Ovarian steroids Sample Clauses

Ovarian steroids. Traditionally oestrogen has been proposed as a promoter of fibroid growth. The risk of fibroids is greatest in women likely to have a high level of unopposed oestrogen such as nullips, those with early menarche or those who are obese. Furthermore GnRH analogues, which have a hypooestrogenic effect, tend to stop or reverse fibroid growth (Xxxxxxxx et al. 1988; Xxxxxxx et al. 2001). Even though the levels of circulating ovarian steroid hormones in women with fibroids are not different from those in women without fibroids, the local oestradiol concentration in fibroids is elevated compared to homologous myometrium. This is perhaps due to lower levels of 17β - hydroxy – steroid dehydrogenase which accelerates conversion of oestradiol to oestrone. In normal myometrium this enzyme is up – regulated by progesterone in the luteal phase of the cycle something that does not happen in fibroids (Xxxxxx et al. 1978; Xxxxx et al. 1982). Oestrogen also acts to increase the number of oestrogen and progesterone receptors in the myometrium. Accordingly the numbers of both receptors rise in the follicular phase whilst they fall in the luteal phase either because of lower oestradiol levels of or because of a feedback effect of progesterone (Xxxxxxx et al. 1998). The concentration of oestrogen and progesterone receptors is higher in fibroids compared to autologous myometrium while it is unclear whether receptors in fibroids are subject to the cyclical variation observed in normal myometrium (Xxxxxxx et al. 1998). Even though fibroids have been found to have a higher proliferation index throughout the menstrual cycle there is no evidence that this mitogenic effect is directly mediated by oestrogen. It is known however that fibroids’ proliferative index is higher in the secretory phase of the cycle (Xxxxxxxxx et al. 1991; Xxxxxxx et al. 1999). In addition, the regression effect produced by GnRH analogues can be abolished by concomitant medroxyprogesterone administration (Xxxx et al. 1993). The effect of progesterone can also be seen in pregnancy when a minority of fibroids increase in size and undergo “red degeneration” (Otubu et al. 1982; Xxxxxxxx et al. 1994). These findings have led some to suggest that the growth mechanism of fibroids includes a priming action for oestrogen, increasing the number of receptors available for a mitogenic effect mediated by progesterone (Xxxx et al. 1995; Xxxxx et al. 2003).