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Adolescent 1. DEFINITION
CONTENTS

PCOS 2. PREVALENCE
3. DIAGNOSIS
Prof. Aboubakr
4. EVALUATION
Elnashar
5. TREATMENT
CONCLUSION
Benha university, Egypt
elnashar53@hotmail.com

ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR

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1. DEFINITION 2. PREVALENCE
Adolescence 1.8 and 15 %
From Latin adolescere, meaning to grow up depending on:
Transitional stage of physical diagnostic criteria
and psychological development from puberty to ethnicity [Li et al, 2013]
.
adulthood
Increasing
Adolescents (WHO)
{increasing prevalence of childhood obesity}
Young people between the ages of 10&19 years
(Hassan et al, 2007).
Adolescent PCOS
Unexplained persistent hyperandrogenic anovulation
(American Academy of Pediatrics, 2015).
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Risk factors Course:

 Premature pubarche (before 8 yr old) ±Progressive course

 Obesity :full-blown picture of adult PCOS

(evidence is contradictory) (Coviello et al, 2006)
 Family Hx

 Ethnicity Risk for progress of adolescent to adult PCOS

more common in – African-American •Persistent irregular cycles 6 y after menarche
(Venturoli et al, 1987)

•Persistent anovulatory cycles 3y after menarche

(Venturoli et al, 1994)

•Increased BMI
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3. DIAGNOSIS
 Diagnostic criteria of adult PCOS
 Specific & very strict criteria:
1. Irregular menstrual cycles plus
2. Hyperandrogenism and/or
3. Hyperandrogenaemia

All criteria require exclusion of other conditions:

nonclassic congenital adrenal hyperplasia, hypothyroidism, Cushing
syndrome, hyperprolactinemia or androgen producing tumours which can
cause a PCOS-like picture.
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1. Irregular menstrual cycles (ESHRE, 2018) 2. Hyperandrogenism

 Post menarche:  Isolated hirsuitism, acne and/or alopecia is not
 < 1y: Irregular cycles are normal {pubertal transition}. diagnostic criteria (LevelC).
 > 1 y: 90 days for any one cycle  Severe acne:No universally accepted visual assessments for
evaluating acne.
 > 1 to < 3 y: < 21 or > 45 days.  Severe or progressive hirsutism (Jeffrey CR, Coffler, 2007;
 > 3 years: < 21 or > 35 days or < 8 cycles/y. ESHRE, 2018)

 Primary amenorrhea by
age 15 or
> 3 years post thelarche (breast development).

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 Alopecia: Ludwig score mild but obvious female

 Hirsutism: Modified Ferriman & Assess severity and distribution pattern hair loss
Gallwey

 9 sites assessed (mFG)

 ≥ 4 - 6 on mFG depending

on ethnicity

 > 3 in White and Black Female androgenic alopecia

women Frontal and temporal hair loss

 > 5 in Mongoloid Asian Grading scale for female pattern hair loss
 Perception is more important
than severity

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3. Hyperandrogenaemia (ESHRE, 2018)

 Calculated FT, FAI or bioavilable T is recommended
 If clinical hyperandrogenism is unclear
 Use upper limits of reference ranges
 High quality assays: should be used
 Hormonal contraception must be off for 3 months
 liquid chromatography–mass
spectrometry(LCMS)/mass spectrometry

 Extraction/chromatography immunoassays
 Normal range: 7-10
 Direct FT assays: should not be used.
{poor sensitivity, accuracy and precision}.

 Radiometric or enzyme-linked assays

 DHEAS & androstenedione:

ABOUBAKR ELNASHAR limited role ABOUBAKR ELNASHAR

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 US criteria: AMH:
 should not be used < 8 years after menarche should not yet be used (ESHRE, 2018)
{high incidence of multi-follicular ovaries in this life stage}
(ESHRE, 2018)
No well-defined cutoffs (Rosenfield et al, 2012).
 Ovarian volume
•>4.5 ng/mL: useful as a substitute for ovarian
 >10 cm3 ( AE-PCOS Society, 2014)
morphology when no accurate ovarian US is available
 >12 ml ( Pediatric society, 2015) (Dewailly et al, 2011).

•6.1ng/mL (Yetim et al, 2016)

7.25 ng/ml (Savas-Erdeve et al, 2016)

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 IR, compensatory hyperinsulinemia, or obesity  At risk of PCOS (ESHRE, 2018)

 should not be considered  If ONLY irregular cycles OR hyperandrogenism
as diagnostic criteria for PCOS in adolescents
(Level A).  US is not indicated
 Symptomatic treatment

 Regular re-evaluations.
1. Menstrual cycle re-evaluation after 3 years
post menarche
2. US evaluation after 8 years post menarche.
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4. EVALUATION 2. Obesity
1. Cutaneous manifestations {Increased adiposity, particularly abdominal, is associated

Physical examination should document cutaneous with hyperandrogenemia and increased metabolic risk }

manifestations of PCOS: Screening for increased adiposity, by

 Terminal hair growth  BMI calculation

 Acne  Measurement of WC
 Alopecia (1+++O).

 Acanthosis nigricans (Endocrine Society Clinical Practice, 2013)

 Skin tags
(1+++O).
(Endocrine Society Clinical Practice, 2013)
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3. Depression 4. Sleep-disordered breathing/obstructive sleep

screening for depression and anxiety by history and,
if identified: referral and/or treatment
(2++OO).
(Endocrine Society Clinical Practice, 2013)
apnea (OSA)
screening overweight/obese adolescents for
symptoms suggestive of OSA
when identified: definitive diagnosis using
polysomnography: referred for tt
(2++OO).
(Endocrine Society Clinical Practice, 2013)

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5. Type 2 diabetes mellitus (T2DM) 6. Cardiovascular risk

{they are at high risk for such abnormalities} screened for CVD risk factors:
OGTT family history
HgbA1c: if unable or unwilling to complete OGTT cigarette smoking,
Rescreening: IGT/T2DM
/3–5 y hypertension
more frequently if: dyslipidemia
central adiposity OSA
substantial weight gain, and/or
symptoms of diabetes develop obesity
(Endocrine Society Clinical Practice, 2013)
especially increased abdominal adiposity
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(Endocrine Society Clinical Practice, 2013)

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5. TREATMENT
(A E PCOS Society; Pediatric endocrine society, 2015)
7. Subclinical hypothyroidism
Objectives:
may be concealed
 Symptomatic
±investigated for autoimmune thyroiditis.
Restoration of body wt
(Nezi et al, 2016)
Cycle regulation
Reducing signs of hyperandrogenism
Prophylactic: of long term health hazards.
 Infertility
 Metabolic syndrome
 Obesity
 Diabetes
ABOUBAKR ELNASHAR  Heart disease. ABOUBAKR ELNASHAR

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At risk:: should be treated (ESHRE/ASRM; 2012, ESHRE, 2018) I. LIFESTYLE THERAPY
 First-line strategy (ESHRE, 2018)
 Acnae
Overweight or obese.
 Obesity
Wt loss 2-5%   testosterone by 21%: resume
 Hirsutism
regular ovulation in 50% women (McCartney et al, 2009).
 Irregular menses

Calorie-restricted diets
No evidence that one type of diet is superior
Beneficial for both reproductive & metabolic dysfunction.
{obesity during adolescence: an important factor that
conditions the evolution of ovarian function
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 Anti-obesity medications (ESHRE, 2018)  Exercise (Endocrine Society Clinical Practice, 2013)
 Can be considered with lifestyle, considering  improves weight loss
 cost  reduces
 contraindications  CV risk factors
 side effects  diabetes risk
 availability  60 mins/d: moderate to vigorous intensity
 regulatory status  3 times/w: muscle& bone strengthening(ESHRE, 2018)

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 Avoid In normal-weight girls:

 Alcohol  Prevention of wt gain
 Monitoring of weight
 Smoking
 Increasing physical activity
 Psychosocial stressors
effective in reducing the development of metabolic
syndrome (Level C).
 Weight loss
not supported by RCTs (Level C).

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II. FIRST LINE PHARMACOLOGICAL THERAPY  WHO Contraindications:

1. History of migraine with aura
COCP alone (ESHRE, 2018)
2. DVT/pulmonary emboli (PE)
 Should be considered in adolescents 3. Known thrombogenic mutation
1. with clear diagnosis of PCOS for management of clinical 4. Multiple risk factors for arterial CVD
hyperandrogenism and/or irregular menstrual cycles.
5. History of ischemic heart disease or stroke
2. who are“at risk” but not yet diagnosed with
6. Complicated valvular heart disease,
PCOS, for management of cl hyperandrogenism & irregular
7. Breast cancer
menstrual cycles.
8. Neuropathy
9. Severe cirrhosis
ABOUBAKR ELNASHAR
10.Malignant liver tumours
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BMI:  Type:
≤35 kg/m2 with no specific metabolic and/ or CV abnormalities  No COCP preparation is superior
Any type  Use lowest effective estrogen dose:
Choice acc to: preferences of the physician and patient
 20-30 ug EE or equivalent
specific clinical characteristics of the patient.
(Italian society of endocrinology, 2015)

≥35 kg/m2 : COC should be prescribed with caution  COCPs containing

≥40 kg/m2:  Levonorgestrel
Not used (RCOG, 2011).  Norethisterone associated with lowest risk of DVT.
If contraception is needed:  Norgestimate
alternative measures, such as progestin-only methods.
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(Italian society of endocrinology, 2015)

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 35 ug EE plus cyproterone acetate

III. Second line pharmacological therapies
Not first line in PCOS
1. COCP + Metformin
(higher DVT risk)
Should be considered in
 Should only be used when treating
Management of metabolic features
 Moderate to severe hirsutism or
Where COCP+ lifestyle does not achieve goals.
 Acne
 Most androgenic progestin:
 Levonorgestrel, norethisterone Could be considered in
 Low androgenicity: norgestimate and desogestrel Adolescent PCOS
 Progestins with antiandrogenic activity BMI ≥ 25kg/m2
 Drospirenone, CPA, Dienogest
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2. COCP + Anti-androgens 3. Metformin

Can be considered Should be considered in
After 6/12 cosmetic treatment+ COCP Adolescents with a
if they fail to reach hirsutism goals. Clear diagnosis of PCOS or
With androgenic alopecia. At risk: Symptoms of PCOS before diagnosis is
made.
 Anti-androgens reduce androgen excess features
more than metformin in monotherapy (Level B). Most useful with
 Spironolactone is the most commonly (Level C). BMI ≥ 25kg/m2
 Anti-androgens should only be used when contraceptive High risk ethnic groups.
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measures are guaranteed.

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 Metformin does not promote wt loss in obese Inositol

adolescent PCOS [RCT: Ladson et al, 2011]. should be considered experimental
 2 g daily combined with diet &exercise for 6 months did not with emerging evidence of efficacy highlighting the
induce greater wt loss compared with diet&exercise alone need for further research.
 In overweight or obese adolescents with PCOS: (ESHRE, 2018)

beneficial effects (Level A).

 In non-obese adolescents with PCOS and

hyperinsulinemia: improves ovulation& testosterone
levels (Level B).

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Duration of COCP or metformin

Morris et al, 2016
Not yet been determined.
 until the patient is gynecologically mature
(5y postmenarcheal) or
PCOS lifestyle COC Met Antiandrogen
 has lost a substantial amount of excess wt. Menstrual Dysfunction +++ +++ +
(Rosenfield; 2015) Hirsutism + +++ + +++
Acne + +++ + +++
Hyperandrogenemia + +++ + +++
obesity +++
IGT/2DM +++ +++
Psychological +
+++: strong evidence
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+: Low evidence

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CONCLUSIONS Evaluation:
Metabolic,CV risks, psychologic, dermatologic,SHT
Diagnosis:
Treatment
Early & accurate diagnosis is essential
 Should be individualized depending on: age,
Criteria for the diagnosis differ from those used for
symptoms, risk factors & choices
adult
 1st line: lifestyle modifications
Irregular menstruation plus
 1st line pharmacological: COCP
Moderate to severe hyperandrogenism and/or
 2nd line pharmacological:
hyperandrgemia
 COCP+ Metformin
Exclusion of other causes of hyperandrogenism with
 COCP+ Antiandrogen
menstrual irregularity
ABOUBAKR ELNASHAR
 Metformin. ABOUBAKR ELNASHAR

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You can get this lecture from:

1. My scientific page on Face book: Aboubakr
Elnashar Lectures.
https://www.facebook.com/groups/2277448840913
51/
2. Slide share web site
3. elnashar53@hotmail.com
4. My clinic: Elthwara St. Mansura

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