Comparison of Probiotics, Metformin & Their Combination Therapy in the Treatment of PCOS

Not Applicable

Completed

• Conditions: Polycystic Ovary Syndrome
• Interventions: Drug: Probiotic Agent; Drug: Metformin

• Registration Number: NCT04009603
• Lead Sponsor: Ziauddin University

Brief Summary

Polycystic ovary syndrome (PCOS) is a common gynecological state worldwide characterized by numerous small cysts in the ovaries mainly due to the imbalance of endocrine hormones in premenopausal women. Metformin is long being used for different symptoms of PCOS along with other medication. This study involves the assessment of different parameters of PCOS.

Detailed Description

Polycystic ovary syndrome (PCOS) is a hormonal disorder affecting the women of reproductive age. It is a heterogeneous health condition that affects 1 in every 10 women of childbearing age. Women of all races and ethnicities are at risk for PCOS, but risk increases multiple folds if the BMI is greater than 30kg/m2. The common signs and symptoms, the women usually represent with are menstrual irregularities, hyperandrogenemia and multiple cysts in ovaries. The exact cause of PCOS is still unknown but genetic and obesity is considered to be the most common cause.

Metformin has been considered as the first line agent for the treatment of non-insulin dependent diabetes mellitus and up till now it has been used as a first line drug for PCOS. Despite its beneficial effects in PCOS it has several adverse effects. Moreover, patients usually seek two or more drugs along with metformin to relieve maximum symptoms of PCOS like for ovulation clomiphene citrate must be given etc. So there is a need of novel and comprehensive agent that can prove to be effective in improving maximum symptoms of this disease. Probiotics have received renewed attention in the 21st century through research studies. World Health Organization's (WHO) 2001 defines probiotics as live micro-organisms that, when administered in adequate amounts, confer a health benefit on the host. In recent year it has shown tremendous promising effect in treatment of different diseases like diarrhea, gingivitis and obesity etc with negligible side effects.

In this context the investigators are going to evaluate and compare the effects of probiotics, metformin and their combination therapy in treatment of various symptoms of PCOS.60 newly diagnosed PCOS patient will be assigned in the open label randomized clinical trial. As mentioned above patients will be divided into three groups with 20 patients each. In group 1, the dosage of metformin will be 500mg B.D and 2 gm of probiotic sachet O.D, the second group will be given metformin 500mg B.D. and the third group will be 2mg of probiotics B.D. It would be a follow-up study that would be conducted in Gynecology OPD of Tertiary Care Hospital

Study Timeline

• Study Start: 2018-12-06
• Study First Submitted: 2019-03-28
• Primary Completion: 2019-06-30
• Study First Submitted QC: 2019-07-02
• Study First Posted: 2019-07-05
• Study Completion: 2020-01-28
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-04
• Last Update Posted: 2020-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 78

Inclusion Criteria

• The patient will be included according to the Rotterdam European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine sponsored a PCOS consensus criterion which says the presence of any two of the following three features must be present for the patient to be diagnosed as a case of PCOS:

  • Oligomenorrhea and/or amenorrhea (Oligomenorrhea>45 days or <8 cycles per year and amenorrhea >3 months in women with previous periodic menses) for a period of 6 months
  • Clinical and/or biochemical hyperandrogenemia, the presence of acne, hirsutism (FG score>8), and alopecia
  • Polycystic ovaries on sonography (>12 follicles in one or both ovaries, 2-9 mm in diameter and/or increased ovarian volume >10 mL).

Exclusion Criteria

• History of chronic diseases
• Allergic to probiotic or metformin
• Current or previous (within the last 6 months) use of chemotherapy or other drugs.
• History of smoking
• Individuals with autoimmune disease
• Individuals with autoimmune disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Probiotic	Probiotic Agent	Group no 2(26 patients): will be given probiotics alone at a dose of 180mg B.D for 12 weeks
Metformin and Probiotic	Probiotic Agent	Group no 3(26 patients): will be given metformin 500mg B.D and probiotics 180mgram O.D. for 12 week
Metformin	Metformin	Group no 1(26 patients) Metformin tablets at a dose of 500mg BD for 12 weeks
Metformin and Probiotic	Metformin	Group no 3(26 patients): will be given metformin 500mg B.D and probiotics 180mgram O.D. for 12 week

Primary Outcome Measures

Name	Time	Method
Luteinizing Hormone	12 weeks	LH; The concentration of this endocrine hormones is determined will be obtained on day 2 or 3 of the normal menstruation cycle and at any time in women with amenorrhea.; LH: 1.9 to 12.5 IU/L
Follicle-stimulating hormone	12 weeks	The concentration of this endocrine hormones is determined will be obtained on day 2 or 3 of the normal menstruation cycle and at any time in women with amenorrhea.; LH: 4.5 to 21.5 IU/L
Change in cyst size on Ultrasonography	12 weeks	Ovary cyst size: The size of the cyst will be measured before the start and at the end of the study, considering 12 or more follicles in at least 1 ovary or both-measuring 2-9 mm in diameter-or a total ovarian volume greater than 10 cm3
INSULIN LEVELS	12 weeks	Fasting serum insulin: The sample is collected after fasting of 12 to 14 hours will be measured before and after intervention; fasting insulin \< 25 mIU/L
Hormonal parameter:	12 weeks	Androgens: The concentration of these hormones will be evaluated at the baseline and at the end of treatment usually in the morning between 8:00 am to 9:00 am after overnight fasting; Serum testosterone:15 and 70 ng/dL
Biochemical parameter:	12 weeks	Fasting serum glucose: The blood sample for FBS will be collected on day 2 or 3 of the menses. The blood samples will be taken before the start and at the end of the treatment.; fasting glucose 80-100 mg/dl
Lipid	12 weeks	Lipid profile: 1. Total cholesterol; 2. LDL; 3. HDL; 4. Triglyceride; The serum lipid concentrations will be evaluated spectrophotometrically by means of commercial kits at baseline and at the end of the study; Total cholesterol \< 200; Triglyceride: \<150 mg/dl; HDL: \> 60mg/ dl; LDL: \< 130mg /dl
LH and FSH ratio	12 weeks	LH:FSH The serum levels of FSH:LH ratio will be assessed before the start and at the end of the management on day 2 or 3 of the normal menses and at any time in women with amenorrhea.; 1.5:1

Secondary Outcome Measures

Name	Time	Method
Hirsutism	12 week	Hirsutism: History and physical examination, including pelvic examination at the start and at the end of treatment using the Ferriman-Gallwey scale for hirsutism.
Change in Physical symptoms in PCOS	12 weeks	Weight: The body weight of the females will be recorded at baseline and at the end of the treatment with the help of weighing machine in kg.
Acne	12 week	Acne: Acne score will be taken at baseline and at the end of the treatment through the Global Acne grading system.
Menstruration	12 weeks	Menstrurational irregularities: All study participants will be asked about menstruation irregularities at the time of enrollment.They will also be enquired about for long they have their cycles have been disturbed.They will be asked to maintain their cycle dates as well.

Trial Locations

Locations (1)

Dr. Urooj; 🇵🇰 Karachi, Sindh, Pakistan