it describes an overview of the integrated medical care in women with PCOS.

1. Polycystic Ovarian Syndrome:
An integrated Care
DR/ MAHMOUD ABDEL-ALEEM, MD
PROF OF OBSTETRICS AND GYNECOLOGY. ASSIUT
UNIVERSITY

2. What is Integrated Medical
care?
A concept bringing together inputs, delivery,
management and organization of services related to
diagnosis, treatment, care, rehabilitation and health
promotion.
Integration improves services in relation to access,
quality, user satisfaction and efficiency

5. PCOS

6. Why PCOS as an example?
1- An old and enigmatic disease.
2- An area of hot research.
3- Different definitions, many treatments with
contradictory results.
4- Many phenotypes… presentations…
associations.. long term complications.. Non-
reproductive effects.
5- No final decision for its best way of
management. Is it medical …is it surgical….

9. PCOS
and
Iceberg

11. PCOS is a Challenging syndrome
1- Big research, humble outcomes
2- Terminology of the syndrome.
3- Many theories are there, but None is ideal.
4- Definition (s) of the syndrome.
5- Diagnostic modalities
6- Treatment challenges.

12. Challenge #1
BIG COLLABORATION, HUMBLE OUTCOMES

13. ESHRE/ASRM-sponsored PCOS
consensus meetings
First: Rotterdam; 2003: diagnostic criteria.
Second: Thessaloniki; 2007: infertility management.
Third: Amsterdam; October 2010: women’s health
aspects of PCOS.

14. Total Recommendations= 123 points
“Agreement” points
61 points
A= 5
B= 43
C= 8
GPP= 5
“Lack of agreement” points
62 points
A= ≥1 RCT
B= Clinical trial, NO RCT
C= Expert opinion
GPP=

15. Challenge #2: Terminology of
the syndrome
WHY DO WE STEP AFTER STEIN AND
LEVENTHAL?

16. Year: 1700-1800
The findings of polycystic (or cystic oophoritis or
sclerocystic) ovaries
Vallisneri A. Istoria della Generazione dell’Uomo, e degli Animali, se sia da’ vermicelli
spermatici, o dalle uova. Venezia: Appreso Gio Gabbriel Hertz, 1721.
Chereau A. Memoires pour servir a l’etude des maladies des ovaries. Paris: Fortin,
Masson & Cie, 1844
Rokitanski C. A manual of pathological anatomy. Philadelphia, PA: Blanchard & Lea,
1855.

17. Year: 1900s
The association between hyperandrogenism & glucose
intolerance was first described by Achard and Thiers (1921)
as "the diabetes of bearded women.“
Stein and Leventhal (1935) reported on patients with pco
and oligomenorrhea. They restored their regular menstrual
rhythm by “wedge resection of the ovary”. They named it
PCO.

18. Year: 1990s and 2000s
NIH then Rotterdam consensus tried to find a definition of
the PCO but with putting in mind the earlier S&L description.
HOWEVER, the genuine question should be:
Is PCO a disease?
Or
A sign of different diseases?
Or
Both?

19. There is no such nomination in other diseases or
other disciplines. “to name a disease by one sign”.
For example there is no disease labelled “cough” or
“wheezes” in chest diseases …but search for the
cause of this “cough” or “wheezes” and this will be
the diagnosis (cause) of this symptom or sign.

20. Challenge # 3
MANY THEORIES ARE THERE, BUT
NONE IS IDEAL

21. Why do we try to put all patients with PCO in
one frame?
C.G. Baptiste et al. / Journal of Steroid Biochemistry & Molecular Biology 122
(2010) 42–52

22. Marek Demissie, Richard S. Legro, Andrea Dunaif
PCOS is a multifactorial polygenic disorder. In
addition to phenotypic heterogeneity, genetic
heterogeneity likely exists.

23. Challenge # 4
Definitions
NIH- ROTTERDAM- AES

24. NIH
16-18 April 1990
Six Phenotypes
Voting (survey regarding
their perception) of
speakers and attendees on
potential diagnostic
features: androgen excess,
menstrual dysfunction,
disordered Gn secretion, IR.
No inclusion of PCO.
No inclusion of hormonal
profile.
It is not a real consensus.
Rotterdam
1-3 May 2003
Ten Phenotypes
2-day closed workshop
Based on majority
voting of experts.
An extension rather
than replacement of the
NIH PCOS criteria
adding US-PCO
It is not a formal
consensus process.
AES
2006
Nine Phenotypes
Expert opinion.
The intention is to
provide a basis for
genetic diagnosis of
PCOS.
Hyperandrogenism is
essential
So as in politics, voting
not always comes with
the best thing
January 17, 2003. Crichton argues that ‘‘. . . the work of science has
nothing whatever to do with consensus

26. CHALLENGE #5
DIAGNOSTIC MODALITIES

27. I- General
Referral
bias
Racial
variations
Similar/mimicking
disorders aren’t
standardized
Subjective
Detection of
hirsutism
Variable
circulating
androgen
assayVariable
PCOM
diagnostic
specifics
Phenotype
is changing
over time

28. II- Insulin Resistance
Difficult to assess.
The only standard: euglycemic hyperinsulinemic clamp.
Surrogate indices (fasting G/I(FGIR), the homeostatic model of
assessment (HOMA-R), and the quantitative insulin-sensitivity
check index (QUICKI)): inaccurate.
A frequently sampled intravenous glucose tolerance test
(FSIVGTT) technique is technically difficult.

29. III- Sonography
Current ASRM consensus as an ovary with ≥24 follicles each
is2–9 mm in diameter and/or an increased ovarian volume
(>10 cm3) [at least one ovary].
AMH may be even more precise than US , with a threshold
serum concentration of >35 pmol/l (4.7 ng/dL).
Iliodromiti S et al. Can anti- Mullerian hormone predict the diagnosis of polycystic ovary syndrome? A systematic review and meta-analysis of
extracted data. J Clin Endocrinol Metab. 2013;98(8):3332-3340.

30. IV. Hyperandrogenemia
Bad news for testosterone !
1- Free T Measurement
◦ Direct radioimmunoassay (RIA) (analogue method): inaccurate and
does not reflect the actual free T levels.
◦ Equilibrium dialysis: more accurate but coslty and complex.
2- Total T measurement:
◦ Highly variable, especially in the lower range found in most
women, and in women with lower SHBG levels such as patients
with PCOS
◦ Assays for T have large intra- and interassays variation

31. DHEAS: the best to assay
The metabolite of DHEA.
The best to assay:
◦ 97% - 99% of adrenocortical origin
◦ The most abundant steroid
◦ Stable throughout the day and the menstrual
cycle because of its relatively long-half life.
◦ Is easily measured.

32. V- Are these real associations or
causations or consequences? !!!
1. Chronic thyroiditis: Garelli S, et al; 2013.
2. Vitamin D deficiency.
3. Insulin resistance.
4. LH hypersecretion.
5. Obesity.
6. Epilepsy.
7. Thrombophilias. T. Kazerooni et al.;2013.
8. Psychological disorders: depression, self-harm and suicidal ideation
9. Nonalcoholic Fatty Liver Disease
10. Abnormal WBCs count.
Is PCO a disease?
Or
A sign of different diseases?
Or
Both?

33. PCOS and Heart

34. PCOS and Impaired Glucose
Tolerance

35. PCOS and Psychiatric disorders
Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and
heritability in a nationwide Swedish cohort
Women with PCOS had a 50% increased odds of having a psychiatric disorder
bulimia, schizophrenia, bipolar disorder, depression, anxiety, personality
disorders, autism spectrum disorder, and tics
Ciesta et al., 2016

36. PCOS and liver
disease

37. PCOS and family

38. PCOS and the Offspring
An evidence for a potential causal influence of
prenatal androgen exposure on the
development of male-predominant
neuropsychiatric disorders in female offspring
of women with PCOS.
Cesta CE et al (2019). Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in
offspring: prenatal androgen exposure or genetic confounding? Psychological Medicine 1–9.

39. PCOS in adolescents

40. PCOS in male !!!
Hormonal and metabolic abnormalities exist in male
relatives of women with PCOS.
They have a higher prevalence of early onset (<35 years)
androgenetic alopecia (AGA). 2016

41. The primary defect underlying PCOS may be an upstream endocrine and/or
metabolic disturbance, rather than a defect in the ovaries themselves.
Recognition of this syndrome in men is important

42. CHALLENGE #6
TREATMENT CHALLENGES
MANY ARE PROMOTED, LITTLE ARE REAL

43. I- Vitamin D
1. Well known role of vitamin D deficiency in the
pathogenesis of IR, T2DM and MS
2. In PCOS, low levels of vitamin D are associated with
obesity and IR, impaired β-cell function, IGT and MS,
indicating a possible role of Vitamin D in the
pathogenesis of PCOS [Hahn et al. 2006; Wehr et al. 2009]
3. Vitamin D administration in women with PCOS
improves IR and lipid profile, but the conducted studies
were small and uncontrolled [Kotsa et al. 2009; Selimoglu et al. 2010].

44. II- Other Vitamins
1. Vitamin B12:
1. improves IR.
2. In PCOS patients, IR, obesity and elevated homocystein
levels are associated with lower serum vitamin B12
concentrations [Kaya et al. 2009].
2. Folic acid: increases the effect of metformin on
the vascular endothelium in women with PCOS.
3. Vitamin A: improves acne.
4. Vitamin E: anti-inflammatory. Lowers C-reactive
protein.

45. III. Minerals

46. IV- Insulin sensitizers
Metformin & rosiglitazone improve outcome measures
after treatment.
Rosiglitazone seems to improve insulin resistance
relatively earlier.
Metformin had an earlier and more sustained benefit on
hyperandrogenemia.

47. Ovulation
Morley LC, Tang T, Yasmin E, Lord JM, Norman RJ, Balen AH. Insulinsensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for
women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2016 (In press,

48. Pregnancy
Morley LC, Tang T, Yasmin E, Lord JM, Norman RJ, Balen AH. Insulinsensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for
women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2016 (In press,

49. V- Statins
Resveratrol appears to
be effective in the
treatment of PCOS due
to its antioxidant
properties.
Future clinical studies
with different dosages
might provide useful
application.

50. VI- Acupuncture
May be of value
by amelioration of
insulin resistance.

51. VII- Herbal
medicines
Chinese herbal medicine (CHM)
Green tea
Garlic.
Cinammon
Cannabis
Too little studies
with poor designs.

52. To sum-up
PCOS is urgently
needed to be re-visited
in the context of an
integrative approach
between pediat-gyn-
endocrine-psychiatrist-
lab-nutritionist-
oncologist-
complementary
medicine

53. PCOS for PCOS

54. Thank You
For
Your Kind Attention