STEIN- LEVENTHAL SYNDROME POLYCYSTIC OVARIAN DESEASE SCLEROCYSTOSIS OF OVARIES POLYCYSTIC OVARIES (ICD10 – E28.1)

1. POLYCYSTIC OVARY SYNDROME
PCOSPCOS
LALI PKHALADZE, MD, Ph.D
ARCHIL KHOMASURUDZE INSTITUTE OF REPRODUCTOLOGY
TSU TBILISI GEORGIA

2. 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

3. POLYCYSTIC OVARY SYNDROME

4. STEIN- LEVENTHAL SYNDROME
POLYCYSTIC OVARIAN DESEASE
SCLEROCYSTOSIS OF OVARIES
POLYCYSTIC OVARIES
(ICD10 – E28.1)
POLYCYSTIC OVARY SYNDROMEPOLYCYSTIC OVARY SYNDROME
PCOSPCOS

5. Women of childbearing age_ 5-11%
During oligomenorrhea/amenorrhea – 85%
Among women with hirsutism-70-95%
Patients with adreno-genital syndrome(CAH)-75%
Cases of anovulatory infertility– 80%
PCOS-PCOS- MOST COMMON ENDOCRINE DISORDERMOST COMMON ENDOCRINE DISORDER
PREVALENCEPREVALENCE

6. DIAGNOSTIC CRITERIA
1Hyperandrogenism and/or hyperandrogenemia
2. Menstrual disturbances
NICHD, 1990
(presence of both simultaneusly)
PCOSPCOS

7. ROTTERDAM CRITERIA FOR DIAGNOSING PCOS
ESHRE/ASRAM, 2003
1. Irregular menses and/or absent ovulations
2. Clinical and/or biochemical signs of
hyperandrogenism
3. Polycystic ovaries on pelvic USS (≥12 antral follicles each
ovaries and ovarian volume > 10 ml)
(requres the presence of 2 out of 3 varibles)
PCOSPCOS

8. DDIAGNOSTIC CRITERIA
Androgen Exess and PCOS Society,
2009
1.Hyperandrogenism (clinical and /or biochemical)
2. Ovarian dysfunction (oligomenorrhea/ovulatory
dysfunction and /or polycystic ovarian morphology)
PCOSPCOS
(simultaneous presence of both variables)

9. EXCLUSION CRITERIA
1. Hyperprolactinemia
2. Hypothyroidism
3. Non classical congenital adrenal hyperplasia
4. Cushing syndrome/ acromegaly
PCOSPCOS
(Premature ovarian failure, virilizing adrenal or ovarian
neoplasma and a drug- related condition)

10. CLINICAL FORMS
1. Primary polycystic ovarian syndrome -Stein-
Leventhal syndrome
2. Central form of polycystic ovarian syndrome-
developed on the basis of hypothalamic disfunction
3. Combined form of polycystic ovarian syndrome
developed on the basis of congenital adrenal
hyperplasia
PCOSPCOS

11. Etiology and Pathogenesis
(multifactoral)
 Genetically determined-oligogenic
 Enviromenaltal factors- lifestyle, diet, exercise,
stress
 Peculiarities of prenatal period
PCOSPCOS

12. Pathogenesis
The increase of ovarian androgen production is a fundamental
characteristic of PCOS
 local ovarian factors- Inhibin, Activin, IGF1
 Imbalances between proliferation and apoptosis
of cells
 Genetically determined dysregulation of enzyme
cytochrome P450C17
 Insulin resistance with compensatory
hyperinsulinemia(defect on insulin receptor)
PCOSPCOS

13. PCOS
PATHOPHYSIOLOGY
•Neuroendocrine dysfunction( changes in the frequency and
amplitude of pulses of GNRH- hypersecretion of LH – hypersecretion of
androgens from ovaries);
•Metabolic impairment( insulin resistance and
hyperinsulinemia)-interact with insulin receptor itself in the ovaries;
•Dysfunction of ovarian and adrenal ( alteration in
androgen biosinthesis) steroidogenesis ( hyperactivity of the
enzyme citochrome P450 c17-catalyses the step of progesterone 17 alpha
hydroxyprogesterone to androstendione i.e. to androgens. The enzymatic
activity due to primary genetic defects);
•Ovarian folliculogenesis dysfunction(1.excessive follicular
growth,2.inhibition within the excessive cohort of the emergence of dominant
follicle-“ follicular arrest “).

14.  Significant correlation between basal insulin,
androstendion and testosteron
Burgen, 1980 – Simultaneous preseance of hyperandrogenemia
and insulin resistance in patients with PCOS
PCOSPCOS

15. Archard and Thiers, 1821
“Bearded Diabetic Women”
PCOSPCOS

16. Metabolic syndrome– 40-45%
Obesity – 35-60%
 Insulin resistance – 50-75%
 Glucose intolerance – 35%
 Type 2 diabetes – 7-10%
PCOSPCOS

17. Hyperinsulinemia
inositolo
androgeni
ANDROGENS
IGF-IBP
IGF-I
LH
+ INS
rec
LH rec
IGF-I rec
SHBG
Free testosterone
+
P450
Production of ovarian androgens due to
hyperinsulinemia

18. CLINICAL MANIFESTATIONS
ADOLESCENCE
• Irregular
menses(oligo/amen
orrhoea,
anovulation,
disfunctional
uterine bleeding
• Cosmetic
problems-
hirsutism, alopecia,
acne
REPRODUCTIVE
PERIOD
PPREMENOPAUSE/
POSTMENOPAUSE
• Infertility
• Pregnancy loss
• Gestational
diabetes mellitus
• Hypertension of
pregnant women
METABOLIC
SYNDROME
•Type 2 diabetes
•Ischaemic heart
disease, arterial
hypertension
•Dyslipidaemia
• Endometrial
hyperplasia,
carcinoma
Excess of weight /obesity
visceral distribution of fat, acanthosis nigricans,’’ climacteris hump’’
+ +
PCOSPCOS

19. PCOSPCOS
Clinical symptomsClinical symptoms
* Menstrual diturbances- oligomenorrhea,
amenorrhea, anovulatory dysfunction, acyclic
bleeding.
* Hyperandrogenism- hirsutism, acne, seborrhea,
alopecia, clitoromegaly
*Infertility, spontaneus abortion, gestational
diabetes

20. * Excess weight and obesity
*Symptoms related to
hyperinsulinemia/insulinresistance-visceral (central)
obesity ,’’acanthothis nigricans, ’’ climalcteric hump’’
*Metabolic abnormality
PCOSPCOS
Clinical symptomsClinical symptoms

21. *Type 2 diabetes
*Cardiovascular disease-ischemic heart
disease, hypertension
*Endometrial hyperplasia
*Endometrial carcinoma
PCOSPCOS
Long term health consequencesLong term health consequences

22. * Anamnesis
* Objective data – preasence of hirsutism, acne ,
seborrhea, alopecia, acanthothis nigricans,BMI, fat
distribution
* Gynecological examination
* Body basal temperature
* Biochemical markers (TSH, PRL, 17αOHP, FSH, LH, T,
F T, DHEA-S, ∆A4, SHBG, IRI,Glucose,lipids)
*USS
PCOSPCOS
Diagnostical and laboratory testDiagnostical and laboratory test

23. BMI< 118,5 _insufficiency of mass
PCOSPCOS
BMI, FAT DISTRIBUTIONBMI, FAT DISTRIBUTION
18,5-24,9 _normal
25,0-29,9 _excess weight
30,0-39,9 _obesity
> 40,0 _sevier obesity
BMI>30; W/H>0,85; W≥80cm – central obesity
(probability of MS is high)
BMI= mass (KG)/ height
(M2)

24. PCOSPCOS
BBiochemical markers of hyperandrogenisiochemical markers of hyperandrogenis
I line investigationsI line investigations
• Total testosterone (TT)
• Sex hormone binding globulin (SHBG)
• Free androgen index ( FAI )
• Free testosterone (FT)

25.  Androsterone ( ∆A4 )
 Dehydroepiandrosterone- sulfate (DHEA-S)
 LH, FSH, LH/FSH ratio
 Anti mullerian hormone (AMH)
PCOSPCOS
IIII line investigatioinsline investigatioins

26.  Glucosa (fasting)
 Insuline(basal)
 Index of insulinresistancy
PCOSPCOS
Investigation related to metabolic abnormalitiesInvestigation related to metabolic abnormalities
HOMAHOMA index =index =
> 2,5 (insulinresistance)
insuline(basal) X glucose (fasting)
22,5

27.  LH ↑ (>10 IU/ML)
 LH/FSH ↑ (>2,5)
 SHBG ↓
 FT ↑ ∆A4 ↑ (DHEAS ↑ , 17-OHP ↑ )
 IR ↑, HOMA-IR ↑
 AMH ↑
 Prog. ↓
 E1 ↑ (E2:E1 imbalance)
HORMONAL PROFILE
PCOSPCOS

28. • Preasence of 12 or more antral follicles in each
ovaries on different stage of maturation sized 2-5 mm
• Ovarian volume >10 ml (bilateral or unilateral enlarged
(2-6 fold) ovaries)
• The thickness of capsule is increased more than 10
fold
PCOSPCOS
ON ULTRASOUND SCANON ULTRASOUND SCAN

29. * 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
PCOSPCOS
METABOLIC SCREENMETABOLIC SCREEN

30. •DYSLIPIDEMIA– LDL↑ HDL↓ TRG ↑
•GLUCOSE ≥ 5,6 mmol/l
•TRG ≥ 1,7 mmol/l
•HDL < 1,29 mmol/l
PCOSPCOS
INCREASED RISK FOR METABOLICINCREASED RISK FOR METABOLIC
SYNDROMESYNDROME

31. The options should be focus on the main concern of women
women who do not seek conceive
Lifestyle modification- diete , exercise(Over weight women .
Weight loss in 5% can improve symptoms)
COC (Combined oral contraceptives)- reduces serum
androgen levels by increasing SHBG levels, providing regular
monthly withdrowal bleed and beneficial anti- androgenic effects
Progestin (Medroxsyprogesterone acetate)
Insulinsensitaizers (Metformin)
PCOSPCOS
MANAGMENTMANAGMENT

32. CONTROLLING SYMPTOMS OF HYPERANDROGENISM
 COC(with cyproteron-acetaet, drospirenone)
 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)
 Insulinsensitaizers-Metformin, Roglitazone(may help regulate
menstrual cycles and achive ovulation, is no better than
lifstyle modification, du not sginificantly improve
hirsutism,acne, weight loss despite lowering androgens and
improving insulin sensitivity)
 Eflornihtini facial cream
 Cosmetic (depilatory cream, eleqtroepilation, eleqtrolizis,
lazerovaporization, fotoepilation)
PCOSPCOS
MANAGEMENTMANAGEMENT

33. 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 succeed in pregnancy
•Women with PCOS who undergo IVF
are at increased risk of ovarian
hypertstimulation syndrome

34. Management of infertility in women with PCOS
I line
optionNE
Nonfarmacological
Farmacologica
l
Clomifen citrate
( BMI≤25)
Metformine
(BMI≥30)
Dexametazone +Clomifen citrate
(in cases of combined forms of
PCOS)
Lifestyle
modification- healty
diet, exercise
II line option
Clomifen
citrate+
Metform
in
(BMI≥30
)
Metfor
mine
(BMI≤3
0)
Gonado
tropins
laparasco
py-
ovarian
drilling
Bariatric
surgery(BMI≥
30, 6 Month
of uneffective
treatment )
Inhibitors
of
aromataze
III line option
Alternative methods of treatment- IVF

35. 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 multidisciplinary team

36. THANKS!THANKS!THANKS!THANKS!
TBILISI