Baicalin protects against 17α-ethinylestradiol-induced cholestasis via Sirt1/HNF-1α/FXR pathway / 中国药理学与毒理学杂志

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.

Effect of Shengxuening tablets combined with ethinylestradiol and cyproterone acetate on thickness of endometrium and hemoglobin levels in patients with endometrial polyps for transcervical resection of polyp / 国际中医中药杂志

Objective To investigate the effects of Shengxuening tablets combined with ethinylestradiol and cycloproterone acetate on endometrial thickness and hemoglobin level in patients with endometrial polyps for transcervical resection of polyp. Methods A total of 150 patients with hysteroscopic endometrial polypectomy were randomly divided into three groups, 50 in each group. The control group was treated with hysteroscopy endometrial polyp electrotomy, while the western medicine group was treated with ethinylestradiol and cycloprogesterone acetate tablets on the basis of the control group, and the combined group was treated with Shengxuening tablets on the basis of the western medicine group. The menstrual volume, endometrial thickness and hemoglobin levels were observed before treatment, at 3 month, 6 month and 12 month after treatment, and the clinical efficacy and recurrence during follow-up were evaluated. Results The total effective rate was 98.0％(49/50) in the combined group, 96.0％ (48/50) in the western medicine group, 86.0％ (43/50) in the control group. The total effective rate in the combined group and the western medicine group was significantly higher than that in the control group (χ2=6.643, P=0.036). The menstrual volume (F=28.096, 49.096, 33.303), endometrial thickness (F=11.214, 20.265, 63.947) in the three groups were significantly different after treatment (P<0.01), and which in the combined group were significantly lower than those in the western medicine group, menstrual volume at 36,12 after treatment (t value were 4.747, 2.244, 4.489, P<0.01); endometrial thickness at 3, 6, 12 month after treatment (t value were 3.293, 3.356, 5.293, P<0.01); there were significant differences in hemoglobin levels in the three groups (F=11.002, 8.662, 8.958, P<0.01), and which in the combined group was significantly higher than that in the western medicine group at 3,6,12 month after treatment (t value were 2.722, 2.074, 2.028, P<0.05). During the follow-up period, 2 cases (4.1％) recurred in the combined group, 3 cases (6.3％) recurred in the western medicine group and 9 cases (20.9％) recurred in the control group. The recurrence rate in the combined group or the western medicine group was significantly lower than that in the control group (χ2=6.775, P=0.034). There was no significant difference in the recurrence rate in the combined group and the western medicine group (χ2=0.211, P=0.646). Conclusions The Ethynestradiol and Cyproterone acetate combined with Shengxuening tablets could improve the curative effect, reduce menstrual volume and endometrial thickness, increase hemoglobin level and reduce recurrence rate in patients with endometrial polyps for transcervical resection of polyp.

Association between hormonal contraception and injuries induced by human papillomavirus in the uterine cervix / Associação entre a contracepção hormonal e lesões induzidas pelo vírus do papiloma humano no colo uterino

Abstract Objective To evaluate the association between hormonal contraception and the appearance of human papillomavirus HPV-induced lesions in the uterine cervix of patients assisted at a school outpatient clinic - ObGyn outpatient service of the Universidade do Sul de Santa Catarina. Methods A case-control study, with women in fertile age, performed between 2012 and 2015. A total of 101 patients with cervical lesions secondary to HPV were included in the case group, and 101 patients with normal oncotic colpocytology, in the control group. The data were analyzed through the Statistical Package for the Social Sciences (SPSS, IBM Corp. Armonk, NY, US) software, version 24.0, using the 95% confidence interval. To test the homogeneity of the proportions, the chi-square (χ2) test was used for the qualitative variables, and the Student t-test, for the quantitative variables. Results When comparing the occurrence of HPV lesions in users and non-users of combined oral contraceptives (COCs), the association with doses of 0.03 mg or higher of ethinylestradiol (EE) was observed. Thus, a higher probability of developing cervical lesions induced by HPV was identified (odds ratio [OR]: 1.9 p = 0.039); and when these cases were separated by the degree of the lesion, the probability of these patients presentingwith lowgrade squamous intraepithelial lesion was 2.1 times higher (p = 0.036), but with no impact on high-grade squamous intraepithelial lesions and the occurrence of invasive cancer. No significant differences were found in the other variables analyzed. Conclusion Although the results found in the present study suggest a higher probability of the users of combined hormonal contraceptives with a concentration higher than 0.03 mg of EE to develop low-grade intraepithelial lesions, more studies are needed to conclude causality.

Resumo Objetivo Avaliar a associação entre a contracepção hormonal e a presença de lesões induzidas pelo vírus do papiloma humano (HPV) no colo uterino de pacientes do serviço de ginecologia e obstetrícia do ambulatório de especialidade médicas da Universidadedo Sul de Santa Catarina - AME/UNISUL. Métodos Estudo observacional do tipo caso-controle, commulheres no menacme, no período compreendido entre 2012 e 2015. Foram incluídas 101 pacientes com lesões cervicais secundárias ao HPV, no grupo caso, e 101 pacientes com colpocitologia oncótica normal, no grupo controle. Os dados foram analisados por meio do programa SPSS 24.0, utilizando-se o intervalo de confiança de 95%. Para testar a homogeneidade de proporções foram utilizados o teste do qui-quadrado (χ2) para as variáveis qualitativas e o teste t de Student para as variáveis quantitativas. Resultados Ao comparar-se a ocorrência das lesões pelo HPV em usuárias de contraceptivos orais combinados (COCs) com a em não usuárias, observou-se a associação com doses de 0.03 mg ou superiores de etinilestradiol (EE), na qual se identificou 1.9 vezes mais probabilidade destas desenvolverem lesões cervicais induzidas pelo HPV (p = 0.039); ao separar-se esses casos pelo grau da lesão, a probabilidade destas pacientes apresentarem lesão cervical de baixo grau foi 2.1 vezes maior (p = 0.036), porémsemimpacto nas lesões cervicais de alto grau e na ocorrência de câncer invasor. Não foram encontradas diferenças significativas nas outras variáveis analisadas. Conclusão Embora os resultados encontrados no presente estudo sugiram maior probabilidade das usuárias de contraceptivo hormonal combinado, com concentração superior a 0.03 mg de EE, desenvolverem lesão cervical de baixo grau,mais estudos são necessários para concluir causalidade.

Cálculo del Índice de Pearl de etinilestradiol 30 mcg/drospirenona 3 mg (Genesa®)

Objetivo: Calcular el índice de Pearl de Genesa® en mujeres venezolanas. Métodos: Estudio fase IV, prospectivo y abierto. Las pacientes recibieron etinilestradiol 30 mcg / drospirenona 3 mg (Genesa®): un comprimido diario desde el primer día de la menstruación por 21 días; descanso de siete días y reinicio el día ocho. Resultados: Se ingresaron al estudio 115 pacientes, se obtuvo un índice de Pearl de 0,98. Los efectos adversos fueron: un embarazo, incremento de peso, retención de líquidos, náuseas, manchas en la piel. Conclusiones: Etinilestradiol 30 mcg/drospirenona 3 mg (Genesa®) presenta un adecuado índice de Pearl en mujeres venezolanas.

Objective: To calculate the Pearl index of Genesa® in Venezuelan women. Methods: Phase IV prospective and open study. Patients received ethinylestradiol 30 mcg / drospirenone 3 mg (Genesa®): one tablet daily from the first day of menstruation for 21 days; seven-day break and restart the eighth day. Results: 115 patients were admitted to the study, a Pearl index of 0.98 was obtained. Most common side effects: one pregnancy, weight gain, fluid retention, nausea, skin blemishes. One patient discontinued treatment for adverse effects (vomiting and nausea). Conclusions: Genesa® presents an adequate Pearl Index in Venezuelan woman.

Clinical prevent effect of taking drospirenone and ethinylestradiol tablets on intrauterine adhesion after missed abortion curettage with b-ultrasonic observation / 中国生化药物杂志

Objective To discuss clinical efficacy of taking drospirenone and ethinylestradiol tablets in preventing intrauterine adhesion after missed abortion curettage with b-ultrasonic observation.Methods216 cases of study objects provided with missed abortion curettage with b-ultrasonic observation were divided into control group with 108 cases and research group with 108 cases.Patients in control group were provided with conventional treatment after surgery, while those in research group were provided with conventional treatment and drospirenone and ethinylestradiol tablets.Two groups were compared for condition after surgery such as intrauterine adhesion in 1month after treatment, secondary pregnancy, infertility and abortion in 1 year after treatment.ResultsTime of vaginal bleeding, pelvic effusion and time of return of menses in research group were significantly lower than those in control group, with difference having statistical significance (t=6.114,t=9.481,t=9.201,P0.05).In the case of infertility rate and rate of abortion in 1 year after treatment, control group was higher than research group with difference having statistical significance (χ2=4.317,χ2=5.225,P<0.05).ConclusionTaking drospirenone and ethinylestradiol tablets after missed abortion curettage with b-ultrasonic observation can effectively prevent intrauterine adhesion, which can also reduce complications such as abortion and infertility, therefore, it shall be applied in accordance with specific condition of patients.

Simultaneous determination of levonorgestrel and ethinylestradiol in New Zealand rabbit plasma by liquid chromatography-tandem mass spectrometry and their pharmacokinetics / 中国药理学与毒理学杂志

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determinations of concentrations of levonorgestrel (LNG) and ethinylestradiol (EE) in New Zealand rabbit plasma, and to study their pharmacokinetics in New Zealand rabbits after multiple dosing. METHODS Six female New Zealand rabbits were given LNG/EE patches ten times (5 cm × 4 cm, each patch contained LNG 5.35 mg and EE 0.11 mg), 1 patch every 3 d, for 30 consecutie days. Blood samples were collected at different time points before and after drug administration. The plasma samples were derived with dansyl chloride and then analyzed by HPLC-MS/MS method. The main pharmacokinetic parameters were calculated using DAS3.0 software. RESULTS The linear concentra-tion range of LNG was 0.10-20.00μg · L-1. The lower limit of quantitation was 0.10μg · L-1. The extrac-tion recovery was more than 78.30％. The intra-day and inter-day precisions were both less than 12.89％. The first-dosing pharmacokinetic parameters for LNG were as follows:Cmax (8.10±2.38)μg·L-1, Tmax (2.38±1.45) h, and AUC(0-768) (142.35±36.99) h·μg·L-1. The last administration pharmacokinetic parameters for LNG were as follows:Cmax (7.05±1.07)μg·L-1, Tmax (2.71±1.83) h, and AUC(0-768) (141.95±22.31) h·μg·L-1. The linear concentration range of EE was 0.02-5.00μg·L-1. The lower limit of quantitation was 0.02μg·L-1. The extraction recovery was above 79.99％. The intra-day and inter-day precisions were both less than 12.76％. The first-dosing pharmacokinetic parameters for EE were as follows: Cmax (0.18 ± 0.04)μg · L-1, Tmax (2.50±1.30) h, and AUC(0-768) (2.65±0.56) h·μg·L-1. The last administration pharmacokinetic parame-ters for EE were as follows:Cmax (0.17 ± 0.07)μg · L-1, Tmax (2.17 ± 0.26)h, and AUC(0-768) (2.02 ± 0.82) h ·μg · L-1. CONCLUSION The HPLC-MS/MS determination method is accurate and sensitive, which can be used to simultaneously determine the concentration of LNG and EE. There are no significant differences in main pharmacokinetic parameters between the first dose and the last dose. After repeated administration of this contraceptive patch, there is no accumulation of blood concentration in the rabbit body.

Effects of Compound Leonurus artemisia Ointment Combined with Drospirenone and Ethinylestradiol Tablets on Serum Progesterone and Th1/Th2 Cytokine after Medical Abortion / 中国药房

OBJECTIVE:To investigate the effects of Compound Leonurus artemisia ointment combined with Drospirenone and ethinylestradiol tablets on serum progesterone and T helper (Th) 1/Th2 cytokine after medical abortion.METHODS:A total of 228 patients underwent medical abortion selected from obstetrical outpatient of our hospital during our hospital during Mar.2013 to Jul.2015 as research object were divided into control group (109 cases) and observation group (119 cases) according to random number table.Control group was given Cefuroxime axetil tablets 0.25 g,po,bid,for consecutive 6 d for anti-infective treatment+ Drospirenone and ethinylestradiol tablets one tablet,po,qd,21 d as a treatment course,8 d later receiving second course,3 courses in total after fetal sac exclusion.Observation group was additionally given Compound L.artemisia ointment 10 g,po,bid,7 d as a treatment course,2 courses in total on the basis of control group.The levels of serum progesterone and Th1 (TNF-α,IFN-γ,IL-2)/Th2 cytokine (IL-4,IL-6,IL-10) were observed in 2 groups,and the occurrence of ADR was recorded.RESULTS:Before treatment,there was no statistical significance in serum progesterone or Th1/Th2 cytokine levels between 2 groups (P＞0.05).After treatment,serum progesterone,TNF-α,IL-2 and IL-6 levels of 2 groups were decreased significantly,and above indexes of observation group were significantly lower than those of control group.The levels of IL-4 and IL-10 in 2 groups were increased significantly,and above indexes of observation group were significantly higher than control group,with statistical significance (P＜0.05).After treatment,IFN-γ levels of 2 groups were decreased significantly,but there was no statistical significance between 2 groups (P＞0.05).No obvious ADR was found in 2 groups during treatment.CONCLUSIONS:Compound L.artemisia ointment combined with Drospirenone and ethinylestradiol tablets can regulate immune function of patients after medical abortion,and promote dynamic balance of Th1/Th2 cytokines with good safety.

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.

Dissolution detection of desogestrel and ethinylestradiol tablets by HPLC / 国际药学研究杂志

Objective To develop a HPLC method for determining the dissolution of desogestrel and ethinylestradiol tablets. Methods The dissolution was determined by the second method described in Chinese Pharmacopoeia (ChP) 2015. In total 500 ml of 0.05% sodium lauryl sulfate solution was used as dissolution media, and the rotation speed was 50 r/min. The dissolution time was 30 min and the dissolution was determined by HPLC. The HPLC column was Agilent SB C18 column (150 mm×4.6 mm, 5 µm). The mobile phase: acetonitrile as mobile phase A, acetonitrile-water (50:50, V/V) as mobile phase B with gradient elution. The flow rate was 1 ml/min. The detection wavelength of desogestrel and ethinylestradiol was 210 nm. The column temperature was 40 and the injection volume was 100 µl. Results The average recoveries were 99.68% for desogestrel and 99.40% for ethinylestrsdiol, and the stability of working solutions was acceptable in 12 h. The calibration curves were linear within the range of(0.06-0.36)µg/ml (r=0.9999)for desogestrel, (0.012-0.072)µg/ml (r=0.9999)for ethinylestradiol, respectively. Conclusion The method is convenient and precise in the dissolution determination of desogestrel and ethinylestradiol tablets.

Clinical Observation of Hysteroscopy Combined with Drospirenone Ethinylestradiol in the Treatment of Endometrial Polyps / 沈阳医学院学报

Objective:To explore the clinical efficacy of hysteroscopy combined with drospirenone ethinylestradiol in the treatment of endometrial polyps. Methods:A total of patients with endometrial polyps from Feb 2014 to Dec 2015 were randomly divided into 2 groups.The control group was given hysteroscopic surgery. Intravenous infusion of oxytocin and antibiotics after operation was done. The observation group on the basis of the control group received oral administration of drospirenone and ethinylestradiol tablets (1 tablet/d), taking 3 consecutive weeks, and a total of 3 cycles. In the postoperative 4 months follow-up, the curative effect and complications was compared. Results: There was significant difference in menstrual improvement rate in 2 groups (P<0.05) . The recurrence rate in the control group was significantly higher than that in the observation group (P<0.05), but there was no difference in the pregnancy within 6 months after the surgery and adverse reactions (P>0.05) . Conclusion:The endometrial polyps performed hysteroscopic surgery combined with drospirenone ethinyl estradiol can effectively improve menstrual bleeding and cycle,reduce the recurrence of endometrial polyp,and the adverse reaction.

Dissolution detection of desogestrel and ethinylestradiol tablets by HPLC / 国际药学研究杂志

Objective To develop a HPLC method for determining the dissolution of desogestrel and ethinylestradiol tablets. Methods The dissolution was determined by the second method described in Chinese Pharmacopoeia(ChP)2015. In total 500 ml of 0.05%sodium lauryl sulfate solution was used as dissolution media,and the rotation speed was 50 r/min. The dissolution time was 30 min and the dissolution was determined by HPLC. The HPLC column was Agilent SB C18 column(150 mm×4.6 mm,5μm). The mobile phase:acetonitrile as mobile phase A,acetonitrile-water(50∶50,V/V)as mobile phase B with gradient elution. The flow rate was 1 ml/min. The detection wavelength of desogestrel and ethinylestradiol was 210 nm. The column temperature was 40℃and the injection volume was 100μl. Results The average recoveries were 99.68%for desogestrel and 99.40%for ethinylestrsdiol,and the stability of work?ing solutions was acceptable in 12 h. The calibration curves were linear within the range of(0.06-0.36)μg/ml(r=0.9999)for desoges?trel,(0.012-0.072)μg/ml(r=0.9999)for ethinylestradiol,respectively. Conclusion The method is convenient and precise in the dis?solution determination of desogestrel and ethinylestradiol tablets.

Effects of Ethinylestradiol and Cyproterone Acetate Combined with Metformin on Ovulation Induction of Pa-tients with Polycystic Ovarian Syndrome / 中国药房

OBJECTIVE:To discuss the effect of Ethinylestradiol and cyproterone acetate tablet combined with metformin on ovulation induction of patients with polycystic ovarian syndrome(PCOS). METHODS:184 PCOS patients were randomly divided into control group(92 cases)and observation group(92 cases). Control group orally received 1 Ethinylestradiol and cyproterone ac-etate tablet in 5 d of menstruation,once a day,it stopped after 21 d,the next cycle of treatment was started on the 5th of with-drawal bleeding. Observation group additionally received 3 Metformin tablet,once a day,without drug withdrawal during menstrua-tion,and lasted for 3 menstrual cycles. After 3 menstrual cycles,all patients received ovulation induction treatment [(50-100 mg clomiphene was orally given from the 5th day of the 4th menstrual cycle,for 5 days,or 75-150 U postmenopausal gonadotropin by intramuscular injection,when the dominant follicle diameter was(19.0±2.0)mm,10 000 U human chorionic gonadotropin(HCG) was intramuscularly injected,the ovulation was continuously monitored and whether there was ovarian hyperstimulation syndrome (OHSS)was observed]. Body mass index(BMI),follicle estrogen(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol (E2)and testosterone(T)before and after treatment,fasting plasma glucose(FPG),fasting insulin(FINS),insulin resistance in-dex(HOMA-IR),pregnancy rate,ovulation rate and the incidences of OHSS and adverse reactions in 2 groups were observed.RE-SULTS:Before treatment,there were no significant differences in the BMI,FSH,LH,PRL,E2,T,FPG,FINS and HOMA-IR between 2 groups(P>0.05). After treatment,BMI,LH,PRL,E2,T,FPG,FINS and HOMA-IR in observation group and LH, E2 and FINS in control group were significantly lower than before,and BMI,PRL,E2,T,FPG,FINS and HOMA-IR in observa-tion group were lower than control group,the differences were statistically significant(P0.05). CONCLUSIONS:Ethinylestradiol and cyproterone acetate combined with metfor-min can effectively improve insulin resistance of POCS patients,recovery sex hormone secretion,promote ovulation and improve pregnancy rate,with good safety.

Clinical observation of Drospirenone and Ethinylestradiol Tablets for preventing postoperative complications of induced abortion / 中国生化药物杂志

Objective To observe the clinical effect of postoperative complications in patients with induced abortion by taking Drospirenone and Ethinylestradiol Tablets.Methods 400 patients with induced abortion from November 2015 to May 2016 were randomly divided into the observation group and the control group,200 cases in each group.The control group was treated with routine antibiotic therapy.The observation group treatment with Drospirenone and Ethinylestradiol Tablets based on the control group, 1 per one night, 21d for a course of treatment, continuous use of 6 courses.Compared the 2 groups of patients with postoperative complications of pelvic infection,intrauterine adhesions,pregnancy,recurrent abdominal pain and two groups of postoperative recovery time of menstruation,vaginal bleeding,endometrial thickness.Results In the observation group after pelvic infection,uterine cavity adhesion,pregnancy,periodic abdominal pain incidence were 1.5%,0.5%,0.0%,1.5%,were significantly lower than that of the control group7.0%,3.5%,4.0%,5.5%(P<0.05);the observation group after menstruation recovery time,vaginal bleeding,endometrial thickness respectively(27.2 ±1.7) d,(6.2 ±1.4)d,(7.2 ±2.3) mm,were lower than the control group(32.5 ±6.0) d,(7.8 ±2.7) d,(5.0 ±2.4) mm,two groups of the difference was statistically significant(P<0.05).Conclusion After artificial abortion,taking Drospirenone and Ethinylestradiol Tablets can effectively reduce the incidence of complications,improve the quality of life of patients,the method is simple,safe,effective and good compliance.

Simultaneous Determination of the Content of Ethinylestradiol and Norelgestromin in Hormonal Patches by RP-HPLC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of ethinylestradiol and norelgestromin in hor-monal patches. METHODS:RP-HPLC method was performed on column of WondaCract ODS-2 with mobile phase of metha-nol-0.5% phosphoric acid(68∶32,V/V)at a flow rate of 1.0 ml/min,the detection wavelength was 220 nm,the detection tempera-ture was 25 ℃,and sample volume was 20 μl. RESULTS:The linear relationship was 0.872-130.8 μg/ml for ethinylestradiol(r=0.999 6) and 0.880-132.0 μg/ml for norelgestromin (r=0.999 7);RSDs of precision,reproducibility and stability tests were no more than 1.03%,average recoveries were resectively 101.50%(RSD=0.99%,n=9) and 101.68%(RSD=0.95%,n=9). CON-CLUSIONS:The established method is simple and accurate,and can be used for the content determination of ethinylestradiol and norelgestromin in hormonal patches.

Clinical effect of desogestrel ethinylestradiol in the treatment of adolescent dysfunctional uterine bleeding / 中国基层医药

Objective To observe the clinical efficacy and adverse reactions of desogestrel ethinylestradiol in the treatment of dysfunctional uterine bleeding ( adolescent Dub ) .Methods 86 cases with adolescent functional bleeding were divided into the treatment group and control group ,43 cases in each group .The control group received conjugated estrogen(Premarin) treatment,the treatment group was given desogestrel ethinylestradiol treatment .The hemostatic effect and drug adverse reaction of the two groups were observed .Results The cure rate of the treatment group was 65.1%,that in the control group was 23.3%,there was significant difference between the two groups (χ2 =15.28,P0.05).Conclusion Desogestrel ethinylestradiol in the treatment of ado-lescent functional bleeding has exact curative effect ,it has low incidence of adverse reactions and better acceptance .

Efficacy of rosiglitazone combined with ethinylestradiol cyproterone on treatment of polycystic ovary syndrome / 中国医师进修杂志

Objective To observe the effect of rosiglitazone combined with ethinylestradiol cyproterone on treatment of polycystic ovary syndrome (PCOS).Methods Sixty-eight cases with PCOS combined with insulin resistance (experimental group) and 68 cases with PCOS combined without insulin resistance (control group) were selected.The patients in experimental group were given rosiglihtazone combined with ethinylestradiol cyproterone,the patients in control group were not given rosiglitazone.The level of seurm adiponectin and lepfin was measured before and after treatment in two groups,body mass index (BMI),Homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated before and after treatment in two groups,and drug adverse reaction was observed.Results There was no significant difference in serum adiponeetin,leptin,BMI before treatment between two groups (P ＞ 0.05).HOMA-IR in experimental group was higher than that in control group (3.90 ± 0.87 vs.2.15 ± 0.62),and there was significant difference (P ＜ 0.05).BMI,leptin after treatment in experimental group and control group was decreased compared with that before treatment [experimental group:(25.41 ± 1.01) kg/m2 vs.(30.11 ± 1.51) kg/m2,(0.25 ± 0.08) μ g/L vs.(0.44 ± 0.11) p g/L; control group:(26.68 ± 1.12) kg/m2 vs.(30.55 ± 1.42) kg/m2,(0.23 ± 0.1 0) μ g/L vs.(0.39 ± 0.23) μ g/L],adponectin was increased compared with that before treatment [experimental group:(1.39 ± 1.10) μ g/L vs.(0.89 ± 0.15) μ g/L;control group:(1.42 ± 1.05) μ g/L vs.(0.91 ± 0.44) μ g/L],and HOMA-IR after treatment (2.09 ± 0.68) in experimental group was lower than that before treatment,and there was significant difference (P ＜ 0.05).There was no significant difference between two groups (P ＞0.05).Experimental group did not appear obvious drug adverse reaction in the process of treatment.Conclusion Ethinylestradiol cyproterone can improve metabolic disorders indicators,PCOS combined with insulin resistance should add rosiglitazone to improve insulin resistance.

The ovulation effect of ethinylestradiol and cyproterone acetate combined with metformin on obesity type polycystic ovary syndrome / 中国医师进修杂志

Objective To evaluate the ovulation effect of ethinylestradiol and cyproterone acetate combined with metformin on obesity type polycystic ovary syndrome (PCOS).Methods Sixty-two patients with obesity type PCOS were divided into 2 groups by random digits table method:control group (30 cases) was treated with letrozole;observation group (32 cases) was treated with letrozole after 3 months treated with ethinylestradiol and cyproterone acetate combined with metformin.The weight,body mass index (BMI),glycometabolism indexes [fasting plasma glucose (FPG),fasting insulin (FINS) and homeostasis model of assessment for insulin resistance index (HOMA-IR)],hormone [follicle-stimulating hormone (FSH),luteotrophic hormone (LH),estradiol (E2) and testosterone (T)] before and after treatment and ovulation rate and pregnancy rate were compared between 2 groups.Results There were no statistical differences in weight,BMI,FPG,FINS and HOMA-IR in control group between before treatment and after treatment (P ＞ 0.05).The indexes in observation group after treatment were significantly lower than those before treatment [(55.76 ± 2.69) kg vs.(64.42 ± 4.93) kg,(21.52 ± 1.43) kg/m2 vs.(25.74 ± 1.58) kg/m2,(4.46 ± 0.89) mmol/L vs.(5.69 ± 2.01) mmol/L,(12.24 ± 1.82) mU/L vs.(22.88 ± 2.06) mU/L,2.94 ± 1.76 vs.5.27 ± 1.18],there were statistical differences (P＜ 0.05).There were no statistical differences in FSH and E2 in 2 groups between before treatment and after treatment (P ＞ 0.05).There were no statistical differences in LH and T before treatment between 2 groups (P ＞ 0.05),but after treatment were significantly lower than before treatment [control group:(10.33 ±0.57) mU/L vs.(15.63 ± 1.32) mU/L and (1.22 ±0.96) μg/L vs.(2.21 ± 1.24) μ g/L;observation group:(9.07 ± 0.82) mU/L vs.(16.18 ± 1.24) mU/L and (0.71 ± 1.24) μ g/L vs.(2.43 ± 1.52) μ g/L],furthermore the observation group was lower,there were statistical differences (P ＜ 0.05).The ovulation rate and pregnancy rate in observation group were significantly higher than those in control group [78.12％(25/32) vs.53.33％(16/30) and 53.12％(17/32) vs.26.67％(8/30)],there were statistical differences (P ＜ 0.05).Conclusion Ethinylestradiol and cyproterone acetate combined with metformin is more effective on obesity type PCOS,which can improve the ovulation rate and pregnancy rate.

The clinical research of ethinylestradiol and cyproterone acetate combined with metformin in patients with polycystic ovary syndrome / 中国医师进修杂志

Objective To explore the clinical efficacy of ethinylestradiol and cyproterone acetate (Diane-35) combined with mefformin in patients with polycystic ovary syndrome (PCOS).Methods One hundred and sixty patients with PCOS were divided into control group and observation group by random digits table method with 80 cases each.Patients in the control group were given Diane-35 only,while patients in the observation group were given Diane-35 combined with metformin.The triglycerides (TG),total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),fasting insulin (FINS),fasting blood glucose (FBG),follicle-stimulating hormone (FSH),luteinizing hormone (LH) and testosterone (T) of patients in the two groups were measured before treatment and after treatment 6 months,the rates of pregnancy and abortion were recorded.Results TC,LDL-C,FINS,FBG,FSH,LHt and T of both the 2 groups after treatment decreased obviously than before treatment,and TG in observation group decreased obviously than before treatment,there were statistical differences (P ＜ 0.05).There was no statistical difference in TG in control group between before treatment and after treatment (P ＞ 0.05).After treatment,TG,FINS,FBG,LH in observation group were lower than those in control group [(1.0 ± 0.2) mmol/L vs.(1.6 ± 0.8) mmol/L,(15.2 ± 6.3) mU/L vs.(18.9 ± 6.2) mU/L,(4.5 ± 1.1) mmol/L vs.(5.1 ± 0.9) mmol/L,(6.3 ± 3.0) U/L vs.(7.4 ± 2.9) U/L],there were statistical differences (P ＜ 0.05).After treatment,the rate of pregnancy in observation group was higher than that in control group [61.2％(49/80) vs.42.5％(34/80)],there was statistical difference (x2 =5.633,P＜ 0.05).The rote of abortion in observation group was lower than that in control group [6.1％(3/49) vs.17.6％(6/34)],but there was no statistical difference (x2 =1.694,P ＞ 0.05).Conclusion The clinical effect of Diane-35 combined with metformin in patients with PCOS is better than Diane-35 only.

Beneficios no anticonceptivos de 0, 02 mg de etinilestradiol/2 mg de acetato de clormadinona administrados en un régimen de 24+4 días / Non-contraceptive benefits of 0.02 mg ethinylestradiol /2 mg chlormadinone acetate in a 24 +4 days intake regimen

Objetivo: Demostrar la influencia sobre las molestias emocionales y físicas (beneficios no anticonceptivos) experimentadas durante el primer año de uso de un anticonceptivo oral combinado (AOC) que contiene 0,02 mg de etinilestradiol (EE) y 2 mg de acetato de clormadinona (ACM) administrado en un régimen de 24 + 4 días de placebo. Diseño del estudio: Análisis adicional de las sensaciones subjetivas registradas en los diarios de 1665 participantes de un estudio de Fase III multicéntrico, no controlado, de administración múltiple, después de 13 ciclos de EE/ACM en un régimen de administración de 24 + 4 días, publicado previamente. Resultados: Se informó de menor frecuencia de molestias emocionales y físicas en el ciclo de medicación 13 en comparación con los datos en la admisión y en el ciclo 1. La incidencia de ánimo depresivo se redujo en 84,5 por ciento y 72,2 por ciento respectivamente, y la irritabilidad en 87,3 por ciento y 66,0 por ciento. Las cefaleas se redujeron en 75,5 por ciento y 74,7 por ciento, las molestias mamarias en 77,1 por ciento y 66,1 por ciento, y la dismenorrea preexistente en 77,9 por ciento y 67,6 por ciento respectivamente. El abandono prematuro del estudio a causa de las molestias fue marginal, y el perfil del sangrado fue aceptable. Conclusiones: Un AOC de baja dosis que contiene 0,02 mg de EE + 2 mg de ACM, administrado en un régimen de 24 + 4 días, reduce significativamente la mayor parte de las molestias emocionales y físicas que se presentan durante los ciclos espontáneos de las mujeres, y se combina con un adecuado perfil de sangrado.

Objective: To demonstrate the influence on physical and psychological complaints during the first year of intake of the combined oral contraceptive (COC) 0.02 mg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA), administered in a regimen of 24 days of CMA/EE intake followed by 4 days of placebo intake. Study design: The subjective feelings of non-contraceptive benefits registered in women's diaries of 1,665 subjects participating in a multicentre, uncontrolled, multiadministration, Phase III trial, published elsewhere, were analyzed post-hoc after 13 cycles intake of EE/CMA in a 24 +4 days intake regimen. Results: Emotional complaints were reported less frequently at medication cycle 13 compared with admission and cycle 1. Depressive mood was reduced by 84.5 percent and 72.2 percent, irritability by 87.3 percent and 66.0 percent; physical complaints were also reduced: headaches by 75.5 percent and 74.7 percent, breast discomfort by 77.1 percent and 66.1 percent; pre-existing dysmenorrhea by 77.9 percent and 67.6 percent. Premature termination due to complaints was only marginal, the bleeding profile was accepted. Conclusions: The low-dose COC, 0.02 mg EE/2 mg CMA, administered in a 24 +4 day regimen, reduces significantly most of the emotional and physical complaints occurring during spontaneous cycles of women, combined with an adequate bleeding profile.

Clinical assessment of ethinylestradiol and cyproterone acetate in menstrual irregularities of hyper-androgenic origin / Avaliação clínica do uso de duas preparações de etinilestradiol e acetato de ciproterona em menstruação irregular de origem hiperandrogênica

We report on the results of a double-blind, randomized, controlled clinical trial comparing two preparations of ethinylestradiol and cyproterone acetate in the treatment of women of reproductive age presenting menstrual irregularities of hyper-androgenic origin. After obtaining informed consent, subjects were randomized to a 4-month treatment period consisting of one daily dose of 0.035mg ethinylestradiol + 2mg cyproterone acetate. The treatment regimen cycle consisted of one pill, once daily for 21 days, followed by a 7-day pill-free period. We compared the efficacy of two presentations of the drug combination after each treatment cycle (Visits 2, 3, 4, and 5) in establishment and maintenance of menstrual regulation, intensity of menstrual flow, and dysmenorrhea, as well as a comparison of the two presentations in terms of Global Satisfaction and Drug Satisfaction assessments performed by the patients and the investigating physician. At each study visit, drug compliance and use of concomitant medications, as well as incidence, severity and duration of adverse events were recorded. A total of 86 subjects were randomized to treatment, with 43 subjects in each treatment group. At Visit 2 and each subsequent visit, all patients in both treatment groups reported an episode of withdrawal bleeding during the 7-day hormone-free period. We observed a statistically significant (p<0.0001) decrease in the incidence of dysmenorrhea at each study visit in relation to the pretreatment assessment. There was a significant reduction (p<0.0001) in the number of subjects reporting intermenstrual bleeding at each study visit in both treatment groups. Global Satisfaction scores by the patient and physician increased significantly at each successive study visit in both treatment groups. There were no clinically significant changes in vital signs, weight, and body mass index throughout the study period in either group. The number of subjects reporting adverse events at each visit did not vary between treatment groups. The combined oral contraceptive pill containing ethinylestradiol and cyproterone acetate was found to be both effective and safe in the menstrual irregularities of hyper-androgenic origin (amenorrhea, dysmenorrhea, and intermenstrual bleeding) assessed in this study.