Dr Georgina HawkinsGeneral Obstetrician and Gynaecologist
Fertility Associates
Christchurch
8:20 - 8:40 When Puberty is PCO
Case
PCOS clinical features and pathophysiology
Diagnostic Criteria - adults
Diagnostic Criteria – adolescents
When to investigate
Basic work up
Basic management and follow up
Take home messages
Overview
Alice, 35yo G0P0
Presents to fertility clinic to discuss ‘social egg freezing’
Dx PCOS and started on COCP age 15
Concerned as she was told she would likely be ‘infertile’
Recent new relationship of 6/12 so not ready to start family yet
Case
HCG NegDay 3 FSH 5.9IU/L, LH 5.2IU/LDay 3 Oestradiol 106pmol/LDay 21 progesterone 39nmol/LAMH 16pmol/L (45th centile for age)TSH 1.9 normalPRL 225 normalBooking bloods unremarkableSmear and Swabs NAD
Alice: Investigations
Affects 8-13% of reproductive aged women
Key features include:
Clinical or biochemical hyperandrogenism
Anovulation
Polycystic ovarian morphology
ReproductiveMenstrual irregularityHirsutism/AcneInfertilityPregnancy complications
MetabolicInsulin ResistanceAcanthosis nigricansMetabolic syndrome, ObesityPrediabetes, DiabetesCardiovascular risk factors
PsychologicalAnxietyDepressionLow self imageDisordered eating
PCOS Overview
Stein and Leventhal 1935
National Institutes of Health (NIH) 1990
Rotterdam Criteria 2003
Androgen Excess and PCOS society 2006
CRE-PCOS due 2018
Diagnostic criteria
Women present with a diverse range of clinical features that vary across the lifespan and between ethnicities
Multiple classification systems have been developed over the years
Defining individual components within the diagnostic criteria is challenging
Changes in the understanding of the pathophysiology
Why is PCOS so hard to define?
LH stimulates androgen production in ovarian theca cells
Androgen usually aromatised to estrogen in granulosa cell
High local androgens are converted to potent 5α-reduced androgens which prevent follicular development
New follicle growth continues but arrests before maturation is achieved – resulting in multiple small follicles surrounded by hyperplastic theca cells: PCO
PCOS pathophysiology
2 out of 3 of the following
1. Oligo/anovulation
2. Clinical or biochemical evidence of hyperandrogenism
3. PCOM on USS
And the exclusion of other causes of androgen excess (thyroid disease, non-classic congenital adrenal hyperplasia NCCAH, hyperprolactinaemiaand androgen-secreting tumours)
Rotterdam criteria 2003Endorsed by CRE-PCOS
PCOS
Anovulation
Hyperandrogenism
Hirsutism
Acne
Increased serum androgens
PCOM on USS
Syndrome of insulin resistance
Puberty
Anovulatory cycles common
Changes in body hair type and distribution
Acne
Rise in testosterone levels in anovulatory cycles
PCOM on USS
Transient Insulin resistance not uncommon
Adolescent diagnosis is problematic
Comparison of PCOS symptoms with normal changes at puberty:
An otherwise unexplained combination of both:
1. Abnormal uterine bleeding patterna. Abnormal for age (see table next slide)b. Persistent symptoms for at least 1- 2 years
2. Evidence of hyperandrogenisma. Increased testosterone above adult norms in a reliable reference lab b. Moderate to severe hirsutism (clinical evidence of hyperandrogenaemia)c. Moderate to severe inflammatory acne vulgaris (an indication to test for hyperandrogenaemia)
Based on Witchel S, Oberfield S, Rosenfield R, Codner E, Bonny A, Ibáñez L, et al. The Diagnosis of Polycystic Ovarian Syndrome during Adolescence Horm Res Pediatr. 2015;83 (6):376–389.From Pediatrics, Vol 136, pages 1154-65
Diagnostic criteria for PCOS in adolescencePaediatric Endocrine Society 2015
Primary Amenorrhoea Lack of menarche by age 15 or by 3 years after breast development
Secondary Amenorrhoea >3/12 no period after previous menstruating
Oligomenorrhoea Year post menarche
1 Cycle length >90 days
2 Cycle length > 60 days
3-5 Cycle length >45 days
6+ Cycle length >38 days
Excessive uterine bleeding
cycles <19 days or longer then 7 days
Adolescent cycles Usually 21-45 days
Differentiating menstrual disorder from normal adolescent cycles
Hirsutism Abnormal amount of sexual hair that appears in a male pattern(vs hypertricosis - generalised increase in vellus, non sexual hair)Use modified Ferrimen-Gallwey score to assess:>8 = indication for investigation with serum androgens>15 = moderate hirsutism (sufficient for a diagnosis of hyperandrogenism)
Acne Moderate or severe inflammatory acne (>10 lesions in either face,chest, back) that has not responded to topical treatment issupportive of hyperandrogenism
Female patternhair loss
Virilisation Rare; suspect if: voice deepening, clitoromegaly, severe rapidlyprogressive hirsutism, male pattern hair loss
Hyperandrogenism: clinical thresholds for diagnosis
50% of hyperandrogenic femalesdo not have hirsuitism or acne
Standard Investigations:
1. Total testosterone - normal/increased◦ Normal range = 1.4-2.1 nmol/L◦ PCOS - most will have values <5.2 nmol/L◦ >6.9 nmol/L warrants referral to endocrine to exclude virilising
tumour
2. Calculated Free Testosterone or Free Androgen index -increased
3. SHBG - reduced
Hyperandrogenism: biochemical features
Useful but not part of diagnostic criteria:
AMH - elevations >2 fold are highly specific for PCOS LH: FSH ratio >2-3 is highly suggestive of PCOS
Not routinely required:
DHEA-S - a marker of adrenal androgen synthesis and is moderately elevated in half of PCOS but significantly elevated levels indicate a potential adrenal source (measure if concern for severe or rapidly progressive hyperandrogenism or virilisation)
Other androgens - androstenidione and DHEA require conversion to testosterone to exert androgenic effects and so measurement adds little value
Additional laboratory investigations
TSH
PRL
Day 3 FSH to exclude POF
If raised testosterone → early morning (8am) 17-OHP in follicular phase to rule out non classic congenital adrenal hyperplasia due to 21 hydroxylase deficiency (NCCAH)◦ <6 nmol/L excludes the condition
◦ >30 nmol/L is diagnostic
◦ If unsure refer to endocrine for ACTH stimulation test
Serum cortisol if central obesity ◦ <276 nmol/L reassuring against Cushings
IGF-1 (growth hormone excess is usually identified by characteristic clinical fx but can present similarly to PCOS)
Additional Tests to exclude conditions that mimic PCOSPCOS is a diagnosis
of exclusion
25-50% of normal adolescents meet adult USS criteria for PCOM (AFC ≥12 or ovarian volume >10 ml
Adolescents often have multi-follicular, slightly enlarged ovaries
New high resolution vaginal USS show that small antral follicle counts of up to 24 are normal
The quandary of polycystic ovary morphology in adolescence
USS is not recommended in assessment of PCOS in adolescents and is notrequired for diagnosis
Treatment is primarily symptomatic, directed at:
Abnormal uterine bleeding: COCP (any)
Cutaneous hyperandrogenism: COCP; add anti-androgens (spironolactone 100-200mg daily in divided doses) if no improvement after 6/12 on COCP
Obesity and insulin resistance: metformin
Comorbidities of metabolic syndrome: weight management; lifestyle interventions; exercise
Management
Reduce risk for T2DM, metabolic syndrome and CVD◦ Monitor HbA1c, fasting glucose or OGTT (1-2 yearly)◦ Monitor lipid profile (1-2 yearly)◦ Monitor BP◦ Weight and waist circumference (yearly)◦ Assess risk factors for CVD – smoking, inactivity
Reduce risk for endometrial hyperplasia and cancer (through chronic unopposed estrogen)◦ Avoid prolonged periods of ameno/oliomenorrhoea (schedule withdrawal bleeding with
COCP or cyclic progestin)◦ Low threshold for investigation for abnormal menstrual bleeding with TVUS and endometrial
bx
Long-term goals
1. Menstrual abnormalities in adolescents are common and should be assessed according to age and stage of puberty
2. Consider PCOS in presentations of obesity, hirsuitism, severe acne, acanthosis nigricans and/or depression (menstrual abnormalities may not be the chief complaint)
3. Caution in labelling hyperandrogenic adolescents as PCOS if the menstrual abnormality has not persisted for >2 yrs
4. In the interim, consider these patients as ‘at risk for PCOS’ and review periodically
5. However, if symptoms are sufficiently severe to require treatment, do not delay initiation of diagnostic work up
6. USS is not recommended or required in the assessment and diagnosis of PCOS in adolescents
Take home messages
Alice Menarche age 14, normal BMI Had periods every 2-3 months Mild-Moderate acne, no hirsutism Transabdominal scan 1996 described PCO Off COCP now having regular cycles, no recurrence of acne normal AMH, androgen profile normal Had 2 cycles of COS, total 12 eggs frozen. Conceived spontaneously with
new partner 6 months later!
Back to the Case
Top Related