One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives / Alterações na densidade mineral óssea e nos marcadores de formação óssea em adolescentes usuárias ou não de contraceptivos hormonais orais combinados por período de um ano

Abstract Objective: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. Methods: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n = 42) (20 µg EE/150 µg desogestrel), oral contraceptives 2 (n = 66) (30 µg EE/3 mg drospirenone), and a control group (n = 70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. Results: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. Conclusion: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Resumo: Objetivo: O objetivo deste estudo foi avaliar os efeitos de dois contraceptivos orais combinados de baixa dosagem por um ano sobre o metabolismo ósseo em adolescentes. Métodos: Este foi um estudo quase experimental. As adolescentes foram divididas em três grupos: contraceptivos orais 1 (n = 42) (20 µg de EE/150 µg de desogestrel), contraceptivos orais 2 (n = 66) (30 µg EE/3 mg de drospirenona) e grupo controle (n = 70). As adolescentes foram submetidas à avaliação antropométrica e densitometria (raio-X de dupla energia). Foram avaliados a idade óssea e os marcadores de formação óssea (osteocalcina e fosfatase alcalina óssea). As usuárias de contraceptivos orais foram novamente avaliadas após 12 meses. A análise de regressão linear foi utilizada para estudar, indiretamente, o efeito de cada ano adicional da idade cronológica sobre as variáveis antropométricas e densitométricas e sobre os marcadores ósseos no grupo de controle. Resultados: No início do estudo, não foram observadas diferenças significativas nas variáveis analisadas entre as usuárias de contraceptivos orais 1, contraceptivos orais 2 e o grupo controle. A análise de regressão linear mostrou um aumento na densidade mineral óssea e no conteúdo mineral ósseo para cada ano adicional. Houve uma redução significativa nos níveis de fosfatase alcalina óssea e não foi observada diferença significativa para osteocalcina nos indivíduos controles. A comparação das variáveis do raio-X de dupla energia no início e após um ano não mostrou diferença significativa no grupo de contraceptivos orais 1 ou contraceptivos orais 2. Foi observada uma redução significativa nos níveis de fosfatase alcalina óssea e osteocalcina nos dois grupos contraceptivos orais 1 e contraceptivos orais 2. Conclusão: As adolescentes atingiram o pico de massa óssea durante essa fase da vida. Duas formulações de contraceptivos hormonais orais de baixa dosagem, após um ano de uso, se associaram a menor incremento na densidade mineral óssea e menor concentração de marcadores de formação óssea quando confrontados com resultados de adolescentes não usuárias de contraceptivos.

Autoimmune progesterone dermatitis: A case report

Abstract Introduction Autoimmune progesterone dermatitis (APD) is a rare autoimmune dermatosis characterized by recurrent cutaneous and mucosal lesions during the luteal phase of the menstrual cycle that disappear some days after the menses. Case Report A 34-year-old primipara woman with no significant past medical history and no prior exogenous hormone use, who presented with cyclic skin eruptions starting 1 year after the delivery. The lesions occurred 6 days before the menses and disappeared in between 1 and 2 days after the menstruation ceased. The patient was diagnosed after a positive response to an intradermal test with progesterone and was successfully treated with combined oral contraceptives. The skin eruptions have not returned since the initiation of this therapy. Conclusion Dermatologists, gynecologists, and obstetricians should be aware of this rare entity. Furthermore, if this condition is suspected, a thorough history taking on the menstrual cycle and results of the intradermal progesterone test are mandatory.

Efficacy of acupuncture as adjunctive treatment on infertility patients with polycystic ovary syndrome / 中国针灸

<p><b>OBJECTIVE</b>To observe the efficacy differences between acupuncture combined with medication and medication alone for infertility patients with polycystic ovary syndrome (PCOS).</p><p><b>METHODS</b>According to random number table, a total of 60 infertility patients with PCOS were randomly assigned into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with diane-35 from the 3rd day into menstruation, and one menstrual cycle was taken as a session of treatment. At the same time of using diane-35, the patients in the observation group were treated with acupuncture at Guanyuan (CV 4), Qihai (CV 6), Sanyinjiao (SP 6), Zusanli (ST 36), Zigong (EX-CA 1), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21) and Ganshu (BL 18) during non-menstruation period; the acupuncture was given once every two days, three treatments per week. The patients in both groups were treated for two sessions. The basic sex hormone and body mass index (BMI) were compared between the two groups before and after treatment. After ovulation induction treatment, the endometrial thickness, amount of mature follicle, ovulation rate, clinical pregnancy rate, occurrence rate of ovarian hyperstimulation syndrome (OHSS) and the number of early spontaneous abortion were compared between the two groups during ovulation.</p><p><b>RESULTS</b>After treatment, the luteinizing hormone (LH), testosterone (T) and BMI reduced in the observation group (all <0.05), while only LH reduced in the control group (<0.05). The reducing of estradiol (E), T and BMI in the observation group was more significant than that in the control group (all <0.05). The ovulation rate was 93.3% (28/30) in the observation group, which was higher than 80.0% (24/30) in the control group (<0.05). The rate of clinical pregnancy was 43.3% (13/30) in the observation group, which was higher than 33.3% (10/30) in the control group (<0.05). The differences of endometrial thickness, amount of mature follicle, occurrence rate of OHSS and number of early spontaneous abortion were not significant between the two groups (all >0.05).</p><p><b>CONCLUSION</b>Acupuncture as adjunctive treatment could improve BMI, reduce the levels of LH, E and T, increase ovulation reaction and effectively shorten reproduction cycles in infertility patients with PCOS.</p>

Análise histomorfométrica da artéria aorta de ratas submetidas à administração repetida da associação de etinilestradiol e gestodeno / Histomorphometric analysis of the aorta of rats submitted to repeated administration of association of ethinylestradiol and gestodene

Introdução: Os anticoncepcionais orais vêm sofrendo alterações em suas concentrações de estrogênio e progestogênio, baseando-se no fato de que doses mais baixas estão associadas a menor incidência de alterações metabólicas e de efeitos adversos, como o comprometimento da morfologia e função da artéria aorta. O objetivo deste estudo é avaliar a influência dos anticoncepcionais nas propriedades morfofuncionais da artéria aorta, através do método histoquímico, demonstrando sua utilidade nas análises histopatológicas. Métodos: Para tanto, foram utilizadas 15 ratas divididas em 3 grupos; Grupo controle (GC), cujos animais não receberam tratamento hormonal; Grupo 2 (G2), onde os animais receberam tratamento diário de 15 µg de etinilestradiol + 60 µg de gestodeno; e Grupo 3 (G3), que recebeu 30 µg de etinilestradiol + 75 µg de gestodeno. Após o tratamento, os animais foram eutanasiados e as artérias retiradas para análise histológica. Resultados: Os valores encontrados com a técnica de coloração histológica de hematoxilina e eosina (HE), bem como na coloração específica em histoquímica com Alcian Blue, demonstram que no G3, tratados com uma dosagem superior de hormônio, 8% das ratas tem aumento relevante da espessura de suas artérias, ou seja, superior ao G2, que recebeu dosagem menor de hormônio, e GC, o qual não recebeu nenhum tipo de tratamento. Conclusão: Este estudo demonstra que existem relações entre o espessamento das artérias, de ratas submetidas a dosagens de etinilestradiol e gestodeno, com a grande quantidade de mucopolissacarídeos depositados entre as túnicas das artérias. (AU)

Introduction: Pharmacological development of hormonal contraceptives has been undergoing changes in estrogen and progesterone doses, based on the fact that lower doses are associated with a lower incidence of metabolic changes and adverse effects, such as impairment of morphology and function of the aortic artery. The aim of this study is to evaluate the influence of contraceptives on the morphofunctional properties of the aortic artery, using the histochemical method, demonstrating its usefulness in histopathological analyzes. Methods: For this purpose, 15 rats were divided into 3 groups; Control group (GC), whose animals did not receive hormonal treatment; Group 2 (G2), where the animals received a daily treatment of 15 µg of ethinylestradiol + 60 µg of gestodene; and Group 3 (G3), whose animals received 30 µg of ethinylestradiol + 75 µg of gestodene. After treatment, the animals were sacrificed and the arteries removed for histologic analysis. Results: The values found, with HE measurements and Alcian Blue histochemical staining, showed that in G3, treated with a higher hormone dosage, there are 8% of the rats with a relevant increase in the thickness of their arteries, that is, higher than that of G2, which received lower dosage of hormone and that of GC, which received no treatment. Conclusion: This study demonstrates that there are relations between the thickening of the arteries of rats submitted to dosages of ethinylestradiol and gestodene with the great amount of mucopolysaccharides deposited between the tunics of the arteries. (AU)

Distribución de esteroides estrogénicos en plantas de tratamiento de aguas residuales municipales / Distribution of estrogenic steroids in municipal wastewater treatment plants

En la actualidad, existe una preocupación creciente por la presencia de estrógenos en el medio acuático, donde pueden ser introducidos a partir de aguas residuales después de su eliminación incompleta en las plantas de tratamiento. Las aguas residuales sistemáticamente reciben estrógenos naturales y sintéticos, y por lo tanto una comprensión más profunda de la suerte de ellos en el medio ambiente es necesaria. Se evaluaron los niveles de estrógenos en los efluentes de las Plantas de Tratamiento de Aguas Residuales (PTARs) Penha e Ilha do Governador, ambos de tipo convencional de flujo continuo de lodo activado con aireación prolongada. Fue utilizado como el parámetro de determinación de algunos compuestos de interés como estrógenos naturales [estrona (E1), 17β-estradiol (E2), estriol (E3)) y sintéticos (17α-etinilestradiol (EE2)]. Las muestras individuales se recogieron posteriormente al tratamiento de cada PTAR y después de los procedimientos de laboratorio se realizó la determinación de estrógenos basado en la extracción en fase sólida (SPE) y la cromatografía líquida de alta resolución con detector de arreglo de diodos (HPLC-DAD). Las concentraciones fueron de: 0,7 a 5,2 μg/l y de 0,5 a 5,6 de E1; 0,9 a 7,7 y 1,2 a 9,2 μg/l para E2; 2,01 a 6,09 y 1,07 a 4,08 μg/l para EE2 en PTAR Penha y PTAR Ilha do Governador, respectivamente. La capacidad de eliminación de estrógenos fue eficaz, pero denota que la eliminación sistemática de la población es en la actualidad alta. Se recomienda instalar mecanismos para mitigar el consumo exagerado de estas sustancias o implementar una eliminación completa más eficaz.

Currently, there is a growing concern over the presence of estrogens in the aquatic environment, where they can be introduced from wastewater after their incomplete elimination in the treatment plants. Wastewater systematically receives natural and synthetic estrogens, and thus a deeper understanding of the fate of them in the environment is extremely necessary. It was evaluated estrogen levels in the effluent from the Sludge Wastewater Treatment Plants (SWTPs) Penha and Ilha do Governador, both of type conventional continuous-flow activated sludge with extended aeration. The determination of some target compounds as natural estrogens was used as the evaluation parameter [estrone (E1), 17β-estradiol (E2), estriol (E3) and synthetic (17α-ethinylestradiol (EE2)]. Individual samples were collected posterior treatment of each SWTP, and after laboratory procedures, the determination of estrogens was performed by a method based on solid phase extraction (SPE) and high performance liquid chromatography-diode array detector (HPLC-DAD). Concentrations ranged from 0.7 to 5.2 μg/l and from 0.5 to 5.6 for E1; 0.9 to 7.7 and 1.2 to 9.2 μg/l for E2; 2.1 to 6.9 and 1.7 to 4.8 μg/l for EE2 at SWTPs Penha and Ilha do Governador, respectively. The removal capacity of estrogens despite its effectiveness denotes that the systematic elimination by the population is high nowadays and urging mechanisms to mitigate the exaggerated consumption or to implement most effective complete removal.

Tromboembolismo e contracepção hormonal: evidências que orientam o aconselhamento / Thromboembolism and hormonal contraception: scientific evidence that can guide counseling

A evolução da contracepção hormonal permitiu à mulher apoderar-se do controle sobre sua fertilidade e beneficiar-se de efeitos que, além de extrapolarem a contracepção, são igualmente desejados. No entanto, dentre os eventos adversos, a ocorrência de tromboembolismo em usuárias de contracepção hormonal segue sendo uma preocupação em contínua avaliação. Nesse sentido, é necessário estabelecer o real papel dos diferentes contraceptivos hormonais (CH) como fator de risco para trombose. Com esse propósito, essa revisão examina as evidências científicas anteriormente publicadas nas bases de dados Medline, Pubmed e Cochrane, utilizando-se os descritores contraceptivos hormonais e tromboembolismo venoso. Após adequação aos critérios de seleção, foram utilizadas onze revisões sistemáticas ou metanálises publicadas entre 1998 e 2014, que incluíram 145 estudos publicados entre 1982 e 2013. As evidências apontam para maior segurança nas formulações com progestogênio isolado e contraceptivos com etinilestradiol em doses iguais ou menores que 35 mcg associado a progestogênios de 1ª geração ou levonorgestrel. Mais estudos são necessários para determinar o risco de tromboembolismo com as formulações combinadas de estradiol associado ao dienogeste e norgestimato, bem como examinar o impacto das vias transdérmica e oral nas formulações comercializadas no Brasil. Assim, não se recomenda privar mulheres de baixo risco para acidentes tromboembólicos dos benefícios da contracepção hormonal. O aconselhamento deve ponderar o risco de tromboembolismo preexistente, o risco de gravidez não planejada e suas complicações biopsicossociais e a composição do CH.(AU)

The evolution of hormonal contraception has enabled women to take control of their fertility and to benefit from effects that go beyond contraception. However, among the adverse effects, the occurrence of thromboembolism in users of hormonal contraception is a concern that has been evaluated, making it necessary to determine the actual role of different hormonal contraceptives (HC) as a risk factor for thrombosis. With that purpose, it was conducted a review of the scientific evidence published in Medline, Pubmed and Cochrane database using the following keywords: hormonal contraceptives and venous thromboembolism. The current review analysed eleven systematic reviews or meta-analyzes published between 1998 and 2014, bringing together 145 studies published between 1982 and 2013. The evidences point to increased security with formulations with isolated progestins and contraceptives with ethynilestradiol in doses equal to or less than 35 mcg associated with a first generation progestin or levonorgestrel. Additional studies are necessary to determine the risk of thromboembolism of estradiol combined formulations associated with dienogeste and norgestimate, as well as transdermal and oral formulations marketed in Brazil. Thus, it is inappropiate to deprive women at low risk for thromboembolic events from the benefits of hormonal contraception. Counseling should consider the risk of pre-existing thromboembolism, the risk of unplanned pregnancy with its biopsychosocial complications and particular HC composition.(AU)

Efeitos de hormônios esteroides de contraceptivos orais combinados sobre os parâmetros comportamentais de Betta splendens (Regan, 1909) / Effects of steroid hormones from combined oral contraceptives on the behavioral and physiological parameters of Betta splendens (Regan, 1909)

Os hormônios esteroides presentes em várias gerações de contraceptivos orais combinados (COC) podem se apresentar como disruptores endócrinos, produzindo alterações no comportamento e na fisiologia de peixes. Diante disso, o objetivo deste trabalho foi avaliar os efeitos de hormônios esteroides presentes em COC sobre os parâmetros comportamentais de Betta splendens, um peixe ornamental usado na aquariofilia e bastante agressivo. Machos adultos foram observados pelo método ad libitum para confecção do etograma e divididos em cinco grupos, controle e expostos aos hormônios: 17β-estradiol (E2); levonorgestrel e etinilestradiol (LEA - segunda geração de COC); gestodeno e etinilestradiol (GEA - terceira geração de COC); e drospirenona e etinilestradiol (DEA - quarta geração de COC). Os peixes foram expostos por 30 dias à concentração final de 10ng/L. Foram avaliados os comportamentos pelos métodos de varredura instantânea e animal-focal, bem como o consumo de ração. No método varredura, o comportamento descansar apresentou o maior valor (54,4±10,1%) no grupo E2 (P<0,05). Os comportamentos agressivos de carga (16,1±3,6%) e recuar e carga (16,4±5,1%) apresentaram os maiores valores no grupo controle em relação aos demais grupos (P<0,05). Os animais do grupo E2 apresentaram maior frequência de comportamentos inativos (76,1%) comparados aos de outros grupos. O comportamento atípico natação errática não foi observado no grupo controle, mas foi observado nos grupos experimentais. Os grupos E2, LEA, GEA e DEA apresentaram redução nos comportamentos agressivos (10%) quando comparados ao grupo controle pelo método animal-focal. Não foram observadas diferenças na exibição desses comportamentos ao se compararem os animais expostos às diferentes gerações de contraceptivos e no consumo de ração. Pode-se concluir que 17β-estradiol causou mais efeitos aos peixes e que diferentes gerações de COC apresentaram efeitos tóxicos semelhantes em relação aos comportamentos observados.

The steroid hormones present in many generations of combined oral contraceptives (COC) can act as endocrine disruptors inducing changes in the behavior and physiology of fish. In this context, the aim of this work was to evaluate the effects of steroid hormones present in COC on behavioral parameters of Betta splendes, an aggressive ornamental fish used in the aquariophily. Adult males were observed with the ad libitum method to develop an ethogram and were divided into five groups, Control and exposed to hormones: 17β-estradiol (E2), levonorgestrel and ethinylestradiol (LEA - 2nd COC generation), gestodene and ethinylestradiol (GEA - 3rd COC generation) and drospirenone and ethinylestradiol (DEA - 4th COC Generation). Fish were exposed for 30 days to a final concentration of 10ng/L. The behavior was evaluated by scan sampling and animal-focal methods, and feed intake. In the scan sampling method, the Resting behavior showed the highest value (54.4±10.1%) in E2 group (P<0.05). The aggressive behavior Rush (16.1±3.6%) and Back and Rush (16.4±5.1%) showed the highest values in the control group, compared to the other groups (P<0.05). Animals in the E2 group showed higher frequency of inactive behaviors (76.1%) compared to other groups. Furthermore, the atypical behavior Erratic swimming was not observed in the control group, but it was observed in the experimental groups. The E2, LEA, GEA and DEA groups showed reduction in aggressive behavior (10%) compared to the control group by the animal-focal method. Moreover, no difference was observed in the exhibition of these behaviors and feed intake comparing animals exposed to the different generations of contraceptives. It can be concluded that 17β-estradiol has caused more effects on fish and different generations of COC showed similar toxic effects in the observed behaviors.

Comparison among measures to prevent intrauterine adhesions after artificial abortion / 中南大学学报(医学版)

OBJECTIVE@#To investigate the clinical efficacy of oral medicine and sodium hyaluronate in prevention of intrauterine adhesions after artificial abortion.
@*METHODS@#A total of 572 patients with early pregnancy termination through artificial abortion, who experienced two or more times of abortion, were retrospectively analyzed. Patients were randomly and voluntarily divided into 4 groups: an artificial cycle group, a drospirenone and ethinylestradiol tablets group, a sodium hyaluronate group, and a control group. The thickness of the endometrium, return time of menses, and the status of intrauterine adhesions were observed.
@*RESULTS@#The thickness of the endometrium in the artificial period group was greater than that in the control group (P<0.001). It was less in the drospirenone and ethinylestradiol tablets group comparing with that in the control group (P<0.001). There was no significant difference in the thickness of the endometrium between the sodium hyaluronate group and the control group (P=0.717). Return time of menses in the artificial menstrual cycle group and the drospirenone and ethinylestradiol tablets group was shorter than that in the control group (P<0.001). There was no significant difference in return time of menses between the sodium hyaluronate group and the control group (P=0.813). The incidence of intrauterine adhesions could be reduced by the 3 preventive measures (All P<0.01).
@*CONCLUSION@#Drugs for artificial cycle and drospirenone and ethinylestradiol tablets medication immediately after artificial abortion can effectively promote endometrial repair and reduce the incidence of intrauterine adhesions. However, for the patients with poor compliance, drospirenoneand ethinylestradiol tablets are the first choice for prevention of intrauterine adhesion.

Changes of serum TOS and TAS levels and their association with apolipoprotein(a) in patients with polycystic ovary syndrome and infertility / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate changes of serum total oxidation status (TOS) and total antioxidant status (TAS) and their association with apolipoprotein (a) [Apo(a)] in patients with polycystic ovary syndrome (PCOS) combined with infertility.</p><p><b>MWTHODS</b>Ninety patients with PCOS and infertility were selected as the study group, including 45 patients treated with antioxidants combined with Diane-35(group A) and 45 with Diane-35 therapy only (group B), with 45 healthy volunteers with normal menstruation and normal dual phase basic body temperatures as the control group. Serum TOS of the participants was determined by dual xylenol orange method, and serum TAS was determined with ABTS method; plasma Apo(a) level was determined by dual wavelength immune transmission turbidity method.</p><p><b>RESULTS</b>Before treatment, serum TOS, OSI, and Apo(a) levels were significantly higher and TAS level was significantly lower in the study group than in the control group (P<0.05). Serum TOS, OSI, and Apo (a) were significantly lowered and TAS was significantly increased in group A after the therapy as compared with the levels before therapy and the levels in group B. The rate of natural recovery of menstruation was significantly higher and the incidence of cardiovascular disease was significantly lower in group A than in group B (P<0.05). Pearson correlation analysis showed that serum TOS and OSI were positively correlated with plasma Apo(a) (r=0.524 and 0.531, P<0.05), and serum TAS was negatively correlated with plasma Apo(a) (r=-0.519, P<0.05).</p><p><b>CONCLUSION</b>Antioxidant therapy can lower TOS, OSI and Apo(a) levels and increase TAS level to lessen oxidative stress, improve the prognosis, and reduce the risks of cardiovascular disease in patients with PCOS and infertility.</p>

Regulamentação do estrogênio sintético 17-etinilestradiol em matrizes aquáticas na Europa, Estados Unidos e Brasil / Regulación del estrógeno sintético 17-etinilestradiol en matrices acuáticas en Europa, Estados Unidos y Brasil / Regulation of the synthetic estrogen 17-ethinylestradiol in water bodies in Europe, the United States, and Brazil

O estrogênio sintético 17α-etinilestradiol, principal componente utilizado em formulações de contraceptivos orais, tem sido apontado como um dos principais compostos responsáveis por provocar efeitos adversos no sistema endócrino de várias espécies. O objetivo deste estudo foi analisar o estado da arte dos dispositivos legais e normativos referentes ao controle desse estrogênio sintético nas águas da Europa e dos Estados Unidos, e traçar um paralelo com a realidade brasileira. No geral, os países têm buscado ampliar a regulamentação e monitoramento de alguns micropoluentes emergentes que antes não eram objeto de atenção por parte dos dispositivos legais. A Europa está mais avançada no que tange à qualidade dos corpos hídricos, enquanto que nos Estados Unidos esta substância é alvo de regulamentação apenas para a água destinada ao consumo humano. No Brasil, ainda não há nenhum dispositivo legal ou normativo que aborde esse estrogênio, o que pode ser associado a uma baixa maturidade do sistema brasileiro quanto ao controle de poluentes hídricos.

El estrógeno sintético 17α-etinilestradiol, principal componente utilizado en fórmulas de contraceptivos orales, ha sido apuntado como uno de los principales compuestos responsables por provocar efectos adversos en el sistema endócrino de varias especies. El objetivo de este estudio fue analizar el estado de la cuestión de los dispositivos legales y normativos referentes al control de este estrógeno sintético en las aguas de Europa y de los Estados Unidos, y trazar un paralelo con la realidad brasileña. En general, los países han buscado ampliar la regulación y el monitoreo de algunos microcontaminantes emergentes que antes no eran objeto de atención por parte de los dispositivos legales. Europa está más avanzada en lo que se refiere a la calidad de los cuerpos hídricos, mientras que en los Estados Unidos esta substancia es objeto de regulación solamente para el agua destinada al consumo humano. En Brasil todavía no existe ningún dispositivo legal o normativo que aborde este estrógeno, lo que puede ser asociado a una inmadurez del sistema brasileño respecto al control de contaminantes hídricos.

The synthetic estrogen 17α-ethinylestradiol, the principal component of oral contraceptives, has been identified as one of the main compounds accounting for adverse effects on the endocrine system in various species. This study aimed to analyze the state-of-the-art in legislation and guidelines for the control of this synthetic estrogen in water bodies in Europe and the United States and to draw a parallel with the Brazilian reality. Countries have generally attempted to expand the regulation and monitoring of certain emerging micropollutants not previously covered by legislation. Europe is more advanced in terms of water quality, while in the United States this estrogen is only regulated in water for human consumption. Brazil still lacks legal provisions or standards for this estrogen, which can be explained by the relatively limited maturity of the country's system for controlling water pollutants.

Determinação simultânea de resíduos de etinilestradiol e gestodeno em superfícies de equipamentos de produção / Simultaneous determination of ethynylestradiol and gestodene residues on manufacturing equipment surfaces

Um método de validação de limpeza foi desenvolvido e validado, baseado na amostragem por swab e na determinação cromatográfica simultânea de resíduos de gestodeno e etinilestradiol. O método apresenta limite de quantificação de 0,036µg/mL de etinilestradiol e 0,009µg/mL de gestodeno. Este foi considerado seletivo, preciso, exato e robusto de acordo com as normas da ANVISA. O fator de recuperação para etinilestradiol foi 90,45% e para gestodeno foi 83,52% em superfície de inox e 87,31% para etinilestradiol e 81,21% para gestodeno em superfície emborrachada. O método foi aplicado com sucesso no teste de amostragem por swab de todos os pontos de superfície dos equipamentos. O método de limpeza foi considerado validado...

A cleaning technique validation method was developed and validated, based on swab sampling and simultaneous chromatographic determination of gestodene and ethynyl estradiol residues. The method exhibited limits of quantitation (LOQs) of 0.036µg/mL for ethynyl estradiol and 0.009µg/mL for gestodene. It was considered selective, precise, accurate and robust, according to the standards set by ANVISA, the Brazilian regulatory agency. Mean swab recovery factors were 90.45% for ethynyl estradiol and 83.52 % for gestodene on an inox surface and 87.31% for ethynyl estradiol and 81.21 % for gestodene on a rubberized surface. The method was successfully applied to the assay of actual swab samples collected from all points on equipment surfaces. The cleaning method was validated...

Adverse effects of 4-tert-octylphenol on the production of oxytocin and hCG in pregnant rats / 한국실험동물학회지

Endocrine-disrupting chemicals (EDCs) are exogenous substances that alter the structure or function of the endocrine system. 4-Tert-octylphenol (OP) is one of the most representative EDCs and has estrogenic effects. In this study, we examined the effects of ethinyl estradiol (EE) and OP on the pituitary gland, placenta, and uterus of pregnant rats. Expression levels of human chorionic gonadotropin (hCG), oxytocin (OT), and contraction-associated proteins (CAPs) were determined, and uterine contractile activity was measured by uterine contraction assay. EE and OP both increased mRNA expression of OT and hCG in the pituitary gland but not the placenta. Since OT and hCG control uterine contraction, we next examined CAP expression in the uterus. Expression of 15-hydroxyprostaglandin-dehydrogenase (PGDH) was upregulated by OP, whereas expression of other CAPs was unaffected. To clarify the effect of OP on uterine contraction in pregnant rats, uterine contraction assay was performed. The 17beta-Estradiol (E2) did not affect contraction of primary uterine cells harvested from pregnant rats in a 3D collagen gel model. However, OP showed different effects from E2 by significantly reducing contraction activity. In summary, we demonstrated that OP interferes with regulation of OT and hCG in the pituitary gland as well as PGDH in the uterus, thereby reducing uterine contraction activity. This result differs from the action of endogenous E2. Collectively, these findings suggest that exposure to EDCs such as OP during pregnancycan reduce uterine contractile ability, which may result in contraction-associated adverse effects such as metratonia, bradytocia, and uterine leiomyomata.

Efficacy comparison between electroacupuncture and dyne-35 in treatment of polycystic ovary syndrome / 中国针灸

<p><b>OBJECTIVE</b>To compare the difference in clinical efficacy on polycystic ovary syndrome (PCOS) between electroacupuncture (EA) and dyne-35 and to explore the effect mechanism.</p><p><b>METHODS</b>Sixty-five patients were randomized into an EA group (33 cases) and a western medication group (32 cases). In the EA group, the selected acupoints were Danzhong (CV 17), Qimen (LR 14), Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Zigong (EX-CA 1), Sanyinjiao (SP 6), Zusanli (ST 36) and Taichong (LR 3), etc. After the arrival of qi, electric stimulation was attached to the acupoints for 30 min. The treatment was given 3 times a week. In the western medication group, dyne-35 was prescribed on the 5th day of natural menstruation or withdrawal bleeding, one tablet a day, continuously for 21 days. The treatment cycle was 3 months in the two groups. The menstrual condition, body mass, body mass index (BMI), serum testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH were compared before and after treatment in the two groups. The clinical efficacy was assessed in the two groups.</p><p><b>RESULTS</b>The total effective rate was 90.6% (29/32) in the EA group and was 93.3% (28/30) in the western medication group. The efficacy was similar in the two groups (P > 0.05). After treatment, the levels of LH and LH/FSH were all reduced significantly in the two groups (all P < 0.01). After treatment, T level in serum was reduced apparently in the western medication group (P < 0.05). Before and after treatment, the differences in body mass and BMI in the EA group were more significant than those in the western medication group (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>EA is the effective method for PCOS, similar to that of dyne-35. The effect of it for weight loss is superior to dyne-35 and no apparent adverse reactions happen. The effect mechanism of EA is related to the regulation of serum sexual hormone levels and their ratio, as well as to the regulation of body lipid metabolism.</p>

Avaliação do padrão de consumo do 17α – etinilestradiol no município de Santa Maria Madalena, RJ / Evaluation of the pattern of consumption of the 17α - ethinylestradiol in the city of Santa Maria Maddalena, RJ

A presença no meio hídrico de contaminantes orgânicos com atividade estrogênica é um tema que tem gerado crescente preocupação na comunidade científica, uma vez que tais contaminantes são capazes de desencadear efeitos adversos no sistema endócrino de várias espécies. O estrogênio sintético 17α-etinilestradiol (principal componente utilizado em formulações de contraceptivos orais) tem sido apontado como um dos principais compostos responsáveis por provocar tais alterações. O principal objetivo deste estudo foi investigar, através de um questionário, o padrão de consumo do 17α-etinilestradiol presente em contraceptivos orais e medicamentos utilizados na TRH feminina, e estimar o aporte deste estrogênio nos corpos hídricos da área urbana do 1° distrito do município de Santa Maria Madalena. Para o desenvolvimento deste trabalho utilizou-se como metodologia um estudo do tipo inquérito realizado com 325 mulheres de 15 a 59 anos de idade, residentes na área de estudo, no período de setembro a dezembro do ano de 2013. Das 325 mulheres entrevistadas, constatou-se que 95 fazem o uso de contraceptivo oral, sendo que destas, 91 fazem uso de formulações que contêm o 17α-etinilestradiol. Tomando a amostra (...) como estatisticamente representativa da área de estudo, pôde-se extrapolar o valor de consumo do 17 α-etinilestradiol para a população total de mulheres (...) na faixa etária estabelecida. Com base nas informações obtidas a partir da elaboração do presente estudo foi possível estimar que há um considerável aporte desta substância nos corpos hídricos da área urbana do 1° distrito do município de Santa Maria Madalena (16 mg/dia), o que sugere a possibilidade de efeitos adversos à biota aquática local. Uma vez que o presente estudo não encerra a discussão sobre o assunto, ao fim desta dissertação há uma proposição para um trabalho futuro no sentido de se avançar neste tema.

The presence of organic contaminants with estrogenic activity in aquatic environment is a topic with growing concern in scientific community, since those contaminants are capable or triggering adverse effects to the endocrine system of many species. The synthetic estrogen 17α-ethinylestradiol (main compound of formulation of oral contraceptives) is being pointed as one of the main compounds responsible for these effects. The main objective of this study was to investigate, using a survey questionnaire, the consumption pattern of 17α-ethinylestradiol, which is found in oral contraceptives and hormone replacement therapies (HRT), and estimate the input of this estrogen in the water bodies of the 1st district of the city of Santa Maria Madalena, Brazil. In this work, an inquiry method was used at 325 women, ranging from 15 to 59 years old, all residents of the study area, from September to December of 2013. It was noticed that, from that sample, 91 women use formulations which contain 17α-ethinylestradiol. Taking the sample (...) as representative of the study area, an extrapolation could be made to the total of resident women (...) in the same age group. Using the information gathered during the course of this study, it was possible to estimate that there is a considerable input of this substance in the water bodies of the urban area of the 1st district of the city of Santa Maria Madalena (16 mg/day), suggesting the possibility of adverse effects to the local aquatic life. Since this study doesn't put an end to the discussion of this topic, a proposition for future works is made at the final part of this dissertation, aiming for further progress in this subject.

Pulmonary embolism and deep vein thrombosis related to oral contraceptive use

Pulmonary embolism (PE) and deep vein thrombosis (DVT) is a serious medical problem causing considerable morbidity and mortality. Risk factors of thrombosis are surgery, trauma, pregnancy, tumor, oral contraceptive as well as genetic risk factors though genetic risk factors were found in about 5% to 10% of cases. Yasmin, a combined oral contraceptive containing ethinylestradiol 30 microg and drospirenon 3 mg was launched in the United Kingdom in 2002. We had experienced a patient, 24-year-old young woman with left inguinal pain on ambulation, and edema of left leg four months after taking Yasmin. We performed chest pulmonary angiography computed tomography (CT) and lower extremity venogram CT. She was diagnosed to PE in both lower lobes and DVT below the level of left external iliac vein, and treated by low molecular weight heparin and warfarin. We report this case with brief review of literatures.

Simultaneous determination of ethinyl estradiol and drospirenone in oral contraceptive by high performance liquid chromatography

A simple, rapid, economical and reliable high performance liquid chromatographic method has been developed and successfully applied in simultaneous determination of ethinyl estradiol and drospirenone in coated tablets. The HPLC method was performed on a LiChroCART® 100RP column (125x4 mm i.d., 5 µm) with acetonitrile:water 50:50 (v/v) as mobile phase, pumped at a flow rate of 1.0 mL.min-1. The fluorescence detection for ethinyl estradiol was made at λex= 280 nm and λem= 310 nm and a UV detection for drospirenone was made at 200 nm. The elution time for ethinyl estradiol and drospirenone were 4.0 and 5.7 min, respectively. The method was validated in accordance to USP 34 guidelines. The proposed HPLC method presented advantages over reported methods and is suitable for quality control assays of ethinyl estradiol and drospirenone in coated tablets.

Um método simples, rápido, econômico e confiável foi desenvolvido empregando a cromatografia líquida de alta eficiência para a determinação simultânea de etinilestradiol e drospirenona em comprimidos revestidos. O método foi realizado utilizando coluna LiChroCART® 100RP (125 x 4 mm d.i., 5 µm), a fase móvel constituída de acetonitrila:água, 50:50 (v/v) com vazão de 1,0 mL.min-1. A detecção foi realizada empregando fluorescência em λex= 280 nm e λem= 310 nm para o etinilestradiol e na região de UV em 200 nm para a drospirenona. O etinilestradiol e a drospirenona tiveram tempo de retenção de 4,0 e 5,7 min, respectivamente. O método foi validado de acordo com as diretrizes da USP 34. O método proposto apresentou vantagens sobre os relatados na literatura e pode ser considerado adequado para o controle de qualidade do etinilestradiol e da drospirenona em comprimidos revestidos.

Preventive effect of omega-3 fatty acids on ethinyl estradiol induced hepatosteatosis in female wistar rat

Hepatic steatosis due to estrogen therapy increases the activity of inflammatory markers, particularly the activity of TNF alpha -which in turn induces more lipogenesis. Omega-3 fatty acids are among the negative regulators of hepatic lipogenesis. In this research, the preventive effect of omega-3 fatty acids on estrogen-induced steatosis in rats was evaluated. 2 mg/kg. BW/SC of 17 alpha-ethiny-lestrasdiol were injected into 25 female wistar rats in 5 equal groups [excluding the control group] over 10 consecutive days. Simultaneously, 3 of estradiol-treated groups were orally given 250, 500, and 1000 mg/kg. BW omega-3 fatty acids, respectively. At the end of the experiment, plasma ALT, AST, and TNF alpha level were determined. Histopathological changes in the liver were also identified by the evaluation of samples stained with H and E and Oil Red O. The histological findings revealed hepatic microvesicular steatosis and fat deposit in ethinylestradiol and, to a lesser extent, in the 250 mg/kg BW omega-3 fatty acids groups. The plasma levels of AST, ALT, and TNF alpha -significantly increased in the ethinylestradiol group compared to the control [p<0.05] and 1000 mg/kg. B.W omega-3 group. Omega-3 fatty acids reduced these parameters in comparison to the estradiol group [p<0.05]. It was concluded that 1000mg/kg.BW of omega-3 protects the liver against steatotic injuries

Effects of 17-α ethynyl estradiol on proliferation, differentiation & mineralization of osteoprecursor cells.

Background & objectives: The steroidal estrogen 17α-ethynyl estradiol (EE) is an orally bio-active estrogen used in almost all modern formulations of estrogen-progestin combination preparations of oral contraceptives. Contrasting effects of treatment with combined oral contraceptives on bone mineral density of pre-, peri-, and post-menopausal women have been reported, and it has been suggested that the estrogen dose and the type of progestogen may be the main contributing factors for these contrasting results. The objective of this study was to evaluate the effects of EE on osteoprecursor cells. Methods: The effects of single component of oral contraceptive, EE, were tested to see the relationship between EE and osteoblast proliferation, differentiation and mineralization. Tests used included a cell viability test, alkaline phosphatase (ALP) test, alizarin red-S staining, and a Western blot analysis. The effect on cell viability was determined by MTT assay. Differentiation and mineralization were examined using an ALP test and alizarin red-S staining. Protein expressions related to bone formation, such as estrogen receptor-alpha (ER-α), estrogen receptor-beta (ER-β), bone morphogenetic protein-2 (BMP-2), osteocalcin (OCN), and osteopontin (OPN) were evaluated by using a Western blot analysis. Results: Cultures growing in the absence of EE presented the lowest value for the MTT value. However, there were no significant changes in viability/proliferation when EE was added in the medium. Cultures growing in the absence of EE presented the highest value for the ALP activity, and the additional presence of EE resulted in dose-dependent decrease concerning ALP activity. Interpretation & conclusions: Our finding showed that EE in tested dosage within MC3T3-E1 cells seem to affect the proliferation and differentiation; however, significant differences are achieved in ALP activity in early differentiation phase and further studies are needed to elucidate the mechanisms of EE on bone.

Oral contraceptive pills decrease pulmonary airway resistance in healthy north Indian women.

Objectives: Oral contraceptive pills (OCPs) are hormonal pills used by females to prevent conception; they are a combination of estrogen and progestin. There is, however, compelling evidence that throughout the reproductive life of a woman, her airways are subject to the influence of the cyclical variations in sex hormones which occur in relation to circadian rhythms. The present study has been designed to investigate the effects of OCPs on airway resistance in terms of spirometric parameters in OCP users and nonusers. Materials and Methods: A total of 100 women (age: 20-40 years) ware selected for the present study. The subjects were provided with a one-month supply of OCPs. The constituents per tablet of MALA-N used were levonorgestrel 0.15 mg and ethinylestradiol 0.03 mg. Peak expiratory flow rate (PEFR), forced expiratory flow in expiring 25-75% air (FEF 25-75), forced expiratory volume percentage in one second (FEV1% or FEV1/FVC), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were recorded. Results: In our study, the FEF 25-75and PEFR increased significantly in OCP users, showing that these hormone pills decrease the resistance offered by small bronchioles.