The potential of herbal medicine in the management of endometriosis.
Endometriosis is a chronic inflammatory disease characterised by the presence of endometrial tissue outside the uterine cavity. (1, 2) It is a condition that affects 10 to 15% of women of reproductive age. Approximately 80% of women with endometriosis experience dysmenorrhoea, dyspareunia, non-menstrual pelvic pain, and constipation. (1-6) There is also increased inflammation, development of scarring and adhesions, fatigue, and negative effects on quality of life. (7) Around 30 to 50% of women with endometriosis experience infertility. (2, 8)
Although the exact mechanisms for the development of endometriosis remain unclear, accumulating evidence suggests that a combination of epigenetic, hormonal, inflammatory, and immunological (including autoimmune) factors are involved in disease progression. (9-12) This article aims to shed light on the pathogenesis of endometriosis and the potential of herbal medicine in the management of endometriosis.
The role of epigenetics in endometriosis
Recent evidence suggests that epigenetic aberrations may be involved in the pathogenesis of many female reproductive conditions, including endometriosis and infertility. (9, 13) Epigenetics relates to changes in chromatin structure and/or gene expression without any mutations in the DNA sequence. Such changes may include methylation status of a promoter region of a gene, changes to the acetylation states of DNA, and modulation of gene expression by microRNAs. (9)
Due to the role of epigenetic modifications in controlling cell development, differentiation, and programming, (14) inflammation is promoted. (9) Local inflammation in endometriotic tissue encourages cell proliferation, evasion of immune surveillance, and local neuroangiogenesis, all of which contribute to the progression of endometriosis. (9)
The role of hormones in endometriosis
It has long been believed that endometriosis is an oestrogen-dependent disease, given its prevalence in reproductive age and regression after menopause. (15-17) Local production of oestrogen in endometriotic lesions can induce the over-expression of cyclooxygenase 2 (COX2), an inflammatory mediator. (18, 19) Oestrogen receptor ([beta] (ER[beta]) levels have been found to be more than 100 times higher in endometriosis than in regular endometrial tissue. A high ER[beta]-to-ER[alpha] ratio in endometriotic stromal cells increases COX 2 levels and is associated with suppressed progesterone receptors. (18) This induces inflammation through the production of prostaglandin E2 (PGE2), establishing a positive feedback cycle, (19) and promoting progesterone resistance. (18)
Moreover, oestradiol (E2), which is primarily found in the ovary, is an effective regulator of endometriosis. (20) Higher levels of oestradiol have been found in menstrual blood of endometriosis patients, compared to healthy women, suggesting that E2 is formed locally in the endometrium. (21) A positive relationship between E2 secretion and the proliferation of endometrial cells further indicates the role of oestrogen in endometriosis progression. (22)
The role of inflammation in endometriosis
Surrounding endometriotic implants is peritoneal fluid. While peritoneal fluid contains a variety of cells, of particular interest are macrophages. (18, 23) Macrophages are increased in total number, concentration, and activation status in women with endometriosis and promote cellular growth through the secretion of pro-inflammatory cytokines (interleukin-1 (IL-1), interleukin-6 (IL-6), interIeukin-8 (IL-8), interleukin-12 (IL-12) and tumour necrosis factor-[alpha] (TNF-[alpha])). (24) The cellular changes in the peritoneal fluid encourage cell proliferation, evasion of immune surveillance, and local neuroangiogenesis. All of these changes contribute to the progression of endometriosis and correlate with the severity of the disease. (24-27)
There is evidence that mast cells play a role in the pathophysiology of endometriosis (28, 29) and activated mast cells have been found to be increased in endometriotic lesions. (29) Elevated oestrogen E2 concentrations may be a key factor for the degranulation and recruitment of mast cells in ovarian endometriomas, which may play a key role in endometriosis-associated dysmenorrhea. (28)
Furthermore, the inflammation involved in endometriosis can stimulate afferent nerve fibres that carry signals to the brain, where they are interpreted as pain. (18) A United States and Canadian study of 3,680 women with endometriosis found that 99% experienced pain attributed to endometriosis and 96% experienced pain during menses. (10) It is therefore comprehensible that the inflammatory response in the peritoneal cavity is a pivotal event in endometriosis that likens the disease to that of chronic inflammation. (1 ,2, 11, 30, 31)
The role of the immune system in endometriosis
Recent studies suggest a link between immunologic and inflammatory responses that are encountered in endometriosis. (1, 2, 7, 11, 31) Women with endometriosis have been found to exhibit altered immune surveillance. (7) Alterations in immune function, particularly cellular immunity, play a role in establishing endometrial implants and sustaining their growth. (18) This promotes the release of inflammatory mediators including cytokines, chemokines, and growth factors. (32)
A link between endometriosis and autoimmunity remains ambiguous. However, it is understood that endometriosis shares characteristics with autoimmune diseases, including polyclonal B cell activation, abnormal functions of T and B cells, and inflammatory tissue damage. (33) The presence of autoantibodies further likens endometriosis to an autoimmune condition, (33) and there have been reports of higher rates of hypothyroidism (p<0.0001), rheumatoid arthritis (p=0.001), systemic lupus erythematosus (p<0.0001), Sjogren's syndrome (p<0.0001), and multiple sclerosis (p<0.0001) in women with endometriosis. (10) Additionally, there are increased rates of food sensitivities, asthma and allergies. (7)
To conclude, it can be said that the dysregulation of hormones, inflammation, and the immune system contribute to amplifying the progression of endometriosis.
Standard management of endometriosis
Current management of endometriosis aims to reduce the severity and recurrence of pain. (9) This is achieved by use of pharmacological medicines that suppress the NF-kappa B pathway and pro-inflammatory cytokines. (34) Standard management utilises non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics to reduce pain, hormonal drugs including oral contraceptives, danazol, gestrinone, GnRH agonists, and dienogest to suppress ovarian function, and laparoscopy to ablate endometriotic lesions. (9, 35) However, long-term administration of these therapies has been associated with concerning adverse effects, including haemorrhage, perimenopausal symptoms, masculinising manifestation, and liver dysfunction. (3) In light of this, herbal medicines have become popular for their effect, not only in pain management, but also in managing other symptoms associated with endometriosis, including general fatigue, anxiety, depression, gastrointestinal upset, and subfertility. (18)
Herbal medicine and its uses
Herbal medicine is widely used in complementary medicine practices, including that of naturopathy. (36) Herbal medicine has been long used for the prevention and treatment of diseases through the use of extracts of the bark, roots, leaves, seeds, flowers, fruits, shrubs, and woody vines from medicinal plants. (37-39) The use of herbal medicine in naturopathy aims to address the individual needs of each patient, with emphasis on the effect of herbal medicines both on individual body systems and the body as a whole. (9, 40)
The World Health Organization estimates that approximately 80% of the world's population use traditional medicine for their primary health care needs, with a focus on herbal medicine. (37) The increased use of herbal medicine in recent years has been welcomed in part because of the growth of research examining various herbal preparations and their effects on the human body. (41) In Australia, the use of complementary medicine is on the rise, with research showing that females are more likely to use it than males. (36) Furthermore, the Australian Longitudinal Study on Women's Health (42) found that women with endometriosis were 50% more likely to have consulted with a naturopath or herbalist than women who had not been diagnosed with endometriosis. The use of herbal medicine in managing endometriosis focuses on the actions of the herbs and their effect on the body. (43) Some of these include anti-inflammatory, antioxidant, antiproliferative, and analgesic actions. (9)
The effect of herbal medicine on endometriosis
As previously noted, endometriosis is a multi-dimensional and complex disease that often requires multi-therapeutic strategies to manage the symptoms. (44) As the symptoms vary in each individual, negatively affecting their quality of life, (43) it is critical that the management of endometriosis is tailored to the individual, with a focus on the symptoms that most afflict that patient. (46)
Research is limited, and the full effect of herbal medicine on endometriosis is relatively unknown. This section includes a number of herbal medicines that have potential in managing endometriosis. These include Cat's claw, Chaste tree, Cramp bark, Dong Quai, Feverfew, Ginger, Green tea, Japanese knotweed, Kudzu, Licorice, St John's wort, Turmeric, and Valerian. Table 1 presents the actions of herbal medicines used in managing endometriosis.
Cat's claw (uncaria tomentosa)
Cat's claw is native to tropical Central and South America and has been used for at least 2000 years among many Peruvian tribes. (47) It has been widely used to treat inflammation and oxidative stress. (48, 49) The bark of Cat's claw contains flavonoids. phenolic acids, diterpenes, and tannins, which contribute to its antiinflammatory, immunomodulatory, and antioxidant properties. (47, 49, 50) The primary mechanism for cat's claw anti-inflammatory effect is its ability to modulate the immune system via suppression of TNF-[alpha], IL-1, IL-6, and IL-8 synthesis. (50, 51)
Chaste tree (vitex agnus-castus)
Chaste tree, or Vitex, is a small tree or shrub native to European, Mediterranean, and Central Asian countries. (52) It is commonly used in the management of female reproductive disorders, notably premenstrual syndrome (PMS) and infertility. (38, 53, 54)
While no human studies have particularly examined the effects of Chaste tree in endometriosis, the herb is widely used for its ability to regulate hormonal balance and improve the oestrogen-to-progesterone ratio, an imbalance that is implicated in endometriosis. (9, 55, 56) In a study of 61 women, 32 patients in the experimental group received 40 drops of Chaste tree for four months throughout the follicular phase. Clinical pregnancy rates in those treated with Chaste tree were higher than that of the control group (34.37% vs. 13.79%, respectively). In this study, Chaste tree helped stimulate and normalise the function of the hypothalamus and pituitary gland, in turn regulating gonadotropin-releasing hormone, luteinizing hormone, and follicle stimulating hormone receptors. Additionally, treatment with Chaste tree significantly decreased oestradiol levels on ovulation day and the average time of serum positive [beta]-HCG test. (38) As infertility affects 30-50% of women with endometriosis, (8) Chaste tree may be an effective treatment for endometriosis-related infertility.
Cramp bark (viburnum opulus)
The use of Cramp bark is widespread throughout Eastern, North-eastern, Western, and Central Europe. Traditionally the fruits of Cramp bark have been used to treat menstrual and stomach cramping, (57) and primary and secondary dysmenorrhoea. (25) Cramp bark contains scopoletin, which is known for its smooth muscle anti-spasmodic activity. Cramp bark also has antiinflammatory, antioxidant, and antinociceptive properties. (58, 59)
Cramp bark has been long used to relieve pain and muscle spasm in the uterus before menstruation. (25) This suggests that it may be used medicinally in women with endometriosis to help relieve muscular cramping and pain associated with menstruation. While the use of Cramp bark in humans with endometriosis requires further research, an experimental study found that its anti-inflammatory property decreases TNF-[alpha], vascular endothelial growth factor (VEGF), and IL-6 levels in peritoneal fluid. (25) As inflammation and pain are associated with endometriosis, Cramp bark may be beneficial in the management of endometriosis.
Dong quai (angelica sinensis)
Dong Quai is a Chinese herbal medicine well-known for its use as a blood tonic to treat gynaecological diseases, including menstrual disorders, dysmenorrhoea, and amenorrhoea. (60, 61) For thousands of years, Dong Quai has been used in Traditional Chinese Medicine to treat blood stasis. Blood stasis is a concept that explains a potential aetiology of endometriosis as an accumulation of damp-heat' in the lower part of the body that contributes to pelvic inflammation. (62, 63)
Over 70 compounds have been isolated and identified from the roots of Dong Quai, with the main constituents being ferulic acid, Z-ligustilide, and butylidenephthalide. (61) Collectively, these constituents exert anti-inflammatory, immunostimulatory, neuroprotective, and hepatoprotective properties. (61) An in vitro study (63) found that the antiinflammatory properties of Z-ligustilide inhibited TNF-[alpha]-mediated NF-kB activation. As NF-kB is thought to promote and maintain endometriosis, (64) its inhibition provides promise of benefit for the management of the disease. (63) Further study is required to understand the effects of Z-ligustilide and other compounds in human endometriotic cells. (65)
Feverfew (tanacetum parthenium)
Feverfew is a herb with long traditional use. It is a popular remedy for fevers and migraines, with its common name derived from the Latin word febrifugia, meaning 'fever reducer'. (66) It is also renowned for its efficacy in the treatment of dysmenorrhoea and rheumatoid arthritis. (67) The prominent active constituents of feverfew are sesquiterpene lactones, namely parthenolide, which possesses antisecretory, anti-inflammatory, and antispasmodic actions. (66)
While feverfew is not traditionally-known for its use in endometriosis, it may be beneficial due to its therapeutic actions. A recent study investigating the effect of parthenolide on human endometriotic cells found that feverfew inhibited NF-kB activity. (67) As local inflammation in the peritoneal fluid is considered a contributing factor in the pathogenesis and progression of endometriosis, inhibition of NF-kB and subsequent cytokine secretion suggests feverfew as an appropriate candidate for managing endometriosis. (67)
Ginger (zingiber officinale)
Ginger is a tropical and sub-tropical plant derived from the Zingiberaceae family. (68) For centuries it has been used as a spice in cooking (69) as well as a traditional medicine and dietary supplement. (68)
In ancient times, ginger was used to treat headaches, nausea, and colds. (68) In recent Western herbal medicine, ginger has gained attention for its use as a potent anti-inflammatory, antioxidant, and analgesic, due to its ability to inhibit the production of pro-inflammatory cytokines. (69) Ginger contains numerous constituents that vary depending on where the rhizomes are grown and whether they are fresh or dry. (69) These primarily include gingerols, paradols, and shogaols. (68)
A recent systematic review and metaanalysis found that ginger was more effective than placebo for pain relief associated with dysmenorrhoea. (70) One of the studies found that administration of 1,500 mg of ginger powder daily for three days was found to be safe and effective in producing analgesia in 105 students with primary dysmenorrhoea. (71) It should be noted that these studies are based on primary dysmenorrhoea, (71-74) however, they provide promising results in the use of ginger as an analgesic in secondary dysmenorrhoea experienced in endometriosis. Ginger is considered safe when used appropriately. (70)
Green tea (camellia sinensis)
Green tea, from the plant Camellia sinensis, was first exported from India to Japan during the 17th century. (75) It is one of the most popular beverages worldwide and is beneficial in a broad variety of ailments, including heart disease and liver disease. (75, 76) The main constituents in green tea are catechins, of which epigallocatechin-3-gallate (EGCG) is most abundant, accounting for 50-80% of catechin content. (76) EGCG possesses antioxidant, anti-inflammatory, anti-angiogenic, and neuroprotective properties. (75, 76) It can induce cell growth arrest and apoptosis by suppressing NF-kB activation and activating killer caspases. (76)
Japanese knotwood (polygonum cuspidatum)
Japanese knotweed is a traditional herbal medicine that has long been used in Japan and China. (77) The most biologically active constituent in Japanese Knotweed is the polyphenol, resveratrol. (78) Resveratrol naturally occurs in certain plants in response to stress stimuli, including microbe infection, ultraviolet radiation, and injury. (77) Resveratrol exhibits antioxidant, anti-inflammatory, anti-angiogenic, hepatoprotective, immunomodulatory, and neuroprotective effects. (3, 78, 79) Due to its ability to suppress cell proliferation, induce apoptosis, and suppress metastasis, resveratrol has been studied for its antitumour effect (78) and is being examined in clinical trials for its effect in several conditions including mood disorders, Alzheimer's disease, schizophrenia, and non-alcoholic fatty liver disease, and as a potential anti-ageing agent. (79)
The effect of resveratrol was investigated in 12 women with endometriosis who failed to obtain pain relief during oral contraceptive use (a combination of drospirenone and ethinylestradiol). A dose of 30 mg of resveratrol was added to the contraceptive regimen. The study showed that 10 of the 12 of patients had complete resolution of dysmenorrhea and pelvic pain after two months of use. This result suggests that resveratrol potentiates the effect of oral contraceptives in the management of endometriosis-associated dysmenorrhoea. (80) Investigation of the effect of resveratrol administration (as a single treatment) in secondary dysmenorrhoea and endometriotic cell growth requires future research. (6)
Kudzu (pueraria lobata)
Kudzu, also known as Japanese Arrowroot, is a perennial leguminous vine native to eastern Asia. It produces an edible tuber, leaves, and flowers, of which the latter is widely consumed as a tea in China, and as a "cure" for hangovers and obesity in Korea and Japan. It is also an ingredient in sweet jelly in the southern United States. (30) Kudzu is rich in isoflavones, including genistein, daidzein, kakkalide, puerarin, and tectoridin. (81) A wide range of actions is attributed to the presence of isoflavones. Some of the actions include anti-inflammatory, antioxidant, hormone-regulating, hepatoprotective, hypoglycaemic, hypolipidaemic, and anti-mutagenic. (30)
Licorice (glycyrrhiza glabra)
Licorice has been used in Europe for several thousand years. It has long been beneficial in an array of conditions including depression, menopause, renal and liver complications, upper respiratory tract congestion, and gastric and duodenal ulcers. (82) The major active constituent obtained from licorice is glycyrrhizin, a triterpene isolated from the herb's root and rhizome. (83) Glycyrrhizin possesses anti-inflammatory, antioxidant, anti-spasmodic, and anti-depressive properties. (83, 84)
A study by Wang, Hao, & Chi (85) investigated the effect of glycyrrhizin on LPS-induced endometriosis. LPS, the major outer membrane protein of E. coli, has the potential to stimulate the release of inflammatory cytokines including TNF-[alpha] and IL-lbeta. The anti-inflammatory properties of glycyrrhizin significantly inhibited LPS-induced TNF-[alpha], IL-1, nitric oxide, and PGE2 production. While this study is experimental, it showed promising effects in the management of endometriosis.
Due to its potential oestrogenic effect, some suggest that Licorice should be avoided by women with endometriosis, as excess oestrogen may aggravate endometriosis. (18) Future analysis of this mechanism is required to determine the usefulness of Licorice in the management of endometriosis.
St John's wort (hypericum perforatum)
St John's Wort is a perennial herbaceous plant that grows in sunny locations throughout Europe, Asia, Northern Africa, and North America. (86) The use of St John's Wort dates back to the time of ancient Greek herbalists, Hippocrates, Theophrastus, Dioscorides, and Galen, who prescribed the flowering herb for treatment of ailments ranging from menstrual cramps to snake or reptile bites to nervous disturbances. (86) St John's wort contains numerous biologically active components, of which flavonoids (rutin, hyperoside, quercetin, and quercitrin), naphthodianthrones (hypericin and pseudohypericin), and acylphloroglucinols (hyperforin and adhyperforin) are abundant. (87) These constituents possess anti-inflammatory, antioxidant, anti-nociceptive, analgesic, and wound-healing properties, all of which are beneficial in the management of pain. (86)
Pain is the single most debilitating factor for many women with endometriosis. (18) This pain is associated with symptoms of dysmenorrhoea, deep dyspareunia, pain after intercourse, and recurrent pain unrelated to menstruation or coitus. (88) Hyperforin increases pain threshold through the activation of an opioid-dependent pathway. (86) This effect, in combination with the low incidence of side effects and low cost, suggests St John's wort as a promising herbal medicine in pain conditions, including that of endometriosis. However, additional clinical controlled trials are necessary to confirm the positive analgesic results. (86)
St John's Wort may also positively affect the quality of life of women suffering from endometriosis. Recent studies (89-91) have found that women with endometriosis who experience chronic pelvic pain are at an elevated risk of experiencing depression, anxiety, psychosocial stress, and poor quality of life. St John's wort has been extensively researched for its use in depression and anxiety, due to the effect of hyperforin on inhibiting the reuptake of serotonin, noradrenaline, and dopamine neurotransmitters. (92) Influencing pain perception and assisting in neurotransmitter synthesis may be beneficial in endometriosis management. (91)
Turmeric (curcuma longa)
Turmeric is a common spice frequently used in Asian cooking that gives curry powder its yellowish colour. (93) The principle polyphenol isolated from the rhizome of turmeric is curcumin. It possesses numerous properties, including anti-inflammatory, antioxidant, anti-angiogenic, and antineoplastic ones. (12, 22) As a powerful antiinflammatory, curcumin suppresses the pro-inflammatory cytokines TNF-[alpha], IL-6, and IL-8, and inhibits mRNA expression of intercellular and vascular cell adhesion molecules in endometriotic stromal cells. (94) As endometriosis is thought to be a chronic inflammatory condition, reducing the expression of pro-inflammatory cytokines may be beneficial in reducing the progression of the disease.
In vitro studies of Curcumin have indicated an effect of reducing levels of oestradiol. (22) As oestrogen plays a crucial role in the maintenance of endometriosis, with high oestradiol E2 values found in endometriotic epithelial and stromal cells, curcumin may be beneficial in suppressing the proliferation of endometrial cells by reducing E2 levels. In doing so, a decrease in the production and release of excess cytokines (TNF-[alpha], IL-1, IL-6, IL-8) may reduce inflammation and therefore the progression of endometriosis. (18, 22)
Valerian (Valeriana officinalis)
Since the 11th century, the roots and rhizomes of valerian have been used for their tranquilising, sedative, and antispasmodic effects. In modern herbal medicine, valerian is prescribed for the treatment of dysmenorrhea, reducing pain, cyclic cramps, anxiety, and stress. (95) The prominent active constituent in valerian is valeric acid, which provides pain relief by inhibiting the release of prostaglandins, thereby preventing smooth muscle contraction of the uterus during menstruation. (96)
In a double-blind, randomised, placebo-controlled trial, (95) 100 students were randomly assigned to receive valerian (n=49) or placebo (n=51) for the treatment of primary dysmenorrhoea. Valerian (255 mg dose) was given three times daily for three days beginning at the onset of menstruation, and continued for two consecutive menstrual cycles. Valerian was found to be effective in reducing pain severity. This is likely to be due to its antispasmodic actions. While this trial focused on the effect of valerian on primary dysmenorrhoea, the prospect of valerian reducing pain severity in secondary dysmenorrhoea associated with endometriosis is possible and worthy of further consideration.
Valerian and St John's wort
Moreover, as quality of life can be compromised in women with endometriosis, two anti-depressant and anxiolytic herbs may be beneficial as part of the management of the disease. Muller, Pfeil, and von den Driesch (97) conducted a study to evaluate the combined effect of Valerian and St John's Wort in the treatment of depression and anxiety. A combination of 500 mg valerian extract and 600 mg St John's wort per day, or 1000 mg valerian extract and 600 mg St John's wort per day were examined. This combined therapy was found to be effective in reducing symptoms of mild to moderate depression (depressed mood, cheerlessness, and exhaustion) comorbid with anxiety (tension, nervousness, and sleep disorders). However, as this study was open and practice-oriented, further controlled trials would be beneficial in clarifying the effectiveness of this combined therapy in the treatment of depression and anxiety.
Endometriosis is a complex disease that presents differently in each patient. Herbal medicines have been used for thousands of years for their health-promoting properties and can play a significant role in the management of endometriosis, both alone and in conjunction with standard medical therapy. Herbal medicines such as Dong Quai, Feverfew, Japanese knotweed, Kudzu, and Turmeric were found to inhibit the NF-kB pathway and suppress pro-inflammatory cytokines. Experimental studies show promise in the reduction of inflammation for Cat's claw, Cramp bark, Green tea, and Licorice. Ginger and Valerian were found effective in the treatment of primary dysmenorrhoea, but clinical trials currently do not show evidence for the use of these herbs in the treatment of secondary dysmenorrhoea. Chaste tree was found effective in regulating hormones and improving pregnancy rates, providing promise in the treatment of endometriosis-induced infertility. St John's Wort is widely used as an anti-depressant and analgesic and may be beneficial in the management of depression, anxiety, and chronic pain that is associated with endometriosis.
Herbal medicines that possess antiinflammatory, antioxidant, anti-angiogenic, anti-depressant, anxiolytic, hepatoprotective, immunomodulatory, and hormone-regulating properties have the potential to positively affect endometriosis. Further research and clinical trials are required to determine the full effect of herbal medicines on endometriosis.
(1.) KennedyS, Bergqvist A, Chapron C, D'Hooghe T, Dunselman G, Greb R, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698-704.
(2.) Facchin F, Barbara G, Saita E, Mosconi P, Roberto A, Fedele L, etal. Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference. J Psychosom Obstet Gynaecol. 2015;36(4):135-41.
(3.) Kong S, Zhang YH, Liu CF, Tsui I, Guo Y, Ai BB, et al. The complementary and alternative medicine for endometriosis: a review of utilization and mechanism. Evidence-based complementary and alternative medicine: eCAM. 2014;2014:146383.
(4.) Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389-98.
(5.) Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235-58.
(6.) Buggio L, Barbara G, Facchin F, Frattaruolo MP, Aimi G, Berlanda N. Self-management and psychological-sexological interventions in patients with endometriosis: strategies, outcomes, and integration into clinical care. Int J Womens Health. 2017;9:281-93.
(7.) KvaskoffM, Mu F, Terry KL, Harris HR, Poole EM, Farland L, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update. 2015;21(4):500-16.
(8.) Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet.2010;27(8):441-7.
(9.) Stephens L, Whitehouse J, Polley M. Western herbal medicine, epigenetics, and endometriosis. J Altern Complement Med. 2013;19(11):853-9.
(10.) Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715-24.
(11.) Christodoulakos G Augoulea A, Lambrinoudaki I, Sioulas V, Creatsas G. Pathogenesis of endometriosis: the role of defective 'immunosurveillance'. Eur J Contracept Reprod Health Care. 2007;12(3):194-202.
(12.) Arablou T, Kolahdouz-Mohammadi R. Curcumin and endometriosis: Review on potential roles and molecular mechanisms. Biomed Pharmacother. 2018;97:91-7.
(13.) Ito F, Yamada Y, Shigemitsu A, Akinishi M, Kaniwa H, Miyake R, et al. Role of Oxidative Stress in Epigenetic Modification in Endometriosis. Reprod Sci. 2017;24(11):1493-502.
(14.) Koike N, Higashiura Y,Akasaka J, Uekuri C, Ito F, Kobayashi H. Epigenetic dysregulation of endometriosis susceptibility genes (Review). Molecular medicine reports. 2015;12(2):1611-6.
(15.) Sasson IE, Taylor HS. Aromatase inhibitor for treatment of a recurrent abdominal wall endometrioma in a postmenopausal woman. Fertil Steril. 2009;92(3):1170 e1-4.
(16.) Kitawaki J, Kado N, Ishihara H, Koshiba H, Kitaoka Y, Honjo H. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83(1-5):149-55.
(17.) Jeon DS, Kim TH, Lee HH, Byun DW. Endometriosis in a postmenopausal woman on hormonal replacement therapy. J Menopausal Med. 2013;19(3):151-3.
(18.) Harris T, Vlass AM. Endometriosis and the Herbal Medicine Approach to Treatment. Journal of the Australian Traditional-Medicine Society. 2015;21(1):10.
(19.) Bulun SE, Yang S, Fang Z, Gurates B, Tamura M, Sebastian S. Estrogen production and metabolism in endometriosis. Ann N Y Acad Sci. 2002;955:75-85; discussion 6-8, 396-406.
(20.) Dassen H, Punyadeera C, Kamps R, Delvoux B, Van Langendonckt A, Donnez J, et al. Estrogen metabolizing enzymes in endometrium and endometriosis. Hum Reprod. 2007;22(12):3148-58.
(21.) Rizner TL. Estrogen metabolism and action in endometriosis. Mol Cell Endocrinol. 2009;307(1-2):8-18.
(22.) Zhang Y, Cao H, Yu Z, Peng HY, Zhang CJ. Curcumin inhibits endometriosis endometrial cells by reducing estradiol production. Iran J Reprod Med. 2013;11(5):415-22.
(23.) Oral E, Olive DL, Arici A. The peritoneal environment in endometriosis. Hum Reprod Update. 1996;2(5):385-98.
(24.) Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev. 2012;11(11):806-14.
(25.) Saltan G, Suntar I, Ozbilgin S, llhan M, Demirel MA, Oz BE, et al. Viburnum opulus L.: A remedy for the treatment of endometriosis demonstrated by rat model of surgically-induced endometriosis. Journal of ethnopharmacology. 2016;193:450-5.
(26.) Eisermann J, Gast MJ, Pineda J, Odem RR, Collins JL. Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery. Fertility and Sterility. 1988;50(4):573-9.
(27.) Asante A, Taylor RN. Endometriosis: the role of neuroangiogenesis. Annu Rev Physiol. 2011;73:163-82.
(28.) Zhu TH, Ding SJ, Li TT, Zhu LB, Huang XF, Zhang XM. Estrogen is an important mediator of mast cell activation in ovarian endometriomas. Reproduction. 2018;155(1):73-83.
(29.) Binda MM, Donnez J, Dolmans MM. Targeting mast cells: a new way to treat endometriosis. Expert Opin Ther Targets. 2017;21(1):67-75.
(30.) Kim JH, Woo JH, Kim HM, Oh MS, Jang DS, Choi JH. Anti-Endometriotic Effects of Pueraria Flower Extract in Human Endometriotic Cells and Mice. Nutrients. 2017;9(3).
(31.) Khan KN, Kitajima M, Hiraki K, Yamaguchi N, Katamine 5, Matsuyama T, et al. Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. Fertil Steril. 2010;94(7):2860-3 e1-3.
(32.) Halme J, Becker S, Haskill S. Altered maturation and function of peritoneal macrophages: possible role in pathogenesis of endometriosis. Am J Obstet Gynecol. 1987;156(4):783-9.
(33.) Yuk JS, Park EJ, Seo YS, Kim HJ, Kwon SY, Park Wl. Graves Disease Is Associated With Endometriosis: A 3-Year Population-Based Cross-Sectional Study. Medicine. 2016;95(10):e2975.
(34.) Wieser F, Cohen M, Gaeddert A, Yu J, Burks-Wicks C, Berga SL, et al. Evolution of medical treatment for endometriosis: back to the roots? Hum Reprod Update. 2007;13(5):487-99.
(35.) Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327-46.
(36.) Reid R, Steel A, Wardle J,Trubody A, Adams J. Complementary medicine use by the Australian population: a critical mixed studies systematic review of utilisation, perceptions and factors associated with use. BMC Complement Altern Med. 2016:16:176.
(37.) Craig WJ. Health-promoting properties of common herbs. Am J Clin Nutr. 1999;70(3 Suppl):491S-9S.
(38.) Hossein-Rashidi B, Nemati M. Effects of Vitex agnus-castus extract on the secretory function of pituitary-gonadal axis and pregnancy rate in patients with premature ovarian aging (POA). Journal of Herbal Medicine. 2017;10:24-30.
(39.) Firenzuoli F, Gori L. Herbal medicine today: clinical and research issues. Evidence-based complementary and alternative medicine: eCAM. 2007;4(Suppl 1):37-40.
(40.) McEwen BJ. The influence of herbal medicine on platelet function and coagulation: a narrative review. Semin Thromb Hemost. 2015;41(3):300-14.
(41.) Fung FY, Wong WH, Ang SK, Koh HL, Kun MC, Lee LH, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96.
(42.) Fisher C, Hickman L, Adams J, Sibbritt D. Cyclic Perimenstrual Pain and Discomfort and Australian Women's Associated Use of Complementary and Alternative Medicine: A Longitudinal Study. J Womens Health (Larchmt). 2018;27(1):40-50.
(43.) Vickers A, Zollman C. ABC of complementary medicine: herbal medicine. BMJ. 1999;319(7216):1050-3.
(44.) Jones G, Jenkinson C, Kennedy S. The impact of endometriosis upon quality of life: a qualitative analysis. J Psychosom Obstet Gynaecol. 2004;25(2):123-33.
(45.) Denny E. Women's experience of endometriosis. J Adv Nurs. 2004;46(6):641-8.
(46.) Vercellini P, Vigano P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261-75.
(47.) Pilarski R, Zielinski H, Ciesiolka D, Gulewicz K. Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC. Journal of ethnopharmacology. 2006;104(1-2):18-23.
(48.) Navarro-Hoyos M, Alvarado-Corella D, Moreira-Gonzalez I, Arnaez-Serrano E, Monagas-Juan M. Polyphenolic Composition and Antioxidant Activity of Aqueous and Ethanolic Extracts from Uncaria tomentosa Bark and Leaves. Antioxidants (Basel). 2018;7(5).
(49.) Nogueira Neto J, Coelho TM, Aguiar GC, Carvalho LR, de AraujoAG, Girao Ml, et al. Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat's claw) extract. European journal of obstetrics, gynecology, and reproductive biology. 2011;154(2):205-8.
(50.) Allen-Hall L, Cano P, Arnason JT, Rojas R, Lock 0, Lafrenie RM. Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression if lL-lbeta and TNF-alpha. Journal of ethnopharmacology. 2007;109(2):312-7.
(51.) Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med. 2000;29(1):71-8.
(52.) Zahid H, Rizwani GH, Ishaqe S. Phytopharmacological Review on Vitex agnus-castus: A Potential Medicinal Plant. Chinese Herbal Medicines. 2016;8(1):24-9.
(53.) Zamani M, Neghab N, Torabian S. Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Med Iran. 2012;50(2):101-6.
(54.) Rafieian-Kopaei M, Movahedi M. Systematic Review of Premenstrual, Postmenstrual and Infertility Disorders of Vitex Agnus Castus. Electron Physician. 2017;9(1):3685-9.
(55.) Low Dog T. Conventional and alternative treatments for endometriosis. Altern Ther Health Med. 2001;7(6):50-6; quiz 7.
(56.) He Z, Chen R, Zhou V, Geng L, Zhang Z, Chen S, et al. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas. 2009;63(1):99-103.
(57.) Sagdic 0, Ozturk I, YaparN, Yetim H. Diversity and probiotic potentials of lactic acid bacteria isolated from gilaburu, a traditional Turkish fermented European cranberrybush (Viburnum opulus L.) fruit drink. Food Res Int. 2014;64:537-45.
(58.) Erdogan-Orhan I, Altun ML, Sever-Yilmaz B, Saltan G. Anti-acetylcholinesterase and antioxidant assets of the major components (salicin, amentoflavone, and chlorogenic acid) and the extracts of Viburnum opulus and Viburnum lantana and their total phenol and flavonoid contents. J Med Food. 2011;14(4):434-40.
(59.) Dietz BM, Hajirahimkhan A, Dunlap TL, Bolton JL. Botanicals and Their Bioactive Phytochemicals for Women's Health. Pharmacol Rev. 2016;68(4):1026-73.
(60.) Chen XP, Li W, Xiao XF, Zhang LL, Liu CX. Phytochemical and pharmacological studies on Radix Angelica sinensis. Chin J Nat Med. 2013;11(6):577-87.
(61.) Chao WW, Lin BF. Bioactivities of major constituents isolated from Angelica sinensis (Danggui). Chin Med. 2011;6:29.
(62.) Zhou J, Qu F. Treating gynaecological disorders with traditional Chinese medicine: a review. Afr J Tradit Complement Altern Med. 2009;6(4):494-517.
(63.) Su YW, Chiou WF, Chao SH, Lee MH, Chen CC, Tsai YC. Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-kappaB and AP-1 signaling pathways. Int Immunopharmacol. 2011;l1(9):1166-72.
(64.) Guo SW. Nuclear factor-kappab (NF-kappaB): an unsuspected major culprit in the pathogenesis of endometriosis that is still at large? Gynecol Obstet Invest. 2007;63(2):71-97.
(65.) Hook IL. Danggui to Angelica sinensis root: are potential benefits to European women lost in translation? A review. Journal of ethnopharmacology. 2014;152(1):1-I3.
(66.) Pareek A, Suthar M, Rathore GS, Bansal V. Feverfew (Tanacetum parthenium L.):A systematic review. Pharmacognosy reviews. 2011;5(9):103-W.
(67.) Takai E, Taniguchi F, Nakamura K, Uegaki T, Iwabe T, Harada T. Parthenolide reduces cell proliferation and prostaglandin E2 [corrected] in human endometriotic stromal cells and inhibits development of endometriosis in the murine model. Fertil Steril.2013;100(4):1170-8.
(68.) Shao X, Lv L, Parks T, Wu H, Ho CT, Sang S. Quantitative analysis of ginger components in commercial products using liquid chromatography with electrochemical array detection. J Agric Food Chem. 2010;58(24):12608-14.
(69.) AH BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2008;46(2):409-20.
(70.) Chen CX, Barrett B, Kwekkeboom KL. Efficacy of Oral Ginger (Zingiber officinale) for Dysmenorrhea: A Systematic Review and Meta-Analysis. Evidence-based complementary and alternative medicine: eCAM. 2016;2016:6295737.
(71.) Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med. 2012;12:92.
(72.) Shirvani MA, Motahari-Tabari N, Alipour A. The effect of mefenamic acid and ginger on pain relief in primary dysmenorrhea: a randomized clinical trial. Arch Gynecol Obstet. 2015:291(6):1277-81.
(73.) Ozgoli G, Goli M, Moattar F. Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. J Altern Complement Med. 2009;l5(2):129-32.
(74.) Kashefi F, Khajehei M, Tabatabaeichehr M, Alavinia M, Asili J. Comparison of the effect of ginger and zinc sulfate on primary dysmenorrhea: a placebo-controlled randomized trial. Pain Manag Nurs. 2014;15(4):826-33.
(75.) Chacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: a literature review. Chin Med. 2010:5:13.
(76.) Rashidi B, Malekzadeh M, Goodarzi M, Masoudifar A, Mirzaei H. Green tea and its anti-angiogenesis effects. Biomed Pharmacother. 2017;89:949-56.
(77.) Espinoza JL, Trung LQ, Inaoka PT, Yamada K, An DT, Mizuno S, et al. The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans. Oxidative medicine and cellular longevity. 2017:2017:6781872.
(78.) Han G, XiaJ, Gao J, Inagaki Y, Tang W, Kokudo N. Anti-tumor effects and cellular mechanisms of resveratrol. Drug Discov Ther. 2015;9(1):1-12.
(79.) McCubrey JA, Lertpiriyapong K, Steelman LS, Abrams SL, Yang LV, Murata RM, et al. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY). 2017;9(6):1477-536.
(80.) Maia H, Jr., Haddad C, Pinheiro N, Casoy J. Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain. Int J Womens Health. 2012;4:543-9.
(81.) Yao M, Liao Y, Li GQ, Law FC, Tang Y. Quantitative analysis of two isoflavones in Pueraria lobata flowers from eleven Chinese provinces using high performance liquid chromatography. Chin Med. 2010:5:14.
(82.) BahmaniM, Rafieian-Kopaei M, Jeloudari M, Eftekhari Z, Del fan B, Zargaran A, et al. A review of the health effects and uses of drugs of plant licorice (Glycyrrhiza glabra L.) in Iran. Asian Pacific Journal of Tropical Disease. 2014;4(2):S847-S9.
(83.) Gonzalez-Reyes S, Santillan-Cigales JJ, Jimenez-Osorio AS, Pedraza-Chaverri J, Guevara-Guzman R. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epiiepticus in rats. Epilepsy Res. 2016;126:126-33.
(84.) Dastagir G, Rizvi MA. Review - Glycyrrhiza glabra L. (Liquorice). Pak J Pharm Sci. 2016;29(5):1727-33.
(85.) Wang XR, Hao HG, Chu L. Glycyrrhizin inhibits LPS-induced inflammatory mediator production in endometrial epithelial cells. Microb Pathog. 2017;109:110-3.
(86.) Galeotti N. Hypericum perforatum (St John's wort) beyond depression: A therapeutic perspective for pain conditions. Journal of ethnopharmacology. 2017;200:136-46.
(87.) Greeson JM, Sanford B, Monti DA. St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology (Bed). 2001;153(4):402-14.
(88.) Mahmood TA, Templeton AA, Thomson L, Eraser C. Menstrual symptoms in women with pelvic endometriosis. Br J Obstet Gynaecol. 1991;98(6):558-63.
(89.) Friedl F, Riedl D, Fessler S, Wildt L, Walter M, Richter R, et al. Impact of endometriosis on quality of life, anxiety, and depression: an Austrian perspective. Arch Gynecol Obstet. 2015;292(6):1393-9.
(90.) Chen LC, Hsu JW, Huang KL, Bai YM, Su TP, Li CT, et al. Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. J Affect Disord. 2016;190:282-5.
(91.) Cavaggioni G, Lia C, Resta S, Antonielli T, Benedetti Panici P, Megiorni F, et al. Are mood and anxiety disorders and alexithymia associated with endometriosis? A preliminary study. BioMed research international. 2014:2014:786830.
(92.) Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis. J Affect Disord. 2017:210:211-21.
(93.) Prasad S, Gupta SC, Tyagi AK, Aggarwal BB. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnology advances. 2014;32(6):1053-64.
(94.) Kim KH, Lee EN, Park JK, Lee JR, Kim JH, Choi HJ, et al. Curcumin attenuates TNF-alpha-induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and proinflammatory cytokines in human endometriotic stromal cells. Phytother Res. 2012;26(7):1037-47.
(95.) Mirabi P, Dolatian M, Mojab F, Majd HA. Effects of valerian on the severity and systemic manifestations of dysmenorrhea. Int J Gynaecol Obstet. 2011;115(3):285-8.
(96.) Behboodi Moghadam Z, Rezaei E, Shirood Gholami R, Kheirkhah M, Haghani H. The effect of Valerian root extract on the severity of pre menstrual syndrome symptoms. J Tradit Complement Med. 2016;6(3):309-15.
(97.) Muller D, Pfeil T, von den Driesch V. Treating depression comorbid with anxiety-results of an open, practice-oriented study with St John's wort WS 5572 and valerian extract in high doses. Phytomedicine. 2003;10 Suppl 4:25-30.
Georgia Hartmann | BHSc (Naturopathy) Student
Bradley McEwen | PhD, MHSc (Hum Nutr), BHSc, ND (Adv),DBM, DNutr,DSM, M.ATMS, aturopath, Nutritionist and Mentor
Table 1. Actions of herbal medicines used in the management of endometriosis Anti Anti Herbal Medicine Anti- depressant, Anti nociceptive, angiogenic anxiolytic inflammatory analgesic Cat's claw + Chaste tree Cramp bark + + + Dong Quai + + Feverfew + Ginger + + Green tea + + Japanese knotweed + + Kudzu + Licorice + + St John's Wort + + Turmeric + + Valerian + + + Herbal Medicine Anti-oxidant Anti Hepato Hormone- spasmodic protective regulating Cat's claw + Chaste tree + (progestero- genic) Cramp bark + + Dong Quai + + Feverfew + Ginger + Green tea + Japanese knotweed + + Kudzu + + + Licorice + St John's Wort + Turmeric + + + (reduce E2 levels) Valerian + Herbal Medicine Immuno Neuro modulatory protective Cat's claw + Chaste tree Cramp bark Dong Quai + + Feverfew Ginger Green tea + Japanese knotweed + + Kudzu Licorice St John's Wort Turmeric + Valerian
|Printer friendly Cite/link Email Feedback|
|Author:||Hartmann, Georgia; McEwen, Bradley|
|Publication:||Journal of the Australian Traditional-Medicine Society|
|Date:||Mar 22, 2018|
|Previous Article:||Pain, suffering and the vulnerability of the empath.|
|Next Article:||The role of nutritional and environmental health in preventing birth defects.|