Australian Journal of Herbal Medicine 2014 26(4) 145 © NHAA 2014 Article Oestrogen modulation in the management of uterine ibroids: a potential role for herbal medicine Rebecca Reid 1, 2 , David Casteleijn 1 1 Endeavour College of Natural Medicine, Level 2, 269 Wickham St, Fortitude Valley Brisbane, QLD 4006 2 Contact author: reid_rebecca@ymail.com Abstract It is common to utilise herbal extracts such as Silybum marianum and Rosmarinus oficinalis in naturopathic practice to support hepatic function and improve oestrogen clearance, but what pharmacodynamic evidence is there to support this hypothesis? This article explores the potential use of these two traditional hepatic herbs for the potential treatment of uterine ibroids via and their action on speciic CYP450 enzymes. Uterine ibroids are benign smooth muscle overgrowths which occur in various locations in the myometrium and develop from an unknown cause. There is however a wide diversity of known promoters involved in the pathogenesis including steroid hormones, such as oestrogen. Excessive oestrogen synthesis from aromatase P450 can lead to an overexpression of alpha (ER-) and beta (ER-) oestrogen receptors, which through binding activity, causes a cascade of growth factors contributing to ibroid development. Considering this increased oestrogen activity has been implicated in stimulating uterine tissue, a novel approach to treating uterine ibroids is by inducing CYP1A1 and inhibiting CYP3A4 to improve the ratio between 2:16 hydroxy catechol oestrogens. Silybum marianum has shown potential in inhibiting CYP3A4 activity in vitro, but evidence from two small clinical trials did not support this. Rosmarinus oficinalis shows promise by improving 2:16 hydroxy catechol oestrogen ratio equilibrium in vivo by inducing CYP1A1 and inhibiting CYP3A4 activity. Rosmarinus oficinalis may have a role in altering these pathways and therefore may help to reduce the excessive uterotropic action of oestrogen and its metabolites by shifting the metabolism of oestrogen to a less proliferative pathway, but further clinical research is required. Keywords: leiomyomas, ibroids, oestrogen clearance, Rosmarinus oficinalis, Silybum marianum, herbal medicine Introduction Uterine ibroids are benign smooth muscle overgrowths of the uterine myometrium. They are the most common female pelvic tumour, affecting 20-40% of Australian women during their reproductive years. 1 However, racial differences may be correlated with prevelance. 2 Fibroids commonly occur in women aged between 35 to 49 years, 3 and whilst some are asymptomatic, they can also be associated with chronic symptoms such as chronic pelvic pain, menstrual changes, dificulty achieving pregnancy and infertility. 2,3 Menstrual changes occur due to structural uterine changes including an increase in surface area and distortion of the endometrium which may cause further complications such as congested blood low and ulceration. 4 Women with ibroids are more likely to experience changes in haemoglobin levels and are at a higher risk of anaemia due to increased blood loss. 5 Although the exact cause of ibroids is still unclear, their development has been associated with several predisposing factors, initiators, promoters and genetic mechanisms. 6 Risk Factors One of the main risk factors for the development of ibroids is age. It has been suggested that after the age of 30, the rise in ibroid diagnosis is due to years of cumulative circulating oestrogen and progesterone or the increased symptomatology of an already existing ibroid. 6 Another signiicant inluence is increased body weight due to the expression of endocrine activity from adipose tissue. 3 Racial factors appear to be relevant to prevalence as 40% of Caucasian women are diagnosed with ibroids compared to 60% of women of black descent. 7 Whilst the aetiology of this is unknown, some researchers suggest differences in oestrogen metabolism or the involvement of environmental factors. 3 Oral contraceptive use has also been theorised to have a role in ibroid development due to increased exogenous oestrogen, however these theories are not supported by research. 3 Complications associated with ibroid growth As ibroids grow, uterine tissue surface and volume increases which can escalate the low and shedding process of the uterus during menses. One of the biggest complications of ibroid growth and location relates to fertility. Subserosal ibroids are less likely to interfere with conception and implantation whereas submucosal ibroids may require removal prior to conception in order to increase the likelihood of implantation and to provide a less hostile uterine environment for foetal