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May 2, 2023 Presenter : Dr. Jagjit Khosla 1
Polycystic Ovary Syndrome
Presentation : Dr. Jagjit Khosla Junior Resident, Endocrinology, GuruTeg Bahadur Hospital, Delhi
May 2, 2023 Presenter : Dr. Jagjit Khosla 2
Polycystic Ovary Syndrome• First described by Stein & Leventhal
(1935)
• Incidence : 5-10%
• Leading cause of female infertility
• Insulin resistance described later by Burghen (1980)
Polycystic Ovary
Amenorrhea
ObesityHirsutism
May 2, 2023 Presenter : Dr. Jagjit Khosla 3
PCOS - Pathophysiology
May 2, 2023 Presenter : Dr. Jagjit Khosla 4
PCOS – Clinical Features• Hyperandrogenism
• Hirsutism
• Modified Ferriman Gallwey Score
• Acne
• Androgenic alopecia
• Menstrual Irregularity • Oligomenorrhea (70-75%)
• Amenorrhea (20%)
• Infertility (30-70%)
May 2, 2023 Presenter : Dr. Jagjit Khosla 5
PCOS – Clinical Features• Obesity
• Insulin resistance• Acanthosis nigricans
• Skin tags
• Impaired Glucose tolerance
• Type 2 DM
May 2, 2023 Presenter : Dr. Jagjit Khosla 6
PCOS – Evaluation• Biochemical evidence of hyperandrogenism
• S. Total testosterone
• USG evidence of Polycystic ovary• 12 or more follicles in each ovary measuring 2-9 mm in diameter +/- inc. ovarian volume (>10 mL) [Rotterdam criteria]
May 2, 2023 Presenter : Dr. Jagjit Khosla 7
PCOS – Evaluation• Exclusion of other differential diagnoses
• Hyperprolactinemia, hypothyroidism
• Non-Classical Congenital Adrenal Hyperplasia
• Ovarian & Adrenal tumors
• Cushing’s syndrome, Glucocorticoid resistance
• Drugs : Danazol, OCPs
May 2, 2023 Presenter : Dr. Jagjit Khosla 8
PCOS – Diagnostic criteriaNIH (1990)• Menstrual
Irregularity• Hyperandrogenis
m• Exclusion of other
etiologies
Rotterdam (2003)• 2 out of 3
required1. Menstrual
Irregularity2. Hyperandrogenis
m3. USG –
Polycystic ovary• Exclusion of other
etiologies
AES (2006)• Menstrual
irregularity +/- USG - Polycystic ovary
• Hyperandrogenism
• Exclusion of other etiologies
May 2, 2023 Presenter : Dr. Jagjit Khosla 9
PCOS – Management• Lifestyle modifications –
• Low calorie diet
• Regular brisk walk 25-35 min daily
• Hormonal contraceptives – • 1st line T/t of hirsutism, acne and menstrual
irregularity
• Spironolactone • Added to OCPs if suboptimal results after 6 months
Legro, Richard S., et al. "Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline." Journal of Clinical Endocrinology & Metabolism 98.12 (2013): 4565-4592.
May 2, 2023 Presenter : Dr. Jagjit Khosla 10
PCOS – Management• Clomiphene citrate –
• 1st line t/t for infertility
• Insulin sensitizing agents – • Metformin – limited recommendations
• Screening patients for long term complications • Endometrial cancer, Mood disorders, OSA, DM, CVD
Legro, Richard S., et al. "Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline." Journal of Clinical Endocrinology & Metabolism 98.12 (2013): 4565-4592.
May 2, 2023 Presenter : Dr. Jagjit Khosla 11
Spironolactone• Actions
• Androgen receptor blockade
• Steroid synthesis inhibitor
• Aldosterone receptor blockade
• Status is PCOS management• 2nd line drug for T/t of hirsutism, acne
• If used alone, alternative contraception needed
• No endometrial protection
May 2, 2023 Presenter : Dr. Jagjit Khosla 12
Metformin• Actions
• Increase insulin sensitivity
• Directly inhibit human theca cell androgen synthesis
• Status is PCOS management• Women with PCOS and type 2 DM or IGT
• Women who cannot take oral contraceptives
• Adjuvant therapy in women undergoing IVF – prevent ovarian hyperstimulation
ES Guidelines for PCOS 2013
• 3 Recommendations
Diagnosis of PCOS
• 12 Recommendations
Associated Comorbidity & Evaluation
• 12 Recommendations
Treatment of PCOS
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 13
ES Guidelines for PCOS 2013
1 - Diagnosis of PCOS
ES Guidelines for PCOS 2013
1.1 - Diagnosis of PCOS in Adults • Rotterdam (2003) criteria
Androgen excess
Ovulatory dysfunction
Polycystic ovaries (USG)
2 out of 3
+ Exclusion of other etiologies
Clinical or biochemical
Oligo- or anovulation
Atleast one ovary with• 12 follicles 2-9mm• Volume > 10mL
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 15
ES Guidelines for PCOS 2013
1.1 - Diagnosis of PCOS in Adults • Rotterdam (2003) criteria
• Thyroid disease
• Hyperprolactin
• Nonclassical congenital adrenal hyperplasia
• Cushing’s syndrome
• Acromegaly
• Androgen secreting tumors
• Other causes of amenorrhea
Exclusion of other etiologies
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 16
Tuesday, May 2, 2023 17
ES Guidelines for PCOS 2013
1.2 - Diagnosis of PCOS in adolescents• Anovulation and Polycystic ovary NOT reliable
Androgen excess
Persistent oligomenorrhea
Exclusion of other etiologies
+
+
Presentation by : Dr. Jagjit Khosla
>2 yrs beyond menarche
ES Guidelines for PCOS 2013
1.3 Diagnosis in perimenopause and menopause• Long term history of oligomenorrhea & hyperandrogenism
• Polycystic ovary – less likely
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 18
ES Guidelines for PCOS 2013
2 - Associated comorbidity and Evaluation
ES Guidelines for PCOS 2013
2.1 - Documenting cutaneous menifestations
• Hirsutism (Modified Ferriman-Gallwey score)
• Acne
• Adrogenic alopecia (Ludwig score)
• Acanthosis nigricans
• Skin tags
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 20
ES Guidelines for PCOS 2013
2.2 - Screening ovulatory status (even in eumenorrheic patients)
• ↑ Risk of anovulation and infertility
• Menstrual history
• Midluteal S. Progesterone
2.3 - Exclude other causes of infertility in couples
• Obesity, Male factor infertility, tubal occlusionTuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 21
ES Guidelines for PCOS 2013
2.4 - Preconceptual Assessment
• ↑ Risk of pregnancy complications (GDM, Preterm delivery, Pre-eclampsia)
• BMI, BP, OGTT
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 22
ES Guidelines for PCOS 2013
2.5 - No intervention for prevention of PCOS in offspring of PCOS women
• Inconclusive evidence of intrauterine effects
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 23
ES Guidelines for PCOS 2013
2.6 - No routine USG screening for endometrial thickness in PCOS women without abnormal bleeding
• Poor diagnostic accuracy
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 24
ES Guidelines for PCOS 2013
2.7 - Screen for increased adiposity
• Ass. with Hyperandrogenemia and ↑ Metabolic risk
• BMI, Waist circumference
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 25
ES Guidelines for PCOS 2013
2.8 - Screen and manage depression and anxiety
2.9 - Screen and manage Obstructive sleep apnea (OSA)
• Polysomnography
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 26
ES Guidelines for PCOS 2013
2.10 - Awareness about possibility of NAFLD and NASH (No screening)
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 27
ES Guidelines for PCOS 2013
2.11 - Screen for IGT and T2DM• OGTT or HbA1c
• Re-screening every 3-5 years
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 28
ES Guidelines for PCOS 2013
2.12 - Screen for CVD risk factorsAt risk• Obesity
• Cigarette smoking
• Hypertension
• Dyslipidemia
• Subclinical vascular disease
• Impaired glucose tolerance• Family history of premature
CVD
High risk• Metabolic syndrome
• T2DM
• Overt vascular or renal disease,
CVD
• OSA
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 29
ES Guidelines for PCOS 2013
3 - Treatment
ES Guidelines for PCOS 2013
3.1 - Hormonal contraceptives (HC) – First Line management for menstrual abnormalities and hirsutism/acne of PCOS
3.2 - Screen for contraindications of HCs
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 31
ES Guidelines for PCOS 2013
3.3 - Exercise therapy in management of overweight and obesity in PCOS
• 30 min moderate to vigorous exercise daily
3.4 - Weight loss strategies for adolescents and those overweight or obese
• Calorie-restricted diet
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 32
ES Guidelines for PCOS 2013
3.5 - Metformin NOT first line management for• Cutaneous manifestations
• Prevention of pregnancy complications
• Obesity
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 33
ES Guidelines for PCOS 2013
3.6 - Metformin to be used in PCOS women if • T2DM or IGT who fail lifestyle modification
• Menstrual irregularities present and HCs are contraindicated / not tolerated.
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 34
ES Guidelines for PCOS 2013
3.7 - Clomiphene citrate (or Letrozole) as first line treatment for anovulatory infertility in PCOS
3.8 - Metformin as adjuvant for infertility to prevent Ovarian hyperstimulation syndrome (OHSS) in women with PCOS undergoing IVF
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 35
ES Guidelines for PCOS 2013
3.9 - Insulin sensitizers e.g. inositols or thiazolidinediones use NOT recommended
3.10 - Statins only recommended in PCOS if patient meet current indications for statin therapy.
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 36
ES Guidelines for PCOS 2013
3.11 - Treatment of adolescents
• HCs first-line treatment with suspected PCOS
• Lifestyle therapy (calorie-restricted diet and exercise) also first-line if overweight/obesity
• Metformin use to treat IGT/Metabolic syndrome
• Duration not determined
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 37
ES Guidelines for PCOS 2013
3.12 - Start HCs in pre-menarchal girls with hyperandrogenism and advanced pubertal development
• ≥ Tanner stage IV breast development
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 38
Summary
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 39
• Follow Rotterdam criteria in adults• Difficult diagnosis in adolescents & perimenopausal/menopausal
women
Diagnosis of PCOS
Summary
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 40
• Document cutaneous manifestations
• Preconceptual assessment to prevent pregnancy complications
• Look for other causes of infertility in couple
• Screening for anovulation, inc. adiposity, depression, anxiety,
OSA, IGT/T2DM, CVD risk factors
• No screening needed for endometrial cancer, NAFLD, NASH
• No specific intervention to prevent PCOS in offspring
Associated comorbidity and evaluation
Summary
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 41
• HCs first line therapy for PCOS in adults, adolescents and pre-menarchal girls with suspected PCOS
• Lifestyle modifications first line therapy in obese/overweights
• Metformin use recommended only when : • PCOS with T2DM/IGT who fail lifestyle modifications• Menstrual irregularity with contraindication for HCs • Adjuvant therapy to prevent OHSS in PCOS women undergoing
IVF• In Adolescents to treat IGT/ Metabolic syndrome
Treatment
Summary
Tuesday, May 2, 2023 Presentation by : Dr. Jagjit Khosla 42
• Clomiphene citrate or Letrozole first line therapy for anovulatory infertility in PCOS
• Statins only used if indication for statin therapy present
• Insulin sensitizers e.g. inositols & TZDs not recommended in PCOS
Treatment
May 2, 2023 Presenter : Dr. Jagjit Khosla 43
Thank you…