HPE HPE 85 – Spring 2017 - Page 57

Practical therapeutics Issue 85 | Spring 2017 during at least 56 days of a treatment course) during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10mg UA, respectively. Pain and quality of life improved in both groups. UA was well tolerated, with less than 5% of patients discontinuing treatment due to adverse events. 49 The same group further published their results regarding the efficacy and safety of four repeated 12-week courses of 5 or 10mg daily UA for intermittent treatment of symptomatic uterine fibroids. 50 Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and quality of life showed marked improvements from screening, even during the off-treatment intervals. The safety profile of UA was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. 50 The percentage of subjects with endometrial thickness ≥16mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. UA did not increase the occurrence of endometrial features of concern. The frequency of non-physiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. 50 The data regarding long-term use of UA so far appear to be reassuring. The beneficial effects of ulipristal with low rates of adverse events (headaches, flushes, dizziness) demonstrated in all studies make it an attractive alternative to surgery for women with symptomatic of fibroids. Women close to menopause who wish to avoid surgery or who are high risk for surgery are especially likely to benefit from UA therapy. However, it is likely that the PRMs are not useful for the treatment of very large uteri or fibroids because the y cause only a modest decrease in their size. Luyckx et al 51 reported their series of 21 patients who attempted to conceive following ulipristal acetate therapy. Fifteen women (71%) succeeded, totalling 18 pregnancies. Among these 18 Key points • Women with asymptomatic uterine fibroids may not need any active treatment, only periodic monitoring to review size and symptoms. • Symptoms depend on the size and position of the fibroids and range from heavy unpredictable bleeds and bleeding disturbances to chronic pelvic pain and subfertility. • NSAIDs are effectve in reducing heavy menstrual bleedng and dysmenorrhea in women without fibroids but robust evidence for the same benefit is lacking in women with uterine fibroids. • GnRH analouges are useful for short term therapy as temporising measures in the perimenopausal women or pre-operatively to reduce fibroid size, restore haemoglobin levels and influence the type of surgery. • Progesterone receptor modulators have emerged as an effective treatment option for uterine fibroids. The PEARL trials have demonstrated the safety and efficacy of ulipristal acetate for controlling excessive bleeding and fibroid size reduction in selected patient groups. pregnancies, 12 resulted in the birth of 13 healthy babies and 6 ended in early miscarriage. No re-growth of fibroids was observed during pregnancy. 51 There were no maternal complications related to fibroids during pregnancy and all the babies were healthy. One infant had an ectopic kidney, but it was not linked to the treatment. Most deliveries were performed by caesarean section, either because of previous surgery for uterine fibroids, or in an emergency context for preeclampsia or fetal conditions. 51 The data are still insufficient to confirm safety of UA prior to pregnancy and further studies are awaited. GnRHa by 32% after 12 weeks of treatment – this difference was not significantly different. 53 The current evidence is insufficient to recommend the use of aromatase inhibitors for treatment of symptomatic uterine fibroids. Aromatase inhibitors Aromatase inhibitors block peripheral conversion of androgens to estrogens in both ovarian and peripheral tissues. It has been suggested that aromatase expression is increased in fibroid tissue and thus the role for aromatase inhibitors. Evidence A Cochrane systematic review studied the effectiveness and safety of selective oestrogen receptor modulators in women with uterine fibroids. 54 Three studies involving 215 participants were included; the trial size varied from 25 to 100 women. The SERM in all cases was raloxifene. In one study, women in both arms received GnRH analogue and comparison interventions included no treatment and placebo. Two of the three studies found a significant benefit from raloxifene, but the third study found no benefit at three- or six-month follow-up. The overall quality of the evidence was low or very low. All three studies mentioned adverse reactions but data were limited. 54 There is no consistent evidence from the limited number of studies that SERMs reduce the size of fibroids or improve clinical outcomes. Evidence A study of 21 women over 35 years of age, with symptomatic uterine fibroids, assessed the effect of 1mg daily anastrozol on the fibroids. 52 Average reduction of uterine volume of 9.32%, attaining up to 32%, and reduction of symptoms of uterine fibroids (menstrual volume, duration of menstruation, and dysmenorrhoea) were noted. 52 A systematic review evaluated the effectiveness and safety of aromatase inhibitors in women with uterine fibroids. One trial involving 70 participants was included. Significantly fewer women reported hot flushes in the letrozole group than in the GnRH analogue group (0/33 vs 26/27, p<0.05). Use of letrozole reduced fibroid volume by 46% and use of Selective oestrogen receptor modulators (SERMs) Tamoxifen and raloxifene are two SERMs that exert tissue-specific agonist and antagonist effects on oestrogen receptors. Raloxifene is the most studied agent in this group of drugs, mainly in postmenopausal women with fibroids. Other pharmacological treatments Although danazol and gestrinone appear to be effective in treating some symptoms associated with uterine fibroids, there is no reliable evidence available from large hospitalpharmacyeurope.com 55