6. Global prevalence -2.2% to 26%
Roughly 1 in 15 women worldwide, (Lancet, 2007)
36% of women in
India are suffering
from PCOS
Indian J Pediatr. 2012 Jan;79 Suppl 1:S69-73. J Pediatr Adolesc Gynecol. 2011 Aug;24(4):223-7
7. PCOD is a metabolic syndrome
with reproductive implications
Huge impact on the
reproductive , metabolic , and
cardiovascular health of affected
girls and women
“Thief of womanhood”
9. Clinical manifestation of PCOD
Acne Acantosis Hirsutism Obesity
Infertility
HAIR LOSS
IRREGULAR MENSES
10. THREE MAJOR CULPRITS
Central player : Insulin Resistance
• Hyperandrogenism
• altered gonadotropins
• Recently target genes
All interact with each other
11. Insulin Resistance
A pathophysiological contributor in
50 – 80 % of the PCOS women
Indian J Endocrinol Metab. 2011 Oct-Dec; 15(4): 239–241.
12. Insulin resistance is independent of body
fat and
Is seen both in obese and lean PCOD
Indian Journal of Endocrinology and Metabolism, 2011
14. Insulin signaling transduction pathway
GLU T 4
I
R
IRS
Glucose
I= Insulin R = Receptor IRS= Insulin Receptor Substrate
GLUT 4= Glucose Transporter 4
15. 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 GLUT 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.
21. Phosphatidyl inositol 3-kinase is the key
messenger
• We need production & activation of PI 3 kinase
for normal cell glucose metabolism.
• Inositol both produces and 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
23. Inositol levels in PCOS and Normal women
0.2
0.18
0.16
0.14
0.12
0.1
0.08
0.06
0.04
0.02
0
Plasma inositol (μmol/l) 24 h urinary inositol ((μmol/l/day)
0.1
0.19
p=0.035
PCOS Subjects Normal Subjects
2.5
2
1.5
1
0.5
0
2.3
0.7
p= 0.043
PCOS Subjects Normal Subjects
Diabetes Care 2006;29:300–305
Normal Plasma inositol (μmol/l) levels – 0.13-0.28
24. Inositol clearance levels in PCOS and
16
14
12
10
8
6
4
2
0
Normal women
PCOS Subjects Normal
Subjects
15.3
2.7
p= 0.001
Diabetes Care 29:300–305, 2006
Urinary clearance of Inositol
(ml/min)
5 times more
Urinary
clearance of
Inositol in PCOS
25. Deficiency of Inositol decreases
PI3 kinase activity
Glucose
PI3 kinase
IRS
Translocation of
GLUT4
GLUT4
Deficiency of
Inositol decreases
PI3 kinase activity
I
R
26. Thus Metformin acton is limited due to
decreased Inositol levels
Glucose
PI3 kinase
IRS
Translocation of
GLUT4
GLUT4
Inositol both produces
and activates PI3 kinase
I
R
Metformin acton is limited
due to decreased Inositol
levels
31. Inositol was first identified in India, from
Bougainvillea leaves (Mol. Med., 2010).
Myoinositol, a six carbon
sugar alcohol, present
abundantly in the body.
An important component
ofcellular membrane lipids
Is essential for the
smooth running of a
variety of cell functions
32. It is commonly found in
fruits (grapefruit the highest),
vegetables (leafy vegetables the lowest)
and in all foods containing seeds
(beans, almonds and walnuts the highest).
35. • 50 overweight PCOS
patients
• Group A : MYO 2 g / day
• Group B : Folic acid 200 mg
as placebo
• Duration: For 12 weeks
Gynecol Endocrinol, 2013; 29(4): 375–379
36. Myo-inositol decreases
both insulin and BMI
p<0.005
No changes were seen in the patients treated with folic acid
Gynecol Endocrinol, 2013; 29(4): 375–379
37. After 12 weeks of MYO administration, Insulin
sensitivity and HOMA index is significantly
improved.
56%
reduction
Gynecol Endocrinol, 2013; 29(4): 375–379
38. HOMA -IR
• Homeostasis Model Assessment
Is used to predict relationship between beta-cell
deficiency and insulin resistance.
Normal HOMA-IR < 3
HOMA-IR ≥ 2.5 is considered a reasonable indicator of IR
Journal o f Diabetes Investigation Volume 2 Issue 5 October 2011
39.
40. Myo-inositol shows significant reduction in
both Total and free testesterone levels
48 %
Reduction
in total
Testosterone
p<0.001 p<0.001
62%
Reduction
in free
Testosterone
Gynecological Endocrinology, August 2009; 25(8): 508–513
41. Efficacy of myo-inositol in the Rx of cutaneous
disorders in women with polycystic ovary syndrome.
Zacchè MM, Caputo L, Filippis S, Zacchè G, Dindelli M, Ferrari A.
Gynecological-Obstetric Department, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy.
. 50 patients with PCOS were enrolled in the study. BMI, LH, FSH, insulin,
HOMA index, androstenedione, testosterone, free testosterone, hirsutism and
acne were evaluated at the baseline and after receiving MYO therapy for 6
months.
RESULTS:
After 3 months of MYO administration, plasma LH, testosterone, free
testosterone, insulin and HOMA index resulted significantly reduced; no
significant changes were observed in plasma FSH and androstenedione levels.
Both hirsutism and acne decreased after 6 months of therapy.
DISCUSSION:
MYO administration is a simple and safe treatment that ameliorates the
metabolic profile of patients with PCOS, reducing hirsutism and acne.
PMID: 19551544 [PubMed - indexed for MEDLINE]
Gynecological Endocrinology, August 2009; 25(8): 508–513
42. Myo-inositol shows signification
disappearance of hirsutism and acne
Hirsutism Acne
16 - 30%
reduction in Hirsutism
21 - 53%
reduction in Acne
Percent reduction
Gynecological Endocrinology, August 2009; 25(8): 508–513
43.
44. Myo-inositol gives
65% reduction in
testosterone levels
69% patients
ovulated with Myo-inositol
acid
European Review for Medical and Pharmacological Sciences 2009; 13: 105-110
45. 40 % of pregnancies with Myo-inositol
and
90% of pregnancies with fetal heart beat
Gynecol Endocrinol. 2007;23(12):700-703
100
80
60
40
20
0
88
72
40
90
Restored MC Maintained
normal ovulation
Singleton pregnancies Pregnancies with fetal heart beat
Percentage of women
Two pregnancies resulted in spontaneous abortion
46. Myo-inositol offers better clinical pregnancy
rate and delivery rate as compared to placebo
p<0.05
Gynecol Endocrinol, 2013; 29(4): 375–379
47. Myo-inositol shows significant improvement
in metabolic characteristics
Myo-inositol grp Placebo group
Characteristics Baseline After
treatment
Baseline After
treatment
p value
Systolic blood
pressure (mm Hg)
131 127 128 130 0.002
Diastolic Blood
pressure (mm Hg)
88 82 86 90 0.001
Triglycerides
(mg/dl)
195 95 166 148 0.001
Total cholesterol
(mg/dl)
210 171 195 204 0.001
European Review for Medical and Pharmacological Sciences 2009; 13: 105-110
48. 25 PCOS women
• 28 to 38 age years of age
• Characteristics: Hyperandogenemia (elevated levels of total
or free testosterone) Or Oligo- or amenorrhea (six or fewer
menstrual cycles during a period of 1 year).
• Duration: 6 months of treatment
Gynecol Endocrinol. 2007;23(12):700-703
49. • Myo-inositol is a simple and safe treatment capable
of restoring spontaneous ovarian activity .
• This therapy did not cause multiple pregnancy.
Gynecol Endocrinol. 2007;23(12):700-703
50.
51. Myo-inositol for Ovulation
induction
75 infertile women with PCOS
n=36
Myo-inositol plus folic acid
n=39
50 mg clomiphene citrate
daily for 5 days
Follow-up after 6 months
52. 35
30
25
20
15
10
5
0
Pregnancy rate Multiple
pregnancy
33.3
0
28.2
18.1
Rate (%)
Myo-inositol
Clomiphene citrate
Results
Myo-inositol is a simple & safe treatment &
should be primary
method of inducing ovulation in PCOS women
53. Effects of inositol in IVF cycles
Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F.
Source
Sezione di Ginecologia, Dipartimento di Scienze Microbiologiche e Scienze Ginecologiche, Ospedale Santo BambinoUniversità degli
Studi di Catania, Catania, Italia.
METHODS: The patients were divided into two groups: patients of Group A intook 2 g of myo-inositol + 400 μg
of folic acid 2 times a day, continuously for 3 months, while Group B only 400 μg of folic acid.
RESULTS AND CONCLUSION: At the end of treatment, the number
of follicles of diameter >15 mm, visible at ultrasound during
stimulation, and the number of oocytes recovered at the time
of pick-ups were found to be significantly greater in the
group treated with myo-inositol, so as the average number of
embryos transferred and embryo Grade G1. Significantly
reduced was the average number of immature
oocytes (vesicles germ and degenerated oocytes)
too.
Minerva Ginecol. 2010 Dec;62(6):525-31.
55. In IVF progammes
• Improves both the
quality and the
number of mature
oocytes.
• Significant reduction in
number of immature
oocytes.
• Reduces rFSH dosage by
400 IU
• Reduces the chances
of OHSS
• Reduces the number of
wasted IVF cycle
59. Superiority of Myo-inositol over Metformin
Hyperinsulinemic
PCOS women
Metformin N= 123 6 month therapy Inositol N=50
patients on inositol showed significant improvement in
the menstrual frequency and reduction in insulin levels
Better tolerability
Better patient compliance than Metformin
Fertility and Sterility. 2006 September 86,( 3) Supplement 1,S461
62. OCP’s Vs Myo - inositol
• OCP’s are used to control menstrual
irregularity and hyperandrogenism.
• They donot improve the root cause of
IR hence no metabolic advantage
• Can’t be used to improve pregnancy rates
• Decrease insulin sensitivity (Human Reprod., 2005).
This makes Myoinositol
superior to OCP’s
Expert rev. clin. Pharmacol. Early online , 1-9 ( 2014 )
63. No drug interactions documented yet
• Start the treatment as
soon as the diagnosis
of PCOD is made
• Dose is - 2 gm twice
daily
• Duration of Rx is 3
months to 1 year
• Action starts within 3
months
• Safe in pregnancy
• If taken as powder ,
presence of caffiene
decreases its
absorption
Caffeine-induced MYO malabsorption
64.
65. Side - effects
MYO supplementation
is well tolerated and
safe both in obese &
lean PCOD pts.
Side effects, when
present, are mild and
mainly gastrointestinal
(nausea, flatus,
diarrhea).
• Not only safe in
pregnancy but
beneficial.
• Reduces chances of
neural tube
defects.
• Improvement in
gestational diabetes
Gynecol Endocrinol. 2012 Jun;28(6):440-2.
66. 84 gestational diabetes patients
24 received myo-inositol plus folic acid
45 received folic acid 400 mcg/day
All received same diet treatment recommendation according to
American Diabetes Association
recommendations
Duration of treatment: 8 weeks
Myo-inositol supplementation is a simple
and safe step in the treatment of
gestational diabetes
Diabet Med. 2011 Aug;28(8):972-5
67. MYO-INOSITOL - takes
TOTAL CARE OF SYMPTOMS
Improves
insulin
sensitivity Decreases
Myo-inositol
insulin
resistance
levels
Improves
glucose
utilization
Reduces free
testosterone
Restores
menstruation
and normal
ovulation
Improves
pregnancy
rate
