Uterine fibroids can be a very difficult condition to treat clinically. The treatment is often surgical when symptoms are significant enough to cause problems. Uterine fibroids are believed to affect at least 1/3 of North American Women. They cause symptoms such as heavy bleeding, pressure effects on other organs, and fertility concerns: all of which have large impacts on a woman’s health. A study has recently come out from the Centre for Women’s Health Research at Meharry Medical College which concludes that EGCG, an extract from Green tea, may induce apoptosis (cell death) and reduce proliferation of uterine fibroid cells by affecting gene expression. This is the second study from Meharry Medical College on this topic, the first having been released in May 2008. The mechanism studied is in line with recent research indicating that uterine fibroids are correlated with genetic factors and gene expression, evidence for which was examined in a review from the National Institute of Health Sciences, Comparative Pathobiology Group. A study was also released in February 2008 which showed a positive effect of EGCG on fibroids in quail, an animal which is especially prone to these tumors.
Genetic effects of Green Tea on Fibroid Growth
In the study, the EGCG from green tea significantly decreased the expression of the genes PCNA, CDK4, and BCL2(genes which promote growth of fibroid cells) as well as increased the expression of the pro-apoptotic BAX(a gene which promotes cell degeneration in a fibroid cell) in a dose-dependent manner. This indicates that EGCG works along multiple genetic pathways to inhibit fibroid tumor growth.
Fibroids and Hormones : Risk Factors
Factors which are currently thought to promote growth of fibroids are periods of excess estrogen, periods of unopposed estrogen(when there is insufficient progesterone to balance out estrogens), and xenoestrogens (environmental chemicals such as those found in some plastics or pesticides which mimic the effects of estrogen in the body). Risk factors for fibroids are many, and factors such as having an early age of onset of the menses or lack of ovulation give unopposed estrogen more time to stimulate fibroid growth. Risk of fibroids is reduced by having children (also known as the effects of parity- risk is reduced most for women who have several children) which is now thought to be related to ischemic effects on the uterus after birth (reduced blood flow to the uterine tissues and involution of the uterus) which appear to reduce formation and growth of fibroids. Fibroids are more common in women over 40, and this may be related to changes in hormonal mediators during perimenopause, or alternately from 20-30 consecutive years of exposure to estrogen.
Although it has been traditionally thought that estrogen is the only promoter of fibroid growth, research now points to progesterone as a stimulator of fibroid growth. Fibroids contain both progesterone and estrogen receptors which are up and down regulated during the menstrual cycle. A key to stimulation of fibroid growth may be in conversion enzymes. Studies point to increased expression of an enzyme known as aromatase in women who have fibroids. Aromatase is an enzyme which converts androgens to estrogen (androgens are male hormones, and the precursors to estrogen). This information indicates that treatments which work at the level of this enzymatic activity (such as aromatase inhibitors – to be discussed on a future blog post) can bring more balance to the effects of of estrogen on tissues, especially if started at an early stage of the condition.
Fibroids: The Liver and Diet
Another factor which can cause growth of fibroids relates to the clearance of hormones and conversion of estrogen to weaker forms by the liver. If liver function is poor, more estradiol will circulate and increase growth of the fibroids. Dietary factors which are also linked to risk of fibroids include low fibre diets (fibre improves elimination of hormones). Higher fat and lower fibre diets have also been linked to higher levels of estradiol according to a meta analysis of date from the Journal of the National Cancer institute, and obesity is also correlated with a higher risk for fibroids (androgens are converted to estrogens in adipose tissue). Green tea also has thermogenic (fat burning) effects according to multiple studies (effects beyond that of the caffeine it contains), so it may be helpful for women with fibroids from this standpoint as well.
A study from Japan indicated that green tea and other caffeinated beverages reduced serum estrogen by increasing sex hormone binding globulin, which is also of benefit in reducing the rate of estrogen stimulated fibroid growth. Although other caffeinated beverages such as coffee also appeared to increase sex hormone binding globulin, only green tea was correlated to a day 11 lower serum estradiol.
Although more research is needed in this area before firm conclusions can be drawn on this topic, it seems that EGCG has multiple benefits for women who are at risk for fibroid development. Though unlikely to shrink larger developed fibroids to a great extent, it may have a role to play in earlier stages and in prevention of these benign yet troublesome growths.
- Dr. Fiona McCulloch
Alan A.Arslan, Leslie I.Gold, Khushbakhat Mittal, Ting-Chung Suen, Ilana Belitskaya-Levy, Moon-Shong Tang and Paolo Toniolo. 2005. Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review. Human Reproduction 20(4) pp. 852–863.
Baird D, and Dunson, D. 2003. Why is Parity Protective for Uterine Fibroids. Epidemiology. March 14(2): 247-250.
Dong Zhang, Mohamed Al-Hendy, Ayman Al-Hendy. Green Tea Extract (EGCG) Inhibits Proliferation of Human Leiomyoma Cells. Biology of Reproduction. 67. 63. (2008)
Dulloo, A G : Seydoux, J : Girardier, L : Chantre, P : Vandermander, J. 2000. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int-J-Obes-Relat-Metab-Disord. 2000 Feb; 24(2): 252-8.
Folkerd EJ, Newton CJ, Davidson K, Anderson MC, James VH. 1984. Aromatase activity in uterine leiomyomata. J Steroid Biochem 20:1195–1200.
Gordon P. Flake, Janet Andersen, and Darlene Dixon. 2003. Etiology and Pathogenesis of Uterine Leiomyomas: A Review. Environ Health Perspect. June; 111(8): 1037–1054.
Ibrahim H. Ozercan, Nurhan Sahin, Fatih Akdemir, Muhittin Onderci, Soley Seren, Kazim Sahin, Omer Kucuk. 2008. Chemoprevention of fibroid tumors by [−]-epigallocatechin-3-gallate in quail. Nutrition Research – February 28(2): 92-97
Kawaguchi K, Fujii S, Konishi I, Nanbu Y, Nonogaki H, Mori T. 1989. Mitotic activity in uterine leiomyomas during the menstrual cycle. Am J Obstet Gynecol 160:637–641.
Nagata C, Kabuto M, Shimizu H. 1998. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese Women. Nutr Cancer 30(1):21-4
Sumitani H, Shozu M, Segawa T, Murakami K, Yang HJ, Shimada K, et al. 2000. In situestrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism. Endocrinology 141:3852–3861.
Wu A, et al. 1999. Meta-analysis: Dietary Fat Intake, Serum Estrogen Levels, and the Risk of Breast Cancer. J Natl Cancer Inst 1999; 91:492-494, 529-534.
Yamamoto T, Takamori K, Okada H. 1984. Estrogen biosynthesis in leiomyoma and myometrium of the uterus. Horm Metab Res 16:678–679.
Zhang D, Al-Hendy M, Richard-Davis G, Montgomery-Rice V, Rajaratnam V, Al-Hendy A. 2009. Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells. Fertil Steril. Oct 2009. Epub ahead of print.