1) The document discusses polycystic ovarian syndrome (PCOS) and the roles of myo-inositol and D-chiro inositol, which are naturally occurring inositol compounds. 2) Women with PCOS have lower levels of myo-inositol and higher clearance rates of inositols compared to healthy women. Supplementation with myo-inositol and D-chiro inositol in a 40:1 ratio is effective in improving both hormonal and metabolic markers in overweight PCOS patients. 3) A combination therapy of myo-inositol and D-chiro inositol addresses the root causes of PCOS by restoring insulin

1. What is
40 : 1
In management of
Dr. Jyoti Agarwal
Dr. Sharda Jain
Dr. Jyoti Bhaskar

2. Not end of the story
Today knowledge regarding PCOS
has revived and efforts have been undertaken
to explore new options
created significant
development in t/t of
PCOD

4. Indian Journal of Endocrinology and Metabolism, 2011
Central player : IR

5. Insulin Resistance
A pathophysiological contributor in
50 – 80 % of the PCOS women
Indian J Endocrinol Metab. 2011 Oct-Dec; 15(4): 239–241.

6. 75% of PCOS patients are obese

7. • Relative risk of MI is
7.4 times higher wrt
age matched
controls.
• risk of diabetes
associated death.
• PCO is present in 42
% of CVD patients.
J.Clin.Endocrinol.Metab., December 2013
PCOS and metabolic syndrome

8. The use of insulin lowering or insulin
sensitizing therapy may help to
improve ovarian function and
menstrual cyclicity.

9. Word “M”in the PCOS world
First being - Metformin
Miracle pill - Myoinositol

10. MYO-INOSITOL and METFORMIN

11. Myo-
inositol
Improves
insulin
sensitivity Decreases
insulin
resistance
levels
Improves
glucose
utilization
Restores
menstruation
and normal
ovulation
Reduces free
testosterone
Improves
pregnancy
rate
MYO-INOSITOL - takes
TOTAL CARE OF SYMPTOMS

12. Insulin acts like a key
which can open the
door on the cell surface

13. 1
• Insulin binds to its receptor forms a complex called
insulin receptor substrate (IRS).
2
• IRS stimulates messenger called PI 3 kinase
3
• Activated PI 3 kinase activates GLU T 4
4
• Glucose is then taken by GLUT 4 through
glucose channel for utilizing energy.
5
• Then IRS complex breaks down releasing
the receptor to go back to its original site.

14. Phosphatidyl inositol 3-kinase is the
key messenger
• We need production & activation of PI 3 kinase
for normal cell glucose metabolism.
• Inositol produces as well as activates PI3 kinase
Inositol acts as a precursor for PI 3 kinase
Fertility and Sterility Volume 86, Issue 3, Supplement 1, September 2006, S461
J Pediatr Endocrinol Metab 2000;13 Suppl 5:1295-8

15. What is the connection
between PCOS and
inositols ???

16. DIABETES CARE 2006, 29, 300-305

17. Inositol levels in PCOS and Normal women
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
PCOS Subjects Normal Subjects
0.1
0.19
p=0.035
0
0.5
1
1.5
2
2.5
PCOS Subjects Normal Subjects
2.3
0.7
p= 0.043
Diabetes Care 2006;29:300–305
Plasma inositol (µmol/l) 24 h urinary inositol ((µmol/l/day)
Normal Plasma inositol (µmol/l) levels – 0.13-0.28

18. 0
2
4
6
8
10
12
14
16
PCOS Subjects Normal
Subjects
15.3
2.7
p= 0.001
Inositol clearance levels in PCOS and
Normal women
Diabetes Care 29:300–305, 2006
UrinaryclearanceofInositol
(ml/min)
5 -6 times
more Urinary
clearance of
Inositol in PCOS

19. Could inositols be
considered to
treat PCOD ???

20. Myoinositol is not a drug
• It is naturally occuring
one of the nine isomer
of a C6 sugar alcohol
that belongs to the
vitamin B complex
group (B 7 )
• Synthesised in the liver
from glucose in our body
• Water soluble so each
dose is well tolerated
and is devoid of toxicity

21. It is commonly found in fruits
(grapefruit being a rich source),
vegetables (leafy vegetables the lowest)
and in all foods containing seeds
(beans, almonds and walnuts the highest).

22. Enzyme Epimerase converts
Myo inositol to D chiro Inositol
Conversion is insulin dependent

23. When insulin resistance occurs,
the conversion rate is affected
Excess insulin in the ovary
triggers Epimerasation

24. In overweight PCOS BMI > 25
• The insulin resistance
is very high.
• Epimerase activity is
triggered.
• Disturbs the
physiological 40 : 1
plasma ratio of Myo-
inositol : D Chiro
Inositol.

25. Insulin regulates blood glucose
by two ways
1) Promoting
glucose cell uptake
2) Glycogen synthesis
Eur.Rev.Med.Pharmacol.Sci., 2013

26. Insulin action needs
“second messengers”
MYO promotes glucose cell
intake
DCI stimulates glycogen
synthesis.
DCI is present in high
concentrations in glycogen
storage tissue (liver,
muscles and fat)
low in tissue needing
elevated energy levels
(brain, ovary, heart).

27. Myo – inositol
• Acts at ovary
• Increases glucose cell
intake
• Normalises LH :FSH ratio
• Increases oocytes quality
• Reduces the amount of
FSH used during IVF
cycles
• Improves IVF results
DCI
• Acts at peripheral tissues
• Stimulates glycogen
synthesis
• Reduces IR
• Increases insulin sensitivity
• Reduces hyperinsulinemia
• No effect at ovarian level
• No direct effect on fertility
• Reduces risk of metabolic
syndrome

28. • 19 out of 22 obese pts
ovulated (1.2 mgm/day)
• These results were not
confirmed in second
clinical trial when double
dose of DCI was given.
• Negative effect of DCI
at ovaryNestler et al 1999

29. The DCI “paradox” in the ovary
In overwt. PCOS
High Insulin levels
increases conversion of
MI to DCI in the ovary
Ovary unlike other tissues
never shows insulin resistance

30. The DCI “paradox” in the ovary
• In the ovary, MYO
is involved in FSH
signalling, while
• DCI is responsible
for insulin-mediated
testosterone
production.
Endocrine J., 2014

31. Net result is that in the ovary
• Increase DCI
• Promotes androgen
synthesis
• MI depletion
• Worsens the energy
state of the occyctes
These events together impair FSH
signalling and oocyte quality

32. Treat PCOS the right way !!

33. MI/DCI physiological plasma ratio
0
10
20
30
40
50
Study 1 Study 2 Study 1+2

34. Clinical Evidences for
MYO-INOSITOL and D –
chiro inositol combination

35. 50 overwt. PCOS
Treatment results seen at 3 & 6 mnths

36. Significant improvement in plasma
glucose,insulin concentration at 3 months
Improvement in total testosterone and
SHBG was seen at both 3 and 6 months

37. 20 overwt. PCOS

38. With combination therapy a significant
improvement was seen in
• Lipid profile
• BMI
• Waist : Hip ratio
• Blood pressure
• Homa index

39. Thus……
Combined treatment in physiological
ratio of 40 : 1 is able to restore
both hormonal and metabolic
parameters in overweight PCOS
women earlier than with MI alone

40. And hence the
Rationale of
40 : 1
MI : DCI

43. No drug interactions documented yet
• Start the treatment
as soon as the
diagnosis of PCOD is
made
• Dose is 2 grams of
MYO and 50 mg of
DCI twice a day
(powder).
• If taken as powder ,
presence of caffiene
decreases its
absorption
Caffeine-induced MYO malabsorption

44. Carry Home Message
PCOD treatment
is a challenge.
Treatment should address the
root cause.
Best therapy should
include a 360°
approach to the
problem, taking into
consideration the
complexity of the
syndrome.

45. Combined therapy may be
the first line approach in
overweight PCOS
European Review for Medical and
Pharmacological Sciences

46. ADDRESS
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