Inositols for PCOS : An...
Transcript of Inositols for PCOS : An...
![Page 1: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/1.jpg)
Mark H. Ratner, MD Shady Grove Reproductive Science Center
Rockville, Maryland
Inositols for PCOS : An Update
![Page 2: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/2.jpg)
▪ Understanding the role of insulin in PCOS
▪ The relationship between inositols and insulin
▪ Inositols for PCOS : Published studies
▪ Practical considerations
Overview
![Page 3: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/3.jpg)
Understanding the role of insulin
![Page 4: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/4.jpg)
▪ A hormone produced by the pancreas that regulates glucose metabolism
Understanding the role of insulin
![Page 5: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/5.jpg)
GLUCOSE
![Page 6: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/6.jpg)
GLUCOSE
SECOND MESSENGERS
![Page 7: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/7.jpg)
GLUCOSE
SECOND MESSENGERS
![Page 8: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/8.jpg)
GLUCOSE
SECOND MESSENGERS
Energy production
![Page 9: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/9.jpg)
GLUCOSE
SECOND MESSENGERS
Energy production
Energy storage
![Page 10: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/10.jpg)
So, what can go wrong??
![Page 11: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/11.jpg)
GLUCOSE
Type 1 diabetes
![Page 12: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/12.jpg)
GLUCOSE
SECOND MESSENGERS
Insulin resistance
![Page 13: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/13.jpg)
▪ A hormone produced by the pancreas that regulates glucose metabolism
▪ Insulin resistance (IR) is present in 70-80% of women with PCOS – Increased blood sugar (“hyperglycemia”) – Increased serum insulin levels (“hyperinsulinemia”)
▪ Increased serum insulin levels then cause the ovary to produce increased amounts of testosterone
▪ Increased serum insulin and testosterone interfere with ovulation
Understanding the role of insulin
![Page 14: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/14.jpg)
Metformin and PCOS
![Page 15: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/15.jpg)
Metformin and PCOS
▪ Metformin is an insulin sensitizing drug
▪ Improves function of second messengers, and reduces insulin resistance
▪ Reduces hyperinsulinemia and testosterone overproduction
▪ Common side effects: – Bloating
– Nausea
– Diarrhea
– Loss of appetite
![Page 16: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/16.jpg)
▪ Understanding the role of insulin in PCOS
▪ The relationship between inositols and insulin
▪ Inositol for PCOS : Published studies
▪ Practical considerations
Overview
![Page 17: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/17.jpg)
Inositols
![Page 18: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/18.jpg)
Inositols
▪ 6-carbon sugars - similar to mannitol and sorbitol
▪ 9 different types of inositols – “stereoisomers”
![Page 19: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/19.jpg)
![Page 20: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/20.jpg)
![Page 21: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/21.jpg)
Inositols
▪ 6-carbon sugars - similar to mannitol and sorbitol
▪ 9 different types of inositols – “stereoisomers”
▪ Myo-inositol (MYO) and d-chiro inositol (DCI) are key components of the “second messengers”
![Page 22: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/22.jpg)
GLUCOSE
SECOND MESSENGERS
Insulin resistance
![Page 23: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/23.jpg)
GLUCOSE
SECOND MESSENGERS
Insulin resistance
![Page 24: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/24.jpg)
GLUCOSE
SECOND MESSENGERS
Insulin resistance
![Page 25: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/25.jpg)
Inositols
▪ 6-carbon sugars - similar to mannitol and sorbitol
▪ 9 different types of inositols – “stereoisomers”
▪ The insulin receptor’s “second messengers” contain myo-inositol (MYO) and d-chiro inositol (DCI)
▪ Supplementing with MYO and DCI will improve insulin receptor “signaling” and reduce insulin resistance
▪ First inositol/PCOS clinical trial published in 1999 by Nestler, et al, using DCI alone
![Page 26: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/26.jpg)
▪ Understanding the role of insulin in PCOS
▪ The relationship between inositols and insulin
▪ Inositol for PCOS : Published studies
▪ Practical considerations
Overview
![Page 27: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/27.jpg)
Zacche MM, et al, “Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with PCOS”, Gynecol Endocrinology, 2009, 25:8, 508-13
▪ 50 women with PCOS
▪ Treated with 4 g MYO for 3 months
![Page 28: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/28.jpg)
Zacche MM, et al, “Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with PCOS”, Gynecol Endocrinology, 2009, 25:8, 508-13
▪ 50 women with PCOS
▪ Treated with 4 g MYO for 3 months
▪ Testosterone decreased 30% w/ MYO treatment (p=.001)
▪ Insulin resistance decreased 50% (p=.005)
![Page 29: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/29.jpg)
Zacche MM, et al, “Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with PCOS”, Gynecol Endocrinology, 2009, 25:8, 508-13
▪ 50 women with PCOS
▪ Treated with 4 g MYO for 3 months
▪ Testosterone decreased 30% w/ MYO treatment (p=.001)
▪ Insulin resistance decreased 50% (p=.005)
▪ 30% of patients had disappearance of hirsutism
▪ 53% of patients had resolution of acne
![Page 30: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/30.jpg)
Minozzi, et al, “The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill vs. a combination oral contraceptive pill alone on metabolic, endocrine and clinical parameters in PCOS”, Gyn Endoc, 2011, 27:11, 920-924
▪ 155 women with PCOS
▪ Randomized to treatment with either BCP+MYO or BCP alone
![Page 31: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/31.jpg)
Minozzi, et al, “The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill vs. a combination oral contraceptive pill alone on metabolic, endocrine and clinical parameters in PCOS”, Gyn Endoc, 2011, 27:11, 920-924
▪ 155 women with PCOS
▪ Randomized to treatment with either BCP+MYO or BCP alone
Birth Control Pill Birth Control Pill
+ Myo-inositol
Reduction in testosterone
29% 44% P<.05
Reduction in insulin resistance
7% 38% P<.05
![Page 32: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/32.jpg)
Costantino, et al, “Metabolic and hormonal effects of myo-inositol in women with PCOS: a double blind trial”, Eur Rev Med Pharmacol Sci, 2009, 13:2, 105-10
▪ 42 women with PCOS
▪ Randomized to either 4 grams MYO daily or placebo
![Page 33: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/33.jpg)
Costantino, et al, “Metabolic and hormonal effects of myo-inositol in women with PCOS: a double blind trial”, Eur Rev Med Pharmacol Sci, 2009, 13:2, 105-10
▪ 42 women with PCOS
▪ Randomized to either 4 grams MYO daily or placebo
▪ Testosterone decreased 65% in MYO group (p=.003)
▪ Insulin sensitivity increased 80% in MYO group (p=.001)
![Page 34: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/34.jpg)
Costantino, et al, “Metabolic and hormonal effects of myo-inositol in women with PCOS: a double blind trial”, Eur Rev Med Pharmacol Sci, 2009, 13:2, 105-10
▪ 42 women with PCOS
▪ Randomized to either 4 grams MYO daily or placebo
▪ Testosterone decreased 65% in MYO group (p=.003)
▪ Insulin sensitivity increased 80% in MYO group (p=.001)
▪ 70% of subjects in MYO group ovulated during study, compared to 21% in the placebo group
![Page 35: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/35.jpg)
Raffone, et al, “Insulin sensitizer agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women”, Gynecol Endocrinology, 2010, 26:4, 275-80
▪ 120 women with PCOS and chronic anovulation
▪ Randomized to treatment with either metformin or myo-inositol
![Page 36: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/36.jpg)
Raffone, et al, “Insulin sensitizer agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women”, Gynecol Endocrinology, 2010, 26:4, 275-80
▪ 120 women with PCOS and chronic anovulation
▪ Randomized to treatment with either metformin or myo-inositol
Ovulation rate Pregnancy rate
Metformin 50% 18%
Myo-inositol 65% 30%
![Page 37: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/37.jpg)
Raffone, et al, “Insulin sensitizer agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women”, Gynecol Endocrinology, 2010, 26:4, 275-80
▪ 120 women with PCOS and chronic anovulation
▪ Randomized to treatment with either metformin or myo-inositol
Ovulation rate Pregnancy rate
Metformin 50% 18%
Myo-inositol 65% 30%
Clomiphene (Legro, 2014) 48% 19%
![Page 38: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/38.jpg)
Raffone, et al, “Insulin sensitizer agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women”, Gynecol Endocrinology, 2010, 26:4, 275-80
▪ 120 women with PCOS and chronic anovulation
▪ Randomized to treatment with either metformin or myo-inositol
Ovulation rate Pregnancy rate
Metformin 50% 18%
Myo-inositol 65% 30%
Clomiphene (Legro, 2014) 48% 19%
Letrozole (Legro,2014) 62% 28%
![Page 39: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/39.jpg)
Colazingari, et al, “The combined therapy MYO plus DCI, rather than DCI, is able to improve IVF outcomes: results from a randomized controlled trial”, Arch Gyn Obstet, 2013, 288: 1405-1411
▪ 100 women with PCOS and undergoing IVF
▪ Randomized to treatment with either MYO+DCI, or, DCI alone
▪ Combined treatment group had better embryo quality and higher fertilization and pregnancy rate
![Page 40: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/40.jpg)
MYO and DCI play different roles
▪ MYO and DCI are both inositols, but are VERY different molecules
▪ Each produces a different second messenger
▪ MYO improves ovarian function
▪ DCI improves metabolic function in the peripheral tissues
▪ Combined treatment with MYO and “low-dose” DCI together appears to be more effective than either alone
![Page 41: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/41.jpg)
Inositols for PCOS: Practical Concerns
▪ The combination of myo-inositol and d-chiro inositol is an effect treatment for PCOS – 2-4 grams of MYO/day
– 50-100 mg of DCI/day
▪ Safe, inexpensive and completely free of side effects
▪ Available without prescription, as OTC dietary supplements
![Page 42: Inositols for PCOS : An Updatepcoschallenge.org/symposium/2015-los-angeles-presentations/ratner... · Mark H. Ratner, MD Shady Grove Reproductive Science Center Rockville, Maryland](https://reader031.fdocuments.in/reader031/viewer/2022011802/5b1601157f8b9a472e8c5f02/html5/thumbnails/42.jpg)
Questions?