A 63 year-old-male was admitted with a non-ST-segment elevation acute coronary syndrome. Due to poor acoustic windows ventricular function could not be evaluated by echocardiography. Magnetic resonance (CMR) revealed normal biventricular size and function without fibro- sis and portraying a rare finding consisting of a tubular structure originated in the aortic root following a retro aortic course between the aorta and left atrium, traversing through the atrioventricular groove. These characteristics raised the suspicion of an anomalous coronary artery origin. Coronary angiography confirmed the presence of two coronary arteries, the right coronary artery (RCA) and the left circumflex artery (LCx) originating from the right coronary sinus via two separate ostia. The LCx followed a retro aortic course proximally be- fore irrigating the left ventricular lateral wall. From the left coronary sinus, the left anterior descending artery followed its normal course with a thin diagonal vessel that presented an acute plaque. Due to these low-risk findings, medical management was chosen.
OBJECTIVES:To evaluate safety outcomes from clinical studies of a 12-month contraceptive vaginal system (CVS) releasing an average of segesterone acetate (SA) 150 mcg and ethinyl estradiol (EE) 13 mcg daily. STUDY DESIGN:We integrated clinical safety data from nine studies in which women used the CVS for 21 consecutive days and removed it for 7 days of each 28-day cycle. Four studies used the final manufactured CVS, including a 1-year pharmacokinetic study, two 1-year phase 3 trials and a second-year treatment extension study. We assessed safety by evaluating adverse events women reported in a daily diary. We also included data from focused safety studies evaluating endometrial biopsies, vaginal microbiology and liver proteins from one of the phase 3 studies. RESULTS:The combined studies included 3052 women; 2308 women [mean age 26.7±5.1 years; mean body mass index (BMI) 24.1±3.7 kg/m2] received the final manufactured CVS, of whom 999 (43.3%) completed 13 cycles of use. Women using the final CVS most commonly reported adverse events of headache (n=601, 26%), nausea (n=420, 18%), vaginal discharge/vulvovaginal mycotic infection (n=242, 10%) and abdominal pain (n=225, 10%). Few (<1.5%) women discontinued for these complaints. Four (0.2%) women experienced venous thromboembolism (VTE), three of whom had risk factors for thrombosis [Factor V Leiden mutation (n=1); BMI>29 kg/m2 (n=2)]. During 21,482 treatment cycles in the phase 3 studies evaluable for expulsion, women reported partial expulsions in 4259 (19.5%) cycles and complete expulsions in 1509 (7%) cycles, most frequently in the initial cycle [499/2050 (24.3%) and 190/2050 (9.3%), respectively]. Safety-focused studies revealed no safety concerns. CONCLUSION:The 1-year SA/EE CVS has an acceptable safety profile. Additional studies are warranted in obese women at higher risk of VTE. IMPLICATIONS:This 1-year contraceptive vaginal system represents a new long-term, user-controlled and procedure-free option with a safety profile similar to other combination hormonal contraceptives. The same precautions currently used for combination hormonal contraceptive prescriptions apply to this new contraceptive vaginal system.
Introduccion: Los Criterios Medicos de Elegibilidad para el Uso de Anticonceptivos de la Organizacion Mundial de la Salud (OMS) son una guia para la correcta eleccion y uso de los metodos anticonceptivos en variadas condiciones de salud. En este documento revisaremos las principales modificaciones en su quinta y ultima edicion publicada en ingles el ano 2015. Desarrollo: Las modificaciones de la quinta edicion son fundamentalmente la adicion de nuevos metodos y la modificacion de la categoria de recomendacion para algunas condiciones de salud. Se agregan el acetato de medroxiprogesterona de deposito via subcutanea, el anillo vaginal de progesterona, el implante anticonceptivo subcutaneo sinoimplant(II)® y el metodo anticonceptivo de emergencia acetato de ulipristal. Se modifican las recomendaciones para las mujeres en lactancia, permitiendo el uso de algunos metodos de progestageno solo desde el posparto inmediato, salvo el acetato de medroxiprogesterona de deposito por entregar una dosis elevada del esteroide y el dispositivo intrauterino (DIU) con levonorgestrel, el cual sigue las normas de los DIU con cobre. Tambien hay modificacion en las recomendaciones en cuanto al uso de anticonceptivos combinados en el puerperio, con mas restricciones para mujeres sin lactancia. Por ultimo, sobre el uso de terapia antiretroviral, cambian algunas categorias y se amplia el listado de farmacos detallados. Conclusion: Es necesario que los profesionales de salud conozcan estas modificaciones para poder entregar una atencion de calidad a las usuarias de anticoncepcion.
Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥ 2.0-fold change with false discovery rate below 1% using t-test) with the administration of mifepristone vs placebo, or during the transition from pre-receptive to receptive (LH+2 vs LH+7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LH+2 vs LH+7), but only 777 of them were coincident and displayed opposite regulation except for 25. The mRNA level for eight selected genes regulated by mifepristone was confirmed by real-time RT-PCR. We conclude that not all changes in endometrial transcript levels occurring in the transition from LH+2 to LH+7 seem to be regulated by the progesterone receptor and ∼ 37% of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity.
