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Polycystic Ovary Syndrome

Polycystic ovarian syndrome ( PCOS ) is a complex , common endocrine condition affecting reproductive women with a reported prevalence of between 8-15 % depending on the diagnostic criteria and the population studied ( Rhonda Garad , Soulmez Shorakae , Helena Teede 2019 )

HOW common

Most common endocrinopathy among reproductive age women A BJGP article in 2018 states that they suspect that there is a significant under-diagnosis of the condition Prevalence does not appear to vary across different regions of world ( BMJ Best practice ) Responsible for 80-90 % of cases of hyper-androgenism in females

WHAT happens

Despite years of research the etiology of PCOS remains unknown First described by Stein and Leventhal in 1935 PCOS is characterized by
○ androgen excess ( ovarian and or adrenal )
○ ovulatory dysfunction ( chronic anovulation )
○ polycystic ovaries Most common cause of infertility linked to chronic an-ovulation Complex heterogenous familial disorder Actual PCOS gene has not been identified yet but it is suspected that PCOS risk depends on genetic factors Androgen excess is the key features seen in approximately 60-80 % of patients – hirsuitism and hyperandrogenism are manifestations of the excessive androgen production Potential factors involved alteration in
○ steroidogenesis
○ ovarian folliculogenesis
○ neuroendocrine function
○ metabolism
○ insulin secretion
○ insulin sensitivity
○ adipose cell function
○ inflammatory factors
○ sympathetic nerve function

WHY important

Increased risk of anovulation and infertility ↑ ed risk of pregnancy complications like
○ gestational diabetes
○ pre-term delivery
○ pregnancy induced hypertension & pre-eclampsia
○ ↑ ed risk of caesarian delivery , miscarriage and hypoglycemia Endometrial cancer- many of the risk factors associated with endometrial cancer are same as women with PCOS Obesity ↑ ed adiposity – particularly abdominal is linked to hyperandrogenism and ↑ ed metabolic risks Depression Sleep-disordered breathing / Obstructive sleep apnoea ( OSA ) NAFLD and NASH Type 2 diabetes – impaited OGTT and type 2 diabetes risk is significantly ↑↑ ed in PCOS regardless of age Cardiovascular risks – consider screening for CVD risk factors as
○ family h/o early CVD
○ cigarette smoking
○ IGTT /T2DM
○ hypertension
○ dyslipidemia
○ OSA
○ obesity

Presentation –Symptoms begin in adolescence Diagnosis can be difficult as diagnostic pathological features used in adult women may be normal pubertal physiological events Presentation may be varied – heterogenous
○ gynaecological ○ dermatological ○ metabolic manifestations

Diagnostic criteria –National Institutes of Health criteria 1990
clinical or biochemical hyerpandrogenism and oligo / amenorrhoea anovulation Rotterdam criteria 2003
added polycystic ovarian morphology on US to the two NIH criteria European Society of Human Reproduction and Embryology / American Society for Reproductive Medicine ( ESHREA / ASRM ) developed and enlarged criteria – requiring 2 of 3 features
○ anovulation or oligovulation
○ clinical or biochemical hyperandrogenism
○ Polycystic ovarian morphology on US Androgen Excess Society – considers androgen excess as the central event in pathogenesis of PCOS

Investigations –Serum Total & Free testosterone SHBG LH , FSH Serum dehydroepiandrosterone sulfate 
( DHEAS ) Serum 17- hydroxy progesterone 
helpful in excluding 21 – hydroxylase-deficient non-classic 
( adult onset ) adrenal hyperplasia Serum prolactin TSH OGTT / Hba1c Lipid profile

Local policy decision making may affect availability , selection of tests. Consider asking for PCOS screen .

Ultrasound –Ultrasound
 Adam’s criteria has been used previously for for US assessment of the ovaries in women with PCOS Transvaginal US is the most commonly used method Presence of enlarged ovaries with ↑ ed stroma and multiple small peripheral cysts is classical Findings may differ based on route ie transvaginal or transabdominal 
( for eg in adolescents ) and increased ovarian volume of 12 mL is recommended by PCOS society in adults and 10 cms in adolescents Polycystic ovaries may also be seen in up to 25 % of normal women and ♀ with other endocrinopathies as CAH , hyperprolactinaemia or hypothalamic amenorrhoea

Differentials –Thyroid disease Prolactin excess Non-classical 
congenital hyperplasia

Other diagnoses to consider excluding in select women based on presentation
 Pregnancy Hypothalamic amenorrhoea Primary ovarian insufficiency Androgen secreting tumour Cushing’s syndrome Acromegaly



Diagnosis Inform and educate- see links about long term complications
 Consider the fact that in young women menstrual cycles may take up to 2 yrs to regulate after menarche. 
 US may not be reliable CKS states that ” Be aware that polycystic ovaries do not have to be present to make a diagnosis of PCOS and the findings of polycystic ovaries does not alone establish the diagnosis “





Lifestyle –Diet
 Exercise
 Weight loss- even 5 % weight loss can help restore the menstrual cycle and reduce CV risks

These should be considered first line for women with PCOS

○ improves long term outcomes
○ should precede and or accompany pharmacological treatment







Medications –Metformin
Insulin sensitizer
Not licenced for PCOS but used widely in selected groups
Evidence base is of low quality 
Look at RCOG paper on metformin under links Anti-androgens
○ androgen receptor blockers like spironolactone , flutamide
○ finasteride
○ cyproterone acetate Clomifene( can be combined with dexamethasone if adrenal androgen excess is present ) Letrozole Gonadotrophins






Hormonal treatment –If endometrial thickness is normal advice to consider treatment to prevent endometrial hyperplasia with COCP or POP Treatment to induce withdrawal bleed every 3 months reduces the risk of endometrial hyperplasia Choice of preparation can depend on if
○ she wishes to have a regular withdrawal bleed
○ if she has acne , hirsuitism
○ any contra-indications to treatment- options are

◘ a cyclical progestogen as medroxyprogesterone for 14 days every 1-3 months
◘ low dose COCP
◘ Levonorgestrel releasing IUS
 COCPs ( particularly with ethinylestradiol + a progestin component ) addresses multiple concerns in adolescents and adult but no specific formulation can be recommended over another



Cosmetic / Others –Acne – consider COC
 Hirsuitism- discuss methods of hair removal & reduction for e.g
○ bleaching
○ chemical epilation
○ plucking 
○ waxing ,
○ shaving
○ electrolysis and 
○ laser


Consider topical eflornithine
( Vaniqa® )

COCP 





Screening –Offer screening for gestational diabetes to women if diagnosed with PCOS before pregnancy at 24-28 weeks Offer 2 hr OGTT to
○ women with BMI > 25
○ BMI < 25 but have additional risk factors such as advanced age ( > 40 ) , personal hx of gestational diabetes or family hx of type 2 diabetes Offer annual OGTT to
○ ♀ with IFG ( 6.1-6.9 )
○ Impaired GTT Ask about symptoms of sleep apnoea Assess for CVD risk individually 
risk calculators not validated Treat if hypertensive but lipid lowering treatment should be started by specialists Explore psychological issues



Referral Unusual endometrial appearance Infertility or subfertility Virilization – severe or rapid Severe hirsuitism and contra-indication to hormonal contraception Women does not wish to take cyclical hormone treatment or use the LNG-IUS Pregnant women with abnormal gestational diabetic screening result Treatment failure in primary care Significantly raised prolactin ( e.g > 600 ) or raised testosterone ( > 4 )

LINKS AND RESOURCES

PATIENT INFORMATION

Self-help group for women with PCOS Verity PCOS https://www.verity-pcos.org.uk/about-us.html

A large global charity PCOS Challenge https://pcoschallenge.org/about-pcos-challenge/

PCOS Awareness association https://www.pcosaa.org/pcosinfo

Androgen Excess and PCOS Society http://www.ae-society.org/sub/education.php

PCOS Diet support https://www.pcosdietsupport.com/encouragement/pcos-encouragement/

5-page printable leaflet from Royal College Obstetricians & Gynaecologists https://www.rcog.org.uk/globalassets/documents/patients/patient-information-leaflets/gynaecology/pi-pcos.pdf

American College Of Obstetricians and Gynaecologists on PCOS https://www.acog.org/Patients/FAQs/Polycystic-Ovary-Syndrome-PCOS?IsMobileSet=false

NHS Choices on PCOS https://www.nhs.uk/conditions/polycystic-ovary-syndrome-pcos/

Printable leaflet from Jean Hailes https://jeanhailes.org.au/contents/documents/Resources/Fact_sheets/PCOS.pdf

 

 

RESOURCES FOR CLINICIANS

Metformin Therapy for the Management of Infertility in Women with Polycystic Ovary Syndrome (Scientific Impact Paper No. 13 RCOG https://www.rcog.org.uk/en/guidelines-research-services/guidelines/sip13/

International evidence-based guideline for the assessment and management of Polycystic Ovary Syndrome (PCOS), designed to provide clear information to assist clinical decision making and support optimal patient care, is the culmination of the work of over 3,000 health professionals and consumers internationally. https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline

Long-term Consequences of Polycystic Ovary Syndrome Royal College of Obstetricians & Gynaecologists Green- top guideline 33 https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_33.pdf

Links to various PCOS guidelines  https://www.gfmer.ch/Guidelines/Menstruation_disturbances_female_gonadal_disorders/Polycystic_ovary_syndrome.htm

References

  1. Long-term consequences of Polycystic Ovary Syndrome Green Top Guideline No 33 RCOG Nov 2014
  2. Diagnosis and Treatment of Polycystic Ovary Syndrome Tracy Williams et al BMJ Best Practice Polycystic Richard S. Legro, Silva A. Arslanian, David A. Ehrmann, Kathleen M. Hoeger, M. Hassan Murad, Renato Pasquali, Corrine K. Welt, Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 12, 1 December 2013, Pages 4565–4592
  3. Ibáñez L, Oberfield S, E, Witchel S, Auchus R, J, Chang R, J, Codner E, Dabadghao P, Darendeliler F, Elbarbary N, S, Gambineri A, Garcia Rudaz C, Hoeger K, M, López-Bermejo A, Ong K, Peña A, S, Reinehr T, Santoro N, Tena-Sempere M, Tao R, Yildiz B, O, Alkhayyat H, Deeb A, Joel D, Horikawa R, de Zegher F, Lee P, A: An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence. Horm Res Paediatr 2017:371-395. doi: 10.1159/000479371


  4. CKS NHS Polycystic Ovary Syndrome
  5. Polycystic ovary syndrome An Update AFP Volume 41 , No 10 , October 2012 Pages 752-756
  6. Polycystic Ovary Syndrome (PCOS), Diagnostic Criteria, and AMH ,Majid Bani Mohammad and Abbas Majdi Seghinsara
  7. Polycystic ovary syndrome Diagnosis and management Pfieffer, Mary Lauren DNP, FNP-BC, CPN Author Information The Nurse Practitioner: March 2019 – Volume 44 – Issue 3 – p 30–35 doi: 10.1097/01.NPR.0000553398.50729.c0,
  8. BMJ Best Practice Polycystic ovary syndrome

 

 

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