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OBJECTIVE: To provide an evidence-based safety and tolerability overview of dydrogesterone under various progesterone-deficient conditions as a commemoration of its role in managing women's reproductive health over the past 60 years. METHODS: To identify relevant publications, we used a semi-systematic approach, which included performing a structured search through the PubMed and Cochrane central databases as well as an unstructured search for publications published in English from 2010 onward with human clinical data. RESULTS: A total of 32 relevant clinical studies were identified. Results were reported in the context of overall adverse events (AEs) and segregated according to various progesterone-deficient conditions. AEs concerning breasts (breast cancer risk), the endometrium (endometrial cancer risk), venous thromboembolism risk, and cardiovascular risk were found to be minimal when dydrogesterone was used as part of a menopausal hormone therapy regimen lasting ≤260 weeks. Vagina-related AEs, such as bleeding, discharge, irritation, and difficult coitus, occurred less frequently with dydrogesterone when used as luteal phase support in the context of assisted reproductive techniques (ARTs). However, other common AEs, such as headache, dizziness, abdominal pain, flatulence, and nausea, occurred more frequently with dydrogesterone. No maternal complications or congenital anomalies could be linked to dydrogesterone usage during ARTs or during early pregnancy to prevent recurrent miscarriages. Studies on dydrogesterone in endometriosis and premenstrual syndrome remain scarce. CONCLUSIONS: Post-approval, dydrogesterone has displayed a favorable safety and tolerability profile during its 60-year use, which is reassuring, considering its important role in managing women's reproductive health.
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Didrogesterona , Fase Luteal , Didrogesterona/efeitos adversos , Feminino , Humanos , Gravidez , Taxa de Gravidez , Progesterona/uso terapêutico , Técnicas de Reprodução AssistidaRESUMO
Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin®, an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.
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Antígenos de Plantas/uso terapêutico , Fogachos/tratamento farmacológico , Menopausa , Extratos Vegetais/uso terapêutico , Pólen , Síndrome Pré-Menstrual/tratamento farmacológico , Vitamina E/uso terapêutico , Feminino , HumanosRESUMO
Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications.Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties.Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h.Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.
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Androstenos/farmacologia , Anticoncepcionais Orais/farmacologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Inibição da Ovulação/efeitos dos fármacos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate whether a micronutrient supplementation preparation that includes a high amount of omega-3 unsaturated acids, other anti-oxidants and co-enzyme Q10 would have an impact on specific serum parameters in women with polycystic ovary syndrome (PCOS). METHODS: The study was designed as a monocentral, randomized, controlled, double-blinded trial, from June 2017 to March 2018 (Clinical Trials ID: NCT03306745). Sixty women with PCOS were assigned to either the "multinutrient supplementation group" (one unlabeled soft capsule containing omega-3 fatty acids and one unlabeled tablet containing folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, for 3 months) or the "control group" (two unlabeled soft capsules containing 200 µg folic acid each, for 3 months). The main outcome parameters were anti-Mullerian hormone (AMH), total testosterone, and androstenedione. In addition, the focus was on luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, sexual hormone-binding globulin (SHBG), and estradiol. RESULTS: In the multinutrient supplementation group, the LH:FSH ratio (2.5 ± 1.1 versus 1.9 ± 0.5, p = 0.001), testosterone (0.50 ± 0.19 versus 0.43 ± 0.15, p = 0.001), and AMH (8.2 ± 4.2 versus 7.3 ± 3.6, p < 0.001) declined significantly, whereas the other parameters, namely estradiol, LH, FSH, androstenedione, and SHBG remained stable. CONCLUSION: A micronutrient supplementation that includes omega-3 fatty acids, folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, given for a minimum of 3 months, is beneficial for women with PCOS in terms of PCOS-specific parameters (LH:FSH ratio, serum testosterone and serum AMH).
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Suplementos Nutricionais/análise , Micronutrientes/uso terapêutico , Síndrome do Ovário Policístico/terapia , Adulto , Método Duplo-Cego , Feminino , Humanos , Micronutrientes/farmacologia , Estudos Prospectivos , Adulto JovemRESUMO
The role of micronutrients in fertility has recently gained increased attention. We aimed to test the impact of a standardized, multinutrient supplementation on outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a pilot study. One hundred women undergoing IVF/ICSI were prospectively included and randomized to receive either a multinutrient supplementation named PROfertil® female that included folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids (study group; n = 50), or 400 µg folic acid (control group; n = 50). Outcome parameters were embryo quality on day 3 after oocyte retrieval (good quality vs. poor quality) and the clinical pregnancy rate. In an intention-to-treat analyses, a higher rate of women with at least one good quality embryo (with at least 6 cells and a fragmentation rate <20%) were found for the study (29/50, 58.0%) compared to the control group (18/50, 36.0%; p = 0.045 in chi-square test; relative risk 1.611, 95% CI 1.009-2.597). In conclusion, a multinutrient supplementation that includes folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids seems beneficial in terms of embryo quality.
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Suplementos Nutricionais , Fertilidade , Fertilização in vitro , Injeções de Esperma Intracitoplásmicas , Administração Oral , Adulto , Transferência Embrionária , Feminino , Humanos , Recuperação de Oócitos , Projetos Piloto , Gravidez , Taxa de Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: The European CHOICE study was a cross-sectional survey that evaluated women's combined hormonal contraceptive choices before and after contraceptive counseling in Austria, Belgium, Czech Republic and Slovakia, the Netherlands, Poland, Sweden, Switzerland, Israel, Russia, and Ukraine. The changes in method selection before and after counseling were reported previously. In this paper we present the reasons given by the 18,787 participating women for selecting their contraceptive method of choice, as well as their perceptions about the contraceptive pill, patch, and ring after counseling. METHODS: Women with an interest in a combined hormonal contraceptive method (pill, patch, or ring) were counseled using a standardized counseling leaflet. The women completed questionnaires, which included questions on why they had selected a particular method of contraception, and the extent to which they agreed with statements about the attributes of the pill, patch, and ring. The results for each country were compared with the percentages for all countries combined by using a binomial regression model. Multiple logistic regression models were used to investigate the extent to which the probability of choosing a method was related to prespecified aspects (i.e. perceptions) of each contraceptive method. RESULTS: 'Easy to use', 'convenience', and 'regular menstrual bleeding' were important selection criteria. 'Nondaily administration' was one of the main reasons women selected the patch or ring. 'Daily use' and 'will forget to take it' were the primary reasons for not selecting the pill, while the main reasons for not choosing the patch included 'not discrete, visible' and 'can fall off'. In a small number of instances, the ring was rejected because some women don't like to use a 'foreign body'. Women's perceptions influenced their contraceptive decisions: positive perceptions about a method increased the likelihood that a woman would select it. After counseling, many women associated the pill with forgetfulness, and many still did not know about the patch or ring's key attributes. Women's knowledge about a particular method was generally greater if they had chosen it. CONCLUSIONS: To support informed contraceptive decision-making, healthcare professionals should realize that a woman's view of a method's ease of use is more important than perceived efficacy, tolerability, health benefits, or risks.
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Comportamento Contraceptivo/psicologia , Comportamento Contraceptivo/estatística & dados numéricos , Anticoncepção/psicologia , Anticoncepção/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto/estatística & dados numéricos , Adulto , Comportamento de Escolha , Anticoncepcionais Femininos , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Atenção Primária à Saúde/organização & administração , Relações Profissional-Paciente , Fatores Socioeconômicos , Saúde da Mulher/estatística & dados numéricos , Adulto JovemRESUMO
Empirical evidence of the impact of contraceptive counselling and factors affecting women's contraceptive choices are limited. CHOICE (Contraceptive Health Research Of Informed Choice Experience) was a large-scale study in 11 European countries. Women in Austria aged 15-40 years considering a short-acting, reversible form of combined hormonal contraceptive were eligible to participate. The choices included the combined daily pill, weekly transdermal patch, and monthly vaginal ring. This study assessed and compared 2478 women's original preferences with their post-counselling choices and evaluated their perceptions and criteria for their choice. Women who were 'undecided' decreased from 18.1% pre-counselling to 3.2% post-counselling; significantly more women post-counselling chose the monthly ring (8.7% to 23.8%; difference 15.1%, 95% CI 13.3-16.8%; P<0.0001) or the weekly patch (6.2% to 7.8%; difference 1.7%, 95% CI 0.5-2.9%; P=0.0014). Women's primary reasons for choosing a method included 'easy to use' (daily pill, weekly patch and monthly ring) and 'still effective if I experience vomiting, diarrhoea' (weekly patch and monthly ring). Structured and balanced counselling led to changes in the method chosen.
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Comportamento de Escolha , Anticoncepção/métodos , Aconselhamento Diretivo , Adolescente , Adulto , Áustria/epidemiologia , Comportamento de Escolha/fisiologia , Anticoncepção/economia , Anticoncepção/estatística & dados numéricos , Aconselhamento Diretivo/métodos , Aconselhamento Diretivo/estatística & dados numéricos , Feminino , Clínicos Gerais/estatística & dados numéricos , Ginecologia/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Paridade/fisiologia , Papel do Médico , Gravidez , Fatores Socioeconômicos , Adulto JovemRESUMO
Hormonal contraceptives are an effective and safe method for preventing pregnancy. Progestins used in contraception are either components of combined hormonal contraceptives (tablets, patches or vaginal rings) or are used as a single active ingredient in progestin mono-preparations (the progestin-only pill (POP), implants, intrauterine systems or depot preparations). Progestins are highly effective in long-term contraception when used properly, and have a very good safety profile with very few contraindications. A new oestrogen-free ovulation inhibitor (POP) has recently been authorised in the USA and the EU. This progestin mono-preparation contains 4 mg of drospirenone (DRSP), which has anti-gonadotropic, anti-mineralocorticoidic and anti-androgenic properties. The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular-phase levels, preventing oestrogen deficiency. Clinical trials have demonstrated a high contraceptive effectiveness, a very low risk of cardiovascular side effects and a favourable menstrual bleeding pattern. Due to the long half-life of DRSP (30â-â34 hours), the effectiveness of the preparation is maintained even if a woman forgets to take a pill on a single occasion. Studies involving deliberate 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. Following a summary of the current status of oestrogen-free contraception, this review article will describe the clinical development programme of the 4 mg DRSP mono-preparation and the resulting data on the effectiveness and safety of this new oestrogen-free oral hormonal contraceptive.
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[This corrects the article DOI: 10.1055/a-1471-4408.][This corrects the article DOI: 10.1055/a-1471-4408.].
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Compared with nonuse, combined hormonal contraceptives containing estrogen and a progestogen are associated with a roughly 2- to 3-fold increased risk of venous and a 2-fold increased risk of arterial thromboembolism, including stroke and acute myocardial infarction. These events are, however, overall rare among women of reproductive age. Historically, progestin-only pills were not thought to be linked with any thromboembolic risk increase. Therefore, these preparations may be valuable options in women who are ineligible to take combined hormonal contraceptives. Until recently, only progestogens with partial androgenic activities were available. As demonstrated in animal studies, more modern progestogens such as drospirenone with its anti-mineralocorticoid effects may be associated with even more favorable aspects, which have to be clinically demonstrated, however, in future studies.
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Optimizing menopausal hormone therapy (MHT) requires an awareness of the benefits and risks associated with the available treatments. This narrative review, which is based on the proceedings of an Advisory Board meeting and supplemented by relevant articles identified in literature searches, examines the role of progestogens in MHT, with the aim of providing practical recommendations for prescribing physicians. Progestogens are an essential component of MHT in menopausal women with a uterus to prevent endometrial hyperplasia and reduce the risk of cancer associated with using unopposed estrogen. Progestogens include natural progesterone, dydrogesterone (a stereoisomer of progesterone), and a range of synthetic compounds. Structural differences and varying affinities for other steroid receptors (androgen, glucocorticoid, and mineralocorticoid) confer a unique biological and clinical profile to each progestogen that must be considered during treatment selection. MHT, including the progestogen component, should be tailored to each woman, starting with an estrogen and a progestogen that has the safest profile with respect to breast cancer and cardiovascular effects, while addressing patient-specific needs, risk factors, and treatment goals. Micronized progesterone and dydrogesterone appear to be the safest options, with lower associated cardiovascular, thromboembolic, and breast cancer risks compared with other progestogens, and are the first-choice options for use in 'special situations,' such as in women with high-density breast tissue, diabetes, obesity, smoking, and risk factors for venous thromboembolism, among others.
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This multicentre, randomised, controlled cross-over trial was designed to investigate the effect of intra-uterine slow-release insemination (SRI) on pregnancy rates in women with confirmed infertility or the need for semen donation who were eligible for standard bolus intra-uterine insemination (IUI). Data for a total of 182 women were analysed after randomisation to receive IUI (n = 96) or SRI (n = 86) first. The primary outcome was serological pregnancy defined by a positive beta human chorionic gonadotropin test, two weeks after insemination. Patients who did not conceive after the first cycle switched to the alternative technique for the second cycle: 44 women switched to IUI and 58 switched to SRI. In total, there were 284 treatment cycles (IUI: n = 140; SRI: n = 144). Pregnancy rates following SRI and IUI were 13.2% and 10.0%, respectively, which was not statistically significant (p = 0.202). A statistically significant difference in pregnancy rates for SRI versus IUI was detected in women aged under 35 years. In this subgroup, the pregnancy rate with SRI was 17% compared to 7% with IUI (relative risk 2.33; p = 0.032) across both cycles. These results support the hypothesis that the pregnancy rate might be improved with SRI compared to standard bolus IUI, especially in women aged under 35 years.
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Fertilização in vitro/métodos , Infertilidade/terapia , Inseminação Artificial/métodos , Taxa de Gravidez , Adolescente , Adulto , Gonadotropina Coriônica/metabolismo , Feminino , Humanos , Infertilidade/patologia , Nascido Vivo/epidemiologia , Masculino , Gravidez , Doadores de Tecidos , Adulto JovemRESUMO
OBJECTIVE: The objective of the present study is to investigate the relationship of cardiac fat depots with disturbances of the carbohydrate metabolism in women with PCOS. METHODS: An oral glucose tolerance test (OGTT) was realized, and metabolic parameters were collected in 48 women with PCOS and in 20 controls. Intramyocardial fat (MYCL) and pericardial fat (PERI) were measured using 1H-magnetic resonance spectroscopy and imaging. RESULTS: Only in PCOS women, PERI was positively and independently related to parameters of glucose metabolism (HbA1c: p = 0.001, fasting plasma glucose: p < 0.001, stimulated glucose at 30 and 60 minutes in the OGTT). Thus, the disposition index, insulin sensitivity, and adiponectin also declined with the increase of PERI in women with PCOS; however, these results were not independent of BMI and age. In addition, PERI was positively related to atherogenic lipid profiles, BMI, waist circumference, CRP, and liver fat in women with PCOS. A negative relation of PERI with triglycerides and a positive relation with BMI and waist circumference could be observed in the controls. No relationship of MYCL with diabetes-specific parameters could be found in the study population. CONCLUSION: PERI is related to metabolic disturbances in women with PCOS, but not in metabolically healthy lean subjects. This clinical trial was registered at ClinicalTrials.gov and has the registration number NCT03204461.
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OBJECTIVE: The first step in atherosclerosis is characterized by the adherence of lymphocytes and monocytes to cell adhesion molecules expressed by endothelial cells. The precise mechanism by which steroid hormones may be exerting a protective action against atherogenesis remains unclear. Therefore, we wanted to investigate the effect of tibolone on the circulating levels of various selectins in postmenopausal women. METHODS: Thirty healthy postmenopausal women were enrolled in a prospective, randomized, double blind, placebo-controlled outpatient trial. RESULTS: Patients treated with tibolone revealed a significant decrease for the variables sE-selectin, sL-selectin, and sPECAM-1 after 8 weeks of treatment. CONCLUSIONS: By reducing leukocyte adhesion molecule expression on human endothelial cells, tibolone may have the intrinsic potential to exert additional, lipid-independent, cardiovascular protective effects that may explain the clinical benefits of cardiovascular diseases in postmenopausal women.
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Selectina E/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Selectina L/efeitos dos fármacos , Norpregnenos/farmacologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/efeitos dos fármacos , Pós-Menopausa , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Selectina E/sangue , Moduladores de Receptor Estrogênico/administração & dosagem , Feminino , Humanos , Selectina L/sangue , Fator Estimulador de Colônias de Macrófagos/sangue , Fator Estimulador de Colônias de Macrófagos/efeitos dos fármacos , Pessoa de Meia-Idade , Norpregnenos/administração & dosagem , Selectina-P/sangue , Selectina-P/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Pós-Menopausa/sangue , Pós-Menopausa/efeitos dos fármacos , Estudos Prospectivos , Resultado do TratamentoRESUMO
AIMS: There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. METHODS: A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. RESULTS: Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. CONCLUSIONS: Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile.
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Glucose/metabolismo , Metabolismo dos Lipídeos , Síndrome do Ovário Policístico/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fígado/metabolismo , Músculos/metabolismo , Fenótipo , Síndrome do Ovário Policístico/patologia , Adulto JovemRESUMO
OBJECTIVE: The first step in atherosclerosis is characterized by the adherence of lymphocytes and monocytes to cell adhesion molecules expressed by endothelial cells. Therefore, we wanted to investigate the effect of tibolone on the circulating levels of various cell adhesion molecules. DESIGN: Thirty postmenopausal women were enrolled in a double-blind, randomized, placebo-controlled outpatient trial. RESULTS: Tibolone led to a significant decrease in soluble intercellular adhesion molecule-1, soluble intercellular adhesion molecule-3, and soluble vascular cell adhesion molecule-1, but had no effect on monocyte chemotactic protein-1. CONCLUSIONS: The direct favorable effects of tibolone on endothelial cells may explain the clinical benefits of this substance in terms of anti-ischemic effects and osteoporosis prevention.
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Moléculas de Adesão Celular/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Norpregnenos/farmacologia , Pós-Menopausa , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular/sangue , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Projetos PilotoRESUMO
OBJECTIVE: To compare the efficacy and safety of a prostaglandin E2 (PGE2) vaginal insert with PGE2 administered as a vaginal tablet. STUDY DESIGN: A randomized, observational study was performed. Women requiring induction of labor were randomly assigned to receive either a 10-mg PGE2 vaginal insert (group 1, n = 100) or 3-mg PGE2 tablets twice at six-hour intervals (group 2, n = 100). The primary efficacy outcome variable was vaginal delivery within 24 hours of insertion. The criteria for safety were the occurrence of uterine hyperstimulation, abnormal fetal heart rate patterns, use of beta 2-sympathomimetic drugs and fetal outcome. RESULTS: No differences in terms of vaginal delivery or cesarean section within 24 hours of induction were found. The cesarean section rate was 21% in group 1 and 22% in group 2. The interval from insertion of the induction agent to the onset of regular uterine contractions and the insertion-to-delivery interval were not different between the two cohorts. No difference in the frequency of uterine hyperstimulation, use of beta 2-sympathomimetic drugs, abnormal fetal heart rate patterns, fetal outcome, or oxytocin and analgesic requirements were found. In seven of eight patients in group 1 who experienced uterine hyperstimulation, removal of the insert was sufficient to stop it, whereas in group 2, of nine cases, eight needed medical interventions to end hyperstimulation (P = .003). CONCLUSION: The continuous release of PGE2 from the vaginal insert permits controlled induction of labor, and easy removal of the drug in cases of uterine hyperstimulation is possible.
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Dinoprostona/administração & dosagem , Trabalho de Parto Induzido/métodos , Adulto , Anestesia Obstétrica , Cesárea , Parto Obstétrico , Dinoprostona/efeitos adversos , Feminino , Monitorização Fetal , Humanos , Trabalho de Parto Induzido/efeitos adversos , Pessários , Gravidez , Estudos Prospectivos , Simpatomiméticos/uso terapêutico , Comprimidos , Fatores de Tempo , Contração Uterina/efeitos dos fármacos , Ruptura Uterina/etiologia , Vácuo-ExtraçãoRESUMO
OBJECTIVE: To determine differences in expression of corticotropin-releasing hormone receptors R1 and R2 in the myometrium of women delivering preterm or at term, with or without labor. MATERIAL AND METHODS: Small pieces of myometrial smooth muscle were taken from forty patients undergoing caesarian section. One sample each was taken from all preterm and term patients, with and without labor. Antibodies against CRH-R1/2 and CRH-R2 were used for localization by conventional fluorescence immunohistochemistry. The evaluation of staining was based on examination of the entire histologic section by three independent observers. RESULTS: In women at term, CRH-R2 levels were elevated before labor and decreased with the onset of labor. In eight of 10 term samples from women in labor, no staining was detected. In preterm patients we found no difference in CRH-R2 staining between women with and without labor. The intensity of staining for CRH-R1/2 was generally uniform in all four groups. CONCLUSION: The high level of CRH-R2 expression in term patients without labor, together with the subsequent decrease of CRH-R2 in the myometrium during progression of labor, is consistent with the possibility that CRH may have autocrine/paracrine effects on myometrial contractility in the lower segment of the uterus.
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Trabalho de Parto/fisiologia , Miométrio/fisiologia , Trabalho de Parto Prematuro/fisiopatologia , Receptores de Hormônio Liberador da Corticotropina/análise , Cesárea , Regulação para Baixo , Feminino , Imunofluorescência , Idade Gestacional , Humanos , Trabalho de Parto/metabolismo , Miométrio/metabolismo , Trabalho de Parto Prematuro/metabolismo , GravidezRESUMO
OBJECTIVE: The aim of our study was to determine whether a difference exists in expression of corticotropin-releasing hormone receptor-R1 (CRH-R1) and corticotropin-releasing hormone receptor-R2 (CRH-R2) in fetal membranes of preterm and term women with or without labor. MATERIAL AND METHODS: Small pleces of fetal membranes were obtained from the placenta of each of forty patients undergoing cesarean section. Ten samples each were taken from preterm and term patients, with and without labor. Antibodies against CRH-R1/2 and CRH-R2 were used for localization by conventional fluorescence immunohistochemistry. The evaluation of staining was based on examination of the entire histologic section by three independent observers. RESULTS: In women at term without labor, CRH-R2 receptor was predominantly expressed in the amniotic epithelium and the amniotic mesenchyme. In laboring women at term, the expression of CRH-R2 receptor was shown in the chorionic mesenchyme and the cytotrophoblast cells, but no specific staining could be detected in the amniotic membranes. Changes in CRH-R2 receptor expression could not be demonstrated during preterm labor of early pregnancies. In preterm women, the antibody against CRH-R1/2 receptor detected additional signals in the amniotic mesenchyme and epithelium, suggesting expression of CRH-R1 in these tissues. In women at term, the overlapping pattern of CRH-R1/2 was recognized in both the chorionic and amniotic mesenchyme, in contrast to the specific CRH-R2 staining, suggesting expression of CRH-R1 in the mesodermal cell compartments. CONCLUSION: At term, changes in CRH-R2 expression are directly related to the progression of normal labor; such changes were not observed during preterm labor of early pregnancies. The increased CRH-R2 expression in the chorionic mesenchyme may possibly provoke rupture of the membranes or at least play a role in some key regulatory events in the initiation of normal labor. The fact that this mechanism does not occur in preterm labor strengthens the hypothesis that onset of labor could be controlled by distinct mechanisms in preterm and term pregnancies.