safe long-term. ▪Side-effects ▪GI effects ▪dose related ▪self-limiting. ▪low vitamin B12. ▪How to avoid ▪starting low dose ▪500mg increments 1-2 weekly. ▪extended release preparations ▪administration with food ▪Ongoing monitoring ABOUBAKR ELNASHAR
  43. 43. ❑Inositol ▪(in any form) should currently be considered experimental in PCOS ▪with emerging evidence of efficacy highlighting the need for further research. ABOUBAKR ELNASHAR PROGESTINS Irregular cycles ❑ If amenorrhea for 3 months or more ▪ induce withdrawal bleed ▪ with progesterone (after negative pregnancy test) ▪ Hormonal therapy · COCP · Progesterone PRN to induce withdrawal bleeding ▪ Medroxyprogesterone acetate 10 mg daily for 10-14 days ▪ Micronized progesterone 400 mg daily for 10-14 day ▪ Dydrogesrerone ABOUBAKR ELNASHAR
  44. 44. ▪ TREATMENT of adolescent PCOS ▪ Should be individualized depending on: age, symptoms, risk factors & choices ▪ 1st line: lifestyle modifications ▪ 1st line pharmacological: COCP ▪ 2nd line pharmacological: ▪ COCP+ Metformin ▪ COCP+ Antiandrogen ▪ Metformin ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR You can get this lecture and 475 lectures from: 1. My scientific page on Face book: Aboubakr Elnashar Lectures. https://www.facebook.com/groups/227744884091351/ 2. Slide share web site 3. elnashar53@hotmail.com 4. My clinic: Elthwara St. Mansura
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