Immunofluorescence Analysis of Estrogen and Progesterone Receptors and Ki-67 Nuclear Protein in Canine Uteri Treated with Medroxyprogesterone Acetate During Anestrus / Análisis de Inmunofluorescencia de Receptores de Estrógeno y Progesterona y Proteína Nuclear Ki-67 en Úteros Caninos Tratados con Acetato de Medroxiprogesterona Durante el Anestr

SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.

Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.

Effectiveness and follow-up of depot medroxyprogesterone acetate in postpartum and postabortal patients

Background: Contraception is the intentional use of artificial methods or other techniques to prevent pregnancy as a consequence of sexual intercourse. Progesterone only injectables are highly effective in preventing in pregnancy as they do not rely on daily usage of contraceptions as such as oral contraceptive pills and barrier methods. Injection depot-medroxyprogesterone acetate (DMPA) is an effective contraceptive method in lactating mother and postabortal patients. Aims and Objectives: The aims of this study were to study utilization pattern, acceptance, effectiveness, and adverse effects of DMPA in postpartum and postabortal women. Materials and Methods: It was a prospective and observational single-center study and was conducted at tertiary care teaching hospital. The data were collected in patient received Inj. DMPA 150 mg intra muscularly immediately after abortion and delivery before discharge. The follow-up was done after administration of DMPA (usually every 3 months). Results: In this study, 56 (53.34%) patients were in the age group of 18–25 years, while 38 (36.19%) patients were 26–35 years whereas 11 (10.47%) were more than 36 years. Out of 105 patients, 12 patients were administered only one injection, 16 patients administered two injections and 16 patients given three injections of DMPA. Common adverse effects of DMPA are irregular bleeding (43.8%), amenorrhea (22.8%), and heavy bleeding (5.7%). Out of 24 patient who developed amenorrhea after injections of DMPA, total 11 patients had amenorrhea after fourth injection, 5 patients after first injection, and 2 patients after second injection of DMPA. Average time for return of fertility after last injection of DMPA was 9 months. Conclusion: DMPA is very effective contraceptive and apart from menstrual troubles that there are no significant major side (weight gain, mood changes, etc.) effects related to its use. DMPA may cause a delay in the return of fertility, the return of fertility takes 7–10 months from date of last injection, but it is completely reversible.

Progestinas y cáncer de mama en terapia de reemplazo hormonal: cómo actúan y qué alternativas son más seguras / Progestins and breast cancer in hormone replacement therapy: how do they work, and what alternatives are safer

En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.

In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.

Embarazo abdominal a término con recién nacido vivo sin malformaciones. Reporte de caso: revisión de la bibliografía / Abdominal term pregnancy with a live newborn without malformations. Case report: literature review

Resumen ANTECEDENTES: El embarazo abdominal representa el 1% de los embarazos ectópicos, con una mortalidad materna que puede alcanzar, incluso, hasta el 20% y una mortalidad fetal hasta del 90%. CASO CLÍNICO: Paciente de 31 años, en curso de las 39 semanas del segundo embarazo. El primero se atendió, sin complicaciones, en el domicilio cuando tenía 25 años; enseguida se le indicó, como método anticonceptivo, acetato de medroxiprogesterona inyectable trimestral. Acudió al Hospital Regional Docente de Cajamarca debido a un dolor abdominal luego de siete controles prenatales. Se ingresó al servicio de Obstetricia al tercer día con pródromos de labor de parto, feto en transverso y placenta previa. En la cesárea de urgencia el útero se encontró de 18 cm, la placenta adherida al epiplón, intestino, colon sigmoide, recto y pared izquierda del útero. Se obtuvo una recién nacida con Apgar 8-9, sin malformaciones. Se practicaron: extracción de la placenta, histerectomía abdominal subtotal y salpingooforectomía izquierda. El sangrado intraoperatorio fue de 1800 mL por lo que ameritó la transfusión de dos paquetes globulares. La madre y su hija evolucionaron favorablemente por lo que se dieron de alta del hospital, sin complicaciones. CONCLUSIÓN: El embarazo abdominal es un evento raro, sobre todo si llega a término y con un recién nacido vivo saludable. A pesar de los estudios ultrasonográficos, el embarazo abdominal no es de diagnóstico fácil; por eso casi todos se diagnostican durante la cirugía. Si la placenta no afecta estructuras vasculares extensas, ni órganos abdominopélvicos, podrá retirse, con cuidados extremos, para no originar males mayores.

Abstract BACKGROUND: Abdominal pregnancy represents 1% of ectopic pregnancies, with a maternal mortality that can reach up to 20% and a fetal mortality of up to 90%. CLINICAL CASE: 31-year-old female patient, in the course of 39 weeks of her second pregnancy. The first pregnancy was attended, without complications, at home when she was 25 years old; she was immediately prescribed quarterly injectable medroxyprogesterone acetate as a contraceptive method. She went to the Regional Teaching Hospital of Cajamarca due to abdominal pain after seven prenatal check-ups. She was admitted to the obstetrics service on the third day with prodromes of labor, transverse fetus and placenta previa. In the emergency cesarean section the uterus was found to be 18 cm, the placenta adhered to the omentum, intestine, sigmoid colon, rectum and left wall of the uterus. A newborn was obtained with Apgar 8-9, without malformations. Placental extraction, subtotal abdominal hysterectomy and left salpingo-oophorectomy were performed. Intraoperative bleeding was 1800 mL, which required the transfusion of two packs of red blood cells. The mother and daughter evolved favorably and were discharged from the hospital without complications. CONCLUSION: Abdominal pregnancy is a rare event, especially if it is carried to term with a healthy live newborn. Despite ultrasonographic studies, abdominal pregnancy is not easily diagnosed; therefore almost all are diagnosed during surgery. If the placenta does not affect extensive vascular structures or abdominopelvic organs, it can be removed, with extreme care, so as not to cause greater harm.

Effects of medroxyprogesterone acetate combined with a levonorgestrel-releasing intrauterine contraceptive system on sex hormone and vascular endothelial growth factor levels after laparoscopic surgery for moderate and severe endometriosis / 中国基层医药

Objective:To investigate the effects of medroxyprogesterone acetate combined with a levonorgestrel-releasing intrauterine contraceptive system (Mirena) on the levels of sex hormone and vascular endothelial growth factor in patients with moderate and severe endometriosis after laparoscopic surgery.Methods:A total of 102 patients with endometriosis who received laparoscopic conservative surgery in Hangzhou Ninth People's Hospital from October 2015 to May 2018 were retrospectively analyzed. They were randomly assigned to undergo either medroxyprogesterone acetate treatment alone (control group, n = 51) or medroxyprogesterone acetate treatment + levonorgestrel-releasing intrauterine contraceptive system application (observation group, n = 51) for 6 successive months. Clinical efficacy, serum luteinizing hormone, follicle-stimulating hormone, estradiol and vascular endothelial growth factor levels, Visual Analogue Scale score, endometriosis recurrence rate, and adverse reactions were compared between the control and observation groups. Results:Total effective rate in the observation group was significantly higher than that in the control group [94.12% (48/51) vs. 80.93% (41/51), χ2 = 4.320, P < 0.05]. At 6 months after surgery, serum luteinizing hormone, follicle-stimulating hormone, estradiol and vascular endothelial growth factor levels in the observation group were (5.72 ± 0.53) U/L, (5.05 ± 0.91) U/L, (156.02 ± 21.80) pmol/L and (155.39 ± 24.72) ng/L respectively, which were significantly lower than those in the control group [(6.51 ± 0.67) U/L, (5.73 ± 0.68) U/L, (177.20 ± 23.20) pmol/L and (186.22 ± 28.14) ng/L, t = 6.604, 4.275, 4.747 and 5.878, all P < 0.05). At 3 and 6 months after surgery, Visual Analogue Scale score in the observation group were (2.39 ± 0.33) points and (1.27 ± 0.20) points respectively, which were significantly lower than those in the control group [(2.72 ± 0.40) points, (1.52 ± 0.25) points, t = 4.545 and 5.577, both P < 0.05]. Two-year follow-up results revealed that endometriosis recurrence in the observation group was significantly lower than that in the control group [1.96% (1/51) vs. 13.73% (7/51), χ2 = 4.883, P < 0.05]. There was no significant difference in total incidence of adverse reactions between the two groups [15.69% (8/51) vs. 13.73% (7/51), χ2 = 0.078, P > 0.05]. Conclusion:Application of medroxyprogesterone acetate combined with a levonorgestrel-releasing intrauterine contraceptive system after laparoscopic surgery for moderate and severe endometriosis can effectively regulate serum levels of sex hormone and vascular endothelial growth factor, decrease endometriosis recurrence rate and is highly safe. This method is worthy of clinical promotion.

The observation on the effect of medroxyprogesterone acetate tablets combined with oxaliplatin and paclitaxel in the treatment of advanced endometrial cancer / 中国医师进修杂志

Objective:To explore the clinical effect of medroxyprogesterone acetate tablets combined with oxaliplatin and paclitaxel in the treatment of advanced endometrial cancer.Methods:Ninety-two patients with advanced endometrial cancer admitted to Qihe People′s Hospital of Shandong Province from January 2014 to May 2019 were selected. According to the entry number, they were divided into the observation group (the last number was odd, receiving medroxyprogesterone acetate tablets + oxaliplatin + paclitaxel treatment) and the control group (the last number was even, receiving oxaliplatin + paclitaxel treatment). The efficacy and safety of the two groups were evaluated, and the changes of serum human carbohydrate antigen 125 (CA125), vascular endothelial growth factor (VEGF), human epididymal protein (HE4) and immune function, physical status and quality of life before and after the treatment were compared and analyzed.Results:The total efficacy in the observation group was higher than that in the control group: 78.26%(36/46) vs. 58.70%(27/46), the difference was statistically significant ( P<0.05). After treatment, the levels of serum CA125, VEGF, HE4 in the observation group were lower than those in the control group: (23.27 ± 5.65) kU/L vs. (30.55 ± 5.71) kU/L, (214.94 ± 23.89) ng/L vs. (247.62 ± 19.97) ng/L, (26.62 ± 4.23) pmol/L vs. (32.24 ± 6.68) pmol/L, the differences were statistically significant ( P<0.05). After treatment, the levels of serum natural killer cells (NK), helper T lymphoid cells (Th), cytotoxic T lymphoid cells (Tc) in the observation group were higher than those in the control group: (0.287 ± 0.032 vs. 0.239 ± 0.027, 0.403 ± 0.052 vs. 0.333 ± 0.046, 0.261 ± 0.029 vs. 0.228 ± 0.026, the differences were statistically significant ( P<0.05). After treatment, the score of Eastern Cooperative Oncology Group (ECOG) in the observation group were lower than that in the control group: (1.37 ± 0.26) scores vs. (1.89 ± 0.34) scores; the score of Quality of Life Questionnaire(QLQ-C30) in the observation group was higher than that in the control group: (65.69 ± 7.58) scores vs. (58.35 ± 6.26) scores, the differences were statistically significant ( P<0.05). The incidence of adverse reactions between the two groups had no significant difference ( P>0.05). Conclusions:Medroxyprogesterone acetate tablets combined with oxaliplatin and paclitaxel is safe and effective in the treatment of advanced endometrial cancer. This method can reduce the concentration of tumor markers in patients, inhibit tumor angiogenesis, and improve immune function, physical fitness and quality of life.

Improving Transdermal Drug Delivery System For Medroxyprogesterone Acetate By Olive Oil And Dimethylsulfoxide (DMSO) As Penetration Enhancers: In Vitro Penetration Study

Objective: Medroxyprogesterone Acetate (MPA) using a transdermal drug delivery system for contraception by passive diffusion is limited by the skin barrier properties. Penetration enhancers such as olive oil (fatty acid permeation enhancer) and DMSO (chemical enhancer) can be used. The objective of this study was to overcome MPA penetration problem by using olive oil and DMSO. Methods: An in vitro penetration study using the Franz diffusion cells was performed. The first penetration study used MPA in olive oil (O) and MPA in coconut oil (C) with the concentration 100 μg/ml to each sample and MPA suspension as a control with the same concentration. The second study used MPA in olive oil with the concentration 200.0 μg/ml (A), MPA in olive oil with 0.5% DMSO with the concentration 200.0 μg/ml (B), and MPA in olive oil with 1% DMSO with the concentration 200 μg/ml (C). Results: MPA penetration test for olive oil+0.5% DMSO had flux value 4.24±0.074 μg/cm2. hr and it was not significantly different (t-test, P>0.05) with olive oil+1% DMSO. While the MPA penetration test in only Olive oil had flux value 0.90±0.0087 μg/cm2. hr. Conclusion: This research concluded that olive oil and 0.5% DMSO could improve the penetration of MPA into skin membrane by 4.5 times more than olive oil alone.

Differences of blood glucose and insulin in childbearing aged women acceptors of depo medroxy progesterone acetat with non acceptors in Padang City 2017

Background: Contraception was the way to prevent pregnancy, both temporarily and permanently. Depot Medroxyprogesterone Acetate (DMPA) is a contraceptive injection of synthetic progesterone hormone and is injected every three months, which is most commonly used currently, but that emerging consequences of long time usage of contraception, especially the hormonal one, cannot be denied. This research was aimed to see difference in blood sugar, insulin and lipid profile in childbearing aged women who used DMPA injection and Non-Acceptors.Methods: The study was observational with the comparative cross sectional approach. Research was conducted in the Biomedical Laboratory in Andalas University and Regional Technical Service Unit (UPTD) Laboratory in West Sumatera Province. Data was taken from December 2017 until June 2018. The research sampled 48 DMPA acceptors and 48 non-Acceptors. Sampling technique used stratified random sampling. Examination of blood glucose was carried out by the enzymatic method of GOD-PAP, ELISA for insulin. Data were analyzed using independent T-test and if the data was not normal, non parametric Mann-Whitney test was used. The differences were considered statistically significant if the value of p<0.05.Results: The mean blood glucose acceptors 91.27mg/dl, non acceptors 88.83mg/dl and mean Insulin acceptors 23.63mIU/L, non akseptor 24.63mIU/L. The results showed that there were no significant differences between DMPA acceptors and non acceptors (p>0.05) in blood glucose (0.059) and insulin (p = 0.603).Conclusions: There were no significant differences in blood glucose and insulin levels between DMPA acceptors and non acceptors.

Long-term outcomes of progestin plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer patients / 부인종양

OBJECTIVE: The present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception. METHODS: We retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation. RESULTS: Of the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m² and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m² had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively. CONCLUSIONS: MPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m².

Dietary intake and eating behavior in depot medroxyprogesterone acetate users: a systematic review

Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic review of studies describing dietary intake or eating behavior in DMPA users to understand whether the use of DMPA is associated with changes in dietary habits and behaviors leading to weight gain. We searched the PubMed, POPLINE, CENTRAL Cochrane, Web of Science, and EMBASE databases for reports published in English between 1980 and 2017 examining dietary intake or eating behavior in healthy women in reproductive age and adolescents using DMPA (150 mg/mL). Of the 749 publications screened, we excluded 742 due to duplicates (96), not addressing the key research question (638), not reporting dietary intake data (4), and not evaluating the relationship of body weight and dietary or eating behaviors (4). We identified seven relevant studies, including one randomized placebo-controlled trial, one non-randomized paired clinical trial, and five cohort studies. The randomized trial found no association and the other reports were inconsistent. Findings varied from no change in dietary intake or eating behavior with DMPA use to increased appetite in the first six months of DMPA use. Few studies report dietary intake and eating behavior in DMPA users and the available data are insufficient to conclude whether DMPA use is associated with changes in dietary habits or behavior leading to weight gain.

Study of Different Doses of Letrozole and Medroxyprogesterone Acetate Co-treating Endometriotic Rats / 实用妇产科杂志

Objective:To explore the treatment effect on EMT in rats using different doses of letrozole and Medroxyprogesterone acetate (MPA) and their effects on liver,renal,skeletal and reproductive system.To provide lab evidence for treatment of EMT before menopause using letrozole.Methods:Endometriotic rat model was set up by surgical transplantation of autologous uterine tissues to ectopic site outside the uterus.70 EM model rats were randomly divided into 7 groups,each with 10:A ～C:LE 1 mg/(kg · d-1) and MPA [8、4、2 mg/(kg · d-1) respectively];D ～ F:LE 0.5mg/(kg · d-1) and MPA[8、4、2 mg/(kg · d-1) respectively];G:0.9％ saline (control group).The volume of ectopic lesion in each group was compared before and after the treatment.The expression of P450arom and Ki-67 and cell apoptosis in the endometriotic tissues of the rat models were detected.The serum levels of FSH,LH and E2 were determined and liver and renal functions were detected.Bone mineral density(BMD) was measured in the right femur.Results:①Except for group F,the volume of the endometriotic tissues of the five groups reduced significantly compared with the G group(P ＜ 0.05),and the greatest decrease in the volume were in group A and B (P＜0.01);②Compared with the G group,the expression of P450arom and Ki-67 protein decreased while the apoptotic rate increased in tissues of endometriosis (EM) on rat models among group A to group E (P＜0.05),in which group A and B were the most notable (P＜0.01);(③Compared with the G group,the level of FSH,LH and E2 reduced in group A、B and D (P＜0.05),moreover,the E2 level of group A and B was lower than that in group D (P＜0.05);④Compared with the G group,the ovarian weight in group C increased greatly,and the ovaries showed polycystic.The uterine weights decreased among group A to group E,and the endometrium presented atrophy or inhibition of proliferation;⑤There was no change on the bone density among each group(P ＞ 0.05);⑥Abnormal liver function was only detected in group A after treatment,and no ab normal renal function detected in any group(P＞0.05).Conclusions:LE 1 mg/(kg · d-1) associated with MPA 4mg/(kg · d-1) had the most effect on EM rat models.Moreover,it had no influence on liver or renal function.The mechanism may be decreasing the serum level of E2,reducing local estrogen along with increasing the apoptosis while decreasing the proliferation of the ectopic tissues.

Criterios Médicos de elegibilidad para el uso de anticonceptivos de la OMS / Medical eligibility criteria for the use of WHO contraceptives

Introducción: Los "Criterios Médicos de Elegibilidad para el Uso de Anticonceptivos" de la Organización Mundial de la Salud (OMS) son una guía para la correcta elección y uso de los métodos anticonceptivos en variadas condiciones de salud. En este documento revisaremos las principales modificaciones en su quinta y última edición publicada en inglés el año 2015. Desarrollo: Las modificaciones de la quinta edición son fundamentalmente la adición de nuevos métodos y la modificación de la categoría de recomendación para algunas condiciones de salud. Se agregan el acetato de medroxiprogesterona de depósito vía subcutánea, el anillo vaginal de progesterona, el implante anticonceptivo subcutáneo sinoimplant(II)® y el método anticonceptivo de emergencia acetato de ulipristal. Se modifican las recomendaciones para las mujeres en lactancia, permitiendo el uso de algunos métodos de progestágeno solo desde el posparto inmediato, salvo el acetato de medroxiprogesterona de depósito por entregar una dosis elevada del esteroide y el dispositivo intrauterino (DIU) con levonorgestrel, el cual sigue las normas de los DIU con cobre. También hay modificación en las recomendaciones en cuanto al uso de anticonceptivos combinados en el puerperio, con más restricciones para mujeres sin lactancia. Por último, sobre el uso de terapia antiretroviral, cambian algunas categorías y se amplía el listado de fármacos detallados. Conclusión: Es necesario que los profesionales de salud conozcan estas modificaciones para poder entregar una atención de calidad a las usuarias de anticoncepción.

Introduction: The "Medical Eligibility Criteria for Contraceptive Use" published by the World Health Organization (WHO) is a guide for the correct choice and use of the contraceptive methods in many different health conditions. In this document we will review the main changes made in the fifth and last edition of this guide published in English in 2015. Development: The modifications of this last edition are the addition of new contraceptive methods and the modification of the category of the recommendation for some health conditions. It adds the medroxiprogesterone acetate subcutaneous injection, the progesterone vaginal ring, the subcutaneous contraceptive implant sinoimplant(II)® and ulipristal acetate as emergency contraception. There are modifications of the recommendations for breastfeeding women, allowing the use of some progestin only methods since the immediate postpartum, with the exception of medroxiprogesterone acetate because it delivers a high dose of the steroid and the levonorgestrel intrauterine device that follows the same recommendations as the copper intrauterine device. There are also modifications in the recommendations for the use of combined contraceptives in the first 42 days postpartum, with more restrictions for non-breastfeeding women. Finally, on the use of antiretroviral therapy drugs, there were changes of some categories and a detailed categorization for each drug. Conclusion: It is necessary for health care providers to know these changes in order to deliver a quality care to contraception users.

Quantitative analysis of collagen fibrillar structure in canine uterus exposed to acetate of medroxyprogesterone using second harmonic generation microscopy / Análisis cuantitativo de la estructura de fibras colágenas en útero canino expuesto a acetato de medroxiprogesterona utilizando generación microscópica de un segundo harmónico

Collagen is the most abundant structural protein found in organs and is responsible for providing tissues with structure and function. In order to investigate in canine uteri the potential effect of medroxyprogesterone acetate (MPA) on the changes in collagen deposition were grouped as nulliparous (n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5 mg/kg; i.m.). The amount of collagen was studied in the fold and basal regions of the endometrium and myometrium using second harmonic generation with a two-photon spectral confocal microscope, quantified using ImageJ software with a color segmentation plugin, was expressed as fraction area (%) and analyzed by ANOVA (p<0,05). No differences were observed between groups in the fold (p=0,3995) or base (p=0,7392) of the endometrium and myometrium (p=0,1781). In conclusion, our data demonstrate that two doses of MPA (5 mg/kg; i.m.) do not affect the total collagen deposition in canine uteri undergoing contraceptive treatment.

El colágeno es la proteína estructural más abundante presente en órganos y es responsable de proporcionar la sostén y función a los tejidos. Para investigar en caninos el efecto potencial del acetato de medroxiprogesterona (MPA) sobre cambios en el depósito de colágeno en útero, éstos fueron agrupados como nulíparos (n = 11), multíparos (n = 11) y tratados con MPA (n = 11, nulíparos con dos tratamientos 5 mg/kg, im). El colágeno fue evaluado en el pliegue y regiones basales del endometrio y en miometrio utilizando la Generación de un Segundo Harmónico con un microscopio confocal espectral y dos fotones y cuantificado utilizando el software ImageJ a partir de la segmentación de colores. Los resultados fueron expresados y analizados como fracción de área (%; ANOVA; p<0,05). No se observaron diferencias entre los grupos en el pliegue (p = 0,3995) y base (p=0,7392) del endometrio y tampoco en miometrio (p=0,1781). En conclusión, nuestra evidencia demuestra que dos dosis de MPA (5 mg/kg, i.m.) no afectan el depósito total de colágeno en úteros caninos expuestos a tratamiento anticonceptivo.

Body composition, resting energy expenditure and inflammatory markers: impact in users of depot medroxyprogesterone acetate after 12 months follow-up

ABSTRACT Objective The aim of this study was to evaluate for 12 months the changes of body weight using Depot Medroxyprogesterone Acetate (DMPA) and if these changes are related to inflammatory markers. Subjects and methods Twenty women of childbearing age who chose the DMPA, without previous use of this method, BMI < 30 kg/m2, and 17 women using IUD TCu 380A, participated in the study. At the baseline and after one year, changes in weight gain, body composition by the bioimpedance electric method, resting energy expenditure (REE) by the indirect calorimetry method, inflammatory markers and HOMA-IR were assessed. Results After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight (3,01 kg) and BMI, while the IUD group’s only significant increase was observed in the BMI. Relative to REE there was an increase of basal metabolic rate (BMR) in both groups after one year. The sub-group DMPA that gained < 3 kg had increased significant weight, BMI and body surface (BS) with respiratory quotient (RQ) reduction, while the sub-group that gained ≥ 3 kg had a significant increase in weight, BMI, BS, fat-free mass, fat mass, BMR, Leptin, HOMA-IR and waist circumference, with RQ significantly reduced. Conclusion Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus.

Quantification of collagen fibers in canine uteri treated with medroxyprogesterone acetate

Collagen plays essential roles in remodeling uterine tissue during decidualization, implantation, pregnancy and involution. To understand whether the progestational agent medroxyprogesterone acetate (MPA) can modify the organization and deposit of collagen in the uteri of normal bitches (Canis Tlupus familiaris), we assessed uterine tissues by histochemistry. Uteri were grouped as: nulliparous (n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount, location and birefringence of interstitial collagen types I and III in the fold and base of the endometrial stroma and the myometrial muscular layers were studied on sections stained with Picrosirius Red by polarized light microscopy and evaluated by ANOVA. No differences were observed in the endometrium. In the myometrium, differences were observed in collagen type I between MPA-treated and nulliparous uteri vs. multiparous (p<0.05), and differences in collagen type III between nulliparous and multiparous uteri vs. MPA-treated (p=0.0001). In conclusion, two doses of MPA had no significant effect on the investigated collagens in the extracellular matrix.(AU)

Effect and regulation of metformin on endometrial carcinoma subline of progestin-resistance / 中华妇产科杂志

Objective To investigate the effect and mechanism of metformin on endometrial carcinoma subline of progestin-resistance and find whether metformin could regulate progestin-resistance in endometrial carcinoma. Methods Ishikawa endometrial carcinoma cells were cultured for a long period in the presence of the synthetic medroxyprogesterone 17-acetate (MPA) to generate a subline refractory to the growth-suppressive effects of MPA,named Ishikawa/MPA cells. The effect of MPA (1, 5, 10, 20, 40 and 60 μmol/L) or metformin (1, 10, 20, 40, 60, 70 and 80 mmol/L) on proliferation of the Ishikawa/MPA and parental Ishikawa cells was detected by cell counting kit-8 (CCK-8) method. Western blot was used to detect the effect of metformin and(or)MPA on the expression of PR-B in the Ishikawa/MPA and Ishikawa cells. Results The Ishikawa/MPA showed that growth stimulation rather than inhibition in the Ishikawa cells after low MPA concentration treatment. The doubling time of Ishikawa/MPA cell lines were (43±4) hours and that of Ishikawa cell line were (47 ± 3) hours. No changes in doubling time were observed (t=0.349,P=0.572). Low concentration (1 and 5μmol/L) of MPA could promote the growth of Ishikawa/MPA cells (by 3% and 13%). High concentration (10, 20, 40 and 60 μmol/L) of MPA could inhibited the growth of Ishikawa/MPA cells (by 4%, 3%, 9%and 40%) and the growth of Ishikawa cells (by 41%, 55%, 65%and 66%). At the same concentration, the difference of inhibition rates between the two cell lines were statistically significant (P<0.01). Metformin (1, 10, 20, 40, 60, 70 and 80 mmol/L) could inhibite the growth of Ishikawa/MPA (by-10%, 20%, 56%, 89%, 97%, 98%and 99%) greater than those in parental Ishikawa cells (by-6%, 19%, 37%, 54%, 70%, 72%and 83%), and the inhibitory effect was dose-dependent manner. Western blot assay showed that for Ishikawa cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (53.5±4.0)%and (37.7±5.2)%, which were higher than that in the control group [(23.4 ± 3.0)%], and there were significant the differences (P<0.01). For Ishikawa/MPA cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (38.6 ± 1.7)%,(36.3 ± 2.5)%,which were higher than those in the control group [(6.4 ± 1.6)%], and there were also significant differences (P<0.01). Conclusion Metformin may regulate the progestin-resistance in endometrial carcinoma by increasing the expression of PR-B.

Review of Contraception with Depot Medroxyprogesterone Acetate at the University of Port Harcourt Teaching Hospital, Port Harcourt, Southern Nigeria.

Aims: To re- evaluate the use, effectiveness, acceptability and side effects of depot medroxyprogesterone acetate in Port Harcourt, Southern Nigeria. Study Design: Descriptive retrospective analysis. Place and Duration of Study: Family planning clinic, University of Port Harcourt Teaching Hospital, (UPTH), Port Harcourt Nigeria, between 1st January 2004 and 31st December, 2013. Methodology: The case files of all new clients who accepted and used depot medroxyprogesterone acetate at the UPTH were retrieved and their data including the socio-demographic characteristics, side effects, reasons for family planning extracted, coded and entered into a data bank and analysed using SPSS for windows 19.0 version and results expressed in percentages and presented in tables and figures. Results: Six hundred and seventy seven clients out of the total of 7001 new acceptors of contraception during the study period used depot medroxyprogesterone acetate (DMPA) giving an uptake rate of 9.7%. Three hundred and fifty three (52.1%) used it for child spacing while 324 (47.9%) used it for terminal fertility control. Secondary amenorrhea remained the commonest side effect occurring in 503 (74.3%) women. Up to 482 (71.2%) clients were lost to follow up, 43 (6.5%) discontinued voluntarily while 145 acceptors continued to use DMPA, giving a continuation rate of 22.5%. No unintended pregnancy occurred at the end of the observation period, giving a Pearl Index of 0/100 woman years. Conclusion: Depot medroxyprogesterone acetate is highly effective and safe method of fertility control but with declining acceptability, high default and low continuation rates.

Clinical Observation of Medroxyprogesterone or Dydrogesterone Combined with Hysteroscopic Electrosur-gery in the Treatment of Early Estrogen-dependent Endometrial Cancer / 中国药房

OBJECTIVE:To compare the efficacy and safety of medroxyprogesterone or dydrogesterone combined with hystero-scopic electrosurgery in the treatment of early estrogen-dependent endometrial cancer. METHODS:42 patients with early estro-gen-dependent endometrial cancer were randomly divided into medroxyprogesterone group (21 cases) and dydrogesterone group (21 cases). All patients received hysteroscopic electrosurgery. Medroxyprogesterone group received 100 mg Medroxyprogesterone acetate tablet,3 times a day. Dydrogesterone group received 100 mg Dydrogesterone tablet,twice a day. The treatment course for both groups was 6 months. Clinical efficacy,carbohydrate antigen CA125(CA125),body mass and the incidence of adverse reac-tions in 2 groups were observed. RESULTS:After 3 months of treatment,the total effective rate in dydrogesterone group was sig-nificantly lower than medroxyprogesterone group,the difference was statistically significant(P0.05). Before treatment,there were no significant differences in CA125 and body mass in 2 groups (P>0.05). After 3 and 12 months,CA125 levels in 2 groups were significantly lower than before,12 months was lower than 3 months,and dydrogesterone group was higher than medroxyprogesterone group after 3 months,the differ-ences were statistically significant (P0.05). After treatment,the body mass in medroxyprogesterone group was significantly higher than before,the difference was statis-tically significant (P0.05). And the incidence of adverse reactions in dydrogesterone group was significantly lower than medroxyprogesterone group,the difference was statistically significant(P<0.05). CONCLUSIONS:The short-term efficacy of medroxyprogesterone combined with hysteroscopic electrosurgery is superior to dydrogesterone combined with hysteroscopic electrosurgery in the treatment of early estro-gen-dependent endometrial cancer,but medroxyprogesterone combined with hysteroscopic electrosurgery shows high incidence of adverse reactions. Long-term effects of both Dydrogesterone and Medroxyprogesterone are equivalent.

The factors analysis on pregnant outcomes between well-differentiated endometrial cancer and atypical endometrial hyperplasia after conservative treat ment / 实用肿瘤学杂志

Objective To identify factors that might affect establishing pregnancy following conservative treatment by medroxyprogesterone acetate ( MPA)for well -differentiated endometrioid adenocarcinoma ( EC) or a-typical endometrial hyperplasia(AEH).Methods A retrospective study of 65 patients with EC/AEH were divid-ed into a pregnancy group ( n=34 ) and a non -pregnancy group ( n=31 ) .The influent factors on establishing pregnancy were detected by statistical analysis .Results There was no significant difference in clinical character-istics between pregnancy group and non -pregnancy group .There were significantly different between pregnancy group and non-pregnancy in the duration of MPA administration ,the time to disappearance of lesions ,the age of pregnancy permission ,the number of D&C procedures performed ,and endometrial thickness during ovulation ( P<0.05).The multivariate logistic regression analysis identified that the recurrence (OR=2.323,P=0.015),endo-metrial thickness during ovulation (OR=0.283,P <0.001),and age of pregnancy permission (OR=2.524,P=0.039) were significant factors affecting pregnancy outcomes .Conclusion Recurrence, endometrial thickness during ovulation ,and the age of the pregnancy permission were considered to affect pregnant establishment follow -ing conservative treatment with MPA .Assisted reproductive technology immediately after achieving tumor disap-pearance by MPA would therefore be beneficial for patients with disease recurrence ,thin endometrium ,or a higher age of pregnancy permission .

Adesão à dupla contracepção entre mulheres infectadas pelo HIV / Dual contraception adherence among HIV-infected women

OBJETIVO: Verificar a adesão à dupla contracepção entre mulheres infectadas pelo HIV usando acetato de medroxiprogesterona de depósito (AMPD) e condom.MÉTODOS: Corte transversal realizado em centro de referência de dezembro 2013 a setembro 2014. Entrevistadas 114 mulheres HIV (+), 15 a 49 anos, em uso de AMPD e condom para contracepção, aplicando questionário clínico epidemiológico, construído após painel Delphi e validação de conteúdo.RESULTADOS: As médias foram de 33,2±7,2 anos de idade, 8,1±5,2 anos de detecção do HIV, 6,8±5 anos de uso de terapia antirretroviral (TARV) e 737,6±341,1 células CD4/mm3. Adquiriram HIV pelo sexo 98,2% (112/114). Identificadas 85,9% (98/114) usuárias de TARV e 77,7% (84/114) com CD4>500/mm3. Relato de parceria fixa em 78,9% (90/114), havendo sorodiscordância para HIV em 41,2% (47/114), status sorológico do parceiro desconhecido em 21,9% e o parceiro desconhece que era infectada em 37,7% (43/114). Última gestação não planejada referida por 71,9% (82/114). Engravidaram no último ano 14,9%, sendo 70,5% (12/17) não planejadas. Relato de uso atual de AMPD em 64,9% (74/114) com sangramento genital em 48,2% (55/114) e ganho de peso em 67,5% (77/114). O uso de condom masculino foi referido por 62,2% (71/114). Três usuárias de condom feminino sempre e dez eventualmente. Tinham sexo desprotegido vaginal 37,7% (43/114) e anal, 32,4% (37/114). Relato de resistência do parceiro para usar preservativo em 30,7% (35/114). A dupla contracepção com AMPD e condom foi relatada por 42,9% (49/114). Resistência do parceiro para usar condom foi associada com má adesão (RP=0,3; IC95% 0,2-0,7; p<0,001). Parceiro desconhecer a infecção da parceira pelo HIV favoreceu a adesão (RP=1,8; IC95% 1,2-2,7; p=0,013).CONCLUSÃO: Neste estudo, adesão à dupla contracepção com AMPD e condomfoi de 42,9%, mantendo gestações não planejadas e sexo desprotegido. Resistência do parceiro para usar condom aumenta três vezes a chance de a mulher não aderir à dupla proteção e parceiro desconhecer a infecção da mulher quase duplica a chance de ela aderir. Metas: ampliar oferta de novos contraceptivos e envolver parceiros na contracepção e testagem.

PURPOSE: To determine adherence to dual contraception using depot-medroxyprogesterone acetate (DMPA) and condom among HIV-infected women.METHODS: A cross-sectional study carried out from December 2013 to September 2014 at a local reference center, with application of questionnaire elaborated after Delphi panel and content validation to 114 HIV(+) women aged 15 to 49 years, using DMPA plus condom for contraception.RESULTS: Mean age was 33.2±7.2 years, mean time since HIV detection was 8.1±5.2 years, mean time of antiretroviral use was 6.8±5 years and mean CD4 cells/mm3 count was 737.6±341.1. Sexual HIV acquisition was reported by 98.2% (112/114), antiretroviral use by 85.9% (98/114), and 77.7% (84/114) had a CD4>500/mm3 count. Having a single sex partner was reported by 78.9% (90/114), with HIV serodiscordance in 41.2% (47/114) of couples, 21.9% did not know the serological status of their partner and in 37.7% of cases (43/114) the partner was unaware of the HIV(+) status of the woman. The last pregnancy was unplanned in 71.9% of cases (82/114) and 14.9% of the women had become pregnant the year before, with pregnancy being unplanned in 70.5% (12/17) of cases. Current use of DMPA was reported by 64.9% (74/114), with genital bleeding in 48.2% (55/114) and weight gain in 67.5% (77/114). Use of a male condom was reported by 62.2% of the subjects (71/114). Three reported that they always used a female condom and ten that they eventually used it. Unprotected vaginal sex was reported by 37.7% (43/114) and unprotected anal intercourse was reported by 32.4% (37/114). Partner resistance to use a condom occurred in 30.7% of cases (35/114). Dual contraception using DMPA with condom was reported by 42.9% (49/114). A partner who resisted wearing a condom was associated with poor adhesion (PR=0.3; 95%CI 0.2-0.7; p<0.001). A partner who was unaware that a woman was infected with HIV favored adherence (PR=1.8; 95%CI 1.2-2.7; p=0.013).CONCLUSION: The percentage of dual contraception using DMPA plus condom was 42.9%, maintaining unplanned pregnancies and unprotected sex. Resistance of partners to use a condom increased three times the chance of a woman not adhering to dual contraception, and the partner not knowing women's HIV infection almost doubled the chance to adhere to safe contraception. Goals: to offer new hormonal contraceptives and to involve the partners in contraception and serologic detection tests.