Adolescent

PCOS

Aboubakr Elnashar

Benha university,

Egypt

ABOUBAKR ELNASHAR

CONTENTS

1.DEFINITION

2.PREVALENCE

3.PRESENTATION

4.DIAGNOSIS

5.EVALUATION

6.TREATMENT

CONCLUSION

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1. DEFINITION

Adolescence

From Latin adolescere, meaning to grow up

Transitional stage of physical

and psychological development from puberty to

adulthood

Adolescents

Young people between the ages of 10 and 19 years(WHO)

Adolescent PCOS

Unexplained persistent hyperandrogenic anovulation(American Academy of Pediatrics, 2015).

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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).

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Risk factors

Premature pubarche (before 8 yr old)

Obesity

Family Hx

Ethnicity

more common in – African-American

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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

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3. PRESENTATION

Menstrual irregularities

Chronic anovulation

Hyperandrogenism

Acne

Hirsutism

Androgenetic alopecia

Hyperandrogenemia

PCO on US

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If assumed pathological:

over diagnosis of PCOS

unnecessary psychological distress of having a diagnosis associated with future subfertility.

If assumed physiological:

under diagnosis of PCOS

more likely to transition to adulthood and suffer the long term consequences of PCOS.

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4. DIAGNOSIS

Specific and very strict criteria:

Sultan and Paris (2006)

Requires 4 of 5:

1. Oligomenorrhoea or amenorrhoea

2. Clinical hyperandrogenism

3. Biochemical hyperandrogenism

4. Hyperinsulinaemia

5. Polycystic ovary morphology

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Carmina (2010)

Requires the presence of all three of the following:

1. Hyperandrogenism:

biochemical or

progressive hirsutism

2. Ovulatory dysfunction

persisting beyond 2 years post-menarche

3. Polycystic ovarian morphology

ovarian volume > 10 mL

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NIH criteria

The preferred diagnostic criteria in adolescents[Hardy, Norman, 2013; Legro et al, 2013].

Androgen Excess Society Criteria

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1. Chronic Anovulation /Oligomenorrhoea

(<6 cycles/year)

For 2 ys since menarche or

Primary amenorrhoea at 17 y

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2. Hyperandrogenism

Acne or hisutism is not criteria for the

diagnosis

•Acne unresponsive to topical treatment : test

for hyperandrogenemia. (Am Academy of Pediatrics, 2015).

•Progressive hirsutism: important sign of

adolescent PCOS (Jeffrey CR, Coffler, 2007).

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3. Hyperandrogenaemia:

Most consistent marker

Extremely important

No established normal ranges. FT ≥ 1.3 ng/dL,(Piltonen et al, 2005)

TT >1 µg/ml (The Rotterdam consensus workshop group, 2004).

Adult cutoffs should be used until

appropriate pubertal levels are defined.(Endocrine Society Clinical Practice , 2013)

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4. US criteria:

increased ovarian volume (>10 cm3).

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AMH:

Elevated: noninvasive screening or diagnostic

test for PCO

No well-defined cutoffs (Pawelczak et al, 2012; 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)

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5. EVALUATION1. 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)

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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)

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3. Depression

screening for depression and anxiety by history and, if identified: referral and/or treatment(2++OO).(Endocrine Society Clinical Practice, 2013)

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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)

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5. Type 2 diabetes mellitus (T2DM)

OGTT

{they are at high risk for such abnormalities} (1+++O).

HgbA1c:

if unable or unwilling to complete OGTT (2++OO).

Rescreening:

/3–5 y

more frequently if:

central adiposity

substantial weight gain, and/or

symptoms of diabetes develop(2++OO).

(Endocrine Society Clinical Practice, 2013)

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6. Cardiovascular risk

screened for CVD risk factors:

family history

cigarette smoking,

IGT/T2DMhypertension

dyslipidemia

OSAobesity

especially increased abdominal adiposity (1++OO).(Endocrine Society Clinical Practice, 2013)

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6. TREATMENT

Objectives:

symptomatic and prophylactic:

Restoration of body weight

Cycle regulation

Reducing signs of hyperandrogenism

Prevention of long term health hazards.

Infertility

Metabolic syndrome

Obesity

Diabetes

Heart disease.

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Indications

Even in the absence of a definitive diagnosis:

treatment that

alleviate symptoms

decrease the risk for subsequent associated co morbidities (Level B).(Androgen Excess PCOS Society; Pediatric endocrine society, 2015)

Individual PCOS manifestations:

(obesity, hirsutism, irregular menses) should

be treated.(level B)

(ESHRE/ASRM; 2012)

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Lines of therapy

Endocrine Society guidelines (2013):

1. Lifestyle changes (dietary and exercise modification)

2. Followed by either:

OCP {control symptoms of hyperandrogenism} or

Metformin in patients with impaired glucose tolerance or features of metabolic syndrome

[Legro et al, 2013].

± Combine OCP with Met

±Combine Antiandrogen with OCP or Met

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1. Lifestyle therapy:

First-line strategy

Weight loss

Calorie-restricted diets (with no evidence that one type of diet is superior)(2++OO).

Beneficial for both reproductive and metabolic dysfunction.

(Endocrine Society Clinical Practice, 2013)

Why?{obesity during adolescence: an important factor that conditions the evolution of ovarian function(McCartney et al, 2009).wt loss 2-5% testosterone by 21%

resume regular ovulation in 50% womenABOUBAKR ELNASHAR

Exercise

in overweight and obese (2++OO).

{ improves weight lossreduces CV risk factors and diabetes risk}.(Endocrine Society Clinical Practice, 2013)

Avoid alcohol, smoking, psychosocial stressors

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2. Hormonal contraceptives (HCs):

Indications:

First-line management for the

menstrual abnormalities

hirsutism/acne(1++OO).

(Endocrine Society Clinical Practice, 2013)

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Types:

OCP, patch, or vaginal ring(2++OO).

can be used

OCPs either containing or not containing an

antiandrogen(Italian society of endocrinology, 2015)

can be used

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Metabolic effects of COC containing 30ug or less

of EE:

•MildDeterioration of glucose tolerance Worsening of lipid profile

•Should not influence the choice(Italian society of endocrinology, 2015)

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VTE risk is not studied

Odds ratio

1.65 for BMI 25–30 kg/m2

1.84 for BMI 30–35 kg/m2

4.34 for BMI >35 kg/m2

[Murthy, 2010].

Risk is further increased in

CPA or

3rd generation progestins, including

drospirenone[Lenzer, 2011].

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Screening for contraindications

via established criteria(1+++O).

lipid profile and the glucose tolerance should be evaluated before and after 3 months of higher dose OC containing cyproterone acetate(Italian society of endocrinology, 2015)

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BMI:

≤35 kg/m2 with no specific metabolic and/ or CV

abnormalities

Any typeChoice acc to:

preferences of the physician and patientspecific 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)

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3. Metformin:

Indications

To treat IGT/metabolic syndrome (2++OO).

long-term resumption of ovulation

especially thos with an inadequate response

to lifestyle intervention.

Commonly used as

first line monotherapy or

in combination with OCPs or

antiandrogen

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Dose:

Lean:

850 mg daily

Overweight and obese:

1.5 to 2.5 g daily.

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Met and COC*:

have comparable therapeutic effectiveness on cycle regularity

and hirsutism.

Met

significant improvement in insulin sensitivity

COC

deterioration of insulin sensitivity*(30 µg EE and150µg desogestrel=Marvelon)

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4. Combined metformin and OC

:

attenuating the adverse metabolic effects of OC

improving body composition

, as compared with OC alone [Glintborg et al, 2014].

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Duration of HC 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)

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5. Anti-androgenic medications

Spironolactone, flutamide, and insulin sensitizing

agents such as pioglitazone

Indication:

when OCP or metformin fail to produce the

clinically desired outcomes [Conway et al, 2014].

±affect bone mass,

short term data: no effect.

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AntiandrogenMetCOClifestylePCOS

+++++++Menstrual Dysfunction

++++++++Hirsutism

++++++++Acne

++++++++Hyperandrogenemia

+++obesity

++++++IGT/2DM

+Psychological

+++: strong evidence

+: some evidence

Morris et al, 2016

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CONCLUSIONS

Diagnosis:

Early and accurate diagnosis is essential for

implementation of appropriate treatment

Criteria for the diagnosis differ from those used

for adult women

Hyperandrogenaemia:

the most consistent marker

Evaluation:

Metabolic

CV risks,

Psychologic

Dermatologic . ABOUBAKR ELNASHAR

Treatment

lifestyle modifications

Hormonal contraceptives

Metformin

Antiandrogen.

Limited data on the best treatment modalities

Should be individualized depending on:

Age

Symptoms

Personal and familial risk factors

Choices.

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Thanks

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