PCO

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POLYCYSTIC OVARIAN SYNDROME:

POLYCYSTIC OVARIAN SYNDROME DR SHABNAM NAZ CMC, LARKANA SINDH PAKISTAN

References:

References Long term consequences of PCO (RCOG GUID LINES) Differential diagnosis of PCO ogrm 2013 Dewhurst Evidence based Robert shaws

INTRODUCTION :

The PCOS is a heterogeneous collection of signs and symptoms with a mild presentation in some but a severe disturbance of reproductive, endocrine, and metabolic function first described by stein and leventhal in 193. most common endocrine disorder and is most common cause of secondary amenorrhea INTRODUCTION

Slide6:

The Joint Eshre/ASRM Defined PCOS is the presence of two out of the following three criteria Oligo-and /or anovulation (oligomenorrhea or amenorrhea) Hyperandrogenism (clinical and /or biochemical elevation testosterone ) Polycystic ovaries assessed by ultra sound

Incidence:

Incidence - About 10-20% of general population. - 20-33% based on U/S only .

PATHOPHYSIOLOGY OF PCOS:

Pathophysiology of PCOS appears to be multifactorial and polygenic . PATHOPHYSIOLOGY OF PCOS

Slide10:

Hyperinsulinemea Causes hyper secretion of LH and pontetiate action of IGF-1 Both LH and IGF-1 up regulate ovarian and adrenal androgen production such as testosterone and DHEA-S Hyperinsulinism and Hyperandrogenism impair aromatase function which is required for follicular growth AMH antagonize FSH and reduces availability of estrogen required for follicle development , menstrual disturbance, anovulation and subfertlity

Presentation :

Presentation may be asymptomatic Amenorrhea, oligomenorrhea 75% Anovulatory subfertility 40% Obesity 40% Hirsute 30 – 70% Recurrent miscarraiges 50-60% Acne, alopecia Acanthosis nigricans 2%

D/D 0F PCOS:

D/D 0F PCOS Diagnosis of PCOS very challenging because other diseases can cause similar symptoms such as. Congenital adrenal hyperplasia Ovarian hyperthecosis Cushing's syndrome Androgen secreting tumor Exogenous androgen administration Gestational Hyperandrogenism

OVARIAN HYPERTHECOSIS:

OVARIAN HYPERTHECOSIS Mostly occur in postmenopausal women <1% occur in reproductive age It is associated with sever Hyperandrogenism and virilisation Testosterone concentration more than 7nmol/l much higher than PCOS

CONGENITAL ADERNAL HYPERPLASIA:

CONGENITAL ADERNAL HYPERPLASIA It is autosomal recessive disorder Deficiency of 21 hydroxylase activity It has typical features of Hyperandrogenism such as deepening of voice , severe acne , breast atrophy , clitromegaly , and infertility Increase testosterone > 5nmol/l Increased 17 a hydroxyprogesterone Increased levels of urinary ketosteroids

CUSHING’S SYNDROME:

CUSHING’S SYNDROME It is rare but important cause of Hyperandrogenism Hirsutism occur in 80% of patient Increase concentration of cortisol causes Centripetal weight gain ,Facial plethora Supraclavicular fat pad, Abdominal stria Signs of Hyperandrogenism such as acne , Hirsutism , male pattern baldness Diurnal serum cortisol and ACTH levels after a high dose dexamethasone suppressive test (2mg at night for 5 days)

ANDROGEN PRODUCING OVARIN TUMORS:

ANDROGEN PRODUCING OVARIN TUMORS Sudden onset Rapid progression of Hyperandrogenism Early development of frank virilisation Most common ovarian tumor is sertoli lyedig cell tumor and 0.5%of all ovarian tumor . Other virilising tumors include granulosa cell, hair cell and berner tumor

CONT…:

CONT… Characterized by striking elevation in serum testosterone but normal DHEA-S and urinary ketosteroids Ovarian tumor palpable on abdominal examination Evaluate with U/S , CT scan, and MRI

ADRENAL TUMORS:

ADRENAL TUMORS Presented with marked Hirsutism and virilisation Tumor is small and impalpable Commonly occur in premenopausal women Serum testosterone and DHEA-S markedly raise Diagnosed by CT scan and MRI

EXOGENOUS ANDROGEN ADMINISTRATION:

EXOGENOUS ANDROGEN ADMINISTRATION Anabolic androgen steroids can be employed to enhance athletic performance, increase libido in women, or provide cosmetic body building. Their administration can commonly lead to Acne Hirsutism Suborrheic cutaneous changes

GESTATIONAL HYPER ANDROGENISM:

GESTATIONAL HYPER ANDROGENISM There are two main causes of gestational Hyperandrogenism 1)luteomas 2)theca lutein cyst of the ovary Unilateral solid ovarian lesions complicated by androgen excess have an increased risk of malignancy

DIAGNOSIS OF PCOS :

DIAGNOSIS OF PCOS HISTORY Family history of PCOS or infertility Infrequent periods / amenorrhea Obesity and metabolic dysfunction Hyperandrogenism symptoms like Hirsutism Acne Male pattern balding

EXAMINATION:

EXAMINATION BMI and inspection of the fat distribution i.e. identification of truncal obesity Linea nigra Hirsutism should be assessed using standardized system e.g. ferriman- gallway system Full abdominal and gynaecological examination to exclude other causes of menstrual and endocrine disturbance

ULTRASONOGRAPHY:

ULTRASONOGRAPHY 1-Many follicles >12(ovarian volume >10cm3) 2-Follicles 2-9 mm diameter 3-Thickened white capsule 4-Hyperechogenic stroma

BIOCHEMICAL:

BIOCHEMICAL ↑LH in while FSH is either normal or supersede giving a characteristic ratio of (LH/FSH 3:1) Baseline estrogen level is increased Hyperprolactinemia is present in 15% of cases Testosterone is only slightly raised i.e. < 5nmol/l Free androgen index = total testosterone *100/SHBG Increase fasting insulin level

MANAGEMENT OF PCO:

MANAGEMENT OF PCO Principals of management : Confirm diagnosis and identify category. Identify and manage concurrent illness. Identify and manage patient needs. There are numerous options for successful PCO management – medical / surgical

TREATMENT OF OBESITY :

TREATMENT OF OBESITY Weight loss improves endocrine profile ,likelihood of ovulation and a healthy pregnancy . Lifestyle Modification Physical exercise Altered dietary composition-- Low fat, Low Carbohydrate

WEIGHT LOSS MEDICATION:

WEIGHT LOSS MEDICATION Orlistat It is anti obesity drug has been shown to b affective at producing a modest wt loss together with a well balanced diet.

BARIATIC SURGER( GASTRIC BANDING /GASTRIC BYPASS) :

BARIATIC SURGER( GASTRIC BANDING /GASTRIC BYPASS) INDICATION NICE guideline states that: “surgery is recommended as a treatment option for people with morbid obesity. BMI > 40 kg/m2 or more, or with BMI equal or greater than 35kg/m2 in the presence of significant co-morbid condition that could be improved by weight loss If weight loss stretegies have failed.

RISKS OF BARIATRIC SURGERY:

RISKS OF BARIATRIC SURGERY Bowel obstruction Esophagitis Infection Nutritional abnormalities

TREATMENT OF MENSTRUAL IRREGULARITES IN PCO:

TREATMENT OF MENSTRUAL IRREGULARITES IN PCO COCPs Progestrogen - medroxyprogesterone acetate (provera) for 12 days every 1-3 months IUCD such as (mirena) (

TREATMENT OF HIRSUTISM:

TREATMENT OF HIRSUTISM Hirsutism is characterized by terminal hair growth in a male pattern of distribution Standardized scoring system such as modified ferriman – Galway score used to evaluate degree of Hirsutism before and during treatment (DEWHURT”S)

FERRIMAN -GALLWAY SCORE:

FERRIMAN -GALLWAY SCORE Chart is used to provide both an initial score with a score of 0-3 at each 12 points depending on severity and for the monitoring of progress with therapy

CONT….:

CONT…. 0-mild 1-moderate 2-complete light coverage 3-heavy coverage Drug therapies take 6-9 months or longer before any improvement of Hirsutism is perceived (ROBERT SHAW)

PHYSICAL TREATMENT:

PHYSICAL TREATMENT Include electrolysis, waxing, and bleaching may be helpful while waiting for medical treatment work . Only growing follicles are obliterated at each treatment so repeated treatment are required for a near permanent effect

Medical treatment:

Medical treatment Non hormonal Eflornithine inhibits the enzyme ornithine decarboxylase in hair follicles useful for those who wish to avoid hormonal treatment Hormonal Treatment Dinette first line of treatment (combination of ethinyloestradiol 30ug and cyproterone acetate 2mg) rarely causes liver damage so liver function checked annually

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Spironolactone -- week diuretic with anti androgenic property used in women whom COCP is contraindicated Daily dose of 25-100mg Other drugs -- ketoconazole,finastride, flutamide have tried but not widely used due to adverse effect (DEWHURT’S)

Infertility /ovulation induction:

I nfertility /ovulation induction Fertility in PCOS is adversely affected by an individual being overweight or having increased concentration of LH . Strategies to induce ovulation include weight loss and antiestrogen (clomiphene citrate or temoxifen),parenteral gonadotrophins therapy plus laparoscopic ovarian surgery DEWHURT”S

Life style changes :

Life style changes Combination of exercise and diet to acheive weight reduction as overwt women with pcos are at increased risk of fetal congenital malformation ,miscarriages and obstetrical complications like gastational diabetes mellitus and pre eclampsia.

ANTIOESTROGENS:

ANTIOESTROGENS CLOMIPHENE CITRATE First line of treatment Continue 6-12 cycles of treatment Dose 50-100mg Taken from day 2-6 of a natural and artificially induced bleeding Ovulation occurs in 80% while pregnancy occurs in 40%. Alternative of clomiphene citrate is temoxifen. Temoxifen is also antiestrogen. Evidence suggest that both are equally effective.

GONADOTROPHIN:

GONADOTROPHIN

Slide42:

indicated in cases of Clomiphene resistant Dose of FSH-- A low setup regime is most often used starting at 37.51IU/day and 75% women will respond by 75IU/day . Cumulative conception and live birth rates after 6 months 62% and 54% respectively and after 12 months 73% and 62% respectively. Side effects includes multiple pregnancy (10% ) and Ovarian hyperstimualtion syndrome

OVARIAN DIATHERMY:

OVARIAN DIATHERMY Indicated in clomiphene resistant patients Patients with high LH are more likely respond to LOD. Thermal damage may lead to release of inflammatory intraovarian cytokines with a paracrine effects on adrogen production and eventual normalization of puitary LH secretion. Ovution occur in 80% of pts Pregnancy occurs in 60% of pts Low risk of multiple pregnancy. (Evidence based)

INSULLIN SENSITIZING AGENT:

INSULLIN SENSITIZING AGENT Amplify physiological effect of wt loss. Biguanide(metformin) .

Slide45:

MOA--It inhibit hepatic glucose production ,& enhances sensitivity of peripheral tissues to insulin ,there by decreasing insulin secretion ,restore menstrual cyclicity & fertility Dose 850mg BD per orally Conception rate 8% RCT has concluded no benefit of metformin in achieving an increased rate of live birth alone or in combination and so the use of metformin is only recommended when there is IGT or type ii diabetes

LONG TERM CONSEQUENCES OF PCOS:

LONG TERM CONSEQUENCES OF PCOS

1.Endometrial Neoplasia:

1.Endometrial Neoplasia Chronic anovulation associated with PCOS may lead to endometrial hyperplasia and sometimes to frank endometrial cancer . Women with PCOS have a 2.89 fold increase risk for endometrial cancer Endometrial biopsy is indicated in all women with H/O long term unopposed estrogen exposure and in those where endometrial thickness is greater than 7mm. Interval between menstruation of more than 3 consecutive months may be associated with endometrial hyperplasia

How to prevent endometrial carcinoma :

How to prevent endometrial carcinoma Regular induction of a withdrawal bleed with Cyclical gestogen for at least 12 days OCP IUCD (mirena)

RCOG guideline states Women with PCOS do not have a increased risk of ovarian and breast cancer compared to those without PCOS:

RCOG guideline states Women with PCOS do not have a increased risk of ovarian and breast cancer compared to those without PCOS

2.INSULIN RESISTANCE (IR):

2.INSULIN RESISTANCE (IR) IR is defined as reduced glucose response to a given amount of insulin. It occurs in 65%-80% of women with PCOS independent obesity but increase by excess weight

Diagnostic criteria for metabolic syndrome:

Diagnostic criteria for metabolic syndrome Diagnosis is made when 3 or more of these risk criteria are met : ↑ Glucose ≥ 6.1 mmol/l Waist circumference ≥ 80cm. ↓ HDL-C≤ 1.3 mmol/l ↑BP ≥ 130 / ≥ 85 mm Hg ↑TG ≥ 1.7 mmol/l

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The incidence of IGT and Type ii DM are significantly increased in women with PCOS. In one study, IGT and/or Type ii DM were found in 30-40% of patients with the PCOS. A higher prevalence occurs in obese women particularly those with a family history of DM. Rcog recommends 2hour 75g oral glucose tolerance test in Women with PCOS with BMI >25kg/m2 and women not over weight but age > 40 years Previous H/O gestational DM Family H/O type 2 DM DIABETES MELITUS

3.SLEEP APNEA:

3.SLEEP APNEA The prevalence of obstructive sleep apnea is increased in obese women with PCOS Androgen level and insulin are associated with obstructive sleep apnea in PCOS It contributes to insulin resistance in PCOS Continuous positive airway pressure therapy improve insulin sensitivity

Slide54:

Women with PCOS are frequently found to have atherogenic lipids abnormalities that may reflect insulin resistance as well as effect of genetics, ethnicity, obesity and lifestyle factors. 4.DYSLIPIDAEMIA :

5.CARDIOVASCULAR DISEASE:

5.CARDIOVASCULAR DISEASE Risk of CVD is higher in women with PCOS All women with PCOS should be assessed for CVD risk factor such as obesity lack ,of physical activity, smoking , family history of type 2 diabetes, dyslipidemia, hypertension, impaired glucose tolerance test, type 2 diabetes. Women should be assessed for obesity with BMI and waist circumference

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6 . Hypertension Women with PCOS having persistent blood pressure greater than or equal to 140mmhg / diastolic 90mmhg not responding to life style modification than drug therapy given. If blood pressure 130mmhg systolic and diastolic 80mmhg with H/O diabetes and other risk factors than drug therapy requires

QUALITY 0F LIFE IN WOMEN WITH PCOS :

QUALITY 0F LIFE IN WOMEN WITH PCOS Women with PCOS are at increased risk of psychological difficulties such as (depression and anxiety) eating disorder and sexual and relation ship dysfunction. Psychological issues especially depression should be screened according to NICE guide line If pt. have depression than ask two questions During the last month you have been bothered by feeling down depress or hopeless During the last month have you often been bothered having little interest or pleasure in doing things .

Cont….:

Cont…. Psychological issues especially depression should be screened according to NICE guide line If pt. have depression than ask two questions During the last month you have been bothered by feeling down depress or hopeless During the last month have you often been bothered having little interest or pleasure in doing things

Conclusions :

Conclusions Obesity plays a central role in development of PCOS leading to Hyperinsulinemea in susceptible individuals this may alter androgen metabolism via a variety of mechanisms, the net result of which Hyperandrogenism. The management of patients with PCOS depends upon the individual patient’s complaints. Hyperandrogenism is optimally dealt with by reducing insulin drive to the ovary, such as exercise and reducing diet

Slide60:

30y age of pt. nullipara married for 5y having H/O acne & Hirsutism her BMI was 30kg/m2 which was reduced after diet control & exercise she took clomiphene citrate for infertility which was failed you switched her to parenteral gonadotrophins therapy and counseled the couple for better results with this treatment cumulative rate & live birth rate after 6 months is? (A)62%-54% (B) 73%-62% (C) 82%-72% (D) 92%-82% (E) none of these

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30y age of pt. p2+1 diagnosed case of PCOS having H/O of one twin pregnancy after ovulation induction with gonadotrophins which end up into still birth at 32 week and history of one miscarriage now came to your clinic to seek advise for fertility she has heard that multiple pregnancy is a common complication of ovulation induction and OHSS and she is afraid of repeat pregnancy loss after induction. you explained her different options which one of the following options is associated with less risk of multiple pregnancy and OHSS (a) Clomiphene citrate (b) Human menopausal gonadotrophins (c) Laproscopic ovarian drilling (d) In vitro fertilization

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