Effect of Propolis Administration for Dysmenorrhea in Endometriosis Patient With Levonorgestrel Implant Therapy

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate the effect of propolis administration on dysmenorrhea in endometriosis patient. the main questions it aims to answer are: Does the propolis administration reduce symptoms of dysmenorrhea in endometriosis? Does the propolis administration reduce the amount of oxidative stress biomarkers in endometriosis? Does the propolis administration reduce the amount of Inflammatory biomarkers in endometriosis? Participants will be given an intervention in the form of propolis at a dose of 1 drop per 10 kilogram of body weight per administration, twice a day. there will be a control group that will be given an intervention in the form of a placebo containing 70% caramel alcohol dye solution.

Official Title
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Effect of Propolis Administration as Levonorgestrel (LNG) Implant Adjuvant for Dysmenorrhea in Endometriosis: Focus on Clinical Improvement, Oxidative Stress Biomarkers and Inflammation

Conditions
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Endometriosis, Dysmenorrhea

Intervention / Treatment
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* Dietary Supplement: Propolis
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 20-49 years and already menstruating with complaints of menstrual pain referred to the obstetrics and gynecology polyclinic for LNG implant placement Willing to have LNG implant installed after receiving explanation about implants Not receiving hormonal treatment for endometriosis within the last 3 months Can receive drops (propolis) during the study Exclusion Criteria: Impaired liver function, degenerative diseases (DM, hypertension and cardiovascular disease), benign tumors, cancer Pregnancy and breastfeeding Hypersensitivity to levonogestrel Thromboembolic disease Experiencing bleeding for unknown reasons History of allergies to honey and its processed products Currently taking supplements/drugs that are not included in the standard management of endometriosis patients at RSCM Have consumed propolis before Received hormonal treatment within the last 3 months

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Endometriosis patients with menstrual pain who received LNG implant therapy were divided into two groups, each group consisted of 12 samples. The control group only received LNG, the treatment group received LNG with the addition of propolis. Propolis is given 2 times a day, namely in the morning before breakfast and at night before going to bed, with a dose of 1 drop /10 kg body weight (kgBW). Both groups were followed and reassessed after 1 month, 3 months both clinical and laboratory. Prior to receiving therapy, all subjects received education and signed informed consent for their willingness to participate in the study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propolis<br>the subjects were asked to consume propolis 1 drop/10 kgbw/time given 2 times a day for 12 weeks. the dose will be calculated based on body weight by the certified nutritionist during the interview after the subject signs the informed consent form | Dietary Supplement: Propolis<br>* intervention will use propolis extract (liquid-based) with 1 drop/10kgBW/times, 2 times in a day for 12 weeks. propolis will be given to intervention group<br>|
| Placebo Comparator: Placebo<br>the subjects were asked to consume placebo (glucose-only contained) 1 drop/10 kgbw/time given 2 times a day for 12 weeks. the dose will be calculated based on body weight by the certified nutritionist during the interview after the subject signs the informed consent form | Other: placebo<br>* intervention will use placebo with 1 drop/10kgBW/times, 2 times in a day for 12 weeks. propolis will be given control group<br>* Other names: 70% caramel alcohol dye solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Malondialdehyde (MDA) | blood biochemical test for oxidative stress biomarker from lipid peroxidation product, using ng/mL numeric scale | week 0 | 
| Malondialdehyde (MDA) | blood biochemical test for oxidative stress biomarker from lipid peroxidation product, using ng/mL numeric scale | week 4 | 
| Malondialdehyde (MDA) | blood biochemical test for oxidative stress biomarker from lipid peroxidation product, using ng/mL numeric scale | week 12 | 
| Superoxide dismutase (SOD) | blood biochemical test for oxidative stress biomarker from lipid peroxidation product, using nmol/mLnumeric scale | week 0 | 
| Superoxide dismutase (SOD) | blood biochemical test for oxidative stress biomarker from lipid peroxidation product, using nmol/mLnumeric scale | week 4 | 
| Superoxide dismutase (SOD) | blood biochemical test for oxidative stress biomarker from lipid peroxidation product, using nmol/mLnumeric scale | week 12 | 
| interleukin 6 | will test the outcome with ELISA test from blood sample for inflammatory biomarker, using ng/mL numeric scale | week 0 | 
| interleukin 6 | will test the outcome with ELISA test from blood sample for inflammatory biomarker, using ng/mL numeric scale | week 4 | 
| interleukin 6 | will test the outcome with ELISA test from blood sample for inflammatory biomarker, using ng/mL numeric scale | week 12 | 
| tumor necrosis factor alpha (TNF alfa) | will test the outcome with ELISA test for inflammatory biomarker, using ng/mL numeric scale | week 0 | 
| tumor necrosis factor alpha (TNF alfa) | will test the outcome with ELISA test for inflammatory biomarker, using ng/mL numeric scale | week 4 | 
| tumor necrosis factor alpha (TNF alfa) | will test the outcome with ELISA test for inflammatory biomarker, using ng/mL numeric scale | week 12 | 
| pain scale | to measure the outcome, the investigators use Visual Analogue Scale for measure the pain from the subject, from 0 to 10. The scale consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be'). the subject will be asked to rate their current level of pain by placing a mark on the line. | week 0 | 
| pain scale | to measure the outcome, the investigators use Visual Analogue Scale for measure the pain from the subject, from 0 to 10. The scale consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be'). the subject will be asked to rate their current level of pain by placing a mark on the line. | week 4 | 
| pain scale | to measure the outcome, the investigators use Visual Analogue Scale for measure the pain from the subject, from 0 to 10. The scale consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be'). the subject will be asked to rate their current level of pain by placing a mark on the line. | week 12 | 
| Glutathione | measure the outcome with blood biochemical test using spectrofotometri in µg/mL numeric scale | week 0 | 
| Glutathione | measure the outcome with blood biochemical test using spectrofotometri in µg/mL numeric scale | week 4 | 
| Glutathione | measure the outcome with blood biochemical test using spectrofotometri in µg/mL numeric scale | week 12 | 
| 8-hydroxy-2-deoxyiguanosine (8-OHdG) | measure the outcome with ELISA from blood sample in ng/mL numeric scale | week 0 | 
| 8-hydroxy-2-deoxyiguanosine (8-OHdG) | measure the outcome with ELISA from blood sample in ng/mL numeric scale | week 4 | 
| 8-hydroxy-2-deoxyiguanosine (8-OHdG) | measure the outcome with ELISA from blood sample in ng/mL numeric scale | week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levonorgestrel implant, Propolis, Oxidative stress