Simultaneous use of contraceptives and hormone replacement therapy in women receiving psychoactive drugs. From theory to integral health practice / Uso simultáneo de anticonceptivos y terapia hormonal de reemplazo en mujeres que reciben psicofármacos. De la teoría a la práctica de la salud integral.

Sexuality in people with mental disorders is a topic usually tinged with prejudice and stigma. Women with severe mental disorders are more exposed to suffer sexually transmitted diseases, becoming victims of gender violence and being involved with unintended pregnancies. In adults and adolescents, sexual intercourse under the influence of alcohol or other drugs, or during worsening or exacerbation of baseline symptoms or condition, are often unplanned, unprotected, with casual partners from high risk groups, without contraceptive methods and with less capacity to agree or deny safe sexual practices. Sexual and reproductive rights as well as gender perspective need to be considered an integral part of women with mental disorders health being and treatment. For this reason, discussing with patients about their desire or not to have children, their sexual life and provide them the most adequate options of contraceptive methods taking into consideration their needs so that and informed decision should be part of the psychiatric consultation. Hormonal contraceptives are widely used globally, being one of the most prescribed groups of drugs. It is estimated that more than 100 million women take oral contraceptives to prevent pregnancy, to treat menstrual pain and/or menstrual heavy bleeding or to control acne. Oral contraceptives result from the combination of estrogen and progestin derivatives, or progestins alone. This review will focus on the description of each hormonal contraceptive methods and hormone replacement therapy and the special features of their concomitant use with psychotropic drugs during treatment of women with psychiatric disorders.

La sexualidad de las personas con trastornos mentales es una temática habitualmente teñida de prejuicios y estigma. Las mujeres con trastornos mentales severos presentan mayor vulnerabilidad a padecer enfermedades de transmisión sexual, ser víctimas de violencia de género y tener embarazos no intencionales. En adultas y adolescentes, las relaciones sexuales bajo la influencia del alcohol o de otras drogas, o en momentos de descompensación de su cuadro de base son a menudo no planificadas, con parejas de riesgo, sin métodos anticonceptivos y con menor capacidad para negociar prácticas sexuales seguras. Desde una perspectiva de género y de derechos humanos, en la atención de mujeres con trastornos mentales, es necesario incluir los derechos sexuales y reproductivos como parte del tratamiento. Por tal motivo, hablar con nuestras pacientes sobre sus deseos de tener hijos, o no, sobre su vida sexual y la provisión de un método anticonceptivo acorde a su elección y necesidades, forma parte de la consulta psiquiátrica. Los anticonceptivos hormonales están ampliamente utilizados a nivel global, constituyendo uno de los grupos de fármacos más prescriptos. Se estima que más de 100 millones de mujeres los consumen para evitar el embarazo, como tratamiento de los sangrados abundantes, las menstruaciones dolorosas o el acné. Resultan de la combinación de derivados estrogénicos y progestágenos, o progestágenos solos. En esta revisión se focalizará en la descripción de los diversos métodos anticonceptivos hormonales, en la terapia hormonal de reemplazo y en las particularidades del uso simultáneo con psicofármacos en mujeres tratadas por trastornos psiquiátricos.

Switching from cetrorelix to dydrogesterone in an IVF cycle - a new strategy for unexpected freeze-all cycles.

Preventing a luteinizing hormone (LH) surge is a major concern in controlled ovarian stimulation (COS). Several strategies have been developed over the years, including protocols with Gonadotrophin Releasing Hormone agonists and antagonists. More recently Progestin Primmed Ovarian Stimulation (PPOS) has shown to be equally effective in pituitary suppression, with comparable clinical and laboratorial outcomes. This is the case of a 34 year old female, with a previous diagnosis of primary infertility due to tubal factor and high ovarian reserve markers. The initial plan was to perform IVF/ICSI. followed by fresh blastocyst transfer. The chosen COS strategy was to use Alfacorifolitropin 150mg (Elonva®) and Cetrorelix acetate 0,25mg (Cetrotide®) in a flexible pituitary suppression protocol. However, because of elevated risk for Ovarian Hyper-stimulation Syndrome (OHSS) detected during ultrasound and hormonal monitoring, in order to diminish financial burden and to have a more patient friendly protocol, we switched cetrorelix acetate to oral dydrogesterone. COS was successful and resulted in 24 retrieved oocytes (16 metaphase 2 oocytes) without any premature LH peak. No OHSS symptoms occurred. Our main goal with this case report is to reinforce the feasibility and efficacy of this innovative approach, especially in patients aiming for a fresh embryo transfer, who present alert sings of OHSS during the stimulation. Developing friendlier and cheaper protocols in assisted reproduction makes the treatment more accessible and affordable.

Exposure to endogenous and exogenous sex hormones and reproductive history influence prognosis in women with ALS.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a higher incidence in men suggesting an influence of sex steroids. Our objective was to investigate past exposure to endogenous and synthetic steroids in female ALS patients and controls. METHODS: We administered a questionnaire to 158 postmenopausal women (75 ALS patients and 83 controls). We calculated reproductive time span (RTS), lifetime endogenous estrogen (LEE) and progesterone exposures (LPE), oral contraceptive pill (OCP) use, and reproductive history. RESULTS: ALS patients showed shorter LEE and LPE, a lower proportion of breast cancer, and 11% showed no history of pregnancies vs. 4% of controls. Odds ratios (ORs) showed that <17 y of LEE and a delayed menarche (>13 y) constitute risk factors for ALS [OR = 2.1 (95% confidence interval {CI}, 1.08-4.2); and OR = 2.4 (95% CI, 1.1-5.1) respectively]. According to Cox survival analysis, for each year the LEE increased over 17 y, it was independently associated with longer survival [hazard ratio (HR) = 0.37 (95% CI, 0.16-0.85)] after adjusting for smoking, age and site of onset. Multivariate regression analysis demonstrated that for each month using OCP for longer than 40 mo increased the risk of ALS [adjusted OR = 4.1 (95% CI, 1.2-13.8)]. DISCUSSION: Thus, longer exposure to endogenous female sex steroids increased survival and reduced ALS susceptibility. In contrast, longer exposure to synthetic sex steroids showed a negative impact by reducing the production of endogenous female sex steroids or due to crossover with other steroid receptors. Given the neuroprotective effects of sex steroids, we suggest that abnormalities of neuroendocrine components may alter motor function in women with ALS.

Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

Macroscopic changes in the mammary glands of healthy cats after progestogen administration / Alterações macroscópicas nas glândulas mamárias de gatas hígidas após administração de progestágeno

The administration of contraceptives in female cats leads to problems such as pyometra, fetal maceration, mammary hyperplasia, and mammary neoplasms. Among the diseases caused by contraceptives, mammary hyperplasia has only been diagnosed in felines. However, few experimental studies have shown that contraceptive administration can cause feline mammary hyperplasia. This study aimed to evaluate the effects of the administration of a single dose of contraceptives in the mammary glands of healthy cats. Twenty cat owners who had administered contraceptives to female cats were selected. Animals were divided into two groups. Contraceptives were administered to cats in the first group, and saline solution was administered to cats in the other group (control). Before drug administration, all cats were clinically examined. Anamnesis, physical examination, blood count, biochemical tests, and abdominal ultrasonography were performed. Thirty days after the administration of contraceptives, all cats were examined, and the examinations were repeated. At 30 days, no changes were observed in the blood count or ultrasound findings. However, upon physical examination, all cats that received contraceptives showed generalized enlargement of their mammary glands. Cats in the control group were clinically normal. Ninety days after the procedure, the cats underwent an ovariohysterectomy. At that time, all cats were clinically normal and mammary enlargement regressed. It was concluded that a single contraceptive application could cause macroscopic mammary changes suggestive of hyperplasia in ten cats.(AU)

A administração de anticoncepcionais em gatas causa problemas como piometra, maceração fetal, hiperplasia mamária e neoplasias mamárias. Dentre as doenças causadas por anticoncepcionais, a hiperplasia mamária tem sido diagnosticada apenas em felinas. No entanto, poucos estudos experimentais comprovaram que a hiperplasia mamária felina pode ser causada pela administração de anticoncepcionais. O objetivo deste estudo foi avaliar os efeitos da administração de dose única de anticoncepcional nas glândulas mamárias de gatas saudáveis. Foram selecionados 20 tutores de gatos que administrariam contraceptivos em suas gatas. Os animais foram divididos em dois grupos. Anticoncepcionais foram administrados às gatas do primeiro grupo, e solução salina foi administrada às gatas do outro grupo (controle). Antes da administração do fármaco, todas as gatas foram examinadas clinicamente. Foram realizados anamnese, exame físico, hemograma, exames bioquímicos e ultrassonografia abdominal. Trinta dias após a administração dos anticoncepcionais, todas as gatas foram examinadas e os exames repetidos. Aos 30 dias, não foram observadas alterações no hemograma ou ultrassonografia. No entanto, ao exame físico, todas as gatas que receberam anticoncepcionais apresentaram aumento generalizado das glândulas mamárias. As gatas do grupo controle estavam clinicamente normais. Noventa dias após o procedimento, as gatas foram submetidas à ovariohisterectomia. Na ocasião do procedimento cirúrgico, todas as gatas apresentavam-se clinicamente normais, havendo regressão do aumento de volume mamário. Concluiu-se que uma única aplicação de anticoncepcional foi capaz de causar alterações mamárias macroscópicas sugestivas de hiperplasia em dez gatas.(AU)

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.

Exposure to levonorgestrel-based birth control pill in early life and its persistent effects in zebrafish.

The consumption of progestins has increased considerably in recent decades, as has their disposal into the environment. These substances can negatively affect the reproduction, physiology, and behavior of non-target organisms, such as fish. We aimed to evaluate the effects of exposure to environmentally relevant concentrations of levonorgestrel-control birth based (1.3, 13.3, 133, and 1330 ng/L) on the development and behavior of zebrafish (Danio rerio) in terms of mortality, hatching, spontaneous movement, and larval and adult behavioral tests. Exposure caused anxiogenic-like behavior in larvae, which persisted in adults, as demonstrated by the light-dark test. In contrast, it caused anxiolytic-like behavior in the novel tank test. There was a high mortality rate at all tested concentrations and increases in the hormone cortisol at 13.3 ng/L that affected the sex ratio. These changes may lead to an ecological imbalance, emphasizing the risk of early exposure to progestins in the environment.

Usos não contraceptivos dos fármacos anticoncepcionais orais hormonais: uma revisão / Non-contraceptive uses of hormonal oral contraceptive drugs: a review

Introdução: os anticoncepcionais orais hormonais são fármacos constituídos por hormônios, geralmente combinados, estrogênio e progestogênio, ou apenas progestogênio. Devido às propriedades características desses hormônios, são também responsáveis por diversos efeitos colaterais, o que tem levado a uma evolução contínua das formulações e tem-se observado vários benefícios não contraceptivos à saúde da mulher. Objetivo: o objetivo dessa revisão foi analisar os usos não contraceptivos dos anticoncepcionais orais hormonais, evidenciando sua eficácia e segurança. Metodologia: A pesquisa foi realizada em bases de dados eletrônicos e portais de busca, priorizando materiais publicados na faixa anual de 2008 a 2018, sendo encontrados 332 e utilizados 148 materiais de estudo. Resultados: esses fármacos tem sido uma alternativa eficaz de tratamento da síndrome do ovário policístico, uma vez que reduzem os androgênios circulantes e induzem a melhora dos sintomas como acne, irregularidade menstrual e dismenorreia. Estão associados ao tratamento da endometriose e à menor incidência de câncer de ovário. Neste último, exercem um efeito protetor durante anos, até mesmo após a interrupção. Conclusão: assim, os anticoncepcionais orais hormonais têm representado uma nova proposta terapêutica simples, segura e eficaz, para diversas utilidades não contraceptivas, e seus benefícios ultrapassam os riscos associados, proporcionando uma terapia adequada e individualizada para cada mulher.

Introduction: hormonal oral contraceptives are drugs consisted by hormones, usually combined, estrogen and progestogen, or just progestins. Due to the characteristic properties of these hormones, they are also responsible for several side effects, which has led to a continuous evolution of the formulations and various non-contraceptive benefits to women's health have been observed. Objective:the objective of this review was to analyze the non-contraceptive uses of hormonal oral contraceptives, showing their effectiveness and safety. Methodology: the research was conducted in electronic databases and search portals, prioritizing materials published in the annual range from 2008 to 2018, with 332 found and 148 study materials used. Results: these drugs have been an effective alternative for the treatment of polycystic ovary syndrome, since they reduce circulating androgens and induce improvement in symptoms such as acne, menstrual irregularity and dysmenorrhea. They are associated with the treatment of endometriosis and a lower incidence of ovarian cancer. In the latter, they have a protective effect for years, even after the interruption. Conclusion: thus, hormonal oral contraceptives have represented a new simple, safe and effective therapeutic proposal, for several non-contraceptive uses, and their benefits outweigh the associated risks, providing an adequate and individualized therapy for each woman

Effect of 20 mg fluorogestone acetate (FGA) sponges on reproductive parameters of dairy ovine breeds in Southern Italy

Background: Intravaginal devices containing progestins are widely used for oestrus synchronization in sheep. Progestins give economic benefits to farmers but may have some limitations and the efficacy strictly depends on farm management. There are different devices, with different molecules (progesterone, medroxyprogesterone acetate, fluorogestone acetate), different dosages and long (12-14 days) and short-term (5-7 days) protocols. Experimental studies often include a limited number of animals and are held at different latitudes and with different system of management. To our knowledge, there are few reports in the literature on field application of the recently licensed 20 mg fluorogestone acetate (FGA) sponges in large ewe flocks, excluding the registration trials. Materials, Methods & Results: This study was designed to evaluate oestrous synchronization in 2 different breeds. A total of 1100 Lacaune (L) and 618 Sarda (S) were assigned to 8 groups, comparing multiparous (M) and nulliparous (N) and those synchronized in November (n) and May (m). The groups were: LMm (n. 556), LNm (n. 180), SMm (n. 70), SNm (n. 32), LMn (n. 242), LNn (n. 222), SMn (n. 440) e SNn (n. 76). The intravaginal sponge was inserted for 14 days. At sponge withdrawal, eCG (400 IU, IM) was injected, and rams were joined into flocks 30 h later with a male/female ratio of 1:8. Transrectal ultrasonography was performed for pregnancy diagnosis after 30 days. Fertility parameters such as oestrus (OR), pregnancy (PR), lambing rates (LR) and prolificacy were calculated. Fisher exact test was used to compare parameters of each group with the corresponding and significance was set at P < 0.01. The use of intravaginal sponges in this study was easily performed in all animals. In nulliparous groups, digital insertion of the sponge, instead of the applicator, was preferred to avoid discomfort. Sponge loss was observed in 2% of treated ewes. At the removal of the sponge, mild vaginal contamination was observed in 90% of the ewes. Ultrasound finding of embryo resorption, pseudopregnancy and pyometra were found in rates under 2%. The loss of pregnancy ranged from 0 to 3.6% without significant differences among groups. The SMn group showed the best performances (0.91 OR, 0.88 PR, 0.85 LR), significantly higher than the other groups. Prolificacy was maximum in the LMn (1.68) and minimum in the SNm group (1.06), without significant differences among groups. Discussion: The 14-day regimen based on 20 mg FGA-releasing intravaginal devices is an easy and satisfactory synchronization regimen to improve the productivity and the fertility of sheep farm, and this can be managed and optimized in different breeding conditions. In this study, Sarda breed shows a good adaption to the environment with adult ewes giving the best results in reproductive season. However young Sarda ewes were less productive especially in non-breading season. Lacaune showed good reproductive potential, young and adult ewes responded to progestins in reproductive and non-reproductive season. It was confirmed that the reproductive performance is affected by season, age, and breed. This study encourages the breeding of indigenous breeds by implementing the management with modern technologies. The imported highly productive breeds, if well managed, can give a production less influenced by seasonal variables and age.

Progesterone receptors in normal breast development and breast cancer.

Progesterone receptors (PR) play a pivotal role in many female reproductive tissues such as the uterus, the ovary, and the mammary gland (MG). Moreover, PR play a key role in breast cancer growth and progression. This has led to the development and study of different progestins and antiprogestins, many of which are currently being tested in clinical trials for cancer treatment. Recent reviews have addressed the role of PR in MG development, carcinogenesis, and breast cancer growth. Thus, in this review, in addition to making an overview on PR action in normal and tumor breast, the focus has been put on highlighting the still unresolved topics on hormone treatment involving PR isoforms and breast cancer prognosis.

Does a single application of contraceptive cause pathological changes in bitches? / [Uma única aplicação de anticoncepcional causa alterações patológicas em cadelas?]

O presente trabalho objetivou avaliar os efeitos da administração em dose única de progestágenos em fêmeas caninas hígidas, as quais nunca haviam recebido tais fármacos. Foram selecionadas 20 cadelas, que foram examinadas clinicamente e por meio de exames complementares. Nessas cadelas, foi aplicado medroxiprogesterona por via subcutânea. Noventa dias após, as fêmeas foram esterilizadas cirurgicamente, sendo os tecidos reprodutivos encaminhados para histopatologia. Foi possível verificar que, aos 30 dias, 12 animais (60%) apresentaram hiperplasia mamária. Aos 90 dias, 18 animais (90%) apresentavam sinais de hiperplasia endometrial cística, tendo cinco (27,77%) destes animais apresentado conteúdo purulento no lúmen uterino. No exame microscópico, apenas uma fêmea não demonstrou alterações patológicas, sendo a única que recebeu o contraceptivo na fase correta (anestro). As demais fêmeas apresentaram alterações que variaram entre alterações circulatórias a hiperplasia endometrial cística grave. Assim, foi possível concluir que uma única aplicação de anticoncepcional em fêmeas hígidas pode causar complicações leves a graves.(AU)

Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study / Preservação da fertilidade com progestágeno oral em pacientes com câncer de mama: é uma opção? Estudo-piloto

ABSTRACT Objective To compare the effectiveness of oral progestins and injectable gonadotropin-releasing hormone antagonist medication in cancer fertility preservation in patients with breast cancer. Methods A cross-sectional study with 40 breast cancer patients submitted to cancer fertility preservation, who were divided into two groups according to histochemical analysis of progesterone receptors to define luteinizing hormone block: if positive, use of gonadotropin-releasing hormone antagonist, if negative, use of oral progestins. The mean age, medication days, antral follicle count, number of oocytes in metaphase II and the occurrence of ovarian hyperstimulation syndrome were compared. Results A total of 20 patients both in the group using gonadotropin-releasing hormone antagonist, and in the group with oral progestins, respectively, had a mean age of 33.9 (32-35.8) and 33.8 (32-35.6) years; days of medications of 11 (9.7-12.3) and 12.8 (11.6-13.9), p=0.037; antral follicle count of 9 (7.11-12) and 8.5 (6-11.9), p=0.370; metaphase II oocyte number of 4 (2.1-9.8) and 7.5 (3.1-10), p=0.348; and ovarian hyperstimulation syndrome of 2 (10%) and 5 (25%) cases, p=0.212. Conclusion The use of oral progestins, in spite of requiring longer treatment time, is effective in relation to the protocol with gonadotropin-releasing hormone antagonist, and offers greater comfort at a lower cost in breast cancer patients with negative progesterone receptors, submitted to cancer fertility preservation.

RESUMO Objetivo Comparar a efetividade dos progestágenos orais em relação à medicação injetável antagonista de hormônio liberador de gonadotrofina na preservação da fertilidade oncológica de pacientes com câncer de mama. Métodos Estudo transversal com 40 pacientes com câncer de mama submetidas à preservação da fertilidade oncológica, que foram divididas em dois grupos, conforme análise histoquímica dos receptores de progesterona, para definir o bloqueio de hormônio luteinizante: se positivos, uso de antagonista de hormônio liberador de gonadotrofina; se negativos, uso de progestágenos orais. Comparou-se média de idade, dias de medicações, contagem de folículos antrais, número de oócitos em metáfase II e ocorrência de síndrome do hiperestímulo ovariano. Resultados Vinte pacientes, tanto no grupo com uso de antagonista de hormônio liberador de gonadotrofina, quanto no grupo com progestágenos orais, respectivamente, apresentaram média de idade de 33,9 (32-35,8) e 33,8 (32-35,6) anos; 11 (9,7-12,3) e 12,8 (11,6-13,9) de dias de medicações com p=0,037; contagem de folículos antrais de 9 (7,11-12) e 8,5 (6-11,9), com p=0,370; número de oócitos metáfase II de 4 (2,1-9,8) e 7,5 (3,1-10), com p=0,348, e síndrome do hiperestímulo ovariano de 2 casos (10%) e 5 casos (25%), com p=0,212. Conclusão O uso de progestágenos orais, apesar de necessitar de maior tempo de tratamento, é efetivo em relação ao protocolo com antagonista de hormônio liberador de gonadotrofina e oferece maior conforto com menor custo em pacientes com câncer de mama com receptores de progesterona negativos, submetidas à preservação da fertilidade oncológica.

Puberty and oestral cycle length in captive female jaguars Panthera onca.

Habitat loss and fragmentation have been leading jaguars to constant conflicts with humans, and as a result, jaguar populations have been declining over the last decades. Captive breeding is often a tool for species conservation, and it is not different for jaguars. However, success is far from optimal due to the lack of basic knowledge about species' reproductive biology. In the present study, we assessed gonadal hormonal profiles of natural oestral cycles and puberty and compared our data to those of other wild felids. We collected faecal samples from two to seven times per week for 18 months from two adults and three pre-pubertal females. We defined baseline levels for progestins and oestrogens in order to estimate oestrous cycle length and age at puberty. We compared our data with 16 other species through generalized linear model, using weight and genus as two explanatory variables. Cycle length was 38.28 ± 2.52 days, ranging from 25 to 44 days, while sexual maturity was attained within 22 months. Due to our analysis of both hormonal and behavioural data, there is a variation between this research from other studies that employed only behavioural observations. Such difference may be caused by the absence of behavioural oestrous at the peri-pubertal period. When compared to wild felids of similar size, puberty and oestral cycle durations of the jaguar females fell within the same range. Our modelling showed that age at maturity was influenced mostly by size and only Leopardus partially explained the observed variation. Conversely, oestral cycle length did not differ among genera or size categories. Our study adds to the body literature in the reproductive endocrinology of wild felids, and because female gametes are more challenging to collect and preserve, a strong understanding on the female reproductive physiology is essential to assisted reproduction and wild population viability assessment.

Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure.

BACKGROUND: Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis. OBJECTIVE AND RATIONALE: We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments. SEARCH METHODS: We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment. OUTCOMES: Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response. WIDER IMPLICATIONS: Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.

Maceração fetal por uso de contraceptivo em gata / Fetal maceration by the use of contraceptive in cat

The population growth of dogs and cats, stray and domiciled, shows the need for contraceptive methods, aiming at controlling overpopulations and increasing the life expectancy of these animals. However, the inappropriate administration of contraceptives in feline females has been associated with serious pathologies of the reproductive system. This work aims to report the case of fetal retention followed by fetal maceration in a cat submitted to the use of contraceptives based on synthetic progesterone. At the Veterinary Clinic Pet Valle Center, a feline, female, mixed breed, 7-month-old, pregnant, who used injectable contraceptives about 2 months ago. During anamnesis and physical examination, he presented apathy, hyporexia and bloody vaginal discharge. The animal underwent hematological and ultrasound examinations, indicating advanced gestational age, non-viability and fetal degeneration, characterizing the process of fetal maceration. With stabilization and subsequent surgical treatment, removing the organs compromised by the technique of ovariosalpingohisterectomy (OSH), the female had excellent recovery.

Maceração fetal por uso de contraceptivo em gata / Fetal maceration by the use of contraceptive in cat

The population growth of dogs and cats, stray and domiciled, shows the need for contraceptive methods, aiming at controlling overpopulations and increasing the life expectancy of these animals. However, the inappropriate administration of contraceptives in feline females has been associated with serious pathologies of the reproductive system. This work aims to report the case of fetal retention followed by fetal maceration in a cat submitted to the use of contraceptives based on synthetic progesterone. At the Veterinary Clinic Pet Valle Center, a feline, female, mixed breed, 7-month-old, pregnant, who used injectable contraceptives about 2 months ago. During anamnesis and physical examination, he presented apathy, hyporexia and bloody vaginal discharge. The animal underwent hematological and ultrasound examinations, indicating advanced gestational age, non-viability and fetal degeneration, characterizing the process of fetal maceration. With stabilization and subsequent surgical treatment, removing the organs compromised by the technique of ovariosalpingohisterectomy (OSH), the female had excellent recovery.(AU)

Consecuencias oncológicas y perinatales del tratamiento conservador de la fertilidad en pacientes con cáncer endometrial tratadas con progestinas / Oncological and perinatal results of conservative treatment of fertility in patients with endometrial cancer treated with progestins

Resumen OBJETIVO: Estimar la tasa de respuesta completa y de embarazo en mujeres con cáncer endometrial en tratamiento conservador con progestinas. MATERIALES Y MÉTODOS: Estudio de cohorte, retrolectivo y transversal efectuado en el Instituto Nacional de Perinatología en mujeres con cáncer endometrial, en estadios tempranos, atendidas entre 2007 y diciembre de 2016. Criterios de inclusión: pacientes con límites de edad de 18 y 40 años, nulíparas, con deseo de fertilidad, haber sido tratadas con megestrol, DIU-levonorgestrel o progesterona micronizada durante seis meses. A todas las pacientes se les tomó una biopsia endometrial a los 6 y 12 meses. Se utilizó estadística descriptiva y comparaciones entre mediciones, χ2 o t de Student según la distribución de cada variable. RESULTADOS: Se incluyeron 11 pacientes con cáncer endometrial con edad promedio de 32 ± 2.4 años. La biopsia tomada a los seis meses fue: respuesta completa en 6/11, respuesta parcial en 2/11 y persistencia en 2/11; en una paciente no se tomó la biopsia a los seis meses por embarazo, no hubo casos de progresión. A los 12 meses de seguimiento hubo 5 respuestas completas, 2 parciales, 2 persistencias, 1 caso de progresión de la enfermedad y otro que suspendió el tratamiento. Se efectuaron 8 ciclos de FIV en 6 pacientes con tasa de embarazo de 25%. La duración del tratamiento fue de 19.3 ± 8 meses, el seguimiento total fue de 31.6 ± 13 meses. CONCLUSIONES: El tratamiento conservador de la fertilidad con progestinas en pacientes con cáncer endometrial, en etapas tempranas, es factible y seguro. El embarazo debe intentarse inmediatamente después de una respuesta completa.

Abstract OBJECTIVE: To estimate the complete response rate and pregnancy in women with endometrial cancer who have received conservative treatment with progestins. MATERIALS AND METHODS: Cohort, retrolective and transversal study carried out in the National Institute of Perinatology, in women with endometrial cancer in early stages between 2007 and December 2016. Including patients between 18-40 years, nulliparous, with desire for fertility. The progestins used were megestrol, IUD-levonorgestrel and micronized progesterone for six months. Endometrial biopsy was performed at 6 and 12 months; The result was classified as a complete, partial response, persistence or progression of the disease. Descriptive statistics and comparisons between baseline measurements at six and 12 months are used using student grid and / or t tests according to the distribution of each variable. It is a statistical program SPSS version 23 for Windows (Chicago, USA). RESULTS: 11 women with endometrial cancer were included. The average age of the women was 32 ± 2.4 years. Morbidity associated with hypothyroidism and type 2 diabetes mellitus. Six-month biopsy was: complete response 6/11 partial response 2/11 and persistence 2/11, in one patient the biopsy was not performed at 6 months by pregnancy, there were no cases of progression. At 12 months of follow-up, there were 5 complete responses, 2 partial responses, 2 persistences, 1 case of disease progression and one case that discontinued treatment. Eight cycles of IVF were performed in 6 patients with a pregnancy rate of 25%, the duration of treatment was 19.3 ± 8 months, the total follow-up was 31.6 ± 13 months. CONCLUSIONS: Conservative fertility therapy with progestins in women younger than 40 years old with early-stage endometrial cancer is feasible and secure in our institution. Pregnancy must be sought immediately after a full response to the cancer treatment. Our findings are similar to the ones found in our systematic review of the international bibliography.

Hormone treatment as first line therapy is safe and relieves pelvic pain in women with bowel endometriosis / O tratamento hormonal como terapia de primeira linha é seguro e melhora a dor pélvica em mulheres com endometriose intestinal

ABSTRACT Objective: To evaluate clinical features and complications in patients with bowel endometriosis submitted to hormonal therapy. Methods: Retrospective study based on data extracted from medical records of 238 women with recto-sigmoid endometriosis treated between May 2010 and May 2016. Results: Over the course of follow-up, 143 (60.1%) women remained in medical treatment while 95 (39.9%) presented with worsening of pain symptoms or intestinal lesion growth (failure of medical treatment group), with surgical resection performed in 54 cases. Women in the Medical Treatment Group were older (40.5±5.1 years versus 37.3±5.8 years; p<0.0001) and had smaller recto sigmoid lesions (2.1±1.9 versus 3.1±2.2; p=0.008) compared to those who had failed to respond to medical treatment. Similar significant reduction in pain scores for dysmenorrhea, chronic pelvic pain, cyclic dyschezia and dysuria was observed in both groups; however greater reduction in pain scores for dyspareunia was noted in the Surgical Group. Subjective improvement in pain symptoms was also similar between groups (100% versus 98.2%; p=0.18). Major complications rates were higher in the Surgical Group (9.2% versus 0.6%; p=0.001). Conclusion: Patients with recto-sigmoid endometriosis who failed to respond to medical treatment were younger and had larger intestinal lesions. Hormonal therapy was equally efficient in improving pain symptoms other than dyspareunia compared to surgery, and was associated with lower complication rates in women with recto-sigmoid endometriosis. Medical treatment should be offered as a first-line therapy for patients with bowel endometriosis. Surgical treatment should be reserved for patients with pain symptoms unresponsive to hormonal therapy, lesion growth or suspected intestinal subocclusion.

RESUMO Objetivo: Avaliar características clínicas e complicações em pacientes com endometriose intestinal submetidos ao tratamento hormonal. Métodos: Dados de prontuários de 238 pacientes com endometriose de retossigmoide tratadas entre maio de 2010 e maio de 2016 foram coletados para este estudo retrospectivo. Resultados: Durante o período de acompanhamento, 143 (60,1%) mulheres mantiveram tratamento clínico, enquanto 95 (39,9%) tiveram piora dos sintomas de dor ou aumento da lesão intestinal (grupo falha de tratamento clínico), sendo 54 submetidas ao tratamento cirúrgico. As mulheres no Grupo Tratamento Clínico eram mais velhas (40,5±5,1 anos versus 37,3±5,8 anos; p<0,0001) e tinham lesões intestinais menores (2,1±1,9 versus 3,1±2,2; p=0,008) em comparação ao grupo falha de tratamento clínico. Redução significativa e semelhante do escore de dor na dismenorreia, dor pélvica crônica, disquezia cíclica e disúria cíclica foi observada nos Grupos Tratamento Clínico e Cirúrgico. Dispareunia, no entato, teve uma redução maior no Grupo Cirurgia. A redução subjetiva dos sintomas dolorosos também foi semelhante entre os Grupos Clínico e Cirúrgico (100% versus 98,2%; p=0,18). O Grupo Tratamento Cirúrgico foi relacionado a uma maior taxa de complicações graves (9,2% versus 0,6%; p=0,001) em comparação ao Grupo Tratamento Clínico. Conclusão: Falha no tratamento clínico em pacientes com endometriose de retossigmoide foi observada em mulheres mais jovens que tinham lesões intestinais maiores. O tratamento clínico hormonal foi igualmente eficaz na melhora dos sintomas de dor, exceto dispareunia, em comparação ao tratamento cirúrgico em mulheres com endometriose intestinal, mas com menor taxa de complicações. O tratamento clínico deve ser oferecido como primeira opção em pacientes com endometriose intestinal, enquanto o tratamento cirúrgico deve ser reservado para pacientes sem melhora nos sintomas de dor com tratamento hormonal, progressão das lesões ou suspeita de suboclusão intestinal.

Monitoring ovarian cycles, pregnancy and post-partum in captive marsh deer (Blastocerus dichotomus) by measuring fecal steroids.

The marsh deer is an endangered species from the marshlands of central South America. This study aimed to characterize certain aspects of the reproductive physiology of marsh deer hinds, including the duration and fecal progestins profile of the estrous cycle, pregnancy and post-partum periods, and evaluate the effect of cloprostenol administration on this species. The experimental group consisted of six females and one fertile male marsh deer. During monitoring of the estrous cycle, the fresh fecal samples were collected daily and, during pregnancy, they were collected twice weekly. The hormonal profile obtained from daily fecal samples indicated that the mean duration of the estrous cycle was 21.3 ± 1.3 days (6.4 days inter-luteal phase and 14.8 days luteal phase; n = 16 estrous cycles). The mean concentration of fecal progestins in the inter-luteal phase was 834 ± 311 ng g-1, in the luteal phase was 3979 ± 1611 ng g-1, value between them was 1457 ng g-1. No significant difference in fecal estrogen concentrations was determined during the estrous cycle. The corpora luteum was not responsive to cloprostenol until Day 6 of the estrous cycle, the period previously described as the inter-luteal phase. Half the females became pregnant following treatment with cloprostenol and two others were fertilized in their natural estrous cycle. Four females delivered fawns, and the mean duration of pregnancy was 253 ± 4 days. Fecal progestin concentrations were similar to those of the estrous cycle during the first 11 weeks of pregnancy and increased significantly ( > 15250 ng g-1) thereafter, providing a presumptive diagnosis guideline. Within 60 days of post-partum analyses, 75% of the deer exhibited behavioural estrus and/or ovarian activity. This study generated a broader understanding of the marsh deer species concerning the production of consistent data related to its reproduction. This knowledge can be used to assist the reproductive management of this species and, consequently, to promote its conservation.