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

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

Women’s preference for laparoscopic or abdominal hysterectomy

In the present study, women’s preferences on advantages and disadvantages of laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH) have been studied. Patients’ preferences were evaluated in individual, structured interviews in women scheduled for hysterectomy and questionnaires in nurses. Forty-three patients and 39 nurses were included. After general information, 84% of patients and 74% of nurses preferred LH over AH. This preference did not change after supplying more detailed information or after hysterectomy. The avoidance of complications was indicated as the most important factor in the decision. More than half of the women evaluated a difference of 1% as the maximum acceptable risk of major complications. When confronted with scenarios based on current evidence, both patients and nurses prefer LH over AH. This study supports further implementation of LH in clinical practice. The actual major complication rate in hysterectomy, however, is perceived as high

Lack of evidence of disease contamination in ovarian tissue harvested for cryopreservation from patients with Hodgkin lymphoma and analysis of factors predictive of oocyte yield

Ovarian cryopreservation is a promising technique to preserve fertility in women with Hodgkin lymphoma (HL) treated with chemotherapy. Thus, the aim of this study was to examine harvested ovarian tissue for subclinical involvement by HL by morphology/immunohistochemistry, and to define patient and treatment factors predictive of oocyte yield. This was a retrospective analysis of 26 ovarian tissue samples harvested for cryopreservation from women with HL. Histology, immunohistochemistry and follicle density (number mm−3) was examined. Disease status and preharvest chemotherapy details were obtained on 24 patients. The median age was 22 years (range 13–29). Seven of 24 patients had infradiaphragmatic disease at time of harvest. Nine of 20 patients had received chemotherapy preharvest (ABVD (Adriamycin®, Bleomycin, Vinblastine and Dacarbazine)=7, other regimens=2). The seven receiving ABVD showed no difference in follicle density compared to patients not receiving treatment (n=14); (median=1555 vs 1620 mm3 P=0.97). Follicle density measurement showed no correlation with patient age (R2=0.0001, P=0.99). There was no evidence of HL involvement in the 26 samples examined (95% CI=0–11%). In conclusion, subclinical involvement of HL has not been identified in ovarian tissue, even when patients have infradiaphragmatic disease. Furthermore, the quality of tissue harvested does not appear to be adversely affected by patient's age or prior ABVD chemotherapy

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