Newer concepts of managing PCOD With Myo-Inositol

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Newer concepts of managing PCOD With Myo-Inositol

  1. 1. Newer concepts of managing With Myo-Inositol Dr. Jyoti Agarwal Dr. Sharda Jain Dr. Jyoti Bhaskar
  2. 2. Is our understanding of polycystic ovary syndrome better now ??? Stein - leventhal
  3. 3. Answer: Surely YES
  4. 4. Tremendous advances and extensive human studies have uncovered the complexity of PCOD
  5. 5. 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
  6. 6. 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”
  7. 7. Thus there is a need for their Care
  8. 8. Clinical manifestation of PCOD Acne Acantosis Hirsutism Obesity Infertility HAIR LOSS IRREGULAR MENSES
  9. 9. THREE MAJOR CULPRITS Central player : Insulin Resistance • Hyperandrogenism • altered gonadotropins • Recently target genes All interact with each other
  10. 10. Insulin Resistance A pathophysiological contributor in 50 – 80 % of the PCOS women Indian J Endocrinol Metab. 2011 Oct-Dec; 15(4): 239–241.
  11. 11. Insulin resistance is independent of body fat and Is seen both in obese and lean PCOD Indian Journal of Endocrinology and Metabolism, 2011
  12. 12. Difficult to deduce “ Cause and Effect ”
  13. 13. Insulin signaling transduction pathway GLU T 4 I R IRS Glucose I= Insulin R = Receptor IRS= Insulin Receptor Substrate GLUT 4= Glucose Transporter 4
  14. 14. 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.
  15. 15. Insulin acts like a key which can open the door on the cell surface
  16. 16. But, is it effective ???
  17. 17. Insulin signaling transduction Glucose enzymatic pathway PI3 kinase IRS Translocation of GLUT4 GLUT4 Metformin stimulates YES I R
  18. 18. But Evidence Says Something Else !!!!!!!! Cochrane Database Curr Opin Endocrinol Diabetes Obes. 2012 Dec;19(6):505-11 Syst Rev. 2010 Jan 20
  19. 19. Why do they SAY so ????
  20. 20. 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
  21. 21. DIABETES CARE 2006, 29, 300-305
  22. 22. 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
  23. 23. 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
  24. 24. Deficiency of Inositol decreases PI3 kinase activity Glucose PI3 kinase IRS Translocation of GLUT4 GLUT4 Deficiency of Inositol decreases PI3 kinase activity I R
  25. 25. 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
  26. 26. What to do ?
  27. 27. Think about Alternatives !!!
  28. 28. Could inositols be considered to treat PCOD ???
  29. 29. YES Myoinositol ≅ Inositol
  30. 30. 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
  31. 31. 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).
  32. 32. Clinical Evidences for MYO-INOSITOL
  33. 33. Inositol Published papers per year (Total = >39,000) Source: PubMed, July 15th, 2014
  34. 34. • 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
  35. 35. 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
  36. 36. After 12 weeks of MYO administration, Insulin sensitivity and HOMA index is significantly improved. 56% reduction Gynecol Endocrinol, 2013; 29(4): 375–379
  37. 37. 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
  38. 38. 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
  39. 39. 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
  40. 40. 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
  41. 41. 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
  42. 42. 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
  43. 43. Myo-inositol offers better clinical pregnancy rate and delivery rate as compared to placebo p<0.05 Gynecol Endocrinol, 2013; 29(4): 375–379
  44. 44. 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
  45. 45. 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
  46. 46. • 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
  47. 47. 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
  48. 48. 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
  49. 49. 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.
  50. 50. Gynecological Endocrinology, 2012; 28(7): 509–515
  51. 51. 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
  52. 52. International society says….. 2 0 1 2 2 0 1 2
  53. 53. Comparing efficacy and safety of Inositols against commonly used Rx of PCOD
  54. 54. Will the treatment outcome be at par with metformin ?? PCOS
  55. 55. 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
  56. 56. MYO-INOSITOL and METFORMIN
  57. 57. Will the treatment outcome be at par with OCP’s?? PCOS
  58. 58. 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 )
  59. 59. 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
  60. 60. 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.
  61. 61. 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
  62. 62. 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
  63. 63. “ RAM BAAN ”……aushadhi
  64. 64. Not enough data is available to support use in patients other than PCOS But its not the END OF THE STORY !!!!!

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