DOI: https://doi.org/10.18370/2309-4117.2020.52.18-22

Optimization of ovarian function and metabolic status in syndrome of polycystic ovaries

Т. Ф Татарчук, Н. В. Косей, Т. М. Тутченко, М. І. Гламазда

Abstract


Objective: to evaluate the effect of the Quinofolic complex (myo-inositol 500 mg, D-chiro-inositol 12.5 mg, methyltetrahydrofolate 250 mcg) on ovarian function, metabolic status and biochemical hyperandrogenism in women with classic phenotypic phenotype of polycystic ovary syndrome (PCOS) and insulin resistance.

Materials and methods. An open comparative study was conducted in 60 women of early/active reproductive age diagnosed with PCOS (classic phenotypic form) and laboratory confirmed insulin resistance, divided into 2 groups: study group received recommendations for lifestyle modification in accordance with clinical guidelines 2018, as well as Quinofolic in a dose of 2 capsules per day; control group received similar recommendations for lifestyle modification and folic acid, similar to the one in Quinofolic for 6 months. End points of the study were: duration of intermenstrual intervals and ultrasonographic signs of ovulation; dynamics of HOMA index, waist/hip ratio, free testosterone index.

Results. At the end of the third month of treatment statistically significant reduction of intermenstrual intervals was recorded in the study group: 45.6 ± 3.2 vs 68.9 ± 8.2 days before treatment. At the end of the sixth month of treatment, the average duration of intermenstrual intervals in the study group was 32.6 ± 2.8 days. Also, the average duration of intermenstrual intervals in the study group differed statistically significantly from the control group: 45.6 ± 3.2 vs 68.2 ± 5.6 days at the end of the 3rd month and 32.6 ± 2.8 vs 56.6 ± 4 8 days at the end of the sixth month. Average duration of intermenstrual intervals in the control group at the end of the third month did not show statistically significant dynamics. The dynamics of waist/hip ratio decrease in the study and control groups was comparable, but these changes were not statistically significant compares to values before the intervention in both groups. At the same time in the study group, a statistically significant decrease of HOMA index and free testosterone index were recorded synchronously with a decrease in waist/hip ratio. Despite the significant effect of lifestyle modification in individual participants in the control group, the average HOMA index and level of free testosterone index did not show statistically significant changes.

Conclusions. Results of the study combined with data on the effectiveness of the combined use of inositol isomers myo-inositol/D-chiro-inositol ratio = 40:1 confirm the feasibility of their use to improve folliculogenesis, reduce hyperandrogenism and insulin resistance in women with PCOS.


Keywords


polycystic ovary syndrome; insulin resistance; anovulation; inositol

References


Rocha, A.L., et al. “Recent advances in the understanding and management of polycystic ovary syndrome.” F1000Research 8 (2019): 565.

Teede, H.J., et al. “Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.” Hum Reprod 33.9 (2018): 1602–18.

Barber, T.M., Franks, S. “Genetic and Environmental Factors in the Etiology of Polycystic Ovary Syndrome.” In: The Ovary. Elsevier (2019): 437–59.

Pundir, J., et al. “Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials.” BJOG: An International Journal of Obstetrics and Gynaecology 125.3 (2018): 299–308.

Food and Drug Administration. Food Ingredients & Packaging. Available from: [https://www.fda.gov/food/food-ingredients-packaging], last accessed Apr 14, 2020.

Carlomagno, G., Unfer, V. “Inositol safety: Clinical evidences.” European Review for Medical and Pharmacological Sciences 15.8 (2011): 931–6.

Nehra, J., et al. “A comparative study of efficacy and safety of myo-inositol versus metformin in polycystic ovarian syndrome in women.“ World Journal of Pharmacy and Pharmaceutical Sciences 5.5 (2016): 884-896

Vitagliano, A., et al. “Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials Omega-3 and fish oil supplementation in pregnancy.” Artic Arch Gynecol Obstet 299.1 (2018): 55–68.

Haesler, E. “Buprenorphine for the management of opioid withdrawal.” In: Public Health Concern: Smoking, Alcohol and Substance Use. Nova Science Publishers, Inc. (2013): 189–93.

Shears, S.B. “Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling.” Journal of Cellular Physiology 233.3 (2018): 1897–912.

Bizzarri, M., Fuso, A., Dinicola, S., et al. “Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease.” Expert Opinion on Drug Metabolism and Toxicology 12.10 (2016): 1181–96.

Laganà, A.S., Garzon, S., Casarin, J., et al. “Inositol in Polycystic Ovary Syndrome: Restoring Fertility through a Pathophysiology-Based Approach.” Trends in Endocrinology and Metabolism 29.11 (2018): 768–80.

Monastra, G., Unfer, V., Harrath, A.H., Bizzarri, M. “Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients.” Gynecological Endocrinology 33.1 (2017): 1–9.

Bevilacqua, A., Dragotto, J., Giuliani, A., Bizzarri, M. “Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model.” J Cell Physiol 234.6 (2019): 9387–98.

Minambres, I., Cuixart, G., Goncalves, A., Corcoy, R. “Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials.” Clin Nutr 38.3 (2019): 1146–52.

Facchinetti, F., Orrù, B., Grandi, G., Unfer, V. “Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials.” Gynecological Endocrinology 35.3 (2019): 198–206.

Stepto, N.K., et al. “Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp.” Hum Reprod 28.3 (2013): 777–84.

Shorakae, S., et al. “Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS.” Clin Endocrinol (Oxf) 89.5 (2018): 628–33.

Azziz, R., et al. “Polycystic ovary syndrome.” Nature Reviews Disease Primers 2.1 (2016): 1–18.

Ibáñez, L., et al. “An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.” Hormone Research in Paediatrics 88.6 (2017): 371–95.

Cassar, S., Misso, M.L., Hopkins, W.G., et al. “Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies.” Hum Reprod 31.11 (2016): 2619–31.

Wang, Z.V., Scherer, P.E. “Adiponectin, the past two decades.” J Mol Cell Biol 8.2 (2016): 93–100.

Condorelli, R.A., et al. “Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.” Journal of Endocrinological Investigation 41.4 (2018): 383–8.

Luhrs, A.R., et al. “Determining changes in bone metabolism after bariatric surgery in postmenopausal women.” Surg Endosc (2019).

Fruzzetti, F., Perini, D., Russo, M., et al. “Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS).” Gynecol Endocrinol 33.1 (2017): 39–42.

Larner, J. “D-chiro-inositol-its functional role in insulin action and its deficit in insulin resistance.” Int J Exp Diabetes Res 3.1 (2002): 47–60.

Baillargeon, J.P., Diamanti-Kandarakis, E., Ostlund, R.E., et al. “Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome.” Diabetes Care 29.2 (2006): 300–5.

Costantino, D., Minozzi, G., Minozzi, F., Guaraldi, C. “Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: A double-blind trial.” Eur Rev Med Pharmacol Sci 13.2 (2009): 105–10.

Januszewski, M., Issat, T., Jakimiuk, A.A., et al. “Metabolic and hormonal effects of a combined Myo-inositol and D-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS).” Ginekol Pol 90.1 (2019): 7–10.

Nordio, N., Basciani, S., Camajani, E. “The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: Comparison with other ratios.” Eur Rev Med Pharmacol Sci 23.12 (2019): 5512–21.


GOST Style Citations


1.            Rocha, A.L., et al. “Recent advances in the understanding and management of polycystic ovary syndrome.” F1000Research 8 (2019): 565.

2.            Teede, H.J., et al. “Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.” Hum Reprod 33.9 (2018): 1602–18.

3.            Barber, T.M., Franks, S. “Genetic and Environmental Factors in the Etiology of Polycystic Ovary Syndrome.” In: The Ovary. Elsevier (2019): 437–59.

4.            Pundir, J., et al. “Inositol treatment of anovulation in women with polycystic ovary syndrome: a meta-analysis of randomised trials.” BJOG: An International Journal of Obstetrics and Gynaecology 125.3 (2018): 299–308.

5.            Food and Drug Administration. Food Ingredients & Packaging. Available from: [https://www.fda.gov/food/food-ingredients-packaging], last accessed Apr 14, 2020.

6.            Carlomagno, G., Unfer, V. “Inositol safety: Clinical evidences.” European Review for Medical and Pharmacological Sciences 15.8 (2011): 931–6.

7.            Nehra, J., et al. “A comparative study of efficacy and safety of myo-inositol versus metformin in polycystic ovarian syndrome in women.“ World Journal of Pharmacy and Pharmaceutical Sciences 5.5 (2016): 884-896

8.            Vitagliano, A., et al. “Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials Omega-3 and fish oil supplementation in pregnancy.” Artic Arch Gynecol Obstet 299.1 (2018): 55–68.

9.            Haesler, E. “Buprenorphine for the management of opioid withdrawal.” In: Public Health Concern: Smoking, Alcohol and Substance Use. Nova Science Publishers, Inc. (2013): 189–93.

10.          Shears, S.B. “Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling.” Journal of Cellular Physiology 233.3 (2018): 1897–912.

11.          Bizzarri, M., Fuso, A., Dinicola, S., et al. “Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease.” Expert Opinion on Drug Metabolism and Toxicology 12.10 (2016): 1181–96.

12.          Laganà, A.S., Garzon, S., Casarin, J., et al. “Inositol in Polycystic Ovary Syndrome: Restoring Fertility through a Pathophysiology-Based Approach.” Trends in Endocrinology and Metabolism 29.11 (2018): 768–80.

13.          Monastra, G., Unfer, V., Harrath, A.H., Bizzarri, M. “Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients.” Gynecological Endocrinology 33.1 (2017): 1–9.

14.          Bevilacqua, A., Dragotto, J., Giuliani, A., Bizzarri, M. “Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model.” J Cell Physiol 234.6 (2019): 9387–98.

15.          Minambres, I., Cuixart, G., Goncalves, A., Corcoy, R. “Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials.” Clin Nutr 38.3 (2019): 1146–52.

16.          Facchinetti, F., Orrù, B., Grandi, G., Unfer, V. “Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials.” Gynecological Endocrinology 35.3 (2019): 198–206.

17.          Stepto, N.K., et al. “Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp.” Hum Reprod 28.3 (2013): 777–84.

18.          Shorakae, S., et al. “Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS.” Clin Endocrinol (Oxf) 89.5 (2018): 628–33.

19.          Azziz, R., et al. “Polycystic ovary syndrome.” Nature Reviews Disease Primers 2.1 (2016): 1–18.

20.          Ibáñez, L., et al. “An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.” Hormone Research in Paediatrics 88.6 (2017): 371–95.

21.          Cassar, S., Misso, M.L., Hopkins, W.G., et al. “Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies.” Hum Reprod 31.11 (2016): 2619–31.

22.          Wang, Z.V., Scherer, P.E. “Adiponectin, the past two decades.” J Mol Cell Biol 8.2 (2016): 93–100.

23.          Condorelli, R.A., et al. “Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.” Journal of Endocrinological Investigation 41.4 (2018): 383–8.

24.          Luhrs, A.R., et al. “Determining changes in bone metabolism after bariatric surgery in postmenopausal women.” Surg Endosc (2019).

25.          Fruzzetti, F., Perini, D., Russo, M., et al. “Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS).” Gynecol Endocrinol 33.1 (2017): 39–42.

26.          Larner, J. “D-chiro-inositol-its functional role in insulin action and its deficit in insulin resistance.” Int J Exp Diabetes Res 3.1 (2002): 47–60.

27.          Baillargeon, J.P., Diamanti-Kandarakis, E., Ostlund, R.E., et al. “Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome.” Diabetes Care 29.2 (2006): 300–5.

28.          Costantino, D., Minozzi, G., Minozzi, F., Guaraldi, C. “Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: A double-blind trial.” Eur Rev Med Pharmacol Sci 13.2 (2009): 105–10.

29.          Januszewski, M., Issat, T., Jakimiuk, A.A., et al. “Metabolic and hormonal effects of a combined Myo-inositol and D-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS).” Ginekol Pol 90.1 (2019): 7–10.

30.          Nordio, N., Basciani, S., Camajani, E. “The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: Comparison with other ratios.” Eur Rev Med Pharmacol Sci 23.12 (2019): 5512–21.





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