CLINICAL EXPERIENCE WITH DLBS3233, A COMBINATION OF CINNAMOMMUM BURMANNII AND LAGERSTROEMIA SPECIOSA, FOR POLYCYSTIC OVARY SYNDROME TREATMENT
Objective: DLBS3233, a new insulin sensitizing agent for Type 2 diabetes, is a combination-bioactive-fraction derived from two herbs, i.e., Lagerstroemia
speciosa and Cinnamomum burmannii. Since insulin resistance plays a central pathogenic role in polycystic ovary syndrome (PCOS), DLBS3233 has the
potential to benefit women with such a condition, in whom menstrual irregularity, chronic anovulation or infertility are manifested. This clinical study
was performed to evaluate the clinical efficacy of DLBS3233 as a single pharmacological therapy in improving follicle maturity in women with PCOS
measured by a transvaginal ultrasonography (USG).
Methods: The open study enrolled 14 PCOS subjects from the Obstetrics and Gynecology Department of Sam Ratulangi University/Prof. Dr. Kandou
Hospital, satellite hospitals, and private practices. Patients were measured for the dominant follicle diameter using transvaginal USG. Subjects were
given DLBSS3233 capsule at a dose of 1 capsule at 100 mg once daily for 30 days of the treatment. At the end of the study, patients' follicle diameters
were re-assessed. The difference in follicle diameters was compared within the group (within-subject) by paired t-test, with a significance level (Î±)
Results: Among 14 PCOS enrolled subjects, 57.2% aged between 26 and 30 years old. There were similar proportions of subjects with normal body
mass index (42.8%) and overweight(42.8%). Before treatment (at baseline), the mean follicle diameter was 4.094Â±1.016 mm. After 30 days of
treatment, it increased significantly to 8.594Â±1.647 mm (p<0.001 versus baseline). There were 10 subjects (71.4%) showed follicles with size ranging
between 5 and 10 mm, while the remaining 4 subjects (28.6%) had them bigger than 10 mm.
Conclusion: Through this study, DLBS3233 at the dose of 100 mg once daily for 30 days showed a potential benefit for PCOS patients, particularly in
improving follicle maturity expressed as an increased follicular diameter.
Keywords: DLBS3233, Cinnamomum burmannii, Follicle diameter, Lagerstroemia speciosa, Polycystic ovary syndrome.
Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. Int J Womenâ€™s Health. 2011;3:25-35. Available at URL: http://dx.doi.org/10.2147/IJWH.S11304
Pauli JM, Raja-Khan N, Wu X, Legro RS. Current perspectives of insulin resistance and polycystic ovary syndrome. Diabet Med. 2011;28:1445-54. Available at URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.2011.03460.x/abstract
Haffner SM, Dâ€™Agostino RJ, Festa A, Bergman RN, Mykkanen L, Karter A, et al. Low insulin sensitivity (S(i) = 0) in diabetic and nondiabetic subjects in the insulin resistance atherosclerosis study: is it associated with components of the metabolic syndrome and nontraditional risk factors? Diabetes Care. 2003;26:2796-803. Available at URL: http://care.diabetesjournals.org/content/26/10/2796.full.pdf
Hanley AJ, Dâ€™Agostino RJ, Wagenknecht LE, Saad MF, Savage PJ, Bergman R, et al. Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study. Diabetes. 2002;51:1263-70. Available a URL: http://diabetes.diabetesjournals.org/content/51/4/1263.full.pdf
Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90:1929-35. Available at URL: http://dx.doi.org/10.1210/jc.2004-1045
Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:48-53. Available at URL: http://dx.doi.org/10.1210/jc.2005-1329
Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism. 2003;52:908-15. Available at URL: http://www.metabolismjournal.com/article/S0026-0495(03)00104-5/abstract
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356-9. Available at URL: http://jama.jamanetwork.com/article.aspx?articleid=194559
Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes. 1992;41:715-22. Available at URL: http://diabetes.diabetesjournals.org/content/41/6/715.full.pdf
Isomaa B AP, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-9. Available at URL: http://dx.doi.org/10.2337/diacare.24.4.683
Trevisan M, Liu J, Bahsas FB, Menotti A, Group. RFaLER. Syndrome X and mortality: a population-based study. Am J Epidemiol. 1998;148:958-66. Available at URL: http://aje.oxfordjournals.org/content/148/10/958.long
Dunaif A. Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Med 1995;98:33S-9S. Available at URL: http://dx.doi.org/10.1097/00006254-199906000-00019
Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999;84:165-9.
Lo JC, Feigenbaum SL, Yang J, Pressman AR, Selby JV, Go AS. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91:1357-63. Available at URL: http://dx.doi.org/10.1210/jc.2005-2430
Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK. Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999;22:141-6. Available at URL: http://dx.doi.org/10.2337/diacare.22.1.141
DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril. 2005;83:1454-60. Available at URL: http://www.fertstert.org/article/S0015-0282(05)00373-0/abstract
Ghazeeri G, Kutteh WH, Bryer-Ash M, Haas D, Ke RW. Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome. Fertil Steril. 2003;79:562-6. Available at URL: http://www.fertstert.org/article/S0015-0282(02)04843-4/pdf
Ota H, Goto T, Yoshioka T, Ohyama N. Successful pregnancies treated with pioglitazone in infertile patients with polycystic ovary syndrome. Fertil Steril. 2008;90:709-13. Available at URL: http://www.fertstert.org/article/S0015-0282(07)00282-8/pdf
Aroda VR, Ciaraldi TP, Burke P, Mudaliar S, Clopton P, Phillips S, et al. Metabolic and Hormonal Changes Induced by Pioglitazone in Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Clinical Trial. J Clin Endocrinol Metab. 2009;94:469-76. Available at URL: http://dx.doi.org/10.1210/jc.2008-1133
Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180-8. Available at URL: http://dx.doi.org/10.1001/jama.298.10.1180
Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng A, et al. Risk of cardiovascular disease and all-cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b4731. Available at URL: http://www.bmj.com/content/bmj/339/bmj.b4731.full.pdf
Basu A, Jensen MD, McCann F, Mukhopadhyay D, Joyner MJ, Rizza RA. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Diabetes Care. 2006;29:510-4. Available at URL: http://dx.doi.org/10.2337/diacare.29.03.06.dc05-2004
Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004;351:1106-18. Available at URL: http://www.nejm.org/doi/pdf/10.1056/NEJMra041001
Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL, et al. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. Diabetes Care. 2000;23:1605-11. Available at URL: http://care.diabetesjournals.org/content/23/11/1605.long
Czoski-Murray C, Warren E, Chilcott J, Beverley C, Psyllaki MA, Cowan J. Clinical effectiveness and cost-effectiveness of pioglitazone and rosiglitazone in the treatment of type 2 diabetes: a systematic review and economic evaluation. Health Technol Assess. 2004;8:iii, ix-x, 1-91.
Tolman KG, Freston JW, Kupfer S, Perez A. Liver safety in patients with type 2 diabetes treated with pioglitazone: results from a 3-year, randomized, comparator-controlled study in the US. Drug Saf 2009;32:787-800. Available at URL: http://link.springer.com/article/10.2165%2F11316510-000000000-00000
Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med. 1998;338:916-7. Available at URL: http://www.nejm.org/doi/pdf/10.1056/NEJM199803263381314
Desouza CV, Shivaswamy V. Pioglitazone in the Treatment of Type 2 Diabetes: Safety and Efficacy Review. Clinical Medicine Insights: Endocrinology and Diabetes 2010;3:43-51. Available at URL: http://www.la-press.com/redirect_file.php?fileId=3000&filename=2194-CMED-Pioglitazone-in-the-Treatment-of-Type-2-Diabetes:-Safety-and-Efficacy-.pdf&fileType=pdf
Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicenter, randomized, open-label trial. Lancet. 2009;373:2125-35. Available at URL: http://dx.doi.org/10.1016/S0140-6736(09)60953-3
Schwartz AV, Sellmeyer DE, Vittinghoff E, Palermo L, Lecka-Czernik B, Feingold KR, et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006;91:3349-54. Available at URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563497/
Nailufar F, Tandrasasmita OM, Tjandrawinata RR. DLBS3233 increases glucose uptake by mediating upregulation of PPARÎ³ and PPARÎ´ expression. Biomedicine & Preventive Nutrition. 2011;1:71-8. Available at URL: http://dx.doi.org/10.1016/j.bionut.2010.12.002
Tandrasasmita OM, Wulan DD, Nailufar F, Sinambel J, Tjandrawinata RR. Glucose lowering effect of DLBS3233 is mediated through phosphorylation of tyrosine and upregulation of PPARÎ³and GLUT-4 expression. International Journal of General Medicine. 2011;4:345-57. Available at URL: https://www.dovepress.com/getfile.php?fileID=9955
Sukandar EY, Sigit JI, Adnyana IK. Acute Toxicity of DLBS3233. Bandung: Bandung Institute of Technology; 2008.
Sukandar EY, Sigit JI, Adnyana IK. Subchronic Toxicity of DLBS3233. Bandung: Bandung Institute of Technology, 2008.
Sukandar EY, Sigit JI, Adnyana IK. Teratogenic Effect of DLBS3233. Bandung: Bandung Institute of Technology, 2008.
Rotterdam E. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19-25. Available at URL: http://dx.doi.org/10.1016/j.fertnstert.2003.10.004
Sam S. Obesity and Polycystic Ovary Syndrome. Obes Manag 2007;3:69-73. Available at URL: http://dx.doi.org/10.1089/obe.2007.0019
Androgen Excess and PCOS Society. Obesity and Insulin Resitance. 2012. Available at URL: http://www.ae-society.org/obesity.
Brettenthaler N, De Geyter C, Huber PR, Keller U. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004;89:3835-Available at URL: http://dx.doi.org/10.1210/jc.2003-031737
Franco JG, Jr.,, Baruffi RLR, Mauri AL, Petersen CG, Oliveira JBA. Ovarian synchrony factor: a new ultrasound parameter in the prognosis of follicular rupture. Hum Reprod 1994;9:1250-2.
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