Intervention review: Chinese herbal medicine for endometriosis

Endometriosis is a disease characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in ectopic locations outside the uterine cavity. Hormonally stimulated cyclical bleeding from the endometriotic deposit appears to contribute to the induction of a local inflammatory reaction, fibrous adhesion, and, in the case of deep implants in the ovary, leads to the formation of an endometrioma or chocolate cyst.Endometriosis classically presents with severe dysmenorrhoea, pelvic pain, dyspareunia (pain on intercourse), menstrual irregularities, and infertility. Systemic symptoms may also occur such as fatigue, an increased incidence of allergies, and autoimmune diseases (Ballweg 2004).Definitive diagnosis is usually made through laparoscopic investigation although recent research suggests that non-invasive symptom evaluation may have a greater positive prediction value (Ling 1999; Winkel 2003).The precise prevalence of endometriosis is unclear but there is a broad consensus that between 5 to 15% of the female population will have signs and symptoms of the disease during their reproductive years (15 to 50) (Eskenazi 1997; Stenchever 2001; Zondervan 2001).Endometriosis is increasingly regarded as a complex, multi-factorial condition of uncertain aetiology where immunological (Ballweg 2004; Lebovic 2001; Sheng 1998), hormonal (Noble 1997), genetic (Bischoff 2004; Malinak 1980), environmental (Ballweg 2004; Ohtake 2003), and possibly even psychological factors (Low 1993, Strauss 1992) combine together to create a context for rogue endometrial cells to develop into a full blown disease.The treatment of endometriosis can be broadly divided into medical and surgical management. Medical treatment ranges from symptomatic control with non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics, through to treatments that aim to suppress the normal ovarian production of oestrogen by either hormonally simulating pregnancy (continuous oral contraceptives (COC) and progestins) or menopause (danazol and gonadotrophin-releasing hormone agonists (GnRH-a's). Surgical intervention can be either 'conservative', involving the removal of endometrial lesions or the severing of the nerve pathways responsible for the transmission of pelvic and uterine pain; or 'definitive', involving the removal of the uterus and ovaries.Danazol, Progestins, GnRH-a's and the COC have comparable short-term rates of success in alleviating the symptoms of endometriosis and in partially reducing the size of endometriosis related lesions (GISG 1996; Parazzini 2000, Prentice 2004; Moore 2004; Vercellini 1993,). Unfortunately the benefits are poorly sustained over time with studies frequently reporting a high level of returning symptoms at six months post treatment (Vercellini 1993) and even studies with more positive findings commonly demonstrate a return of symptoms in over a third of the women who took part two to three years after stopping treatment (Biberoglu 1981; Dmowski 1998).The short-term benefits of conventional medical treatment have to be balanced against the unpleasant and sometimes dangerous side effects resulting from these therapies.COC has recently been associated with increased thromboembolic risks (Anderson 2004), is unsuitable for certain patient groups, such as women over the age of 35 who smoke or who have a history of cardiovascular disease, and is obviously inappropriate for women trying to conceive.Danazol is associated with androgenic changes such as acne and weight gain, menopausal symptoms such as flushing and fatigue. Recent concerns have highlighted its potential role in raising LDL cholesterol levels (Hughes 2004) and in contributing to ovarian cancer (Cottreau 2003).GnRH agonists tend to produce a more hypo-oestrogenic state than danazol with more severe menopausal side effects such as hot flushes, insomnia, reduced libido and vaginal dryness (Prentice 2004). Low oestrogen levels can also cause serious osteoporosis and the long term risks of add-back regimes using small amounts of progesterone and oestrogen have not yet been adequately assessed.Patients using progestin therapy reported a higher incidence of acne, fluid retention, bloating and spotting. In addition progestins are known to unfavourably reduce the level of high-density lipo-proteins in the blood that could potentially increase the risk of cardiovascular side effects such as thrombosis (Vasilakis 1999).The surgical management of endometriosis is also far from satisfactory. Two RCTs (Abbott 2004; Sutton 1994) and several observational studies (Abbott 2003; Fedele 2004; Wheeler 1983) demonstrate significant symptomatic relief from conservative laparoscopic surgery but in many cases these benefits were relatively short lived with up to 44% of women experiencing a return of symptoms after one year (Lapp 2000).Surgery is also associated with the potential for serious side effects with one study reporting 2 to 3% of cases had post operative bowel perforations with peritonitis (Koninckx 1996) and an anonymous survey of 1951 gynaecologists revealing a significant number of unreported complications that suggest that the incidence of complications is higher than is commonly stated (Feste 1999).In summary current treatments all have high rates of re-occurrence and their short-term benefits have to be balanced by concerns over immediate and longer term side effects.Chinese herbal medicine (CHM) is a system of medicine with an unbroken written tradition stretching back over two thousand years. Although endometriosis as a distinct entity did not exist in the classical tradition, the symptoms of dysmenorrhoea, dysuria, dyschezia, menorrhagia and so on, were systematically differentiated and apparently well treated (Wu 1997). A common pattern underlying these conditions is the presence of what is known as stagnation of Blood and Qi (vital energy) causing localised obstructions and leading to pain. This is interestingly similar to the modern bio-medical understanding of the central role that endometrial lesions play in the symptomatology of the disease.We have recently seen increasing integration of Western medicine and CHM in China and in the past 10 years the use of laparoscopic diagnosis has allowed some evaluation of the specific benefits of CHM in the treatment of endometriosis through a number of clinical trials. For example, one review article identified 13 randomised clinical trials on Chinese medicine for treatment of endometriosis from Chinese literature published between 1994 and 2000 (Xu 2004). In these trials, 1076 participants were involved, and Chinese herbal medicines were applied either alone or in combination with biomedical drugs. The suggested mechanism of Chinese medicine for endometriosis may involve regulation of endocrine and immune systems, improvement of blood circulation, and anti-inflammatory activity (Huang 2006; Xu 2004).At present no English language systematic review evaluating the results of these individual studies has been conducted. The available Chinese and English language literature on the subject will be reviewed in an attempt to establish whether Chinese herbal medicine has a valid role in the treatment of this common and disabling condition