1. PCOS and contraception
Prof Helle Karro
Antalya, 2017

2. PCOS
Heterogeneous endocrine disorder, a lifelong syndrome, beginning in the prenatal period with manifestations in childhood, adolescence and adulthood
Multifaceted disease involving uncontrolled ovarian steroidogenesis, aberrant insulin signalling, excessive oxydative stress and genetic/environmental factors Hayek et al, Frontiers in Physiology, 2016
Highly prevalent diorder which affects multiple aspects of womens general health
Multiple studies suggesting that might start in utero, mainly in neonates with risk factors for PCOS. LBW and high BW, who later catch-up on their growth or constantly increase in weight postnatally.
Such factors+ genetic disposation - premature pubarche, adrenarche and later metabolic syndrome

3. PCOS and associated morbidities
Obesity
Childhood obesity as a risk factor for PCOS Pascali et al, 2011
One of the most important features of PCOS
Prevalence varies between 61%-76% Glueck et al,2005
Insulin resistance
Hyperinsulinemia is present in 85% of PCOS patients, incl 95% of obese and 65% of lean women Teede et al 2010, 2011; Stepto et al, 2013
Type II Diabetes Mellitus
1 in 5 women with PCOS will develop DM2 Dunaiff, 1999
Increased risk for gestational diabetes Boomsma, 2006
Increased risk for DM2 Moran, 2011

4. PCOS and associated morbidities
Cardiovascular disease
Several studies have shown significantly elevated levels of biomarkers, incl C reactive protein and lipoprotein Bahceci, 2004, 2007; Meyer 2005; Yilmaz, 2005; Berneis, 2009, Rizzo, 2009
Early cardiovascular dysfunction (arterial stiffness, endotelial dysfunction, coronary artery calcification Meyer, 2005; Moran, 2009
There is discrepancy between studies determining the absolute risk of CVD in patients with PCOS El Hayek, 2016
Infertility
Psychological wellbeing

5. PCOS and associated morbidities
Cancer
Endometrial cancer
Many acssociated risk factors – obesity, insulin resistance, DM2, anovulation Legro, 2013
Women with PCOS have three times higher risk compared to controls Chittenden, 2009; Fauser, 2012, Haoula, 2012; Dumesic and Lobo, 2013
Ovarian cancer
Contradictory evidence exists between PCOS and risk of ov cancer Schildkraut, 1996; Balen, 2001; Dumesic and Lobo, 2013
Breast cancer
Limited data to support association between PCOS and breast ca Fauser, 2012; Dumesic and Lobo, 2013; El Hayek, 2016

6. Criteria for the diagnosis of PCOS
NIH/NICHD, 1990
Dgn :including all of the following (two of two)
ESHRE/ASRM (Rotterdam criteria, 2003
Dgn: includes two of three
AES definitsioon, 2006
Dgn: including all of the following (two of two)
Oligo/anovulation
Ovulatory dysfunction
Ovarian dysfunction and/or polycystic ovarian morphology (PCOM)
Clinical and/or biochemical signs of hyperandrogenism
Polycystic ovarian morphology (PCOM)
Exlusion of other androgen exess or other related disorders
NIH-National Institute of Health; Rotterdam – consensus workshop (ESHRE, ASRM);
AES – Androgen Exess Society

7. Classification of PCOS phenotypes
Phenotype A
Phenotype B
Phenotype C
Phenotype D
Hyperandrogenism and hirsutism + -
Ovulatory dysfunction
Polycystic ovarian morphology
1990 NIH criteria
2006 AE-PCOS criteria
2003 Rotterdam criteria
Daria Lizneva, 2016: NIH consensus workshop suggested in 2012 to use 4 PCOS phenotypes. Tabel summarizes these phenotypes and their relationship to the current criteria
Phenotypic approach is convienent for epidemiological research and clinical practise
It would be helpful to identify those women with PCOS who are at highest risk for metabolic dysfunction – classic PCOS phenotypes A and B
NIH, 2012

11. Hormonal contraceptives use in PCOS
Combined hormonal contraceptives
Noncontraceptive use
Risks versus benefits
Hormonal contraceptive choice

12. Oral contraceptive pills and PCOS
Most commonly used medications have been recommended by the task Force and Endocrine Society (Legro, 2013), the Australian alliance (Misso, 2014) and the PCOS consensus group (Fauser, 2012) as the first-line treatment for the hyperandrogenism and menstrual irregularities
However, PCOS is associated with different comorbidities, and assesment for individual risk factors is needed (risks versus benefits) Dokras, 2016

13. Screening for contraindications
Hormonal contraception is recommended as first-line managment for the menstrual abnormalities, hirsutism/acne
Screening for contraindications
For women with PCOS one formulation is not better than other
For adolescent girls:
HC as a first-line treatment and/or contraception when PCOS is suspected
In addition life style therapy; metformin for IGT/metabolic syndrome
Premenarcheal girls ( >=Tanner 4), HC

14. Oral contraceptive pills (OCP), mechanism of action
supression of the HT-HF-ov axis, OCP decreases LH, increases SHBG and decreases free androgens
decreases adrenal androgens secretion and inhibition of periferial conversion of testosterone to dihydrotestosteron
Improvement in symptoms such as menstrual irregularities, clinical signs of hyperandrogenism and effective contraception

18. PCOS phenotypes: hormonal contraceptive choice
There are no clinical guidelines that recommend a specific CHC for the different phenotypes, there are doubts concerning metabolic and cardiovascular effect
Ideal contraceptive should limit follicular development to reduce androgen synthesis, block the peripheral action of androgenes, assure good menstrual cycle control and minimal metabolic or thromboembolic risk
Mendoza et al. Gynecological endocrinology, 2014

19. PCOS phenotypes: hormonal contraceptive choice
HA/PCOS
CHC (oral, patch or vaginal ring) as first-line treatment, but there are insufficient data to define the optimal treatment
For the androgen excess, the most important parameter for the CHC selection is the type pf progestin with antiandrogen activity; studies on the efficacy of CHC containing DRSP or CPA in the treatment of hirsutism, show a reduction of clinical manifestation of HA after 6-12 months
There are no data providing direct comparisons reagrding the type or dose of estrogens; lowest effective estrogen dose should be used
Research has shown 2–fold increased risk in the VTE among women with PCOS who take CHC and 1,5–fold increased risk among PCOS women not taking CHC Bird, 2013
Few studies comparing EE doses; E2V/DNG seems to be more favorable than EE/LNG on prothrombin, D-dimer, HDL, LDL, insulin and carbohydrate metbolism Fruzetti, 2012
Extended regimes improve follicular control and hormonal supression better Kallio, 2013
Mendoza et al. Gynecological endocrinology, 2014

20. PCOS phenotypes: hormonal contraceptive choice
PCOS/metabolic risk or obesity
Few studies have focused on the possible differences in the effect of CHC lean vs obese women; in lean adverse effect on adiposity, insulin sensitivity/glycose tolerance status and lipid profile are not expressed
In three meta-analyses the use of CHC was not associated with clinically significant adverse metabolic consequences Costello, 2007; Jing, 2008; Halperin, 2011
When arterial hypertension or elevated risk of VTE is present, LngIUS or progestagen-only hormonal contraception should be used instead of CHC WHO MEC
Combination with DRSP could be more advantageous in overweight women whose glycose tolerance is in concern
Low-dose oral CHC is preferable in patients with glycose intolerance or IR Verhaeghe, 2010
A vaginal contraceptive ring appears to be preferred to oral EE/DRSP
Mendoza et al. Gynecological endocrinology, 2014

24. Morbidity of PCOS patients regarding several diseases is significantly increased
Treatment with life-style modification and metformin could be important tools for the prevention of adverse disease outcomes;
OC could be both, benefit and harm
Individual risks should be considered

25. Conclusive remarks
PSOS patients contraceptive needs should be discussed
CHC remains an option for PCOS patients
However individual risk/benefit ratio has to be considered and tailored treatment recommended
Interdisciplinary approach and follow-up should be offered, taking into account the life curve of the patient