Australian and New Zealand Journal of Obstetrics and Gynaecology 2007; 47: 222–225 222 © 2007 The Authors Journal compilation © 2007 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Blackwell Publishing Asia Original Article Letrozole in stage IV for endometriosis Letrozole and desogestrel-only contraceptive pill for the treatment of stage IV endometriosis Valentino REMORGIDA, 1 Luiza Helena ABBAMONTE, 1 Nicola RAGNI, 1 Ezio FULCHERI 2 and Simone FERRERO 1 1 Department of Obstetrics and Gynaecology, and 2 Unit of Anatomy and Histopathology, Di.C.M.I., San Martino Hospital and University of Genoa, Genoa, Italy Abstract Background: It has recently been suggested that aromatase inhibitors may effectively reduce pain symptoms related to the presence of endometriosis both in postmenopausal women and in subjects of reproductive age. Aims: This study aims to evaluate the effectiveness of a combination of letrozole and desogestrel in the treatment of pain symptoms related to the presence of endometriosis. Methods: This open-label prospective study included 12 women with endometriosis-related pain symptoms that were refractory to previous medical and surgical treatments. All women had previous laparoscopy documenting stage IV endometriosis. The treatment protocol included the daily oral administration of letrozole 2.5 mg (Femara®), desogestrel 75 μg (Cerazette®), elemental calcium 1000 mg and vitamin D 880 I.U. The scheduled treatment period was six months. Results: None of the women included in the study completed the six-month treatment because all patients developed ovarian cysts; the median length of treatment was 84 days (range, 56–112). At interruption of treatment, all women reported significant improvements in dysmenorrhoea and dyspareunia. Pain symptoms quickly recurred at three-month follow up. There were no severe adverse effects of treatment; no significant change in the mineral bone density was observed during treatment. Conclusions: The combination of letrozole and desogestrel induces a relief of pain symptoms in women with endometriosis but it causes the development of ovarian cysts. Pain symptoms quickly recur after the completion of treatment. Key words: aromatase inhibitors, chronic pelvic pain, deep dyspareunia, dysmenorrhoea, endometriosis, letrozole. Introduction In the last few years, our understanding of the pathogenesis of endometriosis at the cellular and molecular levels has significantly improved; based on these findings, new agents have been proposed for the medical treatment of endometriosis. 1 Noble et al. 2 demonstrated that cytochrome P-450 aromatase contributes to the pathogenesis of endometriosis having aberrant expression on both eutopic and ectopic endometrium of subjects affected by the disease. This enzyme is responsible for catalysing the conversion of androstenedione and testosterone to estrone and estradiol. Owing to the hormone-dependent character of endometriosis, the presence of aromatase and the consequent local oestrogen production may promote the growth of endometriotic implants. On the basis of these molecular observations, case reports and pilot studies suggested that aromatase inhibitors may effectively reduce pain symptoms related to the presence of endometriosis both in postmenopausal women 3,4 and in subjects of reproductive age. 5–8 Aromatase inhibitors are now an integral part of postmenopausal breast cancer therapy; but information regarding their use in women of reproductive age is still limited. By blocking the conversion of androgens to oestrogens in ovarian granulosa cells, these drugs reduce the negative feedback at the pituitary–hypothalamus level, and therefore increase serum follicle-stimulating hormone levels that stimulate the development of ovarian follicles. 9 Correspondence: Dr Simone Ferrero, Department of Obstetrics and Gynaecology, San Martino Hospital, Largo R. Benzi 1, 16132 Genoa, Italy. Email: dr@simoneferrero.com DOI: 10.1111/j.1479-828X.2007.00722.x Received 29 November 2006; accepted 10 January 2007.