Ulipristal Acetate Before Hysteroscopic Myomectomy: A Systematic Review.

IMPORTANCE: Uterine leiomyomas, also referred to as myomas or fibroids, are the most common benign tumors of the reproductive tract. Ulipristal acetate (UPA) is an active selective progesterone receptor modulator used as preoperative treatment for uterine myomas. PURPOSE: The aim of this review is to provide an overview of the literature about the effects of UPA administration before hysteroscopic myomectomy. The clinical question in "PICO" format was in patients affected by uterine myomas undergoing operative hysteroscopic management, "Does UPA impact the surgical outcomes?" EVIDENCE ACQUISITION: We performed a systematic literature search in PubMed/MEDLINE and Embase for original studies written in English (registered in PROSPERO CRD42018092201), using the terms "hysteroscopy" AND "ulipristal acetate" published up to March 2019. Original articles about UPA treatment before hysteroscopic myomectomy (randomized, observational, retrospective studies) were considered eligible. RESULTS: Our literature search produced 32 records. After exclusions, 4 studies were considered eligible for analysis. Results show that UPA does not worsen the overall technical difficulty of hysteroscopic myomectomy. Moreover, it may increase the chance of complete primary myomectomy in complex hysteroscopic procedures. CONCLUSIONS AND RELEVANCE: Despite the positive results presented in this systematic review, low-quality evidence exists yet on the impact of UPA treatment before hysteroscopic myomectomy. High-quality prospective randomized controlled trials are required to establish the impact of UPA on surgical outcomes of patients treated for uterine myomas by hysteroscopy. Moreover, long-term outcomes of myomectomies after UPA treatment (such as frequency of myoma recurrence, recovery time, and quality of life) should be determined.

Endometrial safety and bleeding profile of a 17ß-estradiol/progesterone oral softgel capsule (TX-001HR).

OBJECTIVE: The aim of the study was to evaluate the effect of a single-capsule 17ß-estradiol/progesterone (E2/P4), TX-001HR, on endometrial safety, to report on amenorrhea and bleeding patterns of users, and to identify predictors of amenorrhea. METHODS: The REPLENISH trial (NCT01942668) evaluated use of TX-001HR in menopausal women (40-65 y) with vasomotor symptoms (VMS) and a uterus. Women were randomized to daily E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, or 0.25/50), or placebo for 12 months. Incidence rate of endometrial hyperplasia was calculated from endometrial biopsies conducted at screening and study completion. Women reported bleeding and spotting in daily diaries. The number of bleeding and/or spotting days and the proportion of women with no bleeding or amenorrhea were compared between treatment and placebo using the Fisher exact test. Predictors of cumulative amenorrhea were assessed by univariate analyses. RESULTS: Women (n = 1,835) who took at least one study dose comprised the safety population; 1,255 had baseline and 12-month biopsies and comprised the endometrial safety population. Incidence of endometrial hyperplasia was ≤0.36% with any dose of TX-001HR after 1 year of use (one-sided upper 95% confidence interval ≤4%). Cumulative amenorrhea (no bleeding/spotting) rates increased over time and were relatively high from cycle 1 to 13 with TX-001HR (56%-73%; placebo 79%; P < 0.05 except with 0.25/50 dose). Few vaginal bleeding adverse events (1.0%-4.6% TX-001HR vs 0.7% placebo) were reported and discontinuations due to bleeding were low (0.4%-1.4% vs 0%). Cumulative amenorrhea was significantly more frequent in older women, those further from their last menstrual period, and those with lower baseline E2 concentrations (all; P < 0.01). CONCLUSIONS: All doses of TX-001HR provided endometrial protection and were associated with an improved bleeding profile over time; older age, further last menstrual period, or lower baseline E2 may predict amenorrhea with TX-001HR.

Coriorretinopatía serosa central aguda bilateral tras terapia anticonceptiva de urgencia con acetato de ulipristal / Acute bilateral serous central chorioretinopathy after emergency contraceptive therapy with ulipristal acetate

CASO CLÍNICO: Mujer de 31 años, sin antecedentes de interés, que consulta por diminución de la visión en ambos ojos. Refiere haber consumido un comprimido de acetato de ulipristal 30 mg como anticonceptivo de urgencia 4 días antes de la aparición de los síntomas. A la exploración presenta una mejor agudeza visual corregida de 0,6 en el ojo derecho y de 0,8 en el ojo izquierdo (según test de Snellen) y un desprendimiento seroso macular bilateral. Se decide observación, y a los 15 días presenta una mejoría significativa funcional y anatómica del cuadro. Discusión: El acetato de ulipristal podría desencadenar coriorretinopatía serosa central por su efecto sobre los receptores de progesterona presentes en coroides y epitelio pigmentario de la retina

CASE REPORT The case concerns a 31 year-old woman with no previous history who consulted due to decreased vision in both eyes. She mentioned taking 1 pill of ulipristal acetate (30 mg) as an emergency contraceptive four days before the visual symptoms appeared. In the examination, a better corrected visual acuity of 0.6 was found in the right eye and 0.8 in left eye (by Snellen chart), and bilateral macular serous detachment. It was decided to observe, and 15 days later she showed a functional and anatomical improvement. DISCUSSION: Ulipristal acetate could lead to serous central chorioretinopathy due to its activity on the progesterone receptors present in choroidal and retinal pigment epithelium

Ulipristal Acetate Before High Complexity Hysteroscopic Myomectomy: A Retrospective Comparative Study.

STUDY OBJECTIVE: To evaluate the efficacy of preoperative treatment with ulipristal acetate (UPA) in patients undergoing high complexity hysteroscopic myomectomy. DESIGN: Retrospective analysis of a prospectively collected database (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Patients of reproductive age requiring hysteroscopic myomectomy with STEPW (size, topography, extension, penetration, and wall) score 5 or 6. INTERVENTIONS: Patients included in the study either underwent direct surgery (group S) or received a 3-month preoperative treatment with UPA (group UPA). Based on a power calculation, 25 patients were required in each study group. MEASUREMENTS AND MAIN RESULTS: Myoma characteristics were similar in the 2 study groups. The 3-month UPA treatment caused a 21.9% (±10.3%) mean (±SD) percentage decrease in myoma volume. The number of complete resections (primary outcome of the study) was higher in group UPA (92.0%) than in group S (68.0%; p = .034). The operative time was lower in group UPA than in group S (p = .048), whereas there was no significant difference in fluid balance between the 2 study groups (p = .256). The incidence of complications was similar in the 2 groups (p = .609). Patient satisfaction at 3 months from surgery was higher in group UPA than in group S (p = .041). CONCLUSION: A 3-month preoperative treatment with UPA increases the possibility of complete resection in high complexity hysteroscopic myomectomy. It decreases the operative time and improves patient satisfaction at 3 months from surgery.

A randomized study on pharmacodynamic effects of vaginal rings delivering the progesterone receptor modulator ulipristal acetate: research for a novel estrogen-free, method of contraception.

OBJECTIVE: To determine whether a 3-month contraceptive vaginal ring (CVR) delivering ulipristal acetate (UPA) can inhibit ovulation in 90% of cycles. STUDY DESIGN: This was a randomized dose-finding parallel group clinical trial. Fifty-five healthy women with normal ovulation at baseline were randomized to receive a low-dose (1500 µg/day) or a high-dose (2500 µg/day) UPA-CVR for two consecutive 12-week treatment periods, followed by a recovery cycle. A subgroup of women received levonorgestrel (LNG) 1.5 mg orally twice (at the end of both 12-week ring periods) or once (at the end of the 24-week treatment). The primary outcome was ovulation suppression assessed by transvaginal ultrasound and hormone levels. Secondary outcomes included endometrial safety and bleeding patterns. RESULTS: All subjects showed normal ovulation at baseline and recovery. Ovulation suppression was seen in 81.8% (95% CI: 73.3%, 88.5%) and 86.1% (95% CI: 78.1%, 92%) of treatment cycles with low and high-dose, respectively. Benign progesterone receptor modulator associated endometrial changes (PAEC) were seen during treatment; 78.8% at week 24, but resolved at recovery cycle. A few cases of heavy bleeding occurred near the end of the 24-week treatment, but a single dose of LNG every 12 weeks reduced the increase in endometrial thickness during the second treatment period and prevented excessive bleeding. CONCLUSION: The 3-month UPA-CVR may become an effective long-acting, user-controlled estrogen-free contraceptive. The greatest suppression of ovulation was seen with the 2500-µg/day ring. IMPLICATIONS: The 3-month CVR delivering UPA 2500 µg/day can become an effective user-controlled estrogen-free contraceptive method. Benign PAEC during treatment returns to normal after discontinuation. The prevention of occasional excessive withdrawal bleeding, either by a progestin or by using higher UPA levels to increase follicle suppression may permit prolonged treatment.

Es carcinoma lobulillar infiltrante igual a carcinoma ductal infiltrante?: seguimiento a largo plazo / Is lobulillar infiltrante carcinoma equal to ductal infiltrante carcinoma?: long term follow

Comparar carcinoma lobulillar infiltrante y carcinoma ductal infiltrante a largo plazo según estadio, tratamiento quirúrgico, terapia neoadyuvante, adyuvante. Estudiamos en la base de datos de CECLINES 841 pacientes, el lobulillar representa 7,25% (61) y ductal 51,24% (431). El seguimiento global 22 años con promedio de 5 años. La sobrevida global: lobulillar 68,1% vs. 60,9% ductal (P=0,772), por estadio fue: I lobulillar 96,3% ductal 90,5 II 94,4% y 88,4% III 90,5% 83,2% (P=0,023). La expresión de receptores de estrógenos positivos en comparación a los CDI fue 87,7% vs. 74,7%,(P=0,031) sobrevida 96,9% vs. 94,0% (P=0,033). El tratamiento preservador del lobulillar en comparación aductal 57,4% vs. 63,2% (P=0,949) y la sobrevida 85,4% vs. 82,9% (P=0,001). La sobrevida de lobulillar sometidos a quimioterapia primaria, quimioterapia adyuvante, radioterapia y hormonoterapia adyuvante en relación al grupo ductal fue 93,4% vs. 91,3%, 91,5% vs. 89,7%, 92,5% vs. 89,8% 92,5% vs. 88,4%, respectivamente (P<0,05). La sobrevida global es igual, la sobrevida por estadio favorece al lobulillar estos presentan más receptores positivos y sobrevida mejor. La tendencia a tratamiento preservador en lobulillar es mayor encontrando excelentes cifras de sobrevida. Dado el perfil hormonal y sobrevida según receptores las pacientes con lobulillar infiltrante son candidatas a participar en protocolos de hormonoterapia primaria. Generalmente el tratamiento para ambos grupos es similar.

Compare infiltrante lobulillar carcinoma and ductal carcinoma in long-term follow up as stage surgical treatment, neoadyuvante, adjuvant therapy. We studied in CECLINES data base 841 patients; lobulillar represents 7.25% (61) and 51.24% ductal (431). The overall followup was up to twenty two years with an average of five years. The overall survival for lobulillar was 68.1%and for ductal 60.9% (P=0.772), the survival according to state was: I lobulillar 96.3% ductal 90.5, II 94.4% vs. 88.4 III 90.5 and 83.2 respectively (P=0.023). Estrogen receptors positive expression for lobulillar compared to ductal was 87.7% vs. 74.7%, (P=0.031) and its survival 96.9% vs. 94.0% (P=0.033). The breast conserving surgery for lobulillar compared to ductal was 57.4% vs. 63.2% (P=0.949) survival 85.4% vs. 82.9% (P=0.001). The survival reported for patients with lobulillar who received neoadyuvante chemotherapy adjuvant chemotherapy radiotherapy and adjuvant hormonotherapy compared to ductal was 93.4% 91.3%, 91.5% 89.7%, 92.5% 89.8% 92.5% 88.4%, respectively P<0.05. The overall survival is equal, survival favors. The lobulillar have more positive receptors and survival is better. The tendency to conservative treatment in lobulillar is increasingly. Given the hormonal profile and survival according to estrogen receptors patients with ILC, are probably good candidates to participate in neoadyuvante hormone therapy protocols. Usually the treatment is the same or similar for both groups.

Tratamiento preservador del cáncer de la mama: dos años de experiencia / Conservative breast cancer treatment: two years of experience

Experiencia de nuestra institución en tratamiento preservador del cáncer de mama, analizando cirugía preservadora en términos de recidiva local, sobrevida global y libre de enfermedad. Estudio descriptivo, retrospectivo durante 2004-2005, en pacientes sometidos a tratamiento preservador: la realización de mastectomía parcial oncológica con márgenes negativos, evaluación quirúrgica de axila mediante técnica del ganglio centinela o disección axilar, el tratamiento adyuvante con radioterapia, y quimioterapia en los casos que tuviesen indicación. 132 cirugías conservadoras. Edad media 51,49 años, Tipo histológico más frecuente fue carcinoma ductal infiltrante (70,06 por ciento), (85,94 por ciento) fueron estadio I y II. La cirugía que más se realizó fue la mastectomía parcial oncológica más disección axilar (80 pacientes, 61,87 por ciento). 10,6 por ciento recibieron neoadyuvancia con quimioterapia. El promedio de ganglios obtenidos fue de 11,37, el 62,6 por ciento estado patológico axilar 0.50 por ciento expresaron receptores de estrógeno y progestágenos positivos el 13,17 por ciento sobre expresaron el Her2neu. 66,66 por ciento recibió quimioterapia adyuvante, 79,84 por ciento radioterapia adyuvante. 56,58 por ciento terapia hormonal adyuvante, seguimiento 39,89 meses promedio. 88,88 por ciento vivas libres de enfermedad, 2,22 por ciento vivas con recaída local, 5,92 por ciento viva con metástasis, 1,48 por ciento viva con recaída local y metastásica 1,07 por ciento muerta por enfermedad. El intervalo libre de enfermedad promedio fue de 25,8 meses y la sobrevida global a los 5 años de 98,24 por ciento. El tratamiento preservador es una terapia primaria efectiva en casos de cáncer de mama estadio I y II.

Presented the experience in our institution in the conservative treatment of breast cancer, we analyzed the surgery, local recurrence, and the global super life, and the disease free survival. These are a descriptive and retrospective study during 2004-2005 in patients underwent conservative treatment: realize of partial oncology mastectomy with negative margins surgical evaluation of axillaries sentinel node technique or axillaries dissection. The adjuvant treatment with radiation therapy and chemotherapy when there are indicated in the patients. We realize 132 conservative surgery, median ages of patients were 51.49 histological type more frequent was ductal infiltrante carcinoma (70.06 percent), (85.94 percent) were stage I and II. The surgical more frequent were partial oncology mastectomy with axillaries dissection (80 patients, 61.87 percent). 10.6 percent received adjuvant chemotherapy. The average of finding nodes was 11.37, the 62.6 percent pathological axillaries state were 0.50 percent expression positive estrogen and progestagen receptors 13.17 percent super expression of Her2neu. 66.66 percent received adjuvant chemotherapy, 79.84 percent adjuvant radiation therapy 56.58 percent adjuvant hormonal therapy. Average vigilance was 39.89 months. 88.88 percent alive free disease, 2.22 percent alive with local recurrence, and 5.92 percent alive with metastases. 1.48 percent alive with local and metastasis recurrence 1.07 percent dead for disease. The free interval of disease was 25.8 month and the global super life to 5 years 98.24 percent. The conservative treatment is a primary and effective in breast cancer therapy for stage I and II.

Menorrhagia, mechanisms and targeted therapies.

PURPOSE OF REVIEW: Efficient treatment options for the increasing complaint of heavy menstrual bleeding are required to avoid the morbidity associated with major surgery. This review summarizes recent developments in the nonsurgical approach to treating menorrhagia. RECENT FINDINGS: Even though the mechanism of menstruation has still not been fully elucidated, there have been promising developments in the attempt to reduce menstrual blood loss. The levonorgestrel-releasing intrauterine system has proven very efficient, and there is a frameless device suitable for enlarged uterine cavities. The side effect of breakthrough bleeding has been the main reason for discontinuing treatment. Recent studies have investigated options of concomitant therapy with antiprogestogens to counter this effect. Another group of novel compounds are selective progesterone receptor modulators, which thus far have been shown to reduce menstrual bleeding without the unwanted effect of unscheduled bleeding episodes. SUMMARY: As menorrhagia is largely a subjective complaint, it is important for successful therapy to be based on an informed patient's choice. Currently, lack of evidence-based practice, poor compliance and unpleasant side effects limit the success of medical therapies contributing to the amount of major surgery performed for this indication. If concomitant therapies succeeded in minimizing the episodes of breakthrough bleeding with the levonorgestrel-releasing intrauterine system, its recommendation as a first choice treatment may be confounded. Further research is needed into efficiency and safety of selective progesterone receptor modulators, which appear to have great potential in reducing menstrual blood loss.

Relaçäo entre tipo histológico e dosagem bioquímica dos receptores de estradiol e progesterona em mulheres com carcinoma primário da mama / Relation into histopatological type and biochemical determination of estradiol receptors and progesterone in women with primary breast neoplasms

Estudaram-se 100 pacientes com carcinoma primário da mama näo tratadas. Analisaram-se o grau de diferenciaçäo tumoral e a dosagem bioquímica dos receptores de estradiol e de progesterona em pacientes, tanto na pré como na pós-menopausa. Utilizou-se o método de carväo dextran, tendo como limites de positividade 10 fmoles/mg para os receptores de estradiol e 20 fmoles/mg para os de progesterona. Näo houve diferença na distribuiçäo do grau histológico na pré e na pós-menopausa. A positividade dos receptores de estradiol foi de 60,0%, sendo 50,0% na pré e 66,7% na pós-menopausa. Para os receptores de progesterona, a positividade foi de 44,0%, sendo 45,0% na pré e 43,3% na pós-menopausa. Nos tumores indiferenciados os receptores de estradiol tiveram menor positividade e concentraçöes inferiores do que em tumores diferenciados na pós-menopausa. Os receptores de progesterona näo variaram significativamente, tanto na pré como na pós-menopausa. Os parâmetros estudados, isto é, positividade e concentraçäo de receptores, näo substituem o valor prognóstico dos graus de diferenciaçäo histológica. Näo säo, pois, intersubstituíveis; porém, quando o tumor for diferenciado e possuir mais do que 50,4 fmoles/mg de estradiol, é possível predizer um prognóstico mais favorável da moléstia