Clinical observation of combined oral contraceptives drospirenone and ethinylestradiol tablets (Ⅱ) in the treatment of dysmenorrhea in Chinese women / 中华妇产科杂志

Objective:To evaluate the efficacy and safety of drospirenone and ethinylestradiol tablets (Ⅱ) in Chinese women with dysmenorrhea.Methods:This was a single-arm, open-label, interventional, multicenter, post-authorization safety/effectiveness study of drospirenone and ethinylestradiol tablets (Ⅱ) across 6 treatment cycles, a total of 526 patients were included in the dysmenorrhea subgroup. Visual analog scale (VAS) was used to assess the severity of menstrual pain. Secondary outcomes included unintended pregnancies, bleeding pattern, cycle control and safety.Results:After treated with drospirenone and ethinylestradiol tablets (Ⅱ), VAS of pain had decreased significantly compared with baselines [(49.5±23.7) vs (32.3±24.9) vs (20.7±19.4) vs (18.4±18.7) mm, P<0.01]. From the second cycle to the fifth cycle, the incidence of scheduled bleeding increased from 93.9% (450/479) to 96.4% (431/447). The duration of scheduled bleeding decreased from (5.7±2.7) to (5.4±1.8) days. The incidence of intermenstrual bleeding decreased from 9.0% (43/479) to 5.6% (25/447). 17.5% (92/526) patients reported adverse drug reactions, most frequently reported adverse events were breast pain, nausea, breast swelling, headache, and uterine bleeding. No death occurred during the study. Conclusion:Drospirenone and ethinylestradiol tablets (Ⅱ) is effective for the treatment of dysmenorrhea and has good safety.

Clinical effect of ethinyl estradiol cyproterone tablets combined with ovulation induction in the treatment of polycystic ovary syndrome infertility / 中国基层医药

Objective To explore the clinical effect of ethinyl estradiol cyproterone tablets ( Diane -35 ) combined with ovulation induction in the treatment of polycystic ovary syndrome infertility .Methods 70 patients with polycystic ovary syndrome were enrolled , and they were randomly divided into two groups according to the random number table of the computer ,35 cases in each group .The control group was treated with Diane -35,the observation group was given ovulation induction .The clinical parameters ,vaginal ultrasound results ,cycle ovulation rate ,pregnancy rate,adverse reaction rate and quality of life were compared between the two groups .Results There were no statistically significant differences in uterine volume , intima thickness , bilateral ovarian volume and bilateral follicle number between the two groups after treatment (t=0.055,0.308,0.991,0.435,0.473,0.248,all P>0.05).The cycle ovulation rate of the observation group was significantly higher than that of the control group (80.88％ vs. 54.05％,χ2 =8.451,P<0.01).The shape,color,thought and energy score of the observation group were significantly higher than those of the control group (t=4.819,3.519,4.735,6.804,all P<0.01).The pregnancy rate of the observation group was significantly higher than that of the control group (25.71％vs.5.71％,χ2 =5.285,P<0.05). Conclusion Diane-35 combined with ovulation induction in the treatment of polycystic ovary syndrome infertility has significant clinical efficacy .

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.

High-sensitivity simultaneous liquid chromatography-tandem mass spectrometry assay of ethinyl estradiol and levonorgestrel in human plasma / 药物分析学报

A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v) solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C18 (50 mm × 4.6 mm, 2.6μm) column with a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.

Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 μg in the treatment of premenstrual dysphoric disorder：a randomized, double blind placebo-controlled study / 中华妇产科杂志

Objective To compare the efficacy and safety of a new low-dose oral contraceptive pill (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 μg with placebo in reducing symptoms of premenstrual dysphoric disorder (PMDD). Methods This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles (84 days) with daily symptom charting; 187 women with symptoms of PMDD were randomized to either placebo group (n=94) or YAZ group (n=93), and assessed with daily record of severity of problems scale (DRSP) and clinical global impressions scale (CGI) before, during and after the treatments. Hormones were administered for 24 days, followed by 4 days of inactive pills. Results Compared with baseline level of DRSP, both groups got improvement after treatment; the YAZ group (median-28.7, range:-82.5 to 2.3) had greater improvement than that in the placebo group (median-23.7, range:-86.0 to 11.8), while there was not significant difference (P>0.05). The main adverse effects of YAZ included intermenstrual bleeding [13% (12/93) versus 3% (3/94)], menorrhagia [9% (8/93) versus 1%(1/94)], nausea [5%(5/93) versus 4%(4/94)] and skin rash [4%(4/93) versus 2%(2/94)]. Conclusions YAZ could improve symptoms of PMDD better than placebo, while without statistic significance in this study. The most common adverse effects are intermenstrual bleeding, menorrhagia, nausea and rash.

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.