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.

Medroxyprogesterone Acetate versus Gonadotropin-Releasing Hormone Antagonist for the Prevention of Premature Luteinizing Hormone Surge in hyper-responder women undergoing controlled ovarian stimulation for IVF/ICSI Cycles.

OBJECTIVE: To compare the effect of Medroxyprogesterone acetate versus Gonadotropin releasing hormone antagonist for the prevention of premature luteinizing hormone (LH) surge in infertile hyper-responder women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) cycles. METHODS: One hundred infertile hyper-responder women who were candidate for IVF/ICSI were randomly assigned into two groups. Group 1 was given 20 mg Medroxyprogesterone acetate from day 1 of the menstrual cycle till trigger day. Group 2 was given GnRH antagonist (injection Cetrorelix 0.25 mg s/c) from the day when the leading follicle reached 14 mm until the day of trigger for the prevention of premature LH surge (flexible protocol). We measured LH serum levels on day 1, day 7 of cycle and on trigger day. The primary outcome measured was the incidence of premature LH surge. Other outcome measures were total number of mature follicles on trigger day, total number of mature oocytes retrieved and number of good quality day-3 embryos. RESULTS: There was no premature luteinizing hormone surge in both groups of our study. The mean number of follicles on trigger day, mean number of M2 oocytes retrieved and mean number of good quality day-3 embryos were comparable in both the groups, with no statistically significant difference. CONCLUSIONS: The results of this study stated that MPA can be an effective alternative to GnRH antagonist for the prevention of premature LH surge in hyper-responder women undergoing COS for IVF. It is easy to use, widely available and cost-effective. It may establish a new regimen of ovarian stimulation using MPA as an oral alternative to GnRH antagonist treatment in hyper-responders.

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.

Acceptability of the contraceptive Sayana® Press when injected every four months: Results from a twelve-month trial in Brazil, Chile and the Dominican Republic.

OBJECTIVE: We assessed the acceptability of subcutaneous depot-medroxyprogesterone acetate 104 mg (Sayana® Press) when injected every 4 months for 12 months. STUDY DESIGN: We assessed acceptability using questionnaires within a clinical trial to evaluate contraceptive effectiveness of Sayana® Press when the reinjection interval was extended from 3 to 4 months. We enrolled 750 women aged 18 to 35 years and at risk of pregnancy at 3 centers in Brazil, Chile, and the Dominican Republic who agreed to use Sayana® Press every 4 months for 12 months. Acceptability outcomes included responses to questions about perception of bleeding patterns and side effects, likes, and dislikes about the regimen. We descriptively compared outcomes across study centers and between those who completed the study and those who discontinued early. RESULTS: Across the 3 centers, participants differed in age, marital status, years of schooling, and race. At the final visit, 90% reported being satisfied with Sayana® Press and 75% reported preferring to use this contraceptive every 4 months. The most common reasons women liked using Sayana® Press were for its duration of effectiveness, followed by amenorrhea. The most common dislike, when a reason was identified, was its effect on uterine bleeding, including amenorrhea reported by some participants. We also observed center-level differences in the proportion of women who liked amenorrhea. CONCLUSIONS: Satisfaction with Sayana® Press injected every 4 months was high across the 3 demographically diverse Latin-American centers. However, participants had varied feelings towards contraceptive-induced amenorrhea. IMPLICATIONS: We found that Sayana® Press when injected every 4 months was highly acceptable among women in 3 Latin American settings despite differences in their feelings toward contraceptive-induced amenorrhea. Our results suggest that there will be interest in using this method every 4 months if introduced into these settings.

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.

Early resynchronization protocols for goats: Progestogens can be used prior to an early pregnancy diagnosis without affecting corpus luteum functionality.

This study aimed to evaluate the exogenous progesterone (P4) effect on the luteal function from Day 16 to Day 21 of the oestrous cycle in inseminated goats with unknown pregnancy status. A total of 54 does passed through a short progestin-based synchronization protocol and, on Day 16 of the following oestrous cycle, 27 does received a new P4 device which was retained until Day 21. Blood samples were collected daily from all does during this period, as well as on Day 24. Pregnancy diagnoses were performed on Day 30. Serum P4 values from 26 animals (GNPSP : Group of non-pregnant does with second sponge: n = 8; GNPNSP : Group of non-pregnant does without second sponge: n = 6; GPSP : Group of pregnant does with second sponge: n = 5; GPNSP : Group of pregnant does without second sponge: n = 7) were determined by radioimmunoassay commercial kits. No P4 differences were found between groups (GNPSP : 3.1 ± 2.8; 1.7 ± 1.8; 0.4 ± 1.0; and 0.0 ± 0.0 vs. GNPNSP : 4.4 ± 1.8; 3.0 ± 2.2; 0.8 ± 0.8; and 0.0 ± 0.0 or GPSP : 4.2 ± 1.0; 3.4 ± 0.6; 3.3 ± 1.6; 3.2 ± 0.9; 3.6 ± 1.2; 3.5 ± 1.3; 2.7 ± 1.3 vs. GPNSP : 4.4 ± 1.6; 3.6 ± 1.5; 3.7 ± 1.5; 3.8 ± 1.4; 3.2 ± 1.2; 3.1 ± 1.2; 3.6 ± 1.1; D16, D17, D18, D19, D20, D21, D24, respectively) or for the interaction of group and time. In conclusion, a second progestogen device had no effect on luteolysis or early pregnancy in the following oestrous cycle.

Changes in calcium metabolism and bone mineral density in new users of medroxyprogesterone acetate during the first year of use.

OBJECTIVE: To evaluate calcium metabolism and bone mineral density (BMD) in new users of depot medroxyprogesterone acetate (DMPA) in the first year of use. METHODS: This prospective, non-randomized study, conducted at the University of Campinas, São Paulo, Brazil, was carried out between February 2011 and February 2013. Women aged from 18 to 40 with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) <30 and with no known history of disease or medication use who chose to use DMPA were paired by age (±1 year) and BMI (±1) with women commencing the use of a copper intrauterine device (IUD). The primary outcomes were BMD measured by dual-energy X-ray absorptiometry and calcium metabolism markers; other variables were body composition and lifestyle habits. Repeated measures analysis of variance (ANOVA) and multiple regression analyses were used to evaluate associations. RESULTS: Twenty-seven women using DMPA and 24 using IUD were evaluated, with a mean age of 29.7 years and 28.6 years, respectively. The DMPA group presented with a 3.6% (P<0.001) loss of lumbar spine BMD, a 2.1% (P=0.100) loss of femoral neck BMD and higher phosphorus (P=0.014) concentrations at 12 months compared to the IUD group. The decreases in BMD were associated with the use of DMPA, while total mass and coffee intake were found to be protective factors. CONCLUSION: Changes in calcium metabolism and a decrease in BMD were found in the DMPA group at 12 months.

Quantification of estradiol cypionate in plasma by liquid chromatography coupled with tandem mass spectrometry: Application in a pharmacokinetic study in healthy female volunteers.

The combination of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg is a highly effective, monthly injectable contraceptive. For the first time, this study presents the development and validation of a sensitive method for estradiol cypionate analysis in human plasma by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Aliquots (500 µL) of plasma were extracted with ethyl ether (100%) and derivatized with dansyl chloride. Its separation was performed on a Jones Chromatography Genesis C8 column and the quantification was performed with a mass spectrometer equipped with an electrospray interface operating in negative ion mode. The run time was 6 min and the calibration curve was linear over the range of 0.005-0.15 ng/mL. The method was applied to evaluate the pharmacokinetics of estradiol cypionate in plasma collected up to 1008 h (42 days) after a single intramuscular administration of 25 mg/mL medroxyprogesterone acetate +5 mg/mL estradiol cypionate to healthy female volunteers (n = 12). The estradiol cypionate maximum plasma concentration (Cmax) was 0.14 ± 0.08 ng/mL reached at 16.83 ± 21.07 h and the area under the plasma concentration versus time curve (AUC0-last) was 14.07 ± 6.32 ng.h/mL. Elimination half-life (t½), apparent volume of distribution (Vd/F), apparent clearance (CL/F) and mean residence time (MRT) were 89.65 ± 76.04 h, 28038 ± 9636 L, 49.02 ± 10.62 L/h and 576.05 ± 238.32 h, respectively, showing that the estradiol cypionate release from the administration site was prolonged and there was no drug accumulation.

Thyroid function during the first year of use of the injectable contraceptive depot medroxyprogesterone acetate.

PURPOSE: The aim of the study was to evaluate thyroid function profile as a possible factor influencing weight and body composition variation in new users of depot medroxyprogesterone acetate (DMPA). MATERIALS AND METHODS: A prospective, non-randomised, comparative study was conducted at the University of Campinas, Brazil. Women aged 18-40 years with a body mass index (BMI) less than 30 kg/m2, normal oral glucose tolerance test, no known diseases, and using no medication, who opted to use DMPA were paired by age (±1 year) and BMI (±1 kg/m2) with women initiating copper intrauterine device (IUD) use. The main outcome measures were thyroid function profile, weight, and body composition, as measured by dual-energy X-ray absorptiometry. We used repeated measures ANOVA to perform comparisons between times and groups. RESULTS: We evaluated 28 DMPA users and 24 IUD users who completed the 12-month follow-up. We observed that FT4 levels were higher at 12 months (compared to baseline) in the DMPA group (p < .0001) and that FT4/FT3 ratio had increased in both groups. Additionally, at 12 months, total body mass had increased around 2 kg and lean mass increased in the DMPA group compared to the IUD group; there was also an increase in weight, BMI, total body mass, and fat mass when compared to baseline. CONCLUSIONS: No changes in thyroid function occurred that could explain the weight increase observed in DMPA users.

Subclinical cardiovascular disease parameters after one year in new users of depot medroxyprogesterone acetate compared to copper-IUD.

PURPOSE: To evaluate markers of cardiovascular disease in women with normal insulin sensitivity who had recently initiated use of depot medroxyprogesterone acetate (DMPA) as a contraceptive. MATERIALS AND METHODS: A prospective, non-randomised, comparative study. Data of 30 women of 18-40 years of age, with normal hyperinsulinaemic-euglycaemic clamp at baseline and body mass index (BMI) < 30, who opted to use DMPA or a copper intrauterine device (IUD) as a contraceptive, were analysed. Serum samples were collected for evaluation of the lipid and hepatic profile, C-reactive protein, TNF-α, interleukin-6, leptin/adiponectin ratio and free fatty acids; body composition was evaluated using DXA, blood pressure and carotid intima-media thickness were measured. Evaluations were performed at baseline and 12 months later. The groups were compared using repeated measures analysis of variance (ANOVA). Significance level was 5%. RESULTS: The mean age of the women in the DMPA and IUD group was 28.7 ± 6.5 and 28.3 ± 5.8 years, respectively; the BMI was 23.0 ± 3.4 and 24.3 ± 2.7 kg/m2, respectively, in the same groups. At 12 months, triglyceride levels were higher in the DMPA group compared to the IUD group and there was an increase in apolipoprotein B-100 in relation to baseline in DMPA group; there were no other difference between the groups. CONCLUSIONS: No clinical cardiovascular effect was found but deterioration in CV markers was observed in the first year of use of DMPA.

Hyperinsulinemic-euglycemic clamp over the first year of use of depot-medroxyprogesterone acetate as a contraceptive.

OBJECTIVE: The literature lacks data on the use of the gold-standard hyperinsulinemic-euglycemic clamp (HEC) technique for the evaluation of insulin resistance (IR) in depot-medroxyprogesterone acetate (DMPA) users. This study assessed carbohydrate metabolism in non-obese users of DMPA using the HEC technique. STUDY DESIGN: A prospective, non-randomized, comparative study conducted at the Family Planning Clinic/Metabolic Unit, University of Campinas, Brazil. Forty-eight women aged 18-39 years underwent HEC: 30 initiating use of DMPA and 18 initiating use of a copper intrauterine device (IUD). Data from 15 women in each group, who completed the follow-up and underwent HEC at12 months, were compared using repeated measures ANOVA. All women were advised to perform aerobic physical exercise for 150 min/week; body composition and total energy intake were evaluated. Main outcome measures were IR defined by M-value <4 mg/kg/min, and blood levels of insulin. Additional outcomes were total cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol, adipokines and free fatty acids. RESULTS: At 12 months, two women in the DMPA group and none in the IUD group had developed IR. The groups were similar in in M-values and in blood levels of insulin, total cholesterol, HDL-cholesterol, LDL-cholesterol, adipokines or free fatty acids. Triglyceride levels increased in the DMPA group when compared to the IUD group, 80.0 (SD 47.8) versus 61.8 (SD 35.8) mg/dL respectively, (p=.033); and increased the total daily energy intake, 1828.3 (SD 518.9) versus 1300.8 (SD 403.4) kilocalories/24hs, respectively in the same groups, (p=.041). All the DMPA users showing higher insulin sensitivity at 12 months reported performing physical activity regularly. CONCLUSIONS: Changes occurred in carbohydrate metabolism in DMPA users in the first year of use of the method. It is possible that the regular aerobic exercise may exert a beneficial and protective effect against the factors that trigger these changes. IMPLICATIONS STATEMENT: Carbohydrate metabolism undergoes adverse changes in few young non-obese women during the first year of DMPA use and regular aerobic exercise may exert a beneficial and protective effect against these changes.

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.

Histomorphometrics and quantitative unbiased stereology in canine uteri treated with medroxyprogesterone acetate.

This article describes the effects of MPA use on the canine uterus using stereological methods. Entire reproductive tracts were removed from normal healthy canine bitches (Canis lupus familiaris) and grouped as: nulliparous (n = 11), multiparous (n = 11) and MPA-treated (n = 11; nulliparous; two treatments; 5 mg/kg). 1 cm samples were cut from the corpus, horn and uterine tube and fixed in 10% formaldehyde. Sections of each were mounted on slides and stained with hematoxylin-eosin. We assessed the fraction area for components of endometrium and myometrium and VV (volume density) and SV (surface density) of the gland and stroma using the M36 test system provided by the STEPanizer Stereological Tool. No gross histological differences were observed between study groups in the uterine tube, uterine corpus and horn. The wall of the uterine corpus and horn in MPA-treated bitches was characterized as being thicker than in the other groups. A cross-section of the uterine corpus revealed no differences between components of uterine wall in the corpus and horn; however, differences were observed in the volume density [VV; %] in variables such as: VV[str.vasc/uterus] (nulliparous vs. multiparous; p = 0.0019) and VV[str.supravasc/uterus] (multiparous vs. nulliparous and MPA; p = 0.0035). In the endometrial gland, differences were detected in SV[gland/endom] (multiparous vs. MPA, p = 0.0442). In the uterine horn, differences were only observed in the variable VV[lumen.gland/endom] (multiparous vs. MPA; p = 0.0019). This study shows quantitative changes in the architecture of the endometrium and myometrium in all the uterine segments, mainly morphological endometrial gland changes of the uterine corpus, increasing the surface area per unit of volume; however, these changes usually do not differ quantitatively from those observed in the uterus of multiparous bitches.

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)

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)

Binge eating and biochemical markers of appetite in new users of the contraceptive depot medroxyprogesterone acetate.

PURPOSE: Weight gain has been cited by women as one of the main reasons for discontinuation of the contraceptive depot medroxyprogesterone acetate (DMPA). This study aimed to evaluate binge eating and the biochemical markers of appetite in new DMPA users. METHODS: In this prospective non randomized study with adult healthy women, twenty-eight users of DMPA and twenty-five users of a copper intrauterine device (IUD) were paired for age (±1 year) and body mass index (BMI) (±1 kg/m2). We evaluated binge eating using the Binge Eating Scale (BES), the serum levels of neuropeptide Y, leptin and adiponectin, and the BMI at baseline and after 12 months in both groups. For statistical analysis was used ANOVA for to compare the means of the repeated measurements. RESULTS: Mean age was 29.6 and 28.6 years and BMI was 23.9 and 24.5 kg/m2 for the DMPA and IUD groups, respectively. After 12 months, the frequency of the scores of binge eating remained low in both groups. There were no significant differences between the groups at 12 months with respect to BMI, levels of NPY, leptin, adiponectin, and BES scores. CONCLUSIONS: Healthy adult women did not present with central stimulation of appetite or binge eating disorder in their first year after starting use of DMPA. This study reinforces the use of the contraceptive DPMA and the need for guidance related to living a healthy lifestyle for women who attribute the increase of body weight to the use of the method.

Comparison of two strategies for the administration of injectable depot medroxyprogesterone acetate: among women who returned to a family planning clinic at three- or six-month intervals.

OBJECTIVES: The aim of this study was to compare the clinical performance of depot medroxyprogesterone acetate (DMPA) in women who received injections every 3 months at the Family Planning Clinic, and those who received every other injection at a health care facility near their place of residence, only returning to the clinic every 6 months. MATERIALS AND METHODS: The medical charts of DMPA users from 2 January 1980 through 31 December 2012 were evaluated for this study. Two cohorts of women were created and compared: those who regularly received DMPA injections every 3 months (3-month group) at the clinic and those who received alternating 3-month injections at a health care facility near their residence house, returning to the clinic every 6 months for an injection (6-month group). In addition, effectiveness rates, reasons for discontinuation, and continuation rates were evaluated. RESULTS: Overall, 2637 women received all injections at 3-month intervals at the clinic, and 1190 women received every other injection at a health care facility near their residence. The women in the 3-month group had higher pregnancy rates and higher discontinuation rates (with the exception of discontinuation due to the loss of libido). CONCLUSION: The women who received alternating injections near their homes were more likely to continue using DMPA as a contraception method and presented lower pregnancy and discontinuation rates (for the majority of reasons), when compared to those women who returned to the clinic every 3 months.

Insulin resistance parameters in users of the injectable contraceptive depot medroxyprogesterone acetate during one year of use.

OBJECTIVES: The aim of the study was to assess insulin resistance parameters using successive homeostasis model assessment (HOMA) and clinical evaluations in healthy new users of depot medroxyprogesterone acetate (DMPA). METHODS: A prospective 12-month study was carried out to compare 31 DMPA users with 25 copper intrauterine device (Cu-IUD; TCu380A) users, matched for age (± 1 year) and body mass index (BMI; ± 1 kg/m(2)). Participants met the following criteria: age 18 to 40 years, BMI < 30 kg/m(2), fasting glucose < 5.5 mmol/l, 2-h glucose after a 75 g oral glucose load < 140 mg/dl. BMI, waist circumference, fasting glucose, fasting insulin and HOMA of insulin resistance (HOMA-IR) were evaluated at baseline and after 6 and 12 months of contraceptive use. Insulin resistance was defined as a HOMA-IR value > 2.7. RESULTS: The DMPA group showed significant increases in BMI, waist circumference, fasting insulin and HOMA-IR throughout the observation period in relation to baseline. Significant increases in BMI and waist circumference were observed in the DMPA group at 12 months compared with the Cu-IUD group. Five DMPA users had abnormal HOMA-IR values, three of whom had gained > 5 kg in weight at 12 months. CONCLUSIONS: HOMA-IR represents a useful tool to indicate changes in carbohydrate metabolism in non-obese DMPA users, especially when accompanied by measurement of clinical parameters such as BMI and waist circumference.