Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women
Abstract
:1. Introduction
1.1. Impact of Uterine Fibroids on Female Fertility
1.2. Currently Available Treatment Options for Uterine Fibroids in Women Desiring Future Fertility
1.3. EGCG (Green Tea Extract) and Uterine Fibroids
1.4. Previous EGCG Clinical Trial in Women with Symptomatic Uterine Fibroids
1.5. Green Tea Extracts and Hepatoxicity
1.6. Objective
2. Materials and Methods
2.1. Study Design
2.2. Inclusion/Exclusion Criteria
2.3. Study Conduct
2.4. Data Management and Statistical Analysis
3. Results and Analysis
3.1. Participant Disposition
3.2. Demographics
3.3. Adverse Events
3.4. Liver Safety and Folate Levels at the End of the Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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EGCG | EGCG + Clomiphene | EGCG + Letrozole | All | p-Value for Comparison among Three Groups | |
---|---|---|---|---|---|
Age (years) | 16 29.6 ± 6.3 28.5 (24.0 to 35.5) | 11 27.2 ± 6.6 28.0 (19.0 to 34.0) | 12 29.3 ± 6.3 27.0 (25.0 to 34.5) | 39 28.8 ± 6.3 28.0 (24.0 to 34.0) | 0.675 |
BMI (kg/m2) | 16 26.1 ± 6.8 24.3 (22.1 to 29.3) | 11 27.4 ± 5.7 28.3 (22.4 to 31.0) | 12 28.4 ± 9.5 25.0 (22.6 to 30.9) | 39 27.2 ± 7.3 25.0 (22.2 to 30.6) | 0.709 |
Hip circumference (cm) | 16 112.9 ± 35.1 104.0 (95.5 to 112.5) | 10 103.6 ± 18.1 108.2 (90.0 to 116.0) | 12 106.2 ± 19.4 105.3 (92.0 to 120.0) | 38 108.4 ± 26.6 104.8 (94.0 to 116.0) | 0.946 |
Waist circumference (cm) | 16 90.7 ± 27.0 80.5 (75.5 to 99.0) | 10 86.0 ± 13.4 89.8 (75.0 to 97.0) | 12 88.6 ± 21.0 88.2 (71.6 to 97.3) | 38 88.8 ± 21.8 84.1 (75.0 to 97.0) | 0.991 |
Ethnicity | 1.000 | ||||
Hispanic or Latino | 2/16 (12.5%) | 2/11 (18.2%) | 2/12 (16.7%) | 6/39 (15.4%) | |
Non-Hispanic | 14/16 (87.5%) | 9/11 (81.8%) | 10/12 (83.3%) | 33/39 (84.6%) | |
Race | 0.763 | ||||
White | 11/16 (68.8%) | 6/11 (54.5%) | 6/12 (50.0%) | 23/39 (59.0%) | |
Black | 2/16 (12.5%) | 2/11 (18.2%) | 1/12 (8.3%) | 5/39 (12.8%) | |
Asian | 2/16 (12.5%) | 2/11 (18.2%) | 4/12 (33.3%) | 8/39 (20.5%) | |
Native Hawaiian/Pacific Islander | 1/16 (6.3%) | 0/11 (0.0%) | 0/12 (0.0%) | 1/39 (2.6%) | |
I prefer not to answer | 0/16 (0.0%) | 1/11 (9.1%) | 1/12 (8.3%) | 2/39 (5.1%) | |
Have ever been diagnosed with fibroids | 3/16 (18.8%) | 2/11 (18.2%) | 1/12 (8.3%) | 6/39 (15.4%) | 0.742 |
Have had endometriosis | 1/15 (6.7%) | 0/10 (0.0%) | 0/11 (0.0%) | 1/36 (2.8%) | 1.000 |
History of smoking | 0.949 | ||||
Never | 13/16 (81.3%) | 9/10 (90.0%) | 9/11 (81.8%) | 31/37 (83.8%) | |
Current | 2/16 (12.5%) | 0/10 (0.0%) | 1/11 (9.1%) | 3/37 (8.1%) | |
Former | 1/16 (6.3%) | 1/10 (10.0%) | 1/11 (9.1%) | 3/37 (8.1%) | |
History of alcohol use | 0.642 | ||||
Never | 1/16 (6.3%) | 1/11 (9.1%) | 3/12 (25.0%) | 5/39 (12.8%) | |
Current | 14/16 (87.5%) | 9/11 (81.8%) | 8/12 (66.7%) | 31/39 (79.5%) |
EGCG | EGCG + Clomiphene | EGCG + Letrozole | All | p-Value for Comparison among Three Groups | |
---|---|---|---|---|---|
≥1 Adverse events | 2/16 (12.5%) | 4/11 (36.4%) | 6/12 (50.0%) | 12/39 (30.8%) | 0.083 |
Abdominal discomfort and loose stool | 0/16 (0.0%) | 0/11 (0.0%) | 1/12 (8.3%) | 1/39 (2.6%) | 0.590 |
Diarrhea | 1/16 (6.3%) | 0/11 (0.0%) | 0/12 (0.0%) | 1/39 (2.6%) | 1.000 |
Dizziness | 0/16 (0.0%) | 1/11 (9.1%) | 0/12 (0.0%) | 1/39 (2.6%) | 0.282 |
Facial flushing, muscle ache, and diarrhea after letrozole | 0/16 (0.0%) | 0/11 (0.0%) | 1/12 (8.3%) | 1/39 (2.6%) | 0.590 |
Greenish discharge | 0/16 (0.0%) | 1/11 (9.1%) | 0/12 (0.0%) | 1/39 (2.6%) | 0.282 |
Headaches | 1/16 (6.3%) | 0/11 (0.0%) | 0/12 (0.0%) | 1/39 (2.6%) | 1.000 |
Insomnia | 0/16 (0.0%) | 1/11 (9.1%) | 1/12 (8.3%) | 2/39 (5.1%) | 0.503 |
Kidney pain | 0/16 (0.0%) | 0/11 (0.0%) | 1/12 (8.3%) | 1/39 (2.6%) | 0.590 |
Loose stool | 0/16 (0.0%) | 0/11 (0.0%) | 1/12 (8.3%) | 1/39 (2.6%) | 0.590 |
Low mood | 0/16 (0.0%) | 1/11 (9.1%) | 0/12 (0.0%) | 1/39 (2.6%) | 0.282 |
Migraine after vaccine | 1/16 (6.3%) | 0/11 (0.0%) | 0/12 (0.0%) | 1/39 (2.6%) | 1.000 |
Nausea with EGCG | 0/16 (0.0%) | 1/11 (9.1%) | 1/12 (8.3%) | 2/39 (5.1%) | 0.503 |
Pelvic cramps, dull and intermittent aching after letrozole | 0/16 (0.0%) | 0/11 (0.0%) | 1/12 (8.3%) | 1/39 (2.6%) | 0.590 |
Vomiting and diarrhea after clomid | 0/16 (0.0%) | 1/11 (9.1%) | 0/12 (0.0%) | 1/39 (2.6%) | 0.282 |
Arms | Label | Mean | Std Dev | Lower Quartile | Upper Quartile |
---|---|---|---|---|---|
EGCG n = 14 | ALT (U/L) | 18.8 | 13.5 | 12.0 | 23.0 |
AST (U/L) | 19.6 | 6.9 | 15.0 | 25.0 | |
Direct bilirubin (mg/dL) | 0.2 | 0.1 | 0.1 | 0.2 | |
Total bilirubin (mg/dL) | 0.5 | 0.6 | 0.2 | 0.4 | |
Mid-Cycle Endo thickness (mm) | 8.6 | 4.4 | 5.4 | 11.2 | |
Folate (U/L) | 12.8 | 4.3 | 8.5 | 15.5 | |
EGCG + Clomiphene n = 11 | ALT (U/L) | 18.6 | 9.6 | 12.0 | 23.0 |
AST (U/L) | 28.3 | 25.5 | 16.0 | 28.0 | |
Direct bilirubin (mg/dL) | 0.2 | 0.1 | 0.1 | 0.2 | |
Total bilirubin (mg/dL) | 0.4 | 0.2 | 0.3 | 0.6 | |
Mid-Cycle Endo thickness (mm) | 11.1 | 4.0 | 7.8 | 12.0 | |
Folate (U/L) | 13.6 | 4.9 | 10.1 | 17.9 | |
EGCG + Letrozole n = 11 | ALT (U/L) | 16.6 | 9.6 | 10.0 | 23.0 |
AST (U/L) | 18.8 | 4.6 | 15.0 | 23.0 | |
Direct bilirubin (mg/dL) | 0.2 | 0.1 | 0.1 | 0.2 | |
Total bilirubin (mg/dL) | 0.5 | 0.4 | 0.3 | 0.6 | |
Mid-Cycle Endo thickness (mm) | 8.8 | 3.6 | 5.7 | 9.7 | |
Folate (U/L) | 10.3 | 4.0 | 7.3 | 12.6 |
EGCG | EGCG + Clomiphene | EGCG + Letrozole | All | p-Value for Comparison among Three Groups | |
---|---|---|---|---|---|
Change in ALT/SGPT (U/L) | n = 15 1.1 ± 5.1 | 11 4.4 ± 11.7 | 12 −1.0 ± 7.6 | 38 0.5 ± 8.4 | 0.237 |
Change in AST/SGOT (U/L) | 15 −3.8 ± 11.0 | 11 7.5 ± 27.9 | 12 −0.5 ± 4.4 | 38 0.5 ± 16.9 | 0.348 |
Change in direct bilirubin (mg/dL) | 15 0.0 ± 0.1 | 10 −0.1 ± 0.1 | 12 0.0 ± 0.0 | 37 −0.0 ± 0.1 | 0.124 |
Change in total bilirubin (mg/dL) | 15 0.1 ± 0.2 | 11 −0.0 ± 0.0 | 12 0.0 ± 0.1 | 38 0.0 ± 0.2 | 0.508 |
Change in folate (ng/mL) | 14 −1.6 ± 4.0 | 10 −3.7 ± 4.3 * | 10 −1.3 ± 3.3 | 34 −2.1 ± 3.9 | 0.716 |
Change in endometrial thickness from screening to mid-cycle (mm) | 13 −1.9 ± 4.3 | 11 1.4 ± 2.0 | 11 0.6 ± 2.7 | 35 −0.0 ± 3.6 | 0.146 |
Liver Function Test | Screening (n = 39) | Visit 1 (n = 38) | Visit 2 (n = 36) | Visit 4 (n = 36) |
---|---|---|---|---|
ALT or AST ≥ 3×ULN | 0 | 0 | 0 | 0 |
BILI ≥ 2×ULN | 0 | 0 | 0 | 0 |
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Siblini, H.; Al-Hendy, A.; Segars, J.; González, F.; Taylor, H.S.; Singh, B.; Flaminia, A.; Flores, V.A.; Christman, G.M.; Huang, H.; et al. Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women. Nutrients 2023, 15, 320. https://doi.org/10.3390/nu15020320
Siblini H, Al-Hendy A, Segars J, González F, Taylor HS, Singh B, Flaminia A, Flores VA, Christman GM, Huang H, et al. Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women. Nutrients. 2023; 15(2):320. https://doi.org/10.3390/nu15020320
Chicago/Turabian StyleSiblini, Hiba, Ayman Al-Hendy, James Segars, Frank González, Hugh S. Taylor, Bhuchitra Singh, Ainna Flaminia, Valerie A. Flores, Gregory M. Christman, Hao Huang, and et al. 2023. "Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women" Nutrients 15, no. 2: 320. https://doi.org/10.3390/nu15020320