this is about the latest guideline 2023, for adolescent PCOS, How to diagnose, and the latest change in the management protocols.

1. FROM
evidence-basedESHRE
International 2023 Guidelines
for
ADOLESCENT – PCOS
Dr. Pushp Lata Sankhwar
MBBS , MS , FICS , FICOG,MNAMS
Professor
Dept. of Obgyn, KGMU, Lko

2. 0 Incidence of PCOS and see if PCOS starts before puberty?
0 Are the adult criteria for PCOS applicable in adolescent
patients and what are the problems in diagnosis?
0 Is an adolescent PCOS different?
0 Managing PCOS in adolescence – Is it also different?
What the Latest Guideline have to say about adolescent PCOS?

3. The transitional phase of growth and
development of a girl between childhood and
adulthood.
This period is between 10 and 19 years of age.
(WHO)

4.  Prevalence of PCOS in Indian
adolescents is 9.13%*
 In an another Indian study in girls with
menstrual irregularities….prevalence
of PCOS found to be 36%**
*J Pediatr Adolesc Gynecol. 2011Aug;24(4):223-7.
** Indian J Pediatr. 2012 Jan;79 Suppl 1:S69-73.

5. Diagnosing polycystic ovary syndrome (PCOS)
during adolescence is both
? CONTROVERSIAL AND CHALLENGING.
 Features of normal pubertal development overlap with adult
diagnostic criteria.
 PCOS is generally underdiagnosed during adolescence

6. But
Unfortunately,not always diagnosed at that age
Because - Clinical presentation is inconsistent

7. In a study, by Battaglia et al Human Reprod 2002; 17: 771-776
1. (14/15) 93% had PCO if their mothers had
PCOS Vs
0% in control daughters.
 Low birth weight and rapid postnatal weight gain
✓ Precocious Adrenarche / Pubarche
Increases the risk for progressionto functional ovarian
hyperandrogenism and PCOS
Ibáñez L et al. J Clin Endocrinol Metab. 2011;96(8):E1262-7.

8. Anovulatory
Infertility
Genetic/
epigenetic
Environmental
Hyper
Androgenemia
DM-2
Hypertension
CVD
Hyper
Insulinaemia
PCOS Hirsutism,
Acne,
Alopecia
Menstrual
irregularities
Metabolic
Syndrome

9. Burgert T et al. Current and Emerging Concepts. Springer Science & Business Media. Chapter 14, pP245-264.

10. Hunter MH et al. Indian Journal of Clinical Medicine. 2010:1 7–13.

11. Hunter MH et al. Indian Journal of Clinical Medicine. 2010:1 7–13.

12. PCOS definition
NIH 1990
Patient demonstrates
both:
1. Clinical and/or
biochemical signs
of
hyperandrogenism
2. Oligo- or chronic
anovulation
Rotterdam
criteria 2003
(ESHRE/ASRM)
Two of the following
three manifestations:
1.Irregular or absent
ovulation
2.Hyperandrogenis
m (clinical or
biochemical)
3 PCO on USG
AES Criteria
2006
Patient demonstrates
both:
1. Hirsutism and/or
hyperandrogenemia
2. Oligo-
anovulation and/or
polycystic
ovaries
Azzizet al. JCEM2006;
91: 4237-45
Exclude other etiologies of androgen excess – Late onset
congenital adrenal hyperplasia, Androgen secreting tumours,
Cushing’s syndrome

13. “Multicystic” ovaries
No
Normal Adolescents
Oligomenorrhea
Amenorrhoea
Acne

14. Anovulation:
*85 percent of
cycles
anovulatory in
first year of
menstruation.
*59 percent of
cycles
anovulatory in
the third year
*25 percent of
the cycles still
anovulatory in
the sixth year
ovaria
adrenal
Metabolic features
Insulin resistance
insulin due high
GH
hyperpulsatile
GnRH secretion
decreased levels
SHBG
n &
androgen
PCOM at USG
in 40%, 35% &
33.3% at 2, 3
& 4 years
after
menarche
Corresponds to
a physiologic
condition
during early
adolescence
Not associated
with
abnormalities
in
ovulation
menstrual
cycle duration
androgens or
IR
However all return to
normal at the end of
Normal adolescent
normal puberty but
remain elevated in PCOS RCOG Scientific Study Group, 2010

15. 0 84% Overweight
0 60% Androgen excess
0 30% Menstrual irregularities
0 9% IGT or T2D
0 Infertility rarely an issue
Bekx. et al. Pediatric and Adolescent Gynecology 2009 Rosefeld. et al. Journal of
Pediatric Endocrinology and
Metabolism 2000

16.  Presentation
 Irregular menses 2 years post-menarche
 And/or evidence of clinical androgen excess
 USG
 Confirmation of abnormal profile
 Measure serum total testosterone and SHBG
 Measure TSH, PRL, 17-hydroxyprogesterone, DHEAS
 Fasting Blood sugar and insulin levels
 Oral GTT
 Assess other metabolic risk factors
 Determine if lifestyle intervention is feasible
 Identify the Risk factors
Ibáñez L et al. J Clin Endocrinol Metab. 1997;82(7):2283-8.

17. Sultan and coll. (Fertil Steril 2006;86(Suppl 1) 56)
have suggested diagnosis on followingcriteria:
0 Clinical Hyperandrogenism
0 Biological Hyperandrogenism
0 Hyperinsulinism
0 Oligo/amenorrhea
0 Polycystic ovaries
Diagnosis of PCOS requires the presence of 4 out of 5

18. Carmina, Oberfield and Lobo. AJOG 2010
Hyperandrogenism
biochemically confirmed
+
Menstrual irregularities
Present for at least 2 years post menarche
+
Polycystic Ovaries
include both increased size and increased number of
follicles

19. What is Known Already:
 The 2018 International PCOS Guideline – It independently evaluated high quality and
integrated multidisciplinary and consumer perspectives from six continents;
 it is now used in 196 countries and is widely cited.
 The guideline transitioned from consensus-based to evidence-based diagnostic criteria and
enhanced accuracy of diagnosis,
but generally very low to low quality, evidence.

20.  Across professional societies and consumer organizations with
multidisciplinary experts and women with PCOS directly involved at all
stages. Extensive evidence synthesis was completed.
 Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-
compliant processes were followed.
 The Grading of Recommendations, Assessment, Development, and
Evaluation (GRADE) framework was applied across evidence quality,
feasibility, acceptability, cost, implementation and ultimately
recommendation strength and diversity and inclusion were considered
thoroughly.

21. The 2023 International Guideline provides clinicians and patients with –
- clear advice on best practices, based on the best available evidence.
Key updates include:
 further refinement of individual diagnostic criteria, a simplified diagnostic algorithm
and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in
adults only;
 ii) strengthening recognition of broader features of PCOS including metabolic risk
factors, cardiovascular disease, sleep apnea, very high prevalence of psychological
features, and high risk status for adverse outcomes during pregnancy;
 iii) emphasizing the poorly recognized, diverse burden of disease

22. ESHRE PCOS guidelines 2023
https://www.monash.edu/__data/assets/pdf_file/0003/3379521/Evidence-Based-Guidelines-2023.pdf

24.  Irregularity is considered Normal in the first year post-
menarche as part of the pubertal transition
 > 1 to < 3 years post menarche: < 21 or > 45 days of menses is
considered abnormal
 > 3 years post menarche to perimenopause: < 21 or > 35 days
or < 8 cycles per year is abnormal
 > 1 year post menarche > 90 days for any one cycle is
abnormal

25.  An 'increased risk' could be considered and reassessment
advised at or before full Reproductive maturity, 8 years post
menarche.
 Before combined oral contraceptive pill (COCP)
commencement,
 those with persisting Features and
 those with significant weight gain in adolescence.
 Ovulatory dysfunction with reg cycles , anovulation needs To
be confirmed with serum progesterone

26. ● Recommended evidence of androgen excess include:
1. Moderate to severe hirsutism;
2. Persistent acne unresponsive to topical therapy; severe acne
3. Persistent elevation of serum total and/or free testosterone
level.
 Total testosterone concentrations >55 ng/dL are generally
considered consistent with hyperandrogenism
 These hormone levels should preferably be drawn in the morning

27. ● Clinical hyperandrogenism in adolescents include
severe acne and hirsutism.
strong recommendation
CCR

28.  that is persistent and poorly responsive to topical treatment
• indication to test for hyperandrogenemia before initiation of
any medical therapies
● Acne:
 moderate or severe comedonal acne (> 10 facial
lesions) in early puberty or
 moderate to severe inflammatory acne during the peri-
Pediatrics. 2013;131(Suppl. 3):S163–86.
menarcheal years. Fertil Steril. 2001;75(5):889–2. J Pediatr. 1997;130(1):30–9.
Level C
ACOG 2017
AAP 2015
Up To Date 2020

29. dr. MohamedAlajami

30. dr. Mohamed Alajami

31. dr. MohamedAlajami

33. dr. MohamedAlajami
֎Mild comedonal acne is common in adolescent girls and considered
normal.

34.  Isolated mild hirsutism (mFG ~ 9 -15) may be normal in the
early postmenarcheal years.
☑ Moderate (mFG ~ 16 -25) to severe (mFG >25) hirsutism
Level C
ACOG 2017
Level B
ACOG 2017
☑ Progressive hirsutism
Jeffrey CR, Coffler, 2007

35. dr. MohamedAlajami
Hirsutism in an adolescent with PCOS

37. Generalized excessive vellus hair growth distributed in a nonsexual
pattern, (predominantly on forearms or lower legs).
 This hair growth is not due to androgen excess.
 may have an ethnic/hereditary, basis or
 may result from malnutrition or
 certain medications, such as phenytoin or cyclosporine.

38. ֎ No studies in adolescents evaluating alopecia in the context of
PCOS.
֎Frank Virilization is unusual in PCOS

39. ●Avoid the assessment of biochemical
hyperandrogenism in women on hormonal
contraception
●A drug withdrawal of > 3 months is recommended.
CPP

40. ☑ Persistent elevation of serum total and/or free testosterone
- CLEAREST SUPPORT
for the presence of hyperandrogenism in an adolescent girl with
symptoms of PCOS ACOG 2017 Level B
ESHRE-ASRM2018
● The upper limit approximates 55 ng/dL for total testosterone and 9 pg/mL
for free testosterone.
J Clin EndocrinolMetab. 2008;93(4):1105–1120
Hum Reprod Update. 2012;18(2): 146–170

41. Androstenedione and dehydroepiandrosterone sulfate (DHEAS)
 limited usefulness in the diagnosis of PCOS
 could be considered if total or free testosterone are not elevated.
 more useful in excluding other causes of hyperandrogenism.
 DHEAS- significant elevations and/or Virilization (clitoris glans width
>5 mm) can be seen in androgen-secreting adrenal tumors.
EBR

42. ●Pelvic ultrasound for PCOS
diagnosis
●Anti-Müllerian hormone (AMH)

43.  newer high definition vaginal imaging techniques show that
small antral follicle counts up to 24 are normal.
 ensure no corpora lutea, cysts or dominant follicles are
present when measure ovarian volume.
dr. MohamedAlajami
CCR

44. ● Pelvic ultrasound indicated if clinical findings are suggestive of
a Virilizing tumor
• Rapid progression
• Clitoromegaly
• Pelvic mass
• a total testosterone level >200 ng/dL
• disorder of sex development.

45. ● ‘Anxiety and depressive symptoms should be routinely screened
in all adolescents and women with PCOS at diagnosis’.
● If the screening results are positive, further evaluation and/or
referral for assessment and treatment.
● high prevalence of moderate to severe anxiety and depressive symptoms in
PCOS in adults and a likely increased prevalence in adolescence.
Arch Pediatr Adolesc Med. 2002;156(6):556–0.
Hum Reprod Update. 2012;18(6): 638–51

46. ●Women with PCOS indicate an increased prevalence of
disordered eating.
●the same applies to adolescent girls with PCOS is yet to be
determined.

47. 0 behavioral problem
0 abnormal eating patterns (21% vs 2.5%)
0 damaged self confidence due to acne, hirsutism
and obesity
0 increased levels of anxiety & depression

48. Antidepressant and anxiolytic treatment
Psychological therapy could be considered first-line
management, andantidepressant medications considered in adults where
mental health disorders are clearly documented and persistent, or if suicidal
symptoms are present,based on general population guidelines.
Lifestyle intervention and other therapies (e.g. COCP, metformin, laser
removal)that target PCOS features should be considered, given their potential to
improvepsychological symptoms.
 Where pharmacological treatment for anxiety and depression is offered in PCOS,
healthcare professionals should apply caution: to avoid inappropriate treatment with
antidepressants or anxiolytics to limit use of agents that exacerbate PCOS symptoms,
including weight gain.
 Healthcare professionals should be aware that not managing anxiety and depression
may impact adherence to PCOS treatment/management.

49. Are advised reassessment at or before full reproductive maturity.
 at 3 years post menarche in relation to menstrual cycle
irregularity
 at 8 years post menarche in relation to the use of pelvic
ultrasound to identify a polycystic ovarian morphology.

50. Treatment Aim
 Regulate menses
 Improve androgenic concerns
 Assess and improve metabolic status, including addressing lifestyle issues
 Prevent and treat co-morbidities

51.  Irregular menses
 Consider combination oral contraceptives
 Intermittent progestin therapy
 Hirsutism or severe acne
 Topical treatment
 Addition of antiandrogen such as spironolactone
 Obesity, glucose intolerance or diabetes
 Focus on diet and exercise changes
 Metformin therapy

52. Main treatment goals
 Protect the endometrium from risk of hyperplasia (with regular progestin exposure)
 Control menorrhagia, rather than focusing on ovulation in this age group
 OCs -the most effective treatment - androgen suppression & menstrual regulation
 Progestin therapy
Van der Spuy ZM et al. Cochrane Database Syst Rev. 2003;(4):CD001125.

53.  Lifestyle modification, as primary therapy
 Weight reduction decreases serum androgen concentrations & improves
insulin resistance
 Reduce the chances of long-term complications like type 2 diabetes
 Induces regular cycles and ovulation
Hoeger K et al. J Clin Endocrinol Metab. 2008;93(11):4299-306.

54. ✓ Decreased insulin and LH levels
✓ Increased SHBG and Decreased Free E2
✓ Improved menstrual function
✓ Reduced hirsutism and acne
✓ Lower testosterone levels
KiddyDS, Hamilton FD , Bush A.– Clin endocrinol 1992
Lifestyle Intervention - Diet and Exercise Important

55. ● The COCP alone for management of clinical hyperandrogenism
and/or irregular menstrual cycles
 should be in adolescents with a clear PCOS diagnosis or
 could be in those ‘at risk’ but not yet diagnosed with PCOS
Pediatrics. 2016;137(5):e20154089
J Clin Endocrinol Metab. 2008;93(11):4299–306
J Clin Endocrinol Metab. 2004;89(4):1592–7
EBR

56. ֎ Improvement in menstrual pattern is generally noted within
the first 2 to 3 months.
֎ Duration of treatment with COC is not yet well defined.
 trial off the COC may be after one or more years of therapy
to allow for recovery of the HPO axis and observe if
spontaneous menstrual regularity returns.

57. combinations of COCP cannot currently be recommended
● Specific types or doses of progestins, estrogens or
among women and adolescents with PCOS.
● COCPs with 35 μg of ethinylestradiol and cyproterone acetate
should not be used as first-line therapy due to
 No greater efficacy
 higher risks, including deep venous thrombosis.
EBR
CCR

58. ● The COCP in combination with metformin could be in
 adolescents with PCOS and a BMI > 25 kg/m2 where the
COCP and lifestyle changes do not achieve desired goals.
EBR

59. ● Metformin in addition to lifestyle interventions could be
considered in adolescents with a clear PCOS diagnosis or with
symptoms of PCOS before a diagnosis is made.
● Metformin dose is 1500–2250 mg per day
● Starting at a low dose, with 500 mg increments 1–2 weekly and
extended release preparations may minimize side effects.
J Clin Endocrinol Metab. 2005;90(8):4593–8.
EBR
CPP

60. ● Recommend use of the COCP alone with cosmetic therapy for
at least 6 months prior to considering antiandrogens.
or poorly tolerated.
● Specific types or doses of antiandrogens cannot currently be
recommended with inadequate evidence in PCOS.
EBR
● Antiandrogens must be used in combination with the COCP
EBR
● antiandrogens could be used alone if COCPs are contraindicated
CPP
EBR

61.  ֎ May offer more immediate results than pharmacotherapy.
 ֎ Electrolysis and laser hair removal therapies more effective.
 ֎ Eflornithine for topical hair removal offers benefit for hirsutism.
 ֎ Eflornithine can be combined with laser therapy for more rapid
 reduction in facial hair.
Dermatol Surg 2006;32:1237-43.
J Am Acad Dermatol 2007;57:54-9.

62. ֎ Potent anti-androgen
֎ can be used in conjunction with COC or metformin.
֎ Combination metformin and spironolactone is superior to
either drug alone in improving hirsutism, serum androgen levels,
and insulin resistance.
J Clin Endocrinol Metab 2013;98:3599-607.

63. ֎ intermittent low-dose oral finasteride is effective for treatment
of hirsutism in adolescent girls with PCOS or idiopathic
J Pediatr Adolesc Gynecol 2014;27:161-5.

64. ● acne that is persistent and poorly responsive to topical
dermatologic therapy are:
 assessed for hyperandrogenemia before instituting
systemic medical treatments.
 ordinarily treated by (COC) pills or the systemic retinoid
Accutane.
Pediatrics. 2013;131(suppl 3):S163–S186
Horm Res Paediatr. 2015;83(6):376–389

66. J Hum Reprod Sci 2018;11:96-118.

67. J Hum Reprod Sci 2018;11:96-118.

69. Treatment of lean
PCOS teenagers: a
follow-up comparison
between Myo-Inositol
and oral contraceptives
Eur Rev Med Pharmacol Sci. 2021 Dec;25(23):7476-7485.

70. Efficacy of myo-inositol and d-chiro-inositol combination on menstrual cycle
regulation and improving insulin resistance in young women with polycystic ovary
syndrome: A randomized open-label study
Int J Gynaecol Obstet. 2022 Aug;158(2):278-284.

71.  Unique pharmacokinetic and pharmacological profile, combining some properties
of 19- nortestosterone derivatives with those of progesterone derivatives.
 In contrast to other nortestosterone derivatives, dienogest has no
 estrogenic,
 antiestrogenic or
 androgenic activity,
 Has strong antiandrogenic properties
Drugs 2010; 70 (6): 681-689

72. Progestogenic
activity
Anti-androgenic
activity
Androgenic
activity
Glucocorticoid
activity
Progesterone + + - -
Dienogest + + - -
Drospirenone + + - -
Levonorgestrel + - + -
Norgistimate + - + -
MPA + - - +
NETA + - + -
Desogestrel + - + -
CPA + + - +
Mueck AO. Expert Rev Obstet Gynecol. 2011; 6(1): 5-15.

73. 3 groups
75
n=525 (DNG-EE)-21/7
Regimen
n=264 (placebo)
n=537 (CPA/EE)
• Inflammatory
lesion count
• Total lesion
count
• Imorovement in
facial acne
Healthy women, age 16-45 yrs.;
mild to moderate facial acne
investigated over 6 treatment
cycles of 28days-Multinational,
multicenter, three arm, double
blind & randomized trial
E. Palombo-Kinne et al. Contraception 2009 Apr; 79 (4): 282-9Diane-35.
Combined oral contraceptive pills for treatment of acne (Review)
Copyright © 2012 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd..

74. Variable DNG/EE Placebo Diane-35
% change in total lesion
count
-54.66 -39.42 -53.56
SD 26.34 33.58 27.49
N 515 259 528
%change in inflammatory
lesion count
-65.6 -49.47 -64.56
SD 29.89 41.04 31.17
N 511 257 526
Improvement in facial acne
according to IGA
477
(91.9%)
199
(76.2%)
480
(90.2%)
E. Palombo-Kinne et al. Contraception 2009 Apr; 79 (4): 282-9Diane-35.

75. DNG/EE is superior to placebo while similar results for all three variables
were obtained for the DNG/EE and CPA/EE (Diane-35) groups in the
treatment of mild to moderate acne, thus providing a valid option for the
treatment of acne in women seeking oral contraception
E. Palombo-Kinne et al. Contraception 2009 Apr; 79 (4): 282-9Diane-35.

76. single group
78
N=120 (DNG/EE)
Reduction in acne
lesions(duration
=12mnths.
Observational study ; cohort of
females; mild to moderate
acne; age-18-30 yrs.n=120
Cardona JP, et.al. Int JWomens Health 2017 Nov 16;9:835-842

77. Cardona JP, et.al. Int JWomens Health 2017 Nov 16;9:835-842
37.8
50
100
40.3
90
100 100
90
94.2
100 100
93.2
0
20
40
60
80
100
120
Comedones Papules Pustules Total lesions
%
Reduction
Month 1 Month 6 Month 12
At the end of follow-up, the percentage of reduction of lesions was 94% and
23% of women had a 100% reduction in acne lesions

78. ● Appropriate diagnostic criteria for PCOS in adolescents are
otherwise unexplained persistent hyperandrogenic anovulation
using age- and stage-appropriate standards
● Great caution before labeling hyperandrogenic adolescents as
having PCOS if the menstrual abnormality has not persisted for
2 years or more.
● Before that point in time, they recommended that such girls be
considered to be “at-risk for PCOS”

79. ● initiation of a diagnostic workup should not be unnecessarily
delayed.
● initiation of diagnostic testing is advisable within 1 year if
treatment is required to control abnormal menstrual bleeding or
comorbidities or if symptoms suggestive of PCOS coexist
● Excessive uterine bleeding may mandate emergency evaluation
early in the course.
● Primary amenorrhea should be evaluated when recognized.

80. ● Importantly, a definitive diagnosis of PCOS is not needed to
initiate treatment.
● Treatment may decrease risk of future comorbidity even in the
absence of a definitive diagnosis.
● Deferring diagnosis, while providing symptom treatment and
regular/ frequent follow-up of symptomology, is a
recommended option.

81. ● Currently the only certain way to differentiate the
hyperandrogenemia of PCOS from that of physiologic
adolescent anovulation is by the persistence of PCOS into
adulthood.

82. I HIGHLY APPRECIATE YOU FOR SPENDING SOME OF YOUR TIME
WITH ME.