Tori Hudson, ND

Green Tea Extract and Uterine Fibroids

A 2013 double-blinded, placebo-controlled randomized clinical trial, led by E. Roshdy, evaluated the efficacy and safety of green tea extract on uterine fibroid burden and quality of life in reproductive aged women with symptomatic uterine fibroids.¹

A total of 39 reproductive aged women (ages 18-50 y.o.) with symptomatic uterine fibroids were recruited.  Eligible women included those with a follicle-stimulating hormone (FSH) less than 10 U/mL and at least moderately severe uterine fibroid related symptoms with a score of  >25 on the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire subscale (UFSQOL). All the women had at least one fibroid measuring 2 cm or larger based on transvaginal and/or transabdominal ultrasound and a total uterine volume of >160 mL by vaginal and abdominal ultrasound. 

Twenty-two were randomized to receive green tea extract and 17 to receive placebo.  Study subjects were randomized to oral green tea extract (45% epigallocatechin gallate= EGCG) or placebo of brown rice, daily, for 4 months.  Each green tea capsule contained 95% polyphenols and 45% EGCG.  Women received two capsules daily of either green tea or placebo—a total of 800 mg/day.

Uterine fibroid volumes were measured at beginning and end of the study.  The fibroid specific symptom severity and quality of life questionnaires were scored at each monthly visit. 

The mean change in both the volume and number of uterine fibroids was assessed by transvaginal ultrasound (TVU) and/or transabdominal ultrasound at baseline and at the end of the 4-month treatment period.

The secondary measure at each visit was the mean change in fibroid-specific health-related quality of life (UFS-QOL), and the health-related quality of life (HRQL) questionnaire.  Blood loss was also assessed monthly with a menstrual log and visual assessment of quantity.

Of the 39 women, 33 were compliant and completed the five-visit study over the 4-month period.  Of the final 11 women who completed the placebo group, fibroid volume increased by 24.3% over the study period.  Of the final 22 women in the green tea extract group, a significant uterine fibroid total volume reduction of 32.6% was observed. The green tea extract group also had a significant reduction in fibroid-specific symptom severity of 32.4% and a significant improvement in HRQL of 18.53% compared to the placebo group.  Anemia improved significantly by 0.7 g/dL in the green tea group and the average blood loss significantlydecreased from 71 mL/month to 45 mL/month. There were no adverse effects or endometrial hyperplasia or pathology in either group.

Commentary: Green tea, especially its epigallocatechin gallate (EGCG) constituent, has anti-inflammatory, antiproliferative, and antioxidant effects. The study’s authors attributed the reduction in fibroid size from EGCG due to an inhibitory effect on leiomyoma tumor cell proliferation and apotosis induction.

More than half of women ages 35-49 in the US are affected by uterine fibroids, which are more prevalent in African American women.  These benign growths can cause acute and chronic pelvic pain, excessive uterine bleeding, dyspareunia, iron deficiency anemia, miscarriage, infertility, constipation and/or irregular bowel habits and urinary incontinence.  The impact of these complications on a woman’s health can be significant and currently, there is no effective long-term medical treatment for these common benign tumors. 

Short-term conventional management options include gonadotropin releasing hormone analogues but are only approved for short-term preoperative adjuvant use due to their risk of significant and irreversible bone loss, osteoporosis and other major side effects. Progestogen or hormonal contraceptive management is sometimes helpful to control bleeding. 

If symptoms impact quality of life significantly, or fibroid removal could improve miscarriage and/or fertility, or there is medical urgency due to bleeding, then management options range include hysteroscopic resection of submucosal fibroids, hysterectomy, myomectomy, uterine artery embolization or image guided focused ultrasound thermal therapy.  Milder cases usually involve just observation, especially in asymptomatic fibroids, or the patient putting up with her symptoms. 

This study, of a simple and safe botanical option such as green tea extract, is a welcomed noninvasive intervention for treatment and/or prevention of uterine fibroids and could be a game changer for many women suffering from uterine fibroids. 

Uterine Fibroids May Be Reduced with Green Tea-Vitamin D Product

Uterine fibroids are the most common benign tumor in the uterus.  Most do not cause any symptoms and don’t require any investigation or treatment.  But, for some women, maybe about a third, women with uterine fibroids, also called uterine myomas may need a therapy—either to control abnormal uterine bleeding, reduce the size due to pressure and affects on bladder and/or digestive function, interference with fertility, or just plain aesthetics and discomfort due to size and abdominal distention.  Conventional treatment options include medications to control bleeding or shrink the fibroids temporarily or surgical options.  All of this depends on the scope and severity of the symptoms, the size, number, and desire for pregnancy.  Minimally invasive surgical procedures are possible for some but not all fibroids.  Others might require a hysterectomy—either abdominally or vaginally. 

Women often seek alternative or integrative medicine options to see if non-surgical or non-pharmaceutical treatments may help.  The research is sparse, and the success is hit and miss.  The most likely help we can offer is to help control abnormal bleeding.  The least likely help we can offer is actually reducing the size of fibroids, especially larger ones.  However, a small amount of research has emerged, including in the area of green tea.  In a 2020 study led by G. Porcaro, vitamin D and epigallocatechin gallate (EGCG) offers some hope with women who had symptomatic fibroids.²

Women were included in the study if they were 18 or older, premenopausal and with at least one myoma >2 cm (either intramural or subserosal and/or submucosal fibroids), as detected on a vaginal and abdominal ultrasound, with moderately severe, myoma-related symptoms—and who required no other treatment.

This pilot study enrolled 30 women with myomas, who were divided into two groups.  One group (n=15) received one tablet of 1,000 IU (25 mcg) vitamin D plus 150 mg EGCG + 5 mg B6, twice daily for 4 months.  The second group (n=15) received no treatment for 4 months.  The primary outcome was the change in volume of myomas as detected by transvaginal and/or transabdominal ultrasound.  The secondary outcomes were variation of the number of myomas, heavier menstrual bleeding, pelvic pressure, fatigue, quality of life, and the severity of any of these symptoms.

None of the women dropped out of the study in either group, and there were no discernable side effects of the treatment.  The total number of myomas in the treated and control group was 23 and 21, respectively.  In the treated group, the incidence of intramural myomas was 43.7%, subserosal 12.5% and submucosal 43.75%.  In the control group it was 47.4% intramural, 10.5% subserosal, and 42.1% submucosal.

A significant reduction in the volume of myomas in the treated group was 10.84 cm at baseline to 8.04 cm after 4 months.  The reduction of the volume of myomas was unrelated to the type of myomas.  In the control group, the volume was 10.17 at baseline to 10.94 after 4 months of treatment.  This translates to a 34.7% reduction in the volume of myomas in the treatment group and an increase of 6.9% in the control or untreated group.  The number of myomas did not change in either group.

While the specifics were vaguely reported, there was an improvement in quality of life and reduction in severity of symptoms in the treatment group. 

Commentary: Uterine myomas, aka uterine leiomyomas, aka uterine fibroids, are monoclonal tumors of the smooth muscle cells of the myometrium.  Myomas consist of an accumulation of collagen, fibronectin, and/or proteoglycan that can form in or on the uterus.  Where they form determines the classification of intramural, subserosal, or submucosal.  A woman can have any combination of these or just one kind.  They are most common between the ages of 35 and 50 and may vary by ethnic groups with African American women having 3-4 times higher risk of developing myomas as compared with Caucasian American women.  Uterine fibroids are the leading cause of hysterectomies in the U.S. accounting for about 39% of all hysterectomies.  Clearly, we are not doing enough to understand the cause and offer successful treatments. 

The exact cause of myomas is still unknown but their development and growth is at least in part affected by estrogen and progesterone.  But also, we must consider the roles and influence of the hormone receptors and that the dysfunction is at the receptor rather than any particular rise or fall of the hormones.  It is a mistake to think that fibroids are only under the influence of estrogen.  For some women, it’s progesterone that can actually adversely affect growth of myomas.  It’s a much longer discussion, and discussion and theories is the name of the game rather than true knowns.  But, we might consider growth factors, cortisol dysregulation, dysfunctions in hormone metabolizing enzymes, environmental endocrine disruptors, body fat and obesogens…and more.  And speaking of more, a robust research effort would be welcomed to explore these theories, questions, and attempts at solutions. 

Back to vitamin D and EGCG.  There is at least one study showing an association between hypovitaminosis D and a higher prevalence of uterine fibroids, along with more severity related to the fibroids. (Int J Womens Health 2013; 5: 93-100.)  Mild symptomatic fibroids may be able to improve once an outright vitamin D deficiency (< 30 ng/mL) is corrected. (Medicine (Baltimore) 2016; 95: e5698.)  In one previous green tea study, EGCG for 4 months reduced the myoma size in premenopausal women.  (Int J Womens Health 2013; 5: 477-486.)

The Porcaro study, along with support of the small amount of previous data on vitamin D and EGCG supports the possibility that a simple and safe approach could at least offer something more than wait and watch, and possibly for some, may spare them a surgery and improve their myoma symptoms and quality of life.  In addition, we could consider an integrative plan, offering the herbal/nutraceutical treatment along with other pharmacological therapies that are being used to control heavy bleeding.  A uterus is worth saving, if possible, and avoiding any surgery, if possible, is wise and worth an effort.  If surgery is necessary, a good surgeon with a broad understanding of pelvic floor support and implications for menopause, is an important part of an integrative treatment team.  

Reducing Breast Density and Possibly Reducing Risk of Breast Cancer with Green Tea

Breast cancer is the most commonly diagnosed cancer in women.  The 5-year cure rate with conventional medicine has become quite good; but even so, at least 40,000 women die each year.  While most breast cancer has no known cause, there are some modifiable risk factors that include alcohol intake, exercise, weight, and breast density as assessed on a mammogram.  It has been reported that there is a 2% higher risk of breast cancer associated with every 1% increase in mammographic density. 

Green tea extract is one potential therapy for reducing breast density in those women who show significant breast density on the mammogram.

In a 2017 study, 1,075 healthy postmenopausal women between the ages of 50 and 70 had heterogeneously dense or extremely dense breast tissue on the screening mammogram.³  These women were randomized to receive either green tea extract (538 women) or placebo (537 women).   In the end, 462 women in the green tea group were analyzed.  A decaffeinated green tea extract capsule containing 328.8 mg of total catechins, 210.7 mg epigallocatechin-3-gallate (EGCG), and less than 4 mg caffeine was taken at a dose of 4 capsules per day for 12 months.  That’s a total of 1,315 mg catechins, 843 mg EGCG, and less than 16 mg caffeine per day.

Each woman had a mammogram at baseline and after 12 months to assess breast density.  Numerous other parameters were done including health questionnaires, some genotyping, select blood tests (plasma insulin-like growth factor 1, IGF binding protein, estrone, estradiol, androstenedione, sex hormone-binding globulin, urinary estrogen metabolites and plasma F2-isoprostanes).

Daily green tea capsules did not significantly reduce percentage mammographic density or absolute mammographic density compared to placebo after adjusting for age and body mass index at 12 months.  However, for the women aged 50 to 55, the 12 months of green tea extract did significantly reduce the percentage of mammographic density, resulting in a 4.4% decrease compared to placebo. Other factors, such as body mass index, years since menopause, alcohol, pregnancy history, and tea drinking showed no effect on percentage mammographic density with green tea intake. This 4.4% decrease in density in women aged 50-55 who consumed green tea extract for 1 year, could potentially translate to an 8.8% reduction in breast cancer risk.  Turns out, a study on tamoxifen (used as an estrogen receptor blocker in breast cancer management) had a similar 4.4% reduction in breast density over 18 months.  This same study reported that after 54 months of treatment, tamoxifen reduced MD by 13.4% in women age 45 or younger; while those older than 55 had  a 1.1% decrease in MD over the same period of time. 

In a 2007 study, women with greater than 75% mammographic density had an increased risk of breast cancer compared to women with less than 10% mammographic density, and the risk was especially greater for women younger than 56 years. For these women younger than 56 years old, 26% of the breast cancer cases and 50% of cancers detected within 12 months of a normal screening mammogram were thought to be due to a mammographic density of 50% or more. 

Commentary: Providers and women should consider strategies to reduce breast density, as a part of reducing the risk of breast cancer. Green tea extract is particularly important for women ages 50 to 55 who have heterogeneously dense or extremely dense breasts. 

Green Tea and Reduction of Breast Cancer Risk and Recurrence

Perhaps you are already a connoisseur of green tea, or perhaps you are already aware of the many health benefits, including the area of breast cancer risk reduction and recurrence.  Based on a study some years back, I have been advising women with stage I and II breast cancer to drink 5 cups/day or take a select number of capsules per day (amount is based on the dose per capsule).  This meta-analysis, led by V. Gianfredi, is a good update on the topic.⁴ The purpose of this systematic review and mata-analysis was to evaluate green tea consumption and breast cancer risk, recurrence, and risk in relationship to menopause status.

A literature search was done following current Systematic Review and Meta-Analysis guidelines, and using 3 search systems (PubMed, Scopus, and the Web of Science).   Observational studies that evaluated breast cancer risk in adult women were included and selected studies evaluated green tea consumption using a questionnaire or interview.  A total of 194 studies were detected but of those 39 were duplicate studies and 115 did not meet the inclusion criteria.  Another 25 studies were excluded because there was insufficient differentiation between the teas that were consumed and 2 studies were excluded due to data insufficiencies.  That left 13 studies that were included in this meta-analysis. Seven were conducted in Japan, five in China, and one in the U.S. 

Seven of these studies analyzed breast cancer recurrence in women with a previous history, and six studies followed healthy women to determine breast cancer risk.  Three of the seven studies on breast cancer recurrence showed a possible protective effect of consuming green tea.  The remaining four did not find a statistically significant correlation.  Of the other six studies analyzing the risk of breast cancer, none of them showed a statistically significant effect.  The potential benefit that was seen in those studies reported five cups of green tea per day. 

In addition to these findings, an analysis was also done comparing the risk of breast cancer in women before and after menopause and the influence of green tea.  A statistically significant protective effect of green tea was seen in pre-menopausal women while no protective effect was seen in postmenopausal women.  The protective effect in the overall meta-analysis was a 15% reduction in breast cancer risk. There was also a significant reduction in breast cancer recurrence in the majority of the cohort studies but not in the case-control studies.   Green tea was not associated with the risk of a new breast cancer diagnosis in those case-control studies; but conversely, green tea consumption significantly reduced breast cancer recurrence by 19%. 

Commentary:  One of the limitations of this meta-analysis was that the amount of green tea consumption varied with some studies reporting in grams and others in cups, and the serving size ranged from 100 mL to 350 mL. In addition, diet, other lifestyle factors, and cultural differences were not considered.  There is also insufficient information about breast cancer staging and what stage and receptor markers might be more influenced by green tea and breast cancer recurrence.  None the less, green tea for risk reduction, at least in pre-menopausal women, and breast cancer recurrence reduction in at least stage I-II breast cancer patients is still good advice.   For both these effects, I would encourage approximately 3-5 cups per day, which is often equal to 1-2 capsules per day of a green tea extract containing 330 mg of green tea leaf extract if it contains 98% polyphenols, 80% catechins, and 45% EGCG (epigallocatechin gallate).

Green Tea with Antibiotics for Simple Bladder infections

Bladder infections in otherwise healthy pre-menopausal and non-pregnant women tend to be uncomplicated and are classified as lower urinary tract infections (UTIs).  UTIs are amongst the most common infections in women, and Escherichia coli (E. coli) is the organism that is responsible for about 75-95% of uncomplicated UTIs.

Trimethoprim-sulfamethoxazole (TMP/SMX), aka co-trimoxazole and brand names Bactrim or Septra, is an inexpensive antibiotic and generally well tolerated and effective.  However, due to its common use, resistance to E. coli strains with this antibiotic has increased significantly; and as many as 20% of cases will be resistant, which is why other first line antibiotics are often chosen.

K. Kheirabadi, et al conducted a study on cystitis in women because there are laboratory studies that have shown antimicrobial effects of green tea catechins against E. coli as well as synergistic effects between the catechins and antibiotics such as the co-trimoxazole against E. coli.⁵

This randomized, blinded, placebo-controlled trial was conducted in Iran.  Healthy premenopausal, nonpregnant women ages 18-50 with acute uncomplicated cystitis were included in the study.  After urine collection, women were given four 500 mg capsules of green tea extract or placebo before bed, daily for 3 days.  All of the patients also received the TMP/SMX at two 480 mg tablets twice daily for 3 days.  Each gram of the green tea contained approximately a total phenol content of 283 mg and 65 mg of epigallocatechin (EGC).  The urine was then tested again in each group on the fourth day.

Results:  Among the 107 eligible women patients, 70 completed the trial.  Women in the green tea group showed a statistically significant decrease in the prevalence of cystitis symptoms at each time point (recorded daily).  The presence of symptoms was as follows:

Baseline:	Green tea 68%; placebo 75%
After 1 day	Green tea 61%; placebo 74%
After 2 days	Green tea 34%; placebo 67%
After 3 days	Green tea 2%; placebo 63%

Also, the addition of the green tea resulted in a statistically significant improvement in the urinalysis in terms of color, bacteria, and white blood cells.  No patients, in either group, had a recurrence of their UTI after 2 weeks.  After 4 weeks, 1 in the green tea group had a recurrence and after 6 weeks, 2 in the TMP/AMX only group had a recurrence. 

Commentary:  One of the unique things in the study design was that the green tea extract was given in a bolus, all four capsules at once, and in the evening.  The rationale of the researchers was that the EGC was better retained in the bladder all night, noting that more than 90% of the urinary EGC is excreted in the first 8 hours of administration, therefore all at once and in the evening before bed would theoretically enhance its effectiveness, if they did not urinate until morning.

In my experience, 49 out of 50 premenopausal non-pregnant women with uncomplicated UTIs can be successfully treated with a combination of herbal ingredients if dosed aggressively (formulas typically would contain cranberry extract, bucchu leaf, Oregon grape root, pipsissewa, uva ursi and marshmallow root);  occasionally I might add mannose powder, along with robust water.  On the atypical occasion that I prescribe an antibiotic, I will consider adding the dosing of green tea extract for 3 days used in the current study, whether the antibiotic is TMX/SMP or another. 

References

1. Roshdy E, Rajaratnam V, Maitra S, et al.  Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int J Womens Health. 2013;5:477-486.
2. Porcaro G, Santamaria A, Giordano D, Angelozzi P.  Vitamin D plus epigallocatechin gallate: a novel promising approach for uterine myomas. European Review for Medical and Pharmacological Sciences 2020; 24: 3344-3351.  
3. Samavat H, Ursin G, Emory TH, et al. A randomized controlled trial of green tea extract supplementation and mammographic density in postmenopausal women at increased risk of breast cancer. Cancer Prev Res (Phila). 2017;10(12):710-718.
4. Gianfredi V, Nucci D, Abalsamo A, et al.  Green tea consumption and risk of breast cancer and recurrence- A systematic review and meta-analysis of observational studies.  Nutrients.  2018 December;10(12):E1886.
5. Kheirabadi K, Mehrabani M, Sarafzadeh F, et al.  Green tea as an adjunctive therapy for treatment of acute uncomplicated cystitis in women:  A randomized clinical trial.  Complementary Therapies in Clinical Practice 2019;34:13-16

Published December 16, 2023

About the Author

Tori Hudson, ND, is a nationally recognized author (book: Women’s Encyclopedia of Natural Medicine second edition, McGraw Hill 2008), speaker, educator, researcher, and clinician. She serves on several editorial boards, advisory panels and as a consultant to the natural products industry.  Dr. Hudson graduated from the National University of Natural Medicine (NUNM) in 1984 and has served the college in several capacities, including Medical Director, Associate Academic Dean, and Academic Dean.   She is currently a clinical adjunct professor at NUNM, Southwest College of Naturopathic Medicine, Bastyr University, and the Canadian College of Naturopathic Medicine. 

Dr Hudson has been in practice for more than 36 years. She is the medical director of her clinic, A Woman’s Time in Portland, Oregon, co-owner and director of product research and education for VITANICA, and the program director for the Institute of Women’s Health and Integrative Medicine. She is also the founder and co-director of NERC (Naturopathic Education and Research Consortium), a non-profit organization for accredited naturopathic residencies.