**7. References**


Current treatments for endometriosis remain unsatisfactory, owing to their focus on treating the symptoms rather than curing the disease. In addition, each treatment proved to have many side effects (Rice, 2002). Hence, there is a need to derive a new therapy to provide a more efficient and specific therapeutic alternatives to eliminate the lesions, while preventing

To provide additional evidence to support the role of green tea in suppressing endometriosis, it would be an important future research goal. Several study areas should be emphasized. These areas include a more detailed molecular and cellular mechanism studies in animals and humans to verify the effects of green tea in humans, compared with those studied in animals. Next, the interactions between the green tea polyphenols and endometriosis have not been extensively investigated. This drawback can cause many important details being vague. Furthermore, the potential interactions of active compounds in green tea with other dietary active components and the roles of polymorphisms on the protective effects of tea need to be examined in future studies. Ultimately, clinical intervention trials should be conducted to verify the mechanisms of action of tea observed

Abbott, J, Hawe, J, Hunter, D, Holmes, M, Finn, P & Garry, R (2004). Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial, *Fertil Steril* 82(4): 878-84. Annabi, B, Lachambre, MP, Bousquet-Gagnon, N, Page, M, Gingras, D & Beliveau, R (2002).

Arumugam, K & Dip, YC (1995). Endometriosis and infertility: the role of exogenous lipid

Balentine, DA, Wiseman, SA & Bouwens, LC (1997). The chemistry of tea flavonoids, *Crit* 

Bedaiwy, MA, Abdel-Aleem, MA, Miketa, A & Falcone, T (2009). Endometriosis: a critical

Beltz, LA, Bayer, DK, Moss, AL & Simet, IM (2006). Mechanisms of cancer prevention by green and black tea polyphenols, *Anticancer Agents Med Chem* 6(5): 389-406. Biberoglu, KO & Behrman, SJ (1981). Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness, *Am J Obstet Gynecol* 139(6): 645-54. Board, RE, Thatcher, N & Lorigan, P (2006). Novel therapies for the treatment of small-cell

Brosens, I, Koninckx, P & Boeckx, W (1981). Endometriosis, *Clin Obstet Gynaecol* 8(3): 639-51. Cabebe, E & Wakelee, H (2007). Role of anti-angiogenesis agents in treating NSCLC: focus

on bevacizumab and VEGFR tyrosine kinase inhibitors, *Curr Treat Options Oncol*

lung cancer: a time for cautious optimism?, *Drugs* 66(15): 1919-31.

peroxides in the peritoneal fluid, *Fertil Steril* 63(1): 198-9.

Green tea polyphenol (-)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells, *Biochim Biophys Acta* 1542(1-3):

appraisal of the advances and the controversies of a challenging health problem,

in animal studies in which tea does not show any unwanted side effect.

Hong Kong Obstetrical and Gynaecological Trust Fund 2010

*Rev Food Sci Nutr* 37(8): 693-704.

*Minerva Ginecol* 61(4): 285-98.

reoccurrence and retaining fertility.

**6. Acknowledgment** 

209-20.

8(1): 15-27.

**7. References** 


Green Tea for Endometriosis 293

Kojima-Yuasa, A, Hua, JJ, Kennedy, DO & Matsui-Yuasa, I (2003). Green tea extract inhibits

Koks, CA, Groothuis, PG, Dunselman, GA, de Goeij, AF & Evers, JL (1999). Adhesion of

Kondo, T, Ohta, T, Igura, K, Hara, Y & Kaji, K (2002). Tea catechins inhibit angiogenesis in

Laschke, MW, Schwender, C, Scheuer, C, Vollmar, B & Menger, MD (2008). Epigallocatechin-

Mahutte, NG & Arici, A (2003). Medical management of endometriosis-associated pain,

McCall, MR & Frei, B (1999). Can antioxidant vitamins materially reduce oxidative damage

McCarthy, M (2003). Antiangiogenesis drug promising for metastatic colorectal cancer,

Miles, EA, Zoubouli, P & Calder, PC (2005). Effects of polyphenols on human Th1 and Th2

Milingos, S, Protopapas, A, Kallipolitis, G, Drakakis, P, Loutradis, D, Liapi, A & Antsaklis, A

Miura, S, Watanabe, J, Tomita, T, Sano, M & Tomita, I (1994). The inhibitory effects of tea

Miura, Y, Chiba, T, Miura, S, Tomita, I, Umegaki, K, Ikeda, M & Tomita, T (2000). Green tea

lipoproteins: an ex vivo study in humans, *J Nutr Biochem* 11(4): 216-22. Mo, X, Li, D, Pu, Y, Xi, G, Le, X & Fu, Z (1993). Clinical studies on the mechanism for acupuncture stimulation of ovulation, *J Tradit Chin Med* 13(2): 115-9. Montagna, P, Capellino, S, Villaggio, B, Remorgida, V, Ragni, N, Cutolo, M & Ferrero, S

(2006). Endometriosis in patients with chronic pelvic pain: is staging predictive of the efficacy of laparoscopic surgery in pain relief?, *Gynecol Obstet Invest* 62(1): 48-54.

polyphenols (flavan-3-ol derivatives) on Cu2+ mediated oxidative modification of

polyphenols (flavan 3-ols) prevent oxidative modification of low density

(2008). Peritoneal fluid macrophages in endometriosis: correlation between the

oxidatively modified lipid-protein complexes in endometrium and endometriosis,

expression of estrogen receptors and inflammation, *Fertil Steril* 90(1): 156-64. Murphy, AA, Palinski, W, Rankin, S, Morales, AJ & Parthasarathy, S (1998). Evidence for

regression of endometriotic lesions in vivo, *Hum Reprod* 23(10): 2308-18. Ma, JX, Zhang, SX & Wang, JJ (2005). Down-regulation of angiogenic inhibitors: a potential pathogenic mechanism for diabetic complications, *Curr Diabetes Rev* 1(2): 183-96. Maas, JW, Groothuis, PG, Dunselman, GA, de Goeij, AF, Struijker-Boudier, HA & Evers, JL

through inhibition of VEGF receptor binding, *Cancer Lett* 180(2): 139-44. Kundu, JK & Surh, YJ (2008). Inflammation: gearing the journey to cancer, *Mutat Res* 659(1-

expression of VEGF receptors, *Life Sci* 73(10): 1299-313.

and electron microscopic study, *Hum Reprod* 14(3): 816-22.

2): 15-30.

*Reprod* 16(4): 627-31.

*Lancet* 361(9373): 1959.

*Fertil Steril* 69(6): 1092-4.

*Obstet Gynecol Clin North Am* 30(1): 133-50.

cytokine production, *Clin Nutr* 24(5): 780-4.

in humans?, *Free Radic Biol Med* 26(7-8): 1034-53.

low density lipoprotein, *Biol Pharm Bull* 17(12): 1567-72.

angiogenesis of human umbilical vein endothelial cells through reduction of

shed menstrual tissue in an in-vitro model using amnion and peritoneum: a light

vitro, measured by human endothelial cell growth, migration and tube formation,

3-gallate inhibits estrogen-induced activation of endometrial cells in vitro and causes

(2001). Development of endometriosis-like lesions after transplantation of human endometrial fragments onto the chick embryo chorioallantoic membrane, *Hum* 


Graham, HN (1992). Green tea composition, consumption, and polyphenol chemistry, *Prev* 

Griffioen, AW & Molema, G (2000). Angiogenesis: potentials for pharmacologic intervention

Guo, Q, Zhao, B, Li, M, Shen, S & Xin, W (1996). Studies on protective mechanisms of four

Gurdol, F, Oner-Yyidothan, Y, Yalcyn, O, Genc, S & Buyru, F (1997). Changes in enzymatic

Halme, J, Becker, S, Hammond, MG, Raj, MH & Raj, S (1983). Increased activation of pelvic

Hamer, M & Steptoe, A (2007). Association between physical fitness, parasympathetic control, and proinflammatory responses to mental stress, *Psychosom Med* 69(7): 660-6. Hansen, KA & Eyster, KM (2006). A review of current management of endometriosis in

Ho, HN, Wu, MY, Chen, SU, Chao, KH, Chen, CD & Yang, YS (1997). Total antioxidant

Hull, ML, Charnock-Jones, DS, Chan, CL, Bruner-Tran, KL, Osteen, KG, Tom, BD, Fan, TP &

Jung, YD & Ellis, LM (2001). Inhibition of tumour invasion and angiogenesis by

Kabbinavar, F, Hurwitz, HI, Fehrenbacher, L, Meropol, NJ, Novotny, WF, Lieberman, G,

Kavtaradze, ND, Dominguez, CE, Rock, JA & Parthasarathy, S (2003). Vitamin E and C supplementation reduces endometriosis related pelvic pain, *Fertil Steril* 80: S221-222.

Kennedy, S, Bergqvist, A, Chapron, C, D'Hooghe, T, Dunselman, G, Greb, R, Hummelshoj,

Khan, N, Afaq, F, Saleem, M, Ahmad, N & Mukhtar, H (2006). Targeting multiple signaling

Khan, N & Mukhtar, H (2007). Tea polyphenols for health promotion, *Life Sci* 81(7): 519-33. Khoury, MJ, Adams, MM, Rhodes, P & Erickson, JD (1987). Monitoring for multiple malformations in the detection of epidemics of birth defects, *Teratology* 36(3): 345-53.

Kistner, RW (1959). Conservative management of endometriosis, *J Lancet* 79(5): 179-83.

menopause, *Res Commun Mol Pathol Pharmacol* 97(1): 38-46.

2006: an evidence-based approach, *S D Med* 59(4): 153-9.

with metastatic colorectal cancer, *J Clin Oncol* 21(1): 60-5.

Kennedy, S (2004). *The Patient's Essential Guide to Endometriosis.*, Alden Press.

treatment of endometriosis, *Hum Reprod* 20(10): 2698-704.

endometriosis, *Hum Reprod* 12(12): 2810-5.

*Clin Endocrinol Metab* 88(6): 2889-99.

in the treatment of cancer, cardiovascular diseases, and chronic inflammation,

components of green tea polyphenols against lipid peroxidation in synaptosomes,

antioxidant defense system in blood and endometrial tissues of women after

macrophages in infertile women with mild endometriosis, *Am J Obstet Gynecol*

status and nitric oxide do not increase in peritoneal fluids from women with

Smith, SK (2003). Antiangiogenic agents are effective inhibitors of endometriosis, *J* 

epigallocatechin gallate (EGCG), a major component of green tea, *Int J Exp Pathol*

Griffing, S & Bergsland, E (2003). Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients

L, Prentice, A & Saridogan, E (2005). ESHRE guideline for the diagnosis and

pathways by green tea polyphenol (-)-epigallocatechin-3-gallate, *Cancer Res* 66(5):

*Med* 21(3): 334-50.

145(3): 333-7.

82(6): 309-16.

2500-5.

*Pharmacol Rev* 52(2): 237-68.

*Biochim Biophys Acta* 1304(3): 210-22.


Green Tea for Endometriosis 295

Scarpellini, F, Sbracia, M, Lecchini, S & Scarpellini, L (2002). Anti-angiogenesis treatment with thalidomide in endometriosis: a pilot study., *Fertil Steril* 78: S87. Schweppe, KW (2001). Current place of progestins in the treatment of endometriosis-related

Schweppe, KW (2005). [Guidelines for the use of GnRH-analogues in the treatment of

Shaw, RW (1988). LHRH analogues in the treatment of endometriosis--comparative results

Simpson, ER, Clyne, C, Rubin, G, Boon, WC, Robertson, K, Britt, K, Speed, C & Jones, M

Slivova, V, Zaloga, G, DeMichele, SJ, Mukerji, P, Huang, YS, Siddiqui, R, Harvey, K,

Spiteller, G (2001). Lipid peroxidation in aging and age-dependent diseases, *Exp Gerontol*

Surrey, ES & Hornstein, MD (2002). Prolonged GnRH agonist and add-back therapy for

Surrey, ES & Schoolcraft, WB (2003). Management of endometriosis-associated infertility,

Sutton, CJ, Ewen, SP, Whitelaw, N & Haines, P (1994). Prospective, randomized, double-

with minimal, mild, and moderate endometriosis, *Fertil Steril* 62(4): 696-700. Sutton, CJ, Pooley, AS, Ewen, SP & Haines, P (1997). Follow-up report on a randomized

Szczepanska, M, Kozlik, J, Skrzypczak, J & Mikolajczyk, M (2003). Oxidative stress may be a

Tang, FY & Meydani, M (2001). Green tea catechins and vitamin E inhibit angiogenesis of

Tonnesen, MG, Feng, X & Clark, RA (2000). Angiogenesis in wound healing, *J Investig* 

Uesato, S, Kitagawa, Y, Kamishimoto, M, Kumagai, A, Hori, H & Nagasawa, H (2001).

Valle, RF & Sciarra, JJ (2003). Endometriosis: treatment strategies, *Ann N Y Acad Sci* 997: 229-39. Vercellini, P, Trespidi, L, Colombo, A, Vendola, N, Marchini, M & Crosignani, PG (1993). A

Vercellini, P, Fedele, L, Pietropaolo, G, Frontino, G, Somigliana, E & Crosignani, PG (2003).

Vercellini, P, Fedele, L, Aimi, G, Pietropaolo, G, Consonni, D & Crosignani, PG (2007).

pelvic pain associated with endometriosis, *Fertil Steril* 60(1): 75-9.

minimal to moderate endometriosis, *Fertil Steril* 68(6): 1070-4.

piece in the endometriosis puzzle, *Fertil Steril* 79(6): 1288-93.

Valachovicova, T & Sliva, D (2005). Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast

symptomatic endometriosis: long-term follow-up, *Obstet Gynecol* 99(5 Pt 1): 709-19.

blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated

controlled trial of laser laparoscopy in the treatment of pelvic pain associated with

human microvascular endothelial cells through suppression of IL-8 production,

Inhibition of green tea catechins against the growth of cancerous human colon and

gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for

Progestogens for endometriosis: forward to the past, *Hum Reprod Update* 9(4): 387-

Association between endometriosis stage, lesion type, patient characteristics and

with other treatments, *Baillieres Clin Obstet Gynaecol* 2(3): 659-75.

(2002). Aromatase--a brief overview, *Annu Rev Physiol* 64: 93-127.

complaints, *Gynecol Endocrinol* 15 Suppl 6: 22-8.

endometriosis], *Zentralbl Gynakol* 127(5): 308-13.

cancer cells, *Nutr Cancer* 52(1): 66-73.

*Obstet Gynecol Clin North Am* 30(1): 193-208.

*Nutr Cancer* 41(1-2): 119-25.

96.

*Dermatol Symp Proc* 5(1): 40-6.

hepatic epithelial cells, *Cancer Lett* 170(1): 41-4.

36(9): 1425-57.


Murphy, AA, Palinski, W, Rankin, S, Morales, AJ & Parthasarathy, S (1998). Macrophage

Murphy, AA, Santanam, N, Morales, AJ & Parthasarathy, S (1998). Lysophosphatidyl

Nakachi, K, Suemasu, K, Suga, K, Takeo, T, Imai, K & Higashi, Y (1998). Influence of

Namnoum, AB, Hickman, TN, Goodman, SB, Gehlbach, DL & Rock, JA (1995). Incidence of

Nap, AW, Griffioen, AW, Dunselman, GA, Bouma-Ter Steege, JC, Thijssen, VL, Evers, JL &

Nisolle, M, Casanas-Roux, F, Anaf, V, Mine, JM & Donnez, J (1993). Morphometric study of the stromal vascularization in peritoneal endometriosis, *Fertil Steril* 59(3): 681-4.

Pierce, SJ, Gazvani, MR & Farquharson, RG (2000). Long-term use of gonadotropin-releasing

Rice, VM (2002). Conventional medical therapies for endometriosis, *Ann N Y Acad Sci* 955:

Richter, ON, Dorn, C, Rosing, B, Flaskamp, C & Ulrich, U (2005). Tumor necrosis factor

Saltiel, E & Garabedian-Ruffalo, SM (1991). Pharmacologic management of endometriosis,

Sampson, JA (1927). Metastatic or Embolic Endometriosis, due to the Menstrual

Santanam, NK, Kavtaradze, N, Dominguez, C, Rock, JA, Parthasarathy, S & Murphy, AA

Sartippour, MR, Heber, D, Zhang, L, Beatty, P, Elashoff, D, Elashoff, R, Go, VL & Brooks,

Sartippour, MR, Shao, ZM, Heber, D, Beatty, P, Zhang, L, Liu, C, Ellis, L, Liu, W, Go, VL &

cytokines in women with endometriosis., *Fertil Steril* 80: S32-33.

induction in human breast cancer cells, *J Nutr* 132(8): 2307-11.

Olive, DL & Pritts, EA (2001). Treatment of endometriosis, *N Engl J Med* 345(4): 266-75. Park, JS, Kim, MH, Chang, HJ, Kim, KM, Kim, SM, Shin, BA, Ahn, BW & Jung, YD (2006).

endometriosis, *J Clin Endocrinol Metab* 83(6): 2110-3.

*Steril* 69(6): 1085-91.

*Cancer Res* 89(3): 254-61.

*Metab* 89(3): 1089-95.

29(5): 1247-52.

*Med* 15(1): 77-96.

343-52; discussion 389-93, 396-406.

*Gynecol Obstet* 271(2): 143-7.

*Clin Pharm* 10(7): 518-31.

93-110 43.

487-91.

scavenger receptor(s) and oxidatively modified proteins in endometriosis, *Fertil* 

choline, a chemotactic factor for monocytes/T-lymphocytes is elevated in

drinking green tea on breast cancer malignancy among Japanese patients, *Jpn J* 

symptom recurrence after hysterectomy for endometriosis, *Fertil Steril* 64(5): 898-902.

Groothuis, PG (2004). Antiangiogenesis therapy for endometriosis, *J Clin Endocrinol* 

Epigallocatechin-3-gallate inhibits the PDGF-induced VEGF expression in human vascular smooth muscle cells via blocking PDGF receptor and Erk-1/2, *Int J Oncol*

hormone analogs and hormone replacement therapy in the management of endometriosis: a randomized trial with a 6-year follow-up, *Fertil Steril* 74(5): 964-8. Rice-Evans, CA & Diplock, AT (1993). Current status of antioxidant therapy, *Free Radic Biol* 

alpha secretion by peritoneal macrophages in patients with endometriosis, *Arch* 

Dissemination of Endometrial Tissue into the Venous Circulation, *Am J Pathol* 3(2):

(2003). Antioxidant supplementation reduces total chemokines and inflammatory

MN (2002). Inhibition of fibroblast growth factors by green tea, *Int J Oncol* 21(3):

Brooks, MN (2002). Green tea inhibits vascular endothelial growth factor (VEGF)


**15** 

 *Iran* 

Jafar Ai and Esmaeil Sadroddiny

*Tehran University of Medical Sciences, Tehran,* 

**Endometrial Stem Cells and Endometriosis** 

*Department of Tissue Engineering, School of Advanced Medical Technologies,* 

Stem cells (SCs) are undifferentiated cells which are able to remain at this state for several generations following cell proliferations. SCs are also able to take part in natural *in vivo*

On this basis, endometrial stem cells (EnSCs), characterized by higher abilities for proliferation, differentiation, fast angiogenesis during menstruation and immune tolerance for embryo during pregnancy, have been considered as a valuable source of stem cells (Gargett, Chan et al. 2007; Meng, Ichim et al. 2007). Several researches have demonstrated presence of highly pleuripotent mesenchymal stem cells in endometrium by differentiation potency to various cell types such as, insulin producer cells (Li, Chen et al. 2010), osteoblasts (Ai, Mehrabani. 2010) , odontoblasts (Ai, Tabatabaei et al. 2009), neurons (Wolff, Gao et al. 2011) (Ai, Tabatabaei et al. 2009) and Myoblast (Ai, Tabatabaei et al. 2009). These findings may open up new opportunities to use endometrial stem cells in tissue engineering and cell

Additionally our previous studies demonstrated that EnSCs are able to participate at a phenomenon like angiogenesis in 3-D cultures which is similar to early stages of endometriosis (Esfandiari, Ai et al. 2007; Esfandiari, Khazaei et al. 2007; Esfandiari, Ai et al. 2008) which may propose a novel mechanism in pathogenesis of endometriosis compared to the traditional theory that emphasis on retrograde menstruation as a possible factor. These studies are supported by others who demonstrated recruitment of bone marrow-derived mesenchymal stem cells to the endometrium (Taylor 2004) and these all may point to the role of stem cells at the pathogenesis of endometriosis (Figueira, Abrão et al.; Sasson and Taylor 2008). Therefore, endometrial stem cells could be considered as binary role-player in natural function of endometrium and endometriosis and potentially could be used as a

The inner layer of uterus (Endometrium) comprises the mucosal lining which is highly regenerative tissue during menstrual cycle. The human endometrium undergoes more than 400 cycles of shedding and regeneration during a woman's reproductive years (McLennan and Rydell 1965). This layer is backed by a thick muscular myometrium which consists of muscular cells. There is no submucosal tissue to separate endometrial glandular tissue from

phenomena such as wound repair after physical damages or tissue regenerations.

**1. Introduction** 

therapy (Ai , Mehrabani. 2009).

target in endometriosis therapy.

**2. Histology of human uterus** 

severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients, *Hum Reprod* 22(1): 266-71.

