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Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. This narrative review aims to provide relevant detailed information on (1) the canine estrus cycle and its impact on canine diabetes mellitus (CDM) etiology and management, (2) the role of pyometra as a further cause of insulin resistance, and (3) useful individual therapeutic and preventive strategies. PRDM is recognized due to diestrus, exogenous progestogen exposure, pregnancy, and P4-production ovarian dysfunction. Pyometra represents additional inflammatory and septic negative influence on insulin sensitivity, and its diagnosis associated with CDM is therapeutically challenging. The estrus cycle's hormone fluctuations seem to modulate peripheric insulin sensibility by influencing insulin receptor (IR) affinity and its binding capacity, as well as modulating tyrosine kinase activity. Pyometra was shown to negatively influence IR compensatory mechanisms to insulin resistance causing glucose intolerance. Spaying and pregnancy termination may cause diabetes remission in PRDM cases in a median time of 10 days (1-51). Pharmacological annulment of progesterone effects may benefit patients unable to undergo surgery; however, remission chances are virtually null. The ALIVE (Agreeing Language in Veterinary Endocrinology) project proposed new criteria for CDM diagnoses and subclinical diabetes recognition. These new concepts may increase the frequency of a PRDM diagnosis and, even more, its relevance. Spaying represents a preventive measure against pyometra and PRDM that should be individually assessed in light of its recognized benefits and harms.

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Effects of conservative treatment on uterine blood flow and morphometric findings are still unknown in bitches. Thus, this study aimed to compare uterine changes of pyometra bitches subjected to distinct modes of treatment. Pyometra bitches were assigned to: OHE (ovariohysterectomy immediately after diagnosis), Aglepristone (days 1, 2 and 8) and Associative (aglepristone treatment coupled with cloprostenol for 7 days) groups. After 9 days, bitches were ovariohysterectomized. Before surgery, uterine area was measured ultrasonographically and the uterine artery Doppler velocimetry analyzed blood flow velocity and indexes. Uterine horns were classified according to resistance index (RI) as more compromised and less compromised. Endometrial vasculature was quantitatively evaluated by color flow Doppler. Blood samples were collected to determine nitric oxide (NO) concentrations. Histological uterine structures were quantified by stereology and VEGF-A (vascular endothelial growth factor) and eNOS were (endothelial nitric oxide synthase) immunohistochemically analyzed. Aglepristone and Associative groups had lower uterine area and vascularization, and higher blood flow velocity and indexes compared to OHE group. Less compromised horn of Associative group had higher blood flow velocity compared to OHE group. Aglepristone group presented lower inflammatory infiltrate and larger uterine stroma. Associative group had lower volume density and absolute surface of endometrial cysts and lower VEGF-A expression for glandular epithelium and stromal cells. Blood NO and e-NOS immunostaining were not different among groups. In conclusion, association between aglepristone and prostaglandin is more effective in decreasing uterine vascularization and modulating uterine blood flow. Moreover, associative therapy promotes marked morphological changes. LAY SUMMARY: This research compared two medical protocols of treatment for uterine infection (pyometra) in bitches, using a hormone blocker (anti-progesterone aglepristone) solely or in association with a uterine contraction inducer (prostaglandin; associative therapy). After treatment, bitches were gonadectomized and a microscopic analysis of uterine blood vessel formation and uterine tissue elements were performed as well as uterine blood flow evaluation through Doppler ultrasonography. According to vascular resistance, uterine horns were additionally classified as more compromised and less compromised. Both treatment protocols led to reduction of uterine dimensions and vascularization, and higher blood flow compared to untreated bitches. Less compromised uterine horn of the associative treatment had higher blood flow compared to untreated bitches. The hormone blocker treatment had lower inflammatory cells and larger uterine histological structure, while associative treatment had less uterine pathological cysts and lower blood vessel formation. The associative therapy is effective in decreasing uterine vascularization and modulating uterine blood flow as well as reestablishing endometrium structure in bitches with uterine infection.

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ABSTRACT: Thirty and forty days after a 50 mg medroxyprogesterone acetate injection, respectively, two mixed-breed, 7 and 8-month-old entire male cats presented diffuse enlargement of thoracic and abdominal mammary glands, with ulceration, abscessation and necrosis. One patient was treated with 10 mg/kg aglepristone, antibiotic therapy, analgesic and non-steroidal anti-inflammatory compound; however a worse enlargement of mammary glands, necrosis and clinical condition was noted two days after antiprogestin injection. The second patient was submitted to surgical procedure without previous medical treatment. A partial bilateral mastectomy and conventional orchiectomy were performed, and both patients presented no clinical abnormalities 10 days after surgical treatment. In the male cat, the interruption of progesterone associated mammary fibroepithelial hyperplasia cannot be based in gonadectomy, being antiprogestin treatment the primary approach. Mastectomy can be a treatment option in selected cases, such as the two cases presented here, in case of antiprogestin treatment failure or in case of extensive ulceration, necrosis and risk of sepsis.

RESUMO: Trinta e quarenta dias após aplicação de acetato de medroxiprogesterona, dois gatos SRD machos não castrados, de sete e oito meses respectivamente, apresentaram aumento difuso de volume em glândulas mamárias torácicas e abdominais, com ulceração, abscedação e necrose. Um paciente foi tratado com 10 mg/kg de aglepristone, terapia antimicrobiana, analgésicos e anti-inflamatório não-esteroidal. Entretanto, apresentou piora dos sinais clínicos, da abscedação e necrose dois dias após a aplicação. O outro paciente foi submetido a procedimento cirúrgico sem tratamento clínico prévio. Mastectomia parcial bilateral e orquiectomia convencional foram realizadas e, ambos os pacientes se apresentaram sem alterações clínicas e receberam alta após 10 dias do procedimento cirúrgico. No felino macho, a interrupção da ação da progesterona associada à ocorrência de hiperplasia fibroadenomatosa mamária, não pode ser obtida por meio de gonadectomia, portanto, o tratamento de eleição deve ser realizado com utilização de antiprogestágeno. Em alguns casos, mastectomia parcial ou total é recomendada quando o tratamento clínico com antiprogestágeno falha ou, em casos de sepse, ulceração extensa e necrose, como nos pacientes deste relato.

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Thirty and forty days after a 50 mg medroxyprogesterone acetate injection, respectively, two mixed-breed, 7 and 8-month-old entire male cats presented diffuse enlargement of thoracic and abdominal mammary glands, with ulceration, abscessation and necrosis. One patient was treated with 10 mg/kg aglepristone, antibiotic therapy, analgesic and non-steroidal anti-inflammatory compound; however a worse enlargement of mammary glands, necrosis and clinical condition was noted two days after antiprogestin injection. The second patient was submitted to surgical procedure without previous medical treatment. A partial bilateral mastectomy and conventional orchiectomy were performed, and both patients presented no clinical abnormalities 10 days after surgical treatment. In the male cat, the interruption of progesterone associated mammary fibroepithelial hyperplasia cannot be based in gonadectomy, being antiprogestin treatment the primary approach. Mastectomy can be a treatment option in selected cases, such as the two cases presented here, in case of antiprogestin treatment failure or in case of extensive ulceration, necrosis and risk of sepsis.(AU)

Trinta e quarenta dias após aplicação de acetato de medroxiprogesterona, dois gatos SRD machos não castrados, de sete e oito meses respectivamente, apresentaram aumento difuso de volume em glândulas mamárias torácicas e abdominais, com ulceração, abscedação e necrose. Um paciente foi tratado com 10 mg/kg de aglepristone, terapia antimicrobiana, analgésicos e anti-inflamatório não-esteroidal. Entretanto, apresentou piora dos sinais clínicos, da abscedação e necrose dois dias após a aplicação. O outro paciente foi submetido a procedimento cirúrgico sem tratamento clínico prévio. Mastectomia parcial bilateral e orquiectomia convencional foram realizadas e, ambos os pacientes se apresentaram sem alterações clínicas e receberam alta após 10 dias do procedimento cirúrgico. No felino macho, a interrupção da ação da progesterona associada à ocorrência de hiperplasia fibroadenomatosa mamária, não pode ser obtida por meio de gonadectomia, portanto, o tratamento de eleição deve ser realizado com utilização de antiprogestágeno. Em alguns casos, mastectomia parcial ou total é recomendada quando o tratamento clínico com antiprogestágeno falha ou, em casos de sepse, ulceração extensa e necrose, como nos pacientes deste relato.(AU)

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Cystic endometrial hyperplasia-pyometra complex is a canine endometrial disorder, considered the most common and important among uterine diseases. The treatment of choice is ovariohysterectomy, but medical treatments have become an alternative. However, no studies have been performed in order to evaluate uterine hemodynamic changes during medical treatment for pyometra bitches. Therefore, the aim of this study was to compare the effectiveness of two medical protocols by means of clinical (heart rate, respiratory rate and body temperature), medullar response (complete blood count (CBC)) and uterine hemodynamic evaluation in pyometra bitches. For such purpose, 10 bitches with pyometra were assigned to two groups: Aglepristone Group (n = 5) and Associative Group (aglepristone + prostaglandin; n = 5). The Associative Group had altered respiratory rate and decreased body temperature. The Aglepristone Group had decreased plasma protein, however, leukocyte count reduced over time for both therapeutic protocols. Uterine area and vascularization score decreased throughout treatment. There was a significant reduction in uterine perimeter, area and vascularization score. The Associative Group had lower final diastolic velocity and higher systole:diastole ratio (S/D), pulsatility index (PI) and resistance index (RI). In conclusion, both medical treatments are effective in reversing clinical and CBC changes of pyometra, especially aglepristone, however they cannot fully restore local uterine changes in a short-term evaluation. Conversely, associative therapy was more effective in decreasing uterine vascularization and modulating uterine blood flow.

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Progesterone (P4) is a requirement for pregnancy development. Previous reports observed a maximal value of serum P4 concentration on 21 days after the first mating after which it slowly declines throughout the rest of pregnancy. Ultrasound examination should be performed to ensure that pregnancy interruption is complete. Limited information is available on the ultrasonic appearance of conceptuses during pregnancy termination in cats The objective was to study serum P4 concentration and ultrasonographic changes during aglepristone (ALI) or cloprostenol (CLO) treatment and to evaluate the fertility after treatment. Two experiments (EXP) were carried out to accomplish this aim. Sixty queens, 12- to 36-month-old, were used. On Days 21 to 22 of pregnancy (EXP I) or 35 to 38 of pregnancy (EXP II), queens were divided into three groups (G). Queens in G1 received ALI (10 mg/kg, sc; EXP I, n = 10; EXP II, n = 10) for 2 consecutive days. Queens in G2 received CLO (5 µg/kg, sc; EXP I, n = 10; EXP II = 10) for 3 consecutive days. Queens in G3 received 1 mL of saline solution (PLA, sc; EXP I, n = 10; EXP II = 10). Blood samples were taken before treatment (Day 0) and every day during 10 days after the treatment to measure serum P4 concentrations. Likewise, after treatment, queens were monitored daily by ultrasonography for 10 days and weekly until the end of gestation to obtain gestational sacs measurements (GS), fetal measurements, and fetal biophysical profile. Data were analyzed by ANOVA. Serum P4 concentrations were significantly different on Day 6 (EXP I) and on Day 1 (EXP II) in ALI and CLO groups compared with PLA group (P < 0.05 and P < 0.01; respectively). The ultrasonographic monitoring during treatment allowed assessing changes in the GS and fetal measurements, embryo-fetal viability, and risk of pregnancy loss. In conclusion, the results from this study reported changes in serum P4 concentration and in ultrasonography measurements during pregnancy interruption with ALI or CLO treatment. Also it was observed that ALI and CLO are safe drugs and can preserve posttreatment queen fertility. Therefore, the results obtained in our work will be applied in feline reproduction practice.

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Feline mammary hyperplasia (FMH) is a benign condition representing a disorder of body related tonatural or synthetic progestogen characterized by rapid cell growth of one or more mammary glands. Havingrapidly evolving and can cause serious systemic changes, it is necessary to use instant protocols, such as the useof aglepristone an antiprogestogen. This study aims to report a case of FMH with aglepristone-based therapy. Acat mongrel, with 9 months old, nulliparous, who received a contraceptive dose, showed an increase in thethoracic right mammary gland M1. The history and physical examination indicated the diagnosis of FMH. Thetherapy established was aglepristone in 3 doses (10mg / kg) every 24 hours. The result was total remission ofsymptoms. The use of aglepristone proved to be effective in the treatment of FMH even without castration.(AU)

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Feline mammary hyperplasia (FMH) is a benign condition representing a disorder of body related tonatural or synthetic progestogen characterized by rapid cell growth of one or more mammary glands. Havingrapidly evolving and can cause serious systemic changes, it is necessary to use instant protocols, such as the useof aglepristone an antiprogestogen. This study aims to report a case of FMH with aglepristone-based therapy. Acat mongrel, with 9 months old, nulliparous, who received a contraceptive dose, showed an increase in thethoracic right mammary gland M1. The history and physical examination indicated the diagnosis of FMH. Thetherapy established was aglepristone in 3 doses (10mg / kg) every 24 hours. The result was total remission ofsymptoms. The use of aglepristone proved to be effective in the treatment of FMH even without castration.

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For many years now, the several drugs used as abortifacients in animals have often been associated with severe adverse effects on the general and reproductive health of treated animals. Aglepristone is a recent antiprogestin (progesterone - receptor antagonist) used for t he induction of abortion in animals. The goal of this study was t o investigate the effect on further fertility after mid - gestation termination of pregnancy with aglepristone in albino rats. Fifteen healthy female , 12 - 14 weeks o ld , albino rats ( Rattus norve gicus ) were used. G roup I (n = 7) comprised rats whose pregnancies were terminated mid - gestation (day 11) with a subcutaneous injection of 10 mg/kg b.w. aglepristone. G roup II (n = 8) comprised rats which were treated mid - gestation with sterile water and h ad normal , spontaneous gestation and parturition . The further fertility of the groups was compared by monitoring the following pa rameters for two subsequent pregnancies: i nterval before pregnancy, gestation length, litter size, litter weight a t birth, feta l weight at birth and percentage of fetuses alive at birth. A s ubcutaneous injection of aglepristone caused abortion in 100% of rats in g roup I. There was a longer (P 0.05) between the groups when gestation length, litter size, litter weight, fetal weight and percentage of live fetuses were compared . In the subsequent preg nancy, b oth groups displayed no differences (P > 0.05) in all the reproductive parameters compared. Aglepristone can be used to induce a single instance of mid - gestation abortion without any severe or prolonged adverse effects on the fertility of treated a nimals. It will be interesting, however, to evaluate the effects on reproduction following prolonged use or repeated induction of abortion with aglepristone.

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For many years now, the several drugs used as abortifacients in animals have often been associated with severe adverse effects on the general and reproductive health of treated animals. Aglepristone is a recent antiprogestin (progesterone - receptor antagonist) used for t he induction of abortion in animals. The goal of this study was t o investigate the effect on further fertility after mid - gestation termination of pregnancy with aglepristone in albino rats. Fifteen healthy female , 12 - 14 weeks o ld , albino rats ( Rattus norve gicus ) were used. G roup I (n = 7) comprised rats whose pregnancies were terminated mid - gestation (day 11) with a subcutaneous injection of 10 mg/kg b.w. aglepristone. G roup II (n = 8) comprised rats which were treated mid - gestation with sterile water and h ad normal , spontaneous gestation and parturition . The further fertility of the groups was compared by monitoring the following pa rameters for two subsequent pregnancies: i nterval before pregnancy, gestation length, litter size, litter weight a t birth, feta l weight at birth and percentage of fetuses alive at birth. A s ubcutaneous injection of aglepristone caused abortion in 100% of rats in g roup I. There was a longer (P < 0.05) interval between abortion and pregnancy in the aglepristone - treated group (23.7 ± 6.6 days) than in g roup II (12.5 ± 2.7 days). However, there were no significant differences (P > 0.05) between the groups when gestation length, litter size, litter weight, fetal weight and percentage of live fetuses were compared . In the subsequent preg nancy, b oth groups displayed no differences (P > 0.05) in all the reproductive parameters compared. Aglepristone can be used to induce a single instance of mid - gestation abortion without any severe or prolonged adverse effects on the fertility of treated a nimals. It will be interesting, however, to evaluate the effects on reproduction following prolonged use or repeated induction of abortion with aglepristone.(AU)

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A piometra é patologia de grande importância na rotina das clínicas veterinárias de pequenos animais. Pode ocorrer em qualquer fase do ciclo estral das cadelas, porém uma maior incidência entre 4 semanas a 4 meses após o estro. O tratamento de eleição é o cirúrgico, com a ovário-histerectomia. No entanto, com a intenção de preservar a funcionalidade reprodutiva das cadelas e evitar os riscos de uma intervenção cirúrgica e protocolos anestésicos, as terapêuticas conservativas estão sendo pesquisadas. Entre as possibilidades medicamentosas disponíveis estão as prostaglandinas e seus análogos, os agonistas da dopamina e mais recentemente os antiprogestágenos. No grupo destes últimos estão o aglepristone, um esteróide sintético que compete com a progesterona pelos seus receptores, inibindo a atuação dessa. Pode ser considerado, portanto, uma excelente opção para o tratamento de patologias progesteronadependentes. O objetivo deste relato é documentar um caso de piometra em uma cadela de 2 anos de idade, reprodutora e em bom estado clínico, que foi submetida ao tratamento conservativo com o antiprogestágenos, aglepristone, obtendo-se sucesso no tratamento, dentro do prazo do protocolo pré-estabelecido, e com preservação da capacidade reprodutiva. Esta fêmea veio a desenvolver nova prenhez logo no estro subseqüente, sem sinais de recidiva da piometra mesmo após um ano do tratamento

The pathology pyometra is of great importance to the lives of small animalveterinary clinics. It can occur at any stage of the estrous cycle of bitches, but a higherincidence between 4 weeks to 4 months after estrus. The proferred treatment is surgery,with ovariohysterectomy. However, with the intention to preserve the reproductivefunction of dogs and avoid the risks of surgery and anesthetic protocols, conservativetherapies are being researched. Among the possibilities are prostaglandins availabledrug and its analogs, dopamine agonists and more recently antiprogestágens. In thelatter group are the aglepristone, a synthetic steroid that competes with progesterone forits receptor, inhibiting the action of this. Can be considered, therefore, an excellentoption for the treatment of progesterone-dependent diseases. The objective of thisreport is to document a case of pyometra in a bitch 2 years of age, breeding and goodclinical status, which was submitted to conservative treatment with antiprogestagens,aglepristone, resulting in successful treatment, within the protocol pre-established, andwith preservation of reproductive capacity. This female came to develop new pregnancyas early as the subsequent estrus, no signs of recurrence of pyometra even after oneyear of treatmen.

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