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Protocols to artificially induce cows and heifers into lactation are effective and commercially available in Brazil. However, these protocols demand long hormonal treatments, which is debatable since little research has been done in the subject. To further understand artificial induction to lactation (AIL) protocols, we conducted two experiments. In experiment 1, our objective was to better characterize steroidal profile during an AIL protocol and assess the estradiol (E2) and progesterone (P4) serum profiles of Jersey cows (n=6) subjected to a conventional protocol. In experiment 2, we aimed to compare milk production and serum E2 concentrations of Holstein heifers induced into lactation by the standard AIL protocol (15 injections of E2 and 8 P4 injections) and by a short protocol in which the number of E2 injections and, consequently, the overall dosage of E2, were reduced (8 injections of E2 and 8 P4 injections). We hypothesized that a short AIL protocol (8 days) would be as efficient as the long standard protocol of 15 days. Our hypothesis was confirmed, since we demonstrated that a shorter protocol was able to induce lactation in Holstein heifers without hindering milk production. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate COMT2, COMT3, CYP1B1, and ESR1 gene polymorphisms and occurrence of endometrial polyps. In addition, we intended to evaluate the clinical and epidemiological features of patients with and without the presence of the disease, characterizing the possible risk factors. A cross-sectional study was performed, with a total of 309 women, including 236 in the group of women with endometrial polyp confirmed by hysteroscopy and anatomical pathological examination and 73 in the group of people with diagnostic hysteroscopy without abnormal findings from the macroscopic point of view. Polymorphisms of four genes were studied: COMT2 (rs4680), COMT3 (rs5031015), CYP1B1 (rs1056836), and ESR1 (rs2234693). Polymorphism genotyping was determined using real-time polymerase chain reaction. Considering the results, no differences were identified between the two groups with respect to age, body mass index, diabetes, dyslipidemia, or smoking. The group of women without endometrial polyps showed higher use of hormone therapy than the other group (16.4 percent versus 3.8 percent, p <.001). The COMT2, COMT3, CYP1B1, and ESR1 genes exhibited no significant difference for the occurrence of endometrial polyp between the two groups. The research concluded that no correlation was identified between the genetic polymorphisms evaluated and the presence of endometrial polyps. [ABSTRACT FROM AUTHOR]

Background and Objective: An important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil. Methods: We performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2–6 mg plus spironolactone 100–200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]). Results: Among 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23–27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76–1.04] and 1.06 [0.94–1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65–0.89] and 0.85 [0.78–0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74–0.91]). Conclusion: Estradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP. Trial Registration: This trial (NCT03220152) was registered on July 18, 2017. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine the dynamics of the discharge of micropollutants in the Amazon River from an advanced wastewater treatment plant (WWTP) and discusses the importance of management in order to minimize impacts. Methodology: A total of 13 micropollutants: ibuprofen (IBP), paracetamol (PCM), atenolol (ATL), loratadine (LTD), fexofenadine hydrochloride (FXF), amoxicillin (AMX), 17α-ethynyl estradiol (EE2), caffeine (CAF), sodium diclofenac (DCF), estrone (E1), estriol (E3), bisphenol A (BPA), and bis(2-ethylhexyl) phthalate (DEHP) were analyzed in effluent samples that came from different treatment stages of a WWTP with advanced treatment technology at different periods of the day. The presence of micropollutants and their quantification were obtained using LC-MS and GC-MS techniques. Originality/Relevance: This is the first study carried out at a WWTP in Manaus, a city in Brazil that is located within one of the most extensive fluvial system in the world. The data obtained are important for understanding the dynamics of the discharge of micropollutants into the Amazon River and its implications. Main results: After the treatment process, the micropollutants paracetamol, fexofenadine hydrochloride, caffeine, sodium diclofenac, and bis(2-ethylhexyl) phthalate were detected in the final effluent. Contributions: The results obtained in this study indicate the need for integrated management, considering technical, governmental, organizational and community-based approaches to minimize the effects of the discharge of micropollutants into the environment. [ABSTRACT FROM AUTHOR]

Objectives: Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW.Methods: This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2-6 mg plus spironolactone 100-300 mg) plus PrEP for 12 weeks, after which they could start any FHT (aFHT). Short- and long-term PK assessment occurred at Weeks 12 and 30-48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24 h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-term PK; aFHT at long-term PK) participants.Results: No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-term PK of noFHT (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg at the long-term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2-65.4) pg/mL at short-term PK (sFHT) and 44.8 (24.70-57.30) pg/mL at long-term PK (aFHT). No participants in this analysis seroconverted during the study.Conclusions: Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT. [ABSTRACT FROM AUTHOR]

We determined the prevalence of Metabolic Syndrome (MetS) and associated factors in 419 women (aged 40 to 65 years) in Northeast Brazil in a cross-sectional study conducted from April to November 2013. We defined MetS using the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Socio-demographic variables, reproductive factors, lifestyle factors, anthropometrics, body composition, quality of life, and physical performance were assessed for their associations. We constructed multivariate Poisson regression models to estimate prevalence rate ratios (PRR) and 95% confidence intervals (CI). We identified 275 (65.6%) cases of MetS. The three most prevalent indicators were obesity (73.5%), reduced high-density lipoprotein level (63.0%), and elevated blood pressure (60.9%). In the final adjusted model, black race (PR 1.30, 95% CI: 1.07–1.57), lower grip strength/body mass index (PR 1.31, 95% CI: 1.15–1.50), and low estradiol levels (PR 1.17, 95% CI: 1.00–1.35) were associated with MetS. MetS is a long-term threat to the health of middle-aged women and a potential public health burden. These results may help in developing health promotion strategies to prevent morbidity and mortality associated with MetS in this vulnerable population. [ABSTRACT FROM AUTHOR]

The association of Ethinylestradiol 0.03 mg and Levonorgestrel 0.15 mg is a hormonal contraceptive that combines estrogen and progestogen. According to a bibliographic survey, these combined drugs present at least 18 known degradation products, which are required to control the potential impurities harmful to human health. The high number of impurities and the low concentrations of the active pharmaceutical ingredients (APIs) and their respective degradation products increase the complexity of the stability-indicating method development for this medicine. Thus, this work aimed to develop and optimize the stability-indicating method using the quality by design (QbD) approach and in-silico tools for application in samples of oral contraceptives sold in Brazil. The analysis samples were initially subjected to a forced degradation study through 7 days of exposure under acid and alkali hydrolysis, oxidative condition, and oxidation by metal ions. In addition to the chemical exposure, the sample was subjected to physical stress through 10 days of exposure under dry heat, moisture, and photolytic degradation. These exposure samples were analyzed in the development and optimization of chromatographic conditions. As a result, the developed method was able to separate 20 known substances, including the two APIs and their respective 18 degradation products, as well as unknown degradation products obtained by the forced degradation study. Finally, this stability-indicating method was successfully applied for comparative analysis of contraceptive drugs marketed in Brazil, newly purchased and subjected to accelerated stability condition at 40 °C and 75% RH over the 6-month period. • The development and optimization of the stability-indicating method using QbD approach and in silico tools. • Monte Carlo method was used for establishing the in silico chromatogram simulator worksheet. • The developed method was able to separate 20 known substances as well as unknown degradation products. • Comparative analysis among contraceptive drugs marketed newly purchased and subjected to accelerated stability condition. [ABSTRACT FROM AUTHOR]

Background and Objectives: The quality of cervical mucus (CM) among the levonorgestrel-releasing intrauterine system (LNG-IUS) users is controversial. The objectives were to assess CM compared to the levels of oestradiol (E2) and the frequency of cycles with luteal activity among users of the LNG-IUS.Materials and Methods: In total, 224 LNG-IUS users for between two months and five years were recruited at a Brazilian family planning clinic. For the cross-sectional part of the study, we enrolled 175 LNG-IUS users at 2, 6 12, 24, 36, 48, and 60 months after insertion (25 women in each group), and we performed one evaluation. For the prospective part of the study, we enrolled 49 LNG-IUS users at the same lengths of use after insertion (7 women in each group), and we evaluated these women once a week for five consecutive weeks. .Results: Mean (± SEM) CM scores of all evaluations among women with single and weekly evaluations were between 3.3 ± 0.9 and 8.5 ± 0.3, respectively independently of the length of use of the LNG-IUS. Mean E2 values ranged from 45.5 ± 6.8 to 472.5 ± 34.7 pg/ml and the maximum ovarian follicle diameter on the days of evaluation varied from 14.0 ± 1.3 to 31.2 ± 0.4 mm.Conclusions: The mean CM score of all evaluations, independent of the length of use of the LNG-IUS and normal levels of serum E2, was below 10 was according to the WHO is inadequate for sperm penetration. [ABSTRACT FROM AUTHOR]

Aim To compare the corticosteroidogenic enzyme activities between normal cycling non-polycystic ovary syndrome ( PCOS), and normoandrogenic PCOS ( NA- PCOS) and hyperandrogenic PCOS ( HA-PCOS) patients. Methods This cohort study was conducted at Julio Muller University Hospital and Tropical Institute of Reproductive Medicine and Menopause, and enrolled 114 non- PCOS women and 355 PCOS patients. The steroidogenic enzyme activities were measured using the serum steroid product/precursor molar ratio. Results In the Δ5 pathway the 17,20 lyase activity was equally low in the NA-PCOS and HA-PCOS women compared with the non- PCOS women ( P < 0.01 and P < 0.001, respectively). In the Δ4 pathway, the 17,20 lyase activity was higher only in the HA-PCOS group ( P < 0.001). The 17-hydroxylase activity was the same in PCOS and non- PCOS subjects ( P > 0.05). The 3β-hydroxysteroid dehydrogenase II (3β- HSDII) activity was higher in the conversion of dehydroepiandrosterone into androstenedione in the HA-PCOS than in the NA-PCOS ( P < 0.05) and the non- PCOS patients ( P < 0.01). The aromatase activity was lower in the HA-PCOS than in the NA-PCOS ( P < 0.05) patients and non- PCOS subjects ( P < 0.01). In HA-PCOS subjects, the 17,20 lyase activity was related to insulin, estradiol, total testosterone concentrations and free androgen index in the Δ5 pathway. 3β- HSDII showed weak correlation with estradiol in the HA-PCOS group. Anthropometric parameters had little impact, if any, on the steroidogenic enzyme activities. Conclusion The NA-PCOS and HA-PCOS patients demonstrated different enzyme activities, and the results provided new directions for future studies including PCOS patients with different phenotypes. [ABSTRACT FROM AUTHOR]

Although several studies have shown the inhibitory effects of Tropaeolum majus extracts (HETM) on angiotensin-converting enzyme (ACE) activity, no studies have been carried out during the beginning of pregnancy, when humoral and hormonal imbalance may affect zygote and early embryo transport. This study investigates whether HETM can affect embryonic development when administered during the one-cell-blastocyst period. Pregnant Wistar rats received orally the HETM (3, 30, and 300 mg/kg/day) from the est to the 7th gestational day. Rats were killed on the 8th day of pregnancy and the following parameters were evaluated: clinical symptoms of toxicity (including organ weights), number of corpora lutea, implants per group, preimplantation losses ratio, and the serum levels of dehydroepiandrosterone (DHEA), estradiol, and progesterone. No clinical symptoms of maternal toxicity were evidenced. On the 8th day of pregnancy, the levels of DHEA and estradiol were increased and significant preimplantation losses were observed at all doses used. The present study reveals that the HETM can raise levels of DHEA and estradiol and induce difficulty in the embryo implantation in the early stages of pregnancy. The data contributes significantly to the safety aspects of using this natural product when trying to get pregnant or during pregnancy. [ABSTRACT FROM AUTHOR]

In this study, the concentrations of the natural hormone 17β-estradiol and the synthetic hormones levonorgestrel and 17α -ethylestradiol were determined in the water of São José do Rio Preto Municipal Dam (SP, Brazil). The SPE method was used to extract the hormones and HPLC/FLU/DAD was used to measure their concentrations. The method was validated according to Resolution-RE 899/2003 from the National Sanitary Vigilance Agency (ANVISA) for bioanalytical methods. The detection limits were 25.0, 100.0, and 50.0 ng L−1 for 17α-ethinylestradiol, 17β-estradiol, and levonorgestrel, respectively. The water samples from the dam were collected near the sewage release point and the city's water supply intake point. The sample analysis did not indicate the presence of the hormones under study, considering the detection limit of the method employed. [ABSTRACT FROM PUBLISHER]

Insomnia is a frequent climacteric symptom. This pilot, double-blind, randomized placebo-controlled trial compared estradiol associated with trimegestone or placebo in 12 women with perimenopausal insomnia. The Pittsburgh Sleep Quality Index (PSQI) was administered, and polysomnography was performed at baseline and after 28 days. Sleep efficiency and median score of the PSQI improved significantly in the hormone therapy group (HT) ( p = 0.041 and p = 0.027, respectively) and not in placebo group. Perimenopausal insomnia improved after short-term HT. [ABSTRACT FROM AUTHOR]

Abstract: In Experiments 1, 2, and 3, we evaluated the effects of temporary weaning (TW), equine chorionic gonadotropin (eCG), and follicle-stimulating hormone (FSH) treatments on results of a fixed-time artificial insemination (TAI) protocol in postpartum Bos indicus cows. In Experiment 1, treatment with 400 IU eCG or with TW for 48h consistently improved pregnancy rates (PRs) at TAI, but, in Experiment 2, FSH treatment was less effective than eCG or TW. In Experiment 3, the inclusion of eCG treatment in cows subjected to TW did not improve PRs. We concluded that TW or 400 IU eCG should be included in the TAI protocol in postpartum Bos indicus cows to enhance fertility. In Experiment 4, we used records from heifers and cows treated with the proposed protocol during the 2006–2007 (n =27,195) and 2007–2008 (n =36,838) breeding seasons from multiple locations in Brazil to evaluate factors potentially affecting PRs. Overall PR at TAI was 49.6% (31,786 of 64,033). Pregnancy rate differed (P <0.01) among farm within location (results ranging between 26.8% and 68.0%; P <0.01), cow group within farm, by breed (Bos indicus, 48.3% [26,123 of 54,145]; Bos taurus, 61.7% [3652 of 5922]; and crossbred Bos indicus × Bos taurus, 50.7% [2011 of 3966]), category (nulliparous, 39.6% [2095 of 5290]; suckled primiparous, 45.2% [3924 of 8677]; suckled multiparous, 51.8% [24,245 of 46,767]; and nonsuckled multiparous, 46.1% [1522 of 3299]), body condition score at TAI (≤2.5, 43.0% [3409 of 7923]; 3.0, 49.6% [18,958 of 38,229]; and ≥3.5, 52.7% [9419 of 17,881]). Days postpartum at beginning of protocol did not affect PR (30 to 60 d, 47.6% [4228 of 8881]; 61 to 90 d, 51.7% [16,325 to 31,572]; and 91 to 150 d, 50.8% [7616 to 14,991]; P >0.1). Pregnancy rate was also consistently affected (P <0.01) by sire (results ranging from 7.2% to 77.3%) and artificial insemination technician (results ranging from 15.1% to 81.8%). [Copyright &y& Elsevier]

Five experiments were conducted on commercial farms in Brazil designed to develop the basis for an estrus synchronization protocol using melengestrol acetate (MGA) in Bos indicus cattle. These studies resulted in the development of the following protocol: 0.5 mg·d-1 of MGA between d -14 and -1; 2.0 mg i.m. injection of estradiol cypionate on d -9; 48 h temporary weaning between d 0 and 2; and natural service beginning on d 0. The basis of this protocol was to induce estrous cyclicity before postpartum loss of body condition, prevent premature luteolysis, eliminate the need for labor required to detect estrus, and consequently increase the likelihood of pregnancy early during the postpartum period. This treatment effectively induced estrous cyclicity among anestrous cows, synchronized estrus activity, and prevented premature luteolysis with no negative effect on pregnancy. [ABSTRACT FROM AUTHOR]

This prospective, multicenter study was conducted to evaluate the contraceptive reliability, cycle control and tolerability of a 21-day oral contraceptive regimen containing 20 μg ethinylestradiol and 75 μg gestodene in four Latin American countries (Mexico, Argentina, Brazil and Colombia). Participants took trial medication daily for 21 days. Contraceptive efficacy, cycle control and tolerability were evaluated over a period of 13 cycles. Efficacy data gathered from 5,109 treatment cycles were obtained from 393 participants. The trial medication proved to be an effective contraceptive and provided good cycle control. One pregnancy because of poor compliance was recorded. This resulted in a study Pearl index of 0.25. Forty-six percent of Latin American women reported one intracyclic spotting bleeding episode and 37.6% reported one intracyclic breakthrough bleeding (medium/excessive bleeding) episode during cycles 2–4 (primary target). Overall, intracyclic bleeding was reported in 41%. Overall, there was a trend towards a lower incidence of spotting in all the countries and this difference had statistical significance between Argentina and the others three countries (p < 0.05) during cycles 2–4. This trend was also apparent with respect to breakthrough bleeding, but again the difference did not achieve statistical significance. The discontinuation rate because of adverse events was low (3%); no serious adverse events were reported. More than 78% of the women in the four countries maintained constant body weight or lost weight (2 kg) during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study. [Copyright &y& Elsevier]

Tambaqui (Colossoma macropomum Cuvier, 1818) is the main native fish species farmed in Brazil, and 17β-estradiol (E 2) is a natural steroid hormone commonly used for the production of female fish monosex population, which, in tambaqui, shows a higher growth rate than the male. Thus, to assess whether the fish meat of treated tambaqui contains hormonal residue levels, a high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS) method for the determination of E 2 residues in fish muscle was developed and validated. A QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) dispersive solid phase extraction method was used for the sample preparation. The chromatographic separation was performed in a Poroshel EC-18 reverse phase column. The mobile phase was a mixture of acetonitrile with 0.01% ammonium hydroxide (A) and water with 0.01% ammonium hydroxide (B). The ratio of A:B phases was 60:40 (v/v) used in an isocratic mode. The method validation was performed according to Commission Decision 2002/657/EC and Veterinary International Conference Harmonization (VICH GL49). Since matrix effects were observed, matrix-matched analytical curves are recommended for quantitation. The linearity, selectivity, intraday and interday precision, accuracy, decision limit, detection capability, and detection and quantitation limits of the method are reported. The limits of detection and quantitation were 0.3 ng/g and 1.0 ng/g, respectively. At these limits and slaughtering fish 7 months after the end of the treatment, the muscle of tambaqui did not show detectable hormone residue level. Thus, consumption of tambaqui edible tissue from fish treated with E 2 for the purpose of sexual reversion is unlikely to represent a risk associated with the exposure of human subjects as residue levels of this hormone are not detected in the fish muscle. Unlabelled Image • UHPLC-MS/MS method for quantitation of 17β-estradiol residues in tambaqui muscle • Reliable bioanalytical method to quantitate 17β-estradiol residues in fish muscle • QuEChERS sample preparation for quantitation of 17β-estradiol in fish muscle • Throughput method for surveillance 17β-estradiol residues in fish muscle • 17β-estradiol not detected in muscle of fish treated for sexual reversion purposes [ABSTRACT FROM AUTHOR]

This trial was to evaluate the effect of progesterone (P4) and/or 17β-estradiol (E2) on incidence of short cycles (SC) after induction of ovulation with calf removal (CR) and GnRH injection in anestrous Nelore cows. Cows (n=142; 43±12 DPP) were evaluated by 2 ultrasound (US) exams 8 d apart (day -16 and day -8) for cyclicity. Anestrous cows (n=114) were randomly assigned to receive a 6 d treatment with an intravaginal P4 device (CIDR® Pfizer Animal Health, Brazil) prior CR and/or 1 mg i.m. injection of 17β-estradiol 48h after beginning of CR (4 treatments; 2x2 factorial design). On day -2 all cows suffered CR for 54h and received a GnRH injection at the end of CR (day 0). Only cows that ovulated within 48 h after GnRH injection (evaluated by US on days 0 and 2) were used (Control, n=23; E2, n=25; P4, n=19; P4+E2, n=18). Blood samples were collected on days 0, 5, 7, 9, 12, 15 and 19 for corpus luteum lifespan evaluation, by serum P4 analysis. Cows were considered having SC if P4 decreased more than 50% between days 5 and 7. Percentage of cows exhibiting SC was analyzed by logistic regression and P4 were analyzed by PROC MIXED of SAS. P4 were higher on day 5 than on day 0 (P<.01) on all treatments. Serum P4 increased (P<.05) between days 5 and 7 on P4 (from 2.3±0.5 to 3.7±0.5 ng/mL) and P4+E2 (from 2.4±0.5 to 3.3±0.5 ng/mL) groups and decreased (P<.01) on Control (from 2.9±0.4 to 1.9±0.4 ng/mL) and E2 (from 1.9±0.4 to 0.8±0.4 ng/mL) groups. Cows treated with P4 (P4 and P4+E2) had higher serum P4 than cows not treated (Control and E2) on days 7, 9, 12 and 15 (P<.01). Incidence of SC was lower in cows treated with P4 than in cows not treated (23.5 vs. 79.2%; P<.01), while treatment only with 17β-estradiol did not differ (P>.10) from control group (76 vs 82.6%). Cows not treated with P4 that showed heat had the same incidence of SC than cows not detected in estrus (75 vs. 80%; P>.1). In conclusion, 6 d treatment with P4 prior ovulation on anestrous cows warranted a normal luteal lifespan, while administration of 1mg of 17β-estradiol did not prevent occurrence of SC. [ABSTRACT FROM AUTHOR]