POLYCYSTIC OVARY SYNDROME
LALI PKHALADZE, MD, Ph.D.
TSU
Zhordania and Khomasuridze Institute of
Reproductology
Prevalence
Polycystic Ovary Syndrome (PCOS) - a common disorder in
reproductological, gynecological, and endocrinological
practice.
The prevalence varies by ethnicity: 6 - 29 %.
PCOS - national disease of georgian women!
Etiology
Multifactorial disease:
Genetic predisposition;
Intrauterine factors;
Environmental factors.
Stein IF, Leventhal ML.
Amenorrhea associated with bilateral polycystic ovaries.
Am J Obstet Gynecol 1935; 29: 181-910
7 women with variety of clinical symptoms (obesity, hirsutism,acne,
amenorrhea) were associated with enlarged bilateral polycystic ovaries)
PCOS
STEIN- LEVENTHAL SYNDROME
POLYCYSTIC OVARIAN DESEASE
SCLEROCYSTOSIS OF OVARIES
POLYCYSTIC OVARIES
(ICD10 – E28.1)
Clinical Manifestations
Hirsutism, acne, seborhea;
Menstrual disturbances - oligomenorrhea, amenorrhea,
abnormal uterine bleeding;
Excessive weight, obesity;
Depression, anxiety;
Infertility;
Pregnancy complications: miscarriage, gestational diabetes,
pregnancy hypertension, premature birth;
Long term health consequences: metabolic syndrome, type 2
diabetes, CVD, dyslipidemia, endometrial
hyperplasia/carcinoma.
Share of PCOS in women with
different conditions
During oligomenorrhea/amenorrhea – 85%
Among women with hirsutism-70-95% A
Cases of anovulatory infertility– 80%
Rotterdam diagnostic
criteria (ESHRE/ASRAM) 2003
Oligo-anovulation(OD)
Hyperandrogenism(HA)
Polycystic Ovarian Morphology
(PCOM)
(requres the presence of 2 out of 3 varibles)
Exclusion criteria
Hyperprolactinemia;
Thyroid dysfunction;
Congenital Adrenal Hyperplasia;
Acromegaly, Cushing’s syndrome.
Pathogenesis
The increase of ovarian androgen production is a
fundamental characteristic of PCOS
Genetically determined dysregulation of enzyme
cytochrome P450C17;
local ovarian factors- Increase in Inhibin, Activin,
IGF1;
Imbalances between proliferation and apoptosis of
cells;
Insulin resistance with compensatory
hyperinsulinemia(defect on insulin receptor).
PATHOPHYSIOLOGY
Ovarian folliculogenesis
dysfunction
[Link] follicular growth,
[Link] within the excessive cohort
of the emergence of dominant
follicle-“ follicular arrest “,
3. Multiple follicules in ovaries.
CARBOHYDRATE METABOLISM
Insulin resistance – 50-75% Arched and Thiers, 1821
“Bearded Diabetic Women”
Glucose intolerance – 35%
Type 2 diabetes – 7-10%
Metabolic syndrome– 40-45%O
Obesity – 35-60%
Production of ovarian androgens due to
hyperinsulinemia
Hyperinsulinemia
LH IGF-IBP
+ IGF-I
INS
rec
SHBG
IGF-I rec
LH rec P450
inositolo +
Free testosterone
androgeni
ANDROGENS
CLINICAL MANIFESTATIONS OF PCOS
REPRODUCTIVE PPREMENOPAUSE/
ADOLESCENCE
PERIOD POSTMENOPAUSE
• Irregular • Infertility METABOLIC
menses(oligo/amen • Pregnancy loss SYNDROME
orrhoea, • Type 2 diabetes
anovulation, + • Gestational
diabetes mellitus
+ • Ischaemic heart
disfunctional disease, arterial
• Hypertension of hypertension
uterine bleeding
• Cosmetic pregnant women • Dyslipidaemia
problems- • Endometrial
hirsutism, alopecia, hyperplasia,
acne carcinoma
Excess of weight /obesity
visceral distribution of fat, acanthosis nigricans,’’ climacteris hump’’
PCOS
Diagnostical and laboratory test
* Anamnesis
* Objective data – preasence of hirsutism, acne ,
seborrhea, allopecia, acanthothis nigricans,BMI, fat
distribution
* Gynecological examination
* Body basal temperature
* Biochemical markers (TSH, PRL, 17OHP, FSH, LH,
T, F T, DHEA-S, A4, SHBG, IRI,Glucose,lipids)
*USS
PCOS
Biochemical markers of hyperandrogenism
l line investigations
• Total testosterone (TT)
• Sex hormone binding globulin (SHBG)
• Free androgen index ( FAI )
• Free testosterone (FT)
II line investigatioins
• Androsterone ( A4 )
• Dehydroepiandrosterone- sulfate (DHEA-S)
• LH, FSH, LH/FSH ratio
• Antimiulerian hormone (AMH)
PCOS
Investigation related to metabolic abnormalities
Glucosa (fasting)
Insuline(basal)
Index of insulinresistancy
HOMA index = insuline(basal) X glucose (fasting)
22,5
> 2,5 (insulinresistance)
PCOS
ON ULTRASOUND SCAN
• Preasence of 12 or more antral follicles in each
ovaries on different stage of maturation sized 2-5 mm
• Ovarian volume >10 mL (bylateral or unilateral enlarged
(2-6 fold) ovaries)
• The thikness of capsule is increased more than 10 fold
PCOS
METABOLIC SCREEN
* Glucose intolerance: glucose- 7,8-11 mmol/l after gucose
tolerance test
* Type 2 diabete: fasting glucose- ≥ 7,0 mmol/l or after 2 h
75 g glucose challenge- 11,1 mmol/l
PCOS
INCREASED RISK FOR METABOLIC
SYNDROME
• DYSLIPIDEMIA– LDL HDL TRG
• GLUCOSE 5,6 mmol/l
• TRG 1,7 mmol/l
• HDL < 1,29 mmol/l
Management
The options should be focus on the main
concern of women
Nonpharmacological: healthy life style with
hypocaloric diet and phisical activity;
Pharmacological: COC, insulin sensitizers,
antiandrogens, antiestrogens for ovulation
induction;
Gibson-Helm et al. 2018; Teede et al. 2018; Domecq et al. 2013Martin et al. 2008.
For women who do not seek conceive
Lifestyle modification -dietition, exercise(Cornstone in an
overweight women. Weight loss in 5% can improve
symptoms);
Combine Oral Contraceptives (Combined oral contraceptives)-
reduces serum androgen levels by increasing SHBG levels,
providing regular monthly withdrowal bleed and beneficial
anti- androgenic effects;
Progestins (Medroxsyprogesterone acetate);
Insulinsensitaizers (Metformin);
Antiandrogenes – spironolactone, flutamid, finasteride(can be
used to help with acne and hirsutism- take 6-9 month to
improve hear growth, avoid pregnancy- feminize a male
fetus);
Cosmetic (depilatory cream, eleqtroepilation, eleqtrolizis,
lazerovaporization, fotoepilation).
Subfertility
• Weight loss alone may achieve
spontaneous ovulation;
• Ovulation induction with antiesrogens
or gonadotropins;
• Laparascopic ovarian diathermy;
• IVF if ovulation cannot be achieved or
does not succseed in pregnancy;
• Women with PCOS who undergo IVF
are at increased risk of ovarian
hyprtstimulation syndrome.
Management of infertility in women with PCOS
I line
optionNE
Farmacologic
Nonfarmacological al
Lifestyle Letrozol or
Clomifen Metformine
modification-
citrate (BMI≥30)
healty diet,
( BMI≤25)
Dexametazone +Clomifen
exercise
citrate
(in cases of combined forms
of PCOS)
II line option
Clomifen
citrate+ laparasc Bariatric Inhibitor
Metformi Gonad opy- surgery(BMI≥ s of
Metform ne otropi ovarian 30, 6 Month aromataz
in (BMI≤30) of uneffective
(BMI≥30
ns drilling
treatment )
e
)
III line option
Alternative methods of treatment- IVF
PSYCHOLOGICAL ISSUE
• Difficult to manage PCOS
patients;
• Patients requre additional
motivation;
• Symptoms can be distressing
and result in low self- esteem;
• Patients should be manage
sensitively, adopt a holistoc
approach incorporating all
members of the