Long-term treatment of uterine fibroids with ulipristal acetate

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.<p></p> Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.<p></p> Setting: European clinical gynecology centers.<p></p> Patient(s): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.<p></p> Intervention(s): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.<p></p> Main Outcome Measure(s): Amenorrhea, fibroid volume, endometrial histology.<p></p> Result(s): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.<p></p> Conclusion(s): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids

Reprint of: Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities.

peer reviewe

Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice

Abstract This paper describes the success and expansion of ovarian tissue cryopreservation and transplantation as a fertility restoration procedure, with the largest series of 60 live births worldwide reported. By repeating the procedure, ovarian activity can be restored for more than 11 years

Recently advanced computerized technology was applied to the investigation of morphometric, immunohistological and three-dimensional changes of the endometrial mucosa in order to evaluate quantitatively the effects of three doses of a new slow-release vaginal progesterone on the endometrium in post-menopausal women. A total of 20 menopausal women, deprived of ovarian function, were given oestrogen for 12 days and a combined therapy of oestrogen (administered orally) and progesterone for another 12 day period. Progesterone was administered vaginally through a new gel (Crinone) utilizing a bioadhesive, biocompatible polymer as a base to achieve a sustained release effect. An endometrial biopsy was taken before treatment, after oestrogen-only treatment and after the oestro-progestogen therapy. Before treatment, all the patients exhibited an atrophic endometrium. After oestrogen-only treatment, typical proliferative changes occurred: an increase in the endometrium thickness, an increase in the mitotic index, numerous cylinder-like glands and no coiled glands, and high concentrations of oestrogen receptors (ER) and progesterone receptors (PR). After the oestro-progestogen therapy, whatever the dose of progesterone given, a secretory transformation of the endometrial mucosa occurred, mitotic activity decreased significantly, more ramified and coiled glands were observed, and a decrease in PR content was noted in epithelial and stromal nuclei, and a decrease in PR content was also observed in epithelial nuclei but not in stromal nuclei. Accurate new techniques of image analysis have shown that crinone therapy could eliminate the proliferative effects of oestrogen treatment in post-menopausal women, despite doses as low as 45 mg of progesterone administered vaginally every other day. The results suggest that the sustained release effects of Crinone are clinically relevant.

peer reviewedA computerized morphometrical investigation was performed on endometriotic tissue from the peritoneum (n = 225) and rectovaginal nodules (n = 65) to compare histologically and stereologically the rectovaginal septum endometriotic nodule to peritoneal endometriosis. Mitotic activity, stromal vascularization and the epithelium/stroma ratio were found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation revealed a major role of glandular epithelium in rectovaginal nodules where the stroma sometimes appeared absent around glandular epithelium. The study demonstrated opposite effects of gonadotrophin-releasing hormone agonists (GnRHa) and lynestrenol on the two lesions. Indeed, in peritoneal endometriosis, after GnRHa therapy, our study demonstrated a lower rate of mitosis and poor stromal vascularization. The same drug was unable to induce the same effects in the nodule although, in contrast, lynestrenol has a strong effect on nodule vascularization. In conclusion, it is suggested that the rectovaginal adenomyotic nodule is a specific disease, different from peritoneal endometriosis. It is not the consequence of 'deep infiltrating' endometriosis but can probably develop from Mullerian rests present in the rectovaginal septum

Safety after extended repeated use of ulipristal acetate for uterine fibroids

Objective: To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters. Methods: This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety. Results: All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10–18 days after the start of menses following treatment courses 5–8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush. Conclusion: The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures

Recommendations for fertility preservation in patients with lymphoma, leukemia, and breast cancer

Fertility issues should be addressed to all patients in reproductive age before cancer treatment. In men, cryopreservation of sperm should be offered to all cancer patients in reproductive age regardless of the risk of gonadal failure. In women, the recommendation of fertility preservation should be individualized based on multiple factors such as the urgency of treatment, the age of the patient, the marital status, the regimen and dosage of cancer treatment

Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel

<p>Abstract</p> <p>Background</p> <p>To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel.</p> <p>Methods</p> <p>We studied the incidence and duration of amenorrhea induced by two chemotherapy regimens: (i) 6 cycles of 5-fluorouracil 500 mg/m², epirubicin 100 mg/m²and cyclophosphamide 500 mg/m²on day 1 every 3 weeks (6FEC) and (ii) 3 cycles of FEC 100 followed by 3 cycles of docetaxel 100 mg/m²on day 1 every 3 weeks (3FEC/3D). Reversible amenorrhea was defined as recovery of regular menses and, where available (101 patients), premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy.</p> <p>Results</p> <p>One hundred and fifty-four premenopausal patients were included: 84 treated with 6FEC and 70 with 3FEC/3D. The median age was 43.5 years (range: 28–58) in the 6FEC arm and 44 years (range: 29–53) in the 3FEC/3D arm. Seventy-eight percent of patients were treated in the context of the PACS 01 trial. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was similar in the two groups: 93 % in the 6FEC arm and 92.8 % in the 3FEC/3D arm. However, in the year following the end of chemotherapy, more patients recovered menses in the 3FEC/3D arm than in the 6FEC arm: 35.5 % versus 23.7 % (p = 0.019). Among the 101 patients for whom hormone values were available, 43 % in the 3FEC/3D arm and 29 % in the 6FEC arm showed premenopausal levels one year after the end of chemotherapy (p < 0.01). In the 3FEC/3D group, there was a statistically significant advantage in disease-free survival (DFS) for patients who were still amenorrheic after one year, compared to patients who had recovered regular menses (p = 0.0017).</p> <p>Conclusion</p> <p>Our study suggests that 3FEC/3D treatment induces more reversible amenorrhea than 6FEC. The clinical relevance of these findings needs to be investigated further.</p