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Polycystic ovarian syndrome

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Title: Polycystic ovarian syndrome


1
Polycystic ovarian syndrome
  • Dr Thenmozhi Needhirajan DGO, MRCOG
  • Fellowship (University college London)
  • Consultant Obstetrician and Gynaecologist
  • Kurinji Hospitals, Coimbatore
  • Karpagam Medical College, Coimbatore
  • Poole Hospitals NHS Trust, United Kingdom

2
My work in India
  • CEMENDS (Centre for Menstrual disorders Gynae
    Endoscopy) Ambulatory Gynaecology
  • Lifetime screening programme for cervical cancer
  • Computerised recall system, Periodical smears,
    Colposcopy
  • Vulvoscopy for vulval leisions
  • Cervical cancer Vaccination
  • Cryotherapy

3
CEMENDS Ambulatory Gynaecology
  • Non Hysterectomy Options for Menstrual
    disorders
  • Office Hysteroscopy for menstrual
    disorders
  • Medical management of fibroid
  • LNG-IUS
  • Transcervical Resection of Endometrium
    (TCRE)
  • Transcervical Resection of Fibroid/ polyp
    (TCRF)
  • NOVASURE Endometrial Ablation
  • Hysteroscopic Uterine Septoplasty for uterine
    septum
  • Menopause and Hormone Replacement Therapy

4
History and Epidemiology
  • 1st described by Irving Stein and Michael
    Leventhal as a triad of amenorrhea, obesity and
    hirsutism (1935)
  • The most common endocrine disorder in women of
    reproductive age 2-8 of women
  • Current suggested prevalence
  • Caucasian 4.8
  • African American 8.0
  • Hispanic or Latino 13
  • 5-10 of women

Knochenhauer ES et al, Journal of Clinical
Endocrinology Metabolism, 1998.
Azziz R et al, Journal of Clinical Endocrinology
Metabolism, 2004.
Goodarzi MO et al, Fertility and Sterility, 2005.
Ehrmann DA, New England Journal of Medicine, 2005.
5
What is PCOS?
  • A chronic condition characterized by
  • anovulatory infertility,
  • hyperandrogenism , hyperinsulinaemia, insulin
    resistance
  • with clinical manifestations of
  • oligomenorrhoea,hirsutism and acne

6
Definition
  • 1990 NIH DEFINITION
  • 1. OLIGOMENORRHEA
  • 2. HYPERANDROGENEMIA
  • 3. Absence of other disorders such as
  • NCAH, Hyperprolactinemia, thyroid
  • dysfunction.

7
Rotterdam Criteria (2003)
  • Two of the three
  • Menstrual irregularity due to anovulation or
  • oligo-ovulation
  • Clinical signs (Acne, Balding, Hirsuitism) or
  • biochemical hyperandrogenism
  • Polycystic ovaries on ultrasound

8
Pathogenesis
  • OVARIAN HYPOTHESIS
  • Thecal ( ovarian interstitial tissue)
    hypertrophy,
  • leading to hyperandrogenemia
  • excessive activity of an enzyme called 17,20
    lyase
  • CENTRAL HYPOTHESIS
  • abnormal GnRH pulse generation from the
  • hypothalamus leading to abnormal, increased LH
  • pulse amplitude and frequency

9
Clinical Features
  • Remember it is a syndrome, not a disease!
  • Its the most common disorder of the
  • Endocrine system in women, 5-10
  • Frequently begins around time of puberty
  • Strong genetic component, frequently a
  • family history of type 2 DM

10
Consensus Workshop
  • 3rd PCOS consensus workshop- Netherlands
  • Oct 2010
  • Adolescence
  • Hirsutism Acne
  • Contraception
  • Menstrual cycle abnormalities
  • Quality of life and sexual health
  • Pregnancy complications
  • Cardiovascular cancer risk

11
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12
PCOS in Adolescence
  • No overall agreement on diagnosis
  • Acne is common in adolescence
  • Hirsutism typically develop over years
  • Irregular periods also common
  • Hyperandrogenaemia consistent marker
  • 85 of the menstrual cycles are anovulatory in
    the first year
  • Increased BMI major risk factor for persistent
    anovulation
  • Only 40 of adolescents with irregular periods
    have polycystic ovaries on USS

13
Diagnosis in Adolescence
  • All 3 elements of Rotterdam criteria should be
    present
  • Conclusions
  • Diagnostic criteria should differ from from those
    used for older women of reproductive age
  • Groups at risk (obese, hirsute, irregular
    periods))should be identified but be cautious of
    over diagnosing
  • Individual manifestations should be treated

14
Adolescent PCOS Lack of knowledge
  • Absence of longitudinal studies
  • Absence of specific diagnostic criteria
  • Absence of normative values for a number of
    biochemical markers
  • Value of intervention
  • Unclear if the severity of the symptoms predicts
    the extent of the disorder in later life

15
Hirsutism/Acne/Alopecia
  • Hirsutism-Good marker for hyperandrogenism
  • Present in 70 of women
    with PCOS
  • Hyperandrogenaemia should be evaluated
    biochemically in all women
  • Acne and Alopecia not commonly associated with
    hyperandrogenaemia
  • If Hirsutism major concern
  • reduction in androgen production
  • decrease the circulating free
    testosterone
  • limit androgen bioactivity to hair
    follicles
  • terminal hair turnover occurs
    slowly- atleast 6 months treatment is essential

16
Treatment of Hirsutism/Acne/Alopecia
  • Focused on
  • Inhibition of ovarian steroid production
  • Decreased bioavailability Increase SHBG
    levels (OCPs)
  • OCPs often combined with antiandrogens to
    block androgen action at hairfollicles
  • Antiandrogens Cyproterone, Spirinolactone,
    flutamide, finasteride drospirenone
  • Antiandrogens should not be used without
    contraception
  • Metformin has little effect on hirsutism and acne
  • Physical approaches to remove hair-
    electrolysis,laser
  • Severe Acne-Isoretinoin is beneficial
  • Topical use of Eflornithine hydrochloride-
    hirsutism
  • No effective pharmacological treatment for
    alopecia

17
Hirsutism/Alopecia/AcneLack of evidence
  • Unclear Best medical therapy for hirsutism
  • Unclear how long therapy should be continued
  • Unclear how best to evaluate hirsutism clinically
  • Measurement of serum androgens is fraught with
    error

18
Menstrual Irregularity
  • Women with PCOS may ovulate spontaneousely
  • How frequent- unknown
  • Oligo/amenorrhoea-90 chance of being diagnosed
    with PCOS
  • Amenorrheic women- most severe hyperandrogenism/hi
    gher antral follicle counts
  • Menstrual cycles become more regular towards
    menopause
  • Irregular periods are associated with increased
    metabolic risk
  • The greater the irregularity the more severe the
    PCOS phenotype

19
Treatment of Menstrual Irregularities
  • Weight Loss
  • Oral Contraceptives
  • Provera
  • 5-10mg for ten days every 4-8 weeks

20
Treatment of Infertility
  • Weight loss 5-10 of body weight , 56
  • had return of ovulatory cycles
  • Gonadotropin Therapy
  • injection of FSH to stimulate ovulation
  • Clomiphene - clomid
  • first line drugs
  • triggers ovulation in 80,
  • Metformin

21
Metformin
  • Metformin PCOS
  • JCEM 2000 Italy (Moghetti et al)
  • N23 PCOS (mean BMI 30)
  • Randomized - Metformin 500 tid or placebo x 6
    months
  • Androstenedione, 17OHP, estradiol, SHBG, lipids
  • OGTT, insulin sensitivity with glucose clamp

22
Metformin PCOS
  • Metformin PCOS - Conclusion
  • Women on metformin lost weight,
  • 50 regular menstrual pattern
  • (of those 79 ovulatory cycles)
  • Reduction in plasma insulin
  • Decrease in Androgen levels
  • baseline predictors-responders
  • higher BMI, higher insulin level, lower
    serum androgens less severe menstrual
    abnormalities
  • Scientific paper (RCOG) 2008 PCOS
    infertility, role of metformin No clear
    role,should be limited to IGT and type 2 DM. not
    a first line option

23
Metformin vs Diane 35
  • JCEM 2000 Finland (Morin-Papunen et al)
  • N 32 (BMI gt 27)
  • Metformin 500 bid x 3m --gt 1000 bid x 6m
  • vs Diane 35
  • Metformin- decrease WHR, insulin, improved
    oxidative glucose utilization fasting free fatty
    acid, and menstrual regularity

24
Metformin vs Diane 35
  • Diane - decrease serum testosterone levels
  • Diane - worsening of glucose tolerance and
    decrease insulin sensitivity
  • Metformin possibly superior to Diane specially
    if fertility is a concern

25
Is it safe to use metformin in women attempting
to conceive?
  • Mouse embryos - doses of 500-2550 mg no major
    malformation of offspring
  • Used in type 2 diabetes during pregnancy -
    S.Africa
  • 5.5 year follow-up published
  • Mig study
  • Seems safe

26
Contraception
  • No methods are contraindicated in PCOS
  • Obesity,insulin resistance- relative CI to COCPs
  • OCPs suppress LH production decrease in ovarian
    androgen production
  • Estrogenic component increases SHBG
  • Progestin in the pill compete for 5alpha
    reductase
  • OCPs also reduces adrenal androgen production

27
Contraception
  • Overall, the benefits of OCPs outweigh the risks
    in most patients
  • In the absence of other risk factors no evidence
    that women with PCOS are at increased risk of CVD
  • No evidence for differences in effectiveness and
    risk among the various progestogens and when used
    in combination with a 20 versus 30 micrograms of
    estrogens
  • OCPs do not negatively affect subsequent
    fertility
  • No definitive evidence that the type of OCP
    determines the efficacy of hirsutism control
    (evidence C)

28
Contraception - Knowledge gaps
  • Head-to Head blinded trials comparing different
    OCP strategies are lacking
  • Lack of longitudinal FU studies after a course of
    OCPs

29
Quality of life (QOL)
  • At risk of psychological and behavioural
    disorders- reduced QOL
  • PCOSQ
  • Significant detrimental effect compared to
    controls
  • Weight issues were most apt to affect QOL
  • Eating disorders/sexual /relational dysfunction
  • Pshycological screening to improve long term
    prognosis

30
Quality of life (QOL)Knowledge gaps
  • Unclear if this increased prevalence is due to
    the disorder itself or its manifestations
  • (Obesity, irregular periods,hirsutism,infertility)

31
Pregnancy
  • Subfertility
  • Obesity,metabolic, inflammatory, endocrine
    abnormalities on ovulatory function,,oocyte
    quality and endometrial receptivity
  • Ovarian hyperandrogenism Hyperinsulinaemia
    premature granulosa cell luteinisation
    distrupt the intrafollicular environment- impairs
    cytoplasmic and nuclear maturation of oocytes
  • These features are not universal

32
Pregnancy
  • Early pregnancy embryo may be exposed to
    androgens long term effects
  • Data on risk of miscarriage conflicting
  • 40-50 risk of GDM and associated macrosomia,
    gestational hypertensive disorders, SFD babies
  • Preconception counselling
  • Miscarriage rates are not increased after natural
    conception,independent of obesity
  • Miscarriage rate after induction of ovulation
    mirror those found in other infertile patients

33
Pregnancy
  • AN care should be closely monitored
  • Pregnancy associated risks are more in
    hyperandrogenic women
  • Babies may have increased morbidity and mortality
  • No evidence for improved live birth rates or
    decreased pregnancy complications with the use of
    metformin either before conception or during
    pregnancy (Level A)

34
Pregnancy - Knowledge gaps
  • Should pregnancies of women with PCOS have
    increased antenatal monitoring including earlier
    screening for GDM, additional dopplers
  • Long term outcome of children born from women
    with PCOS
  • Long term outcome for women with PCOS who develop
    GDM and gestational HT compared with women with
    PCOS who dont conceive

35
Obesity
  • Widespread variability in the prevalence of
    overweight (BMI 25-30 ) and obese(gt30)
  • More likely to have upper body fat distribution
  • Greater abdominal or visceral adiposity IR
  • IR could exacerbate the reproductive and
    metabolic abnormalities
  • Lifestyle interventions substantial
    reproductive and metabolic benefits

36
Type 2 Diabetes (T2D)
  • PCOS is a major risk factor for developing
    IGT/T2D
  • Obesity is an exacerbating factor in the
    development of IGT/T2D in PCOS
  • Screening for IGT and T2D should be performed by
    75 gm OGTT
  • No utility for measuring insulin In most cases
  • Diet and lifestyle are first choice in improving
    fertility and prevention of T2D

37
Cardiovascular disease Risk (CVD)
  • Risk assessment should be done periodically
  • Life long metabolic dysfunction in women with
    PCOS exaggerates CVD risk especially after
    menopause
  • All markers of CVD risk are higher in PCOS women
  • Endothelial dysfunction in PCOS is related to
    abdominal obesity and IR

38
Cancer risk
  • PCOS disrupts normal reproductive physiology
  • Increased risk of the development of CA
    endometrium
  • Moderate quality data to support 2.7 fold
    increased risk for endometrial CA.
  • Most are well differentiated with good prognosis
  • Limited data suggests that PCOS women are not at
    increased risk of Ca ovary/breast

39
Menopause
  • Age may improve many manifestations of PCOS
    including normalizing ovarian size and
    morphology, T levels and oligo-ovulation prior to
    menopause

40
Combined oral contraceptives
  • Majority contain ethinyl estradiol
  • Mestranol and Eastradiol valerate are also used.
  • The dose varies from 20-40 micrograms
  • Always choose a preparation with the lowest
    estrogen and progestogen content which gives good
    cycle control and minimal side effects

41
Combined oral contraceptives
  • Low strength preparations
  • Ethinylestradiol 20 micrograms
  • Std strength preparations
  • -30-35 micrograms
  • Progestogens(3rd generation)
  • desogestrel, drospirenone and gestodene In
    combination with ethinylestradiol- consider for
    women who develop side effects like
    acne,headache, depression, breast symptoms and BT
    bleeding with other progestogens
  • Desogestrel and gestodene -risk of VTE

42
Drospirenone (Yasmin/YAZ)
  • Derivative of spirinolactone
  • Antiandrogenic /antimineralocorticoid effect
  • Useful in
  • Acne/Hirsutism/premenstrual distrophic disorder

43
  • Thank You
  • Questions
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