Prof Aboubakr Mohamed Elnashar

1. 26/12/1441
1
Adolescent
PCOS
Prof. Aboubakr
Elnashar
Benha university, Egypt
elnashar53@hotmail.com
ABOUBAKR ELNASHAR
26/12/1441
2
CONTENTS
1.DEFINITION
2.PREVALENCE
3.DIAGNOSIS
4.EVALUATION
5.TREATMENT
CONCLUSION
ABOUBAKR ELNASHAR

2. 26/12/1441
3
1. DEFINITION
Adolescence
From Latin adolescere, meaning to grow up
Transitional stage of physical
and psychological development from puberty to
adulthood
Adolescents (WHO)
Young people between the ages of 10&19 years
Adolescent PCOS
Unexplained persistent hyperandrogenic anovulation
(American Academy of Pediatrics, 2015).ABOUBAKR ELNASHAR
26/12/1441
4
2. PREVALENCE
1.8 and 15 %
depending on:
diagnostic criteria
ethnicity [Li et al, 2013]
.
Increasing
{increasing prevalence of childhood obesity}
(Hassan et al, 2007).
ABOUBAKR ELNASHAR

3. 26/12/1441
5
Risk factors
 Premature pubarche (before 8 yr old)
 Obesity
 Family Hx
 Ethnicity
more common in – African-American
ABOUBAKR ELNASHAR
26/12/1441
6
Course:
±Progressive course
:full-blown picture of adult PCOS
(evidence is contradictory) (Coviello et al, 2006)
Risk for progress of adolescent to adult PCOS
•Persistent irregular cycles 6 y after menarche
(Venturoli et al, 1987)
•Persistent anovulatory cycles 3y after menarche
(Venturoli et al, 1994)
•Increased BMI
ABOUBAKR ELNASHAR

4. 26/12/1441
7
 Diagnostic criteria of adult PCOS
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.
ABOUBAKR ELNASHAR
26/12/1441
8
3. DIAGNOSIS
 Specific & very strict criteria:
1. Irregular menstrual cycles plus
2. Hyperandrogenism and/or
3. Hyperandrogenaemia
ABOUBAKR ELNASHAR

5. 26/12/1441
9
1. Irregular menstrual cycles (ESHRE, 2018)
 Post menarche:
 < 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/y.
 Primary amenorrhea by
age 15 or
> 3 years post thelarche (breast development).
ABOUBAKR ELNASHAR
26/12/1441
10
2. Hyperandrogenism
 Isolated hirsuitism, acne and/or alopecia is not
diagnostic criteria (LevelC).
 Severe acne:No universally accepted visual assessments for
evaluating acne.
 Severe or progressive hirsutism (Jeffrey CR, Coffler, 2007;
ESHRE, 2018)
ABOUBAKR ELNASHAR

6. 26/12/1441
11
 Hirsutism: Modified Ferriman &
Gallwey
 9 sites assessed (mFG)
 ≥ 4 - 6 on mFG depending
on ethnicity
 > 3 in White and Black
women
 > 5 in Mongoloid Asian
 Perception is more important
than severity
ABOUBAKR ELNASHAR
26/12/1441
12
Grading scale for female pattern hair loss
mild but obvious female
pattern hair loss
Female androgenic alopecia
Frontal and temporal hair loss
 Alopecia: Ludwig score
Assess severity and distribution
ABOUBAKR ELNASHAR

7. 26/12/1441
13
3. Hyperandrogenaemia (ESHRE, 2018)
 If clinical hyperandrogenism is unclear
 High quality assays: should be used
 liquid chromatography–mass
spectrometry(LCMS)/mass spectrometry
 Extraction/chromatography immunoassays
 Direct FT assays: should not be used.
{poor sensitivity, accuracy and precision}.
 Radiometric or enzyme-linked assays
 DHEAS & androstenedione: limited roleABOUBAKR ELNASHAR
26/12/1441
14
 Calculated FT, FAI or bioavilable T is recommended
 Use upper limits of reference ranges
 Hormonal contraception must be off for 3 months
 Normal range: 7-10
ABOUBAKR ELNASHAR

8. 26/12/1441
15
 US criteria:
 should not be used < 8 years after menarche
{high incidence of multi-follicular ovaries in this life stage}
(ESHRE, 2018)
 Ovarian volume
 >10 cm3 ( AE-PCOS Society, 2014)
 >12 ml ( Pediatric society, 2015)
ABOUBAKR ELNASHAR
26/12/1441
16
AMH:
should not yet be used (ESHRE, 2018)
No well-defined cutoffs (Rosenfield et al, 2012).
•>4.5 ng/mL: useful as a substitute for ovarian
morphology when no accurate ovarian US is available
(Dewailly et al, 2011).
•6.1ng/mL (Yetim et al, 2016)
7.25 ng/ml (Savas-Erdeve et al, 2016)
ABOUBAKR ELNASHAR

9. 26/12/1441
17
 IR, compensatory hyperinsulinemia, or obesity
 should not be considered
as diagnostic criteria for PCOS in adolescents
(Level A).
ABOUBAKR ELNASHAR
26/12/1441
18
 At risk of PCOS (ESHRE, 2018)
 If ONLY irregular cycles OR hyperandrogenism
 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.
ABOUBAKR ELNASHAR

10. 26/12/1441
19
4. EVALUATION
1. Cutaneous manifestations
Physical examination should document cutaneous
manifestations of PCOS:
 Terminal hair growth
 Acne
 Alopecia
 Acanthosis nigricans
 Skin tags
(1+++O).
(Endocrine Society Clinical Practice, 2013)
ABOUBAKR ELNASHAR
26/12/1441
20
2. Obesity
{Increased adiposity, particularly abdominal, is associated
with hyperandrogenemia and increased metabolic risk }
Screening for increased adiposity, by
 BMI calculation
 Measurement of WC
(1+++O).
(Endocrine Society Clinical Practice, 2013)
ABOUBAKR ELNASHAR

11. 26/12/1441
21
3. Depression
screening for depression and anxiety by history and,
if identified: referral and/or treatment
(2++OO).
(Endocrine Society Clinical Practice, 2013)
ABOUBAKR ELNASHAR
26/12/1441
22
4. Sleep-disordered breathing/obstructive sleep
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)
ABOUBAKR ELNASHAR

12. 26/12/1441
23
5. Type 2 diabetes mellitus (T2DM)
{they are at high risk for such abnormalities}
OGTT
HgbA1c: if unable or unwilling to complete OGTT
Rescreening:
/3–5 y
more frequently if:
central adiposity
substantial weight gain, and/or
symptoms of diabetes develop
(Endocrine Society Clinical Practice, 2013)
ABOUBAKR ELNASHAR
26/12/1441
24
6. Cardiovascular risk
screened for CVD risk factors:
family history
cigarette smoking,
IGT/T2DM
hypertension
dyslipidemia
OSA
obesity
especially increased abdominal adiposity
(Endocrine Society Clinical Practice, 2013)
ABOUBAKR ELNASHAR

13. 26/12/1441
25
7. Subclinical hypothyroidism
may be concealed
±investigated for autoimmune thyroiditis.
(Nezi et al, 2016)
ABOUBAKR ELNASHAR
26/12/1441
26
5. TREATMENT
(A E PCOS Society; Pediatric endocrine society, 2015)
Objectives:
 Symptomatic
Restoration of body wt
Cycle regulation
Reducing signs of hyperandrogenism
Prophylactic: of long term health hazards.
 Infertility
 Metabolic syndrome
 Obesity
 Diabetes
 Heart disease. ABOUBAKR ELNASHAR

14. 26/12/1441
27
At risk:: should be treated (ESHRE/ASRM; 2012, ESHRE, 2018)
 Acnae
 Obesity
 Hirsutism
 Irregular menses
ABOUBAKR ELNASHAR
26/12/1441
28
I. LIFESTYLE THERAPY
 First-line strategy (ESHRE, 2018)
Overweight or obese.
Wt loss 2-5%   testosterone by 21%: resume
regular ovulation in 50% women (McCartney et al, 2009).
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
ABOUBAKR ELNASHAR

15. 26/12/1441
29
 Anti-obesity medications (ESHRE, 2018)
 Can be considered with lifestyle, considering
 cost
 contraindications
 side effects
 availability
 regulatory status
ABOUBAKR ELNASHAR
26/12/1441
30
 Exercise (Endocrine Society Clinical Practice, 2013)
 improves weight loss
 reduces
 CV risk factors
 diabetes risk
 60 mins/d: moderate to vigorous intensity
 3 times/w: muscle& bone strengthening(ESHRE, 2018)
ABOUBAKR ELNASHAR

16. 26/12/1441
31
 Avoid
 Alcohol
 Smoking
 Psychosocial stressors
ABOUBAKR ELNASHAR
26/12/1441
32
In normal-weight girls:
 Prevention of wt gain
 Monitoring of weight
 Increasing physical activity
effective in reducing the development of metabolic
syndrome (Level C).
 Weight loss
not supported by RCTs (Level C).
ABOUBAKR ELNASHAR

17. 26/12/1441
33
II. FIRST LINE PHARMACOLOGICAL THERAPY
COCP alone (ESHRE, 2018)
 Should be considered in adolescents
1. with clear diagnosis of PCOS for management of clinical
hyperandrogenism and/or irregular menstrual cycles.
2. who are“at risk” but not yet diagnosed with
PCOS, for management of cl hyperandrogenism & irregular
menstrual cycles.
ABOUBAKR ELNASHAR
26/12/1441
34
 WHO Contraindications:
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
10.Malignant liver tumoursABOUBAKR ELNASHAR

18. 26/12/1441
35
BMI:
≤35 kg/m2 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/m2 : COC should be prescribed with caution
≥40 kg/m2:
Not used (RCOG, 2011).
If contraception is needed:
alternative measures, such as progestin-only methods.
(Italian society of endocrinology, 2015)
ABOUBAKR ELNASHAR
26/12/1441
36
 Type:
 No COCP preparation is superior
 Use lowest effective estrogen dose:
 20-30 ug EE or equivalent
 COCPs containing
 Levonorgestrel
 Norethisterone associated with lowest risk of DVT.
 Norgestimate
ABOUBAKR ELNASHAR

19. 26/12/1441
37
 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
 Most androgenic progestin:
 Levonorgestrel, norethisterone
 Low androgenicity: norgestimate and desogestrel
 Progestins with antiandrogenic activity
 Drospirenone, CPA, Dienogest
ABOUBAKR ELNASHAR
26/12/1441
38
III. Second line pharmacological therapies
1. COCP + Metformin
Should be considered in
Management of metabolic features
Where COCP+ lifestyle does not achieve goals.
Could be considered in
Adolescent PCOS
BMI ≥ 25kg/m2
ABOUBAKR ELNASHAR

20. 26/12/1441
39
2. COCP + Anti-androgens
Can be considered
After 6/12 cosmetic treatment+ COCP
if they fail to reach hirsutism goals.
With androgenic alopecia.
 Anti-androgens reduce androgen excess features
more than metformin in monotherapy (Level B).
 Spironolactone is the most commonly (Level C).
 Anti-androgens should only be used when contraceptive
measures are guaranteed.
ABOUBAKR ELNASHAR
26/12/1441
40
3. Metformin
Should be considered in
Adolescents with a
Clear diagnosis of PCOS or
At risk: Symptoms of PCOS before diagnosis is
made.
Most useful with
BMI ≥ 25kg/m2
High risk ethnic groups.
ABOUBAKR ELNASHAR

21. 26/12/1441
41
 Metformin does not promote wt loss in obese
adolescent PCOS [RCT: Ladson et al, 2011].
 2 g daily combined with diet &exercise for 6 months did not
induce greater wt loss compared with diet&exercise alone
 In overweight or obese adolescents with PCOS:
beneficial effects (Level A).
 In non-obese adolescents with PCOS and
hyperinsulinemia: improves ovulation& testosterone
levels (Level B).
ABOUBAKR ELNASHAR
26/12/1441
42
Inositol
should be considered experimental
with emerging evidence of efficacy highlighting the
need for further research.
(ESHRE, 2018)
ABOUBAKR ELNASHAR

22. 26/12/1441
43
Duration of COCP or metformin
Not yet been determined.
 until the patient is gynecologically mature
(5y postmenarcheal) or
 has lost a substantial amount of excess wt.
(Rosenfield; 2015)
ABOUBAKR ELNASHAR
26/12/1441
44
AntiandrogenMetCOClifestylePCOS
+++++++Menstrual Dysfunction
++++++++Hirsutism
++++++++Acne
++++++++Hyperandrogenemia
+++obesity
++++++IGT/2DM
+Psychological
+++: strong evidence
+: Low evidence
Morris et al, 2016
ABOUBAKR ELNASHAR

23. 26/12/1441
45
CONCLUSIONS
Diagnosis:
Early & accurate diagnosis is essential
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
26/12/1441
46
Evaluation:
Metabolic,CV risks, psychologic, dermatologic,SHT
Treatment
 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

24. 26/12/1441
47
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
ABOUBAKR ELNASHAR