PCOS 12.10 by fanzhongqing

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									Polycystic ovarian syndrome

       Dr Alexandra Ward
    Consultant Endocrinologist
              RUH
 Hippocratic writings about the Scythians
in “Medicine: Airs, Waters, Places” (circa
                  400 BC)
“The girls get amazingly flabby and podgy… People
of such constitution cannot be prolific. In the case
of the women, fatness and flabbiness are to
blame. The womb is unable to receive the semen
and they menstruate infrequently and little. As
good proof of the sort of physical characteristics
which are favourable to conception, consider the
case of serving wenches. No sooner do they have
intercourse with a man than they become
pregnant, on account of their sturdy physique and
their leanness of flesh.”
    Structure of the presentation
•   What is PCOS?
•   Why does it matter?
•   How do we diagnose it?
•   How do we approach management?
•   What are the long term implications?
                   Definitions vary
•US: NIH 1990 – ‘classic PCOS’
    – Chronic anovulation
    – Clinical and/or biochemical signs of hyperandrogenism (with exclusion
       of other aetiologies, eg CAH)
    (both criteria needed)

•Europe: Rotterdam 2003
    – Oligo- and/or anovulation
    – Clinical and/or biochemical signs of hyperandrogenism
    – Polycystic ovaries
    (2 of 3 criteria needed)
    (with exclusion of other aetiologies)

Message: It is not essential to have polycystic ovaries on US.
          What is PCOS?
                   Polycystic ovaries




Hyperandrogenism                        Oligo/Amenorrhoea
 What is missing from this list?
• Obesity
  – Only 50% obese
BUT:
Obesity is a major determinant of the
 expression of the syndrome

NB Check waist circumference in ‘lean’
 patients
             PCOS and insulin
• Important player in
  pathophysiology
• Lean and obese
  women with PCOS
  are more insulin
  resistant than wt-
  matched controls
• Obesity amplifies
  insulin resistance in
  PCOS
        Why is it important?
• 5-10% women of reproductive age
• Principle cause of anovulatory infertility
• High rates of psychological morbidity
• Significant impact on current and future
  health
AND
• It is early enough to do something about it
         What are the important
             differentials?
• Late-onset congenital adrenal hyperplasia
• Cushing’s syndrome
• Androgen-secreting tumour

•   Hypothyroidism
•   Acromegaly
•   Hyperprolactinaemia
•   Drugs – Danazol, androgenic progestogen
               Normal adrenal
    ACTH


       Cholesterol

-                        17-OH-         Adrenal
       Progesterone
                         progesterone   androgens



              21-hydroxylase



       Aldosterone       Cortisol
    CAH – 21-hydroxylase def
    ACTH


       Cholesterol

-                                      Adrenal
       Progesterone         17-OH-P
                                       androgens


                 21-hydroxylase


       Aldosterone          Cortisol
      How do we diagnose it?
• Clinical assessment
  – Anovulation
     • Detailed menstrual history from menarche
  – Hyperandrogenism
     • Hirsutes, acne, frontal balding
  – Hyperinsulinaemia
     • BMI, Acanthosis nigricans, BP
  – Features of other endocrinopathy?
• Biochemistry
• Ultrasound (ideally transvaginal)
  – Ovarian morphology
  – Endometrial thickness
    Biochemical investigation
• Exclude pregnancy!
• Fasting bloods (Day1-3 if menstruating)
  – LH, FSH, PRL
  – Testo, SHBG
  – TSH
  – FPG, Lipids
  – (17-OH progesterone)
  – (Androstenedione, DHAS)
  – (24hr urinary free cortisol)
    CAH – 21-hydroxylase def
    ACTH


       Cholesterol

-                                      Adrenal
       Progesterone         17-OH-P
                                       androgens


                 21-hydroxylase


       Aldosterone          Cortisol
           Cushing’s syndrome
    ACTH


       Cholesterol

-                                      Adrenal
       Progesterone         17-OH-P
                                       androgens


                 21-hydroxylase


       Aldosterone
                            Cortisol
    Approach to management
• Explanation
• Lifestyle, lifestyle, lifestyle
• Symptom-directed approach
  – What are the current problems/concerns?
  – What does the patient want?
  – Management changes with time
• Counsel about future problems
• Complication surveillance
Ideally via multi-disciplinary team
             Lifestyle therapy
• Diet
  – Few PCOS-specific studies
  – Usual principles – low fat, low GI (whole
    grains), 500kCal deficit
• Exercise
  – Studies have tried to examine type best suited
    to PCOS
• Psychological support
               Lifestyle advice
• Weight loss is more difficult in women with PCOS
   – Hyperinsulinaemia promotes fat storage
   – Evidence of reduced post-prandial thermogenesis
• 5-10% weight loss dramatically improves hormonal
  profile, metabolic consequences, ovulation and
  fertility
• Emphasise benefits of lifestyle even without wt loss
• All deserve formal dietetic referral to an ‘interested’
  dietician with follow up
• Specific exercise advice
           Oligo/Amenorrhoea
• Lifestyle – weight loss
• Combined oral contraceptive
  – Low oestrogen ideally, non-androgenic
    progestogen
• Progesterone withdrawal bleed
  – MPA 10mg for 10/7 every 3 months (min 4
    bleeds per year
• Mirena
                   Infertility
•   Lifestyle – weight loss
•   Clomiphene
•   Clomiphene + MFN?
•   Low dose FSH
•   Ovarian diathermy

Refer fertility clinic
                     Hirsutism
• Ovarian
   – PCOS (>80%)
   – Ovarian tumours (sex cord stromal tumours; Sertoli-
   Leydig cell tumours; adrenal-like tumours of the ovary)
   (<1%)
• Adrenal
   – Congenital adrenal hyperplasia (classical 1%;non-
   classical [late-onset] 3%)
   – Cushing’s syndrome (<1%)
   – Adrenal tumours (adenoma; carcinoma) (<1%)
• Idiopathic
   – with raised androgens (5%)
   – without raised androgens (7%)
       Hirsutism - approach
• Evaluation
  – Extent – Ferriman Gallwey score
         Hirsutism - approach
• Evaluation
  – Extent – Ferriman Gallwey score – (cut off >8 vs >3)
  – Frequency of hair removal
  – Psychological impact on patient
• Cosmetic control – debulk the myths!
• Weight loss
• Very careful explanation of therapeutic options
  and their limitation
• Medical therapy
• Re-evaluation after 4-6 months
                 Medical therapy
• Topical (direct action on follicle)
   – Eflornithine 11.5% (Vaniqa)
• Systemic
   – Combined oral contraceptive
      •  SHBG
      • Ideally Dianette – added benefit of Cyproterone
   – Antiandrogen (nb contraception)
      •   Cyproterone acetate
      •   Spirinolactone
      •   Finasteride
      •   Flutamide
                 Eflornithine
• Enzyme inhibitor – reduces rate of growth
   – Not a ‘hair removal’ product
• Can be used alongside cosmetic methods and systemic
  therapies
• Applied bd continuously
• 70% women show ‘at least some improvement’ after 4
  months compared with 41% placebo.
• 32% vs 9% show significant improvement
• Some evidence of improved efficacy of laser therapy
• No head to head studies with anti-androgens
        Eflornithine - BCAP
• Green
• Specialist recommended
• “For the treatment of facial hirsutism
  restricted to use in women for whom
  alternative drug therapy is ineffective,
  contra-indicated or considered
  inappropriate. For non cosmetic reasons”
• Cost £152-312pa vs £24 for Dianette
 What happened to Metformin?
• Early 1990s – initial small trials suggested
  improved ovulation and fertility
• Conflicting results from larger trials
• Latest evidence from systemic reviews
  – No significant weight loss
  – No increase in live birth rates
  – No benefit to hirsutism
  – Possible role in diabetes prevention
        Does it still have a role?
•   Cheap
•   Free from significant adverse effects
•   Seems to work well for some individuals
•   Still consider in obese, clearly insulin-
    resistant patients
 Future health risks 1 - diabetes
• GDM: OR 2.94 (1.7-5.1)
• Prevalence of metabolic syndrome (NCEP
  criteria) in young women 35-45% (4 studies)
• Longitudinal study of IGT and T2D
  – Increased conversion rate cf non-PCOS

                                    •PCOS 2x risk of
                                    T2DM
                                    •PCOS + obesity
                                    3X
       Screening - diabetes
• Rotterdam consensus
  – Obese PCO
    • OGTT and lipids at baseline
    • Repeat 1-3yearly
  – Non-obese
    • No consensus
       Risk reduction - diabetes
•   Make diagnosis early
•   Intensive input early – dietetic referral
•   Avoid obesity in lean patients
•   Consider MFN in high risk individuals
  Future health risks 2 - cancer
• Prolonged amenorrhoea = unopposed
  insulin
• Risk of endometrial hyperplasia and
  carcinoma
• Screening – pelvic ultrasound
• Risk reduction – ensure at least 4 bleeds
  per year
   Future health risks 3 - CVD
• Epidemiological studies do not yet confirm
  significantly increased risk, though follow
  up may not yet be sufficient
• Likely to confer increased risk given risk of
  DM
• Manage as per other patients with
  metabolic syndrome
   Future health risks 4 - OSA
• Increased rates on PCOS independent of
  BMI
• Screening
  – Ask about daytime somnolence
  – Epworth sleepiness score
• Refer to sleep clinic if postive
         Further information
• Verity – PCOS patient support group
  – www.verity-pcos.org.uk
         Further information
• Verity – PCOS patient support group
  – www.verity-pcos.org.uk
• PCOS-UK – professional body
  – www.pcos-uk.org.uk
  – Useful resource pack

								
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