RP-HPLC method for determination of norethindrone in dissolution media and application to study release from a controlled release nanoparticulate liquid medicated formulation

Several methods are available for the determination of norethindrone. These methods are either complicated or needvalidation. The objective of this work was to develop and validate a simple reversed phase-high performance liquidchromatographic method for the determination of norethindrone in dissolution media. A Thermo Scientific C18column (250 mm × 4.6 mm ID, 5 µm pore size) was used. A mobile phase consisting of deionized water: acetonitrile(50:50, v/v) and 5 ml/l acetic acid was used. The flow rate was 1.3 ml/minute and the wavelength of the detectionwas 245 nm. Validation of linearity, accuracy and precision, limit of detection, limit of quantification, specificity, andstability (degradation) was carried out according to the International Conference on Harmonization guidelines. Thedeveloped and validated method was used to study norethindrone release from a nanoparticulate liquid medicatedformulation (LMF). The results indicated that the method was simple, accurate and precise, and met the acceptancecriteria. The drug exhibited higher stability in basic media when compared to acidic media. Drug release from a LMF(nanoemulsion) followed zero order kinetics. In conclusion, a simple method was developed, validated, and usedsuccessfully in evaluating in vitro drug release from a sustained release/controlled release nanoparticulate LMF.

Clinical effect of Ejiao Huangqi oral liquid combined with norethisterone in treatment of dysfunctional uterine bleeding and its effect on improving anemia / 中国基层医药

Objective To observe the clinical effect of Ejiao Huangqi oral liquid combined with norethis-terone in treating dysfunctional uterine bleeding and its effect on improving anemia .Methods 100 patients with dysfunctional uterine bleeding were randomly divided into study group ( 50 cases ) and control group ( 50 cases ) according to the order of admission .The control group was given oral norethindrone treatment ,the study group was given Ejiao Huangqi oral liquid on the basis of the control group ,10mL per time,2 times a day.Both two groups were treated for 3 menstrual cycles.The fasting blood samples were taken to test the red blood cells (RBC) and hemoglobin(Hb). All patients were followed up for 3 months to evaluate clinical efficacy .Results The levels of RBC and Hb in the study group and control group were (3.05 ±0.58) ×1012/L and (3.67 ±0.65) ×1012/L,(86.75 ±6.30) g/L and (97.95 ±6.53) g/L,respectively,which were significantly higher than those before treatment (all P<0.05).The levels of RBC and Hb in the study group were significantly higher than those in the control group (P<0.05).The total effective rate of the study group was 92％(46/50),which was significantly higher than that of the control group [84％(42/50)],the difference was statistically significant (Z=-3.334,P<0.01).Conclusion Ejiao Huangqi oral liquid combined with norethisterone has exact effect in treating dysfunctional uterine bleeding , can quickly stop bleeding,improve the symptoms of anemia ,improve the clinical treatment effect ,which is worthy of clinical use .

Effect of norethindrone combined with mifepristone in the treatment of menopausal dysfunctional uterine bleeding / 中国基层医药

Objective To explore the effect of norethindrone combined with mifepristone in the treatment of menopausal transition period of functional uterine bleeding.Methods A total of 100 patients with dysfunctional uterine bleeding after menopause were selected.The patients were randomly divided into two groups by computer,50 patients in each group,the control group and the observation group were treated with norethindrone and norethisterone combined with mifepristone.Results The endometrial thickness [(5.69 ± 1.57)mm],incidence rate of adverse event (2.00％),recurrent bleeding (0.00％),total effective rate (98.00％),FSH[(6.48 ± 1.47) IU/L],LH[(8.24 ±2.65)IU/L],P[(1.32 ±0.12) nmol/L] and E2[(152.48 ±2.51)pmol/L] in the observation group were significantly better than those in the control group [(10.35 ± 1.85) mm,24.00％,18.00％,70.00％,(9.65 ± 2.85) IU/L,(6.41 ±1.05)IU/L,(3.41 ±1.69)nmol/L,(405.36 ±8.95)pmol/L,t =13.580,x2 =10.698,x2 =9.890,x2 =14.583,t =6.990,t =4.539,t =8.722,t =192.369,all P ＜0.05).Conclusion Norethindrone combined with mifepristone in the treatment of menopausal transition dysfunctional uterine bleeding patients has significant effect.

Effects of medroxyprogesterone acetate and compound norethisterone enanthate on the susceptibility of BABL/c mice to lower reproductive tract infection with Chlamydia trachomatis / 中华皮肤科杂志

Objective To compare the effects of medroxyprogesterone acetate (MPA) and compound norethisterone enanthate (CNE) on the susceptibility of BABL/c mice to lower reproductive tract infection with chlamydia trachomatis (Ct). Methods A total of 60 BALB/c mice were randomly and equally divided into 6 groups:MPA-pretreated control group and CNE-pretreated control group inoculated with MyCoy cell suspensions in the vagina on the 5th day after single treatment with MPA and CNE respectively, blank control group receiving no treatment, MPA-pretreated infected group and CNE-pretreated infected group inoculated with 1 × 107 inclusion-forming units(IFU)of Ct serovar E in the vagina on the 5th day after single treatment with MPA and CNE respectively, control infected group inoculated with the same quantity of IFU of Ct serovar E in the vagina but receiving no pretreatment. On day 4, 7 and 14 after inoculation, vaginal irrigation fluid was obtained from all the mice for cell culture of Ct. Three mice were randomly selected from each of these groups at the above three time points and sacrificed, and vaginal and uterine tissue specimens were obtained for hematoxylin-eosin(HE)staining and microscopic examination. Chi-square test and Fisher's exact test were conducted to compare infection rate among different groups. Results No growth of Ct was observed in the three control groups at the above time points. The culture-positive rate of Ct was 1/10 on day 4 but 0 on day 7 and 14 in both the CNE-pretreated infected group and control infected group, 7/10 on day 4, 2/7 on day 7 but 0 on day 14 in the MPA-pretreated infected group. Fisher's exact test revealed that the culture-positive rate of Ct was significantly higher in the MPA-pretreated infected group than in the control infected group and CNE-pretreated infected group on day 4 (both P =0.03), but similar among the three infected groups on day 7 (P = 0.23). Both the MPA-pretreated control group and infected group showed an increase in endovaginal mucus, thinning of vaginal stratified squamous epithelium, mucification of vaginal epithelium, presence of secretions in vaginal lumen and submucosal infiltration of a few inflammatory cells on day 4, 7 and 14, as well as appearance of pathological changes (including the presence of large quantities of purulent secretions in lumen, mild tissue edema and submucosal infiltration of a few inflammatory cells) in the vagina on day 4. Vaginal tissues were normal in both the CNE-pretreated infected group and control group at the above three time points, but mild tissue edema, lumen expansion, secretion retention and infiltration of scattered inflammatory cells were observed in the uterus on day 4 after inoculation. Conclusions MPA can arrest the estrous cycle of mice at diestrus with the mucification of vaginal epithelium, which may increase the susceptibility to Ct vaginal infection in mice. In contrast, CNE has no obvious effect on the estrous cycle and susceptibility to Ct vaginal infection despite of the appearance of pathological changes in the uterus.

Norethindrone-induced masculinization and progeny testing in guppy, Poecilia reticulata (Peters 1859).

Norethindrone(NE) was evaluated for its efficacy on alteration of sex ratio of P. reticulata. Either the young fry or the brooders and the resultant fry were fed a commercial diet incorporated with NE at 0, 25, 50, 75 and 100 mg kg-1 diet (ppm) for 30-40 d in rectangular glass aquaria; this was followed by 40-60 d rearing on NE-free diet in out-door concrete tanks. In general, the androgen treatment altered sex ratio, leading to the production of a dose dependent increase in the percentage of males. The oral administration of the steroid at 75 ppm for 40 d or 100 ppmfor 30 or 40 d to first feeding fry, yielded 100% males. On the other hand, NE administration to brooders before parturition and the resultant fry also produced an all-male population of guppy. The sex ratio of the untreated control was almost 1:1. The survival of fish in all the trials was high, ranging between 67 and 100%. Mating masculinized males (“XX” male) with normal female resulted in an all-female progeny, while crossing normal male (XY) from treatment groups with normal female sired normal sex ratio (1:1), elucidating XX-XY sex determination system in the guppy.

A multicenter prospective randomized open comparative study on the treatment of ovulatory menorrhagia with tranexamic acid and norethisterone in China / 中华妇产科杂志

Objective To compare the efficacy and safety of tranexamic acid(TA)and norethisterone(NET)for the treatment of patients with ovulatory menorrhagia in China. Methods Onehundred and thirty one patients with proven ovulatory menorrhagia from gynecologic clinics of 5 teaching hospitals located in 4 different cities in China were enrolled during Jul 2004 to Dec 2006.Ameng them 128 completed the study.Patients were randomly divided into two therapeutic regimen groups:TA 1g thrice daily during menstrual cycle days(D)1-5,69 cases;or NET 5 mg twice daily on D19-26.59 cases.The drugs were administered for 2 consecutive cycles,then withdrawn and patients were followed-up for 1 more cycle.Data on menstrual blood loss [ estimated by pictorial blood assessment chart(PBAC)],length of menstrual periods,quality of life(QOL)evaluated by a 6 item health-related questionnaire were collectedbefore,during each cycle and were compared.Results Both treatments led to significant decreases of mean PBAC scores and shorter duration of menstrual periods,and improved the QOL ranking during the twotreatment cycles.The mean percentages of PBAC decrements in the TA first and second cycles were significantly greater than those in the NET corresponding cycles(35%VS 17%,P=0.004;4J4%VS 34%,P=0.04 respectively).The success rate of TA second cycle was higher than that of the NET second cycle (41%VS 24%,P=0.04).Improvement of QOL ranking in the TA first cycle was also significantly better than those in the NET first cycle ( P=0.03).The percentage of patients with at least 1 adverse event in TA group(19%)was significantly lower than that in NET group(35%,P=0.04).Patients'willingness tocontinue the treatment in the TA second and follow-up cycles(94%,79%respectively)were significantly higher than those in the corresponding cycles of NET groups(79%,59%respectively;P=0.01,P=0.02).Conclusion The regimen of TA 3 g daily during menstrual days 1-5 is a more effective and tolerable treatment than luteal phase norethisterone for patients with ovulatory menorrhagia.

Avaliação do tratamento hormonal e/ou intervencionista por punção nos tumores císticos de ovários / Evaluation of hormonal treatment and/or intervention through aspiration of ovarian cystic tumors

Objetivo: O objetivo deste estudo foi avaliar em mulheres com tumores císticos de ovário, a proporção que, somente com o tratamento clínico e/ou punção, não necessitaram de cirurgia; a influência da medicação e das doenças associadas na indicação de cirurgia e se a punção reduziu significativamente o tamanho dos cistos. Casuística e métodos: Selecionaram-se 71 mulheres com idade entre 19 e 70 anos de idade, portadoras de tumores císticos de ovário maior que 5 cm, com características de benignidade ao ultra-som transvaginal com Doppler colorido e pulsado e com perfil endócrino e marcadores séricos tumorais normais. Foram divididas em cinco grupos: 1) Grupo A: 15 mulheres que fizeram uso de acetato de noretisterona; 2) Grupo B: 13 mulheres que fizeram uso de acetato de medroxiprogesterona; 3) Grupo C: 14 mulheres que utilizaram contraceptivo oral; 4) Grupo D: 15 mulheres que foram tratadas com análogo de GnRH e 5) Grupo E: 14 mulheres que não fizeram uso de medicação. Todos os grupos foram acompanhados por um ano. No final do primeiro trimestre, se o cisto persistiu, foi realizada a punção. No final do segundo trimestre, se houve recidiva do cisto, foi indicada cirurgia. As pacientes tiveram alta após um ano de acompanhamento com o tratamento do cisto concluído. Resultados: Não houve diferenças significantes entre os cinco grupos. Constatou-se que a condição de uso de medicação para doença associada teve influência significativa no resultado dos tratamentos. Verificou-se que a redução do tamanho do cisto com a punção foi efetiva após 9 meses de acompanhamento. Observou-se que 7% das mulheres tiveram indicação direta para cirurgia sem a punção, portanto, a proporção de recidiva da punção foi de 19,3% enquanto a porcentagem de mulheres que não fizeram a cirurgia foi de 73,2%. Conclusão: A proporção de mulheres que responderam adequadamente somente com o tratamento clínico e/ou a punção, não necessitando pois de cirurgia foi de 73,2%...

Objectives: To evaluate the rate of women with ovarian cystic tumors submitted to diferent regimens of hormonal treatment and/or aspiration that didn’t need surgery. To access the effectiveness of ovarian cyst aspiration guided by ultrasonography (USG) and to study the influence of medication and associated diseases in the need for surgery. Patients and Methods: Seventy one (71) women, in an age range from 19 to 70 years, diagnosed with ovarian cysts larger than 5 cm in length, with benign aspect, examined using an ultrasonographic transvaginal probe and color Doppler. All the women have been submitted to measurements of ser um tumor markers and hormonal levels. They were grouped in five different categories: 1) Group A: 15 women treated with noretisterone acetate; 2) Group B: 13 subjects treated with medrooxiprogesterone acetate; 3) Group C: 14 patients treated with combined oral contraceptive; 4) Group D: 15 women treated with GnRH analog, and 5) Group E: 15 women with no treatment control). After 3 months, all the patients were reevaluated. In those ones whose cysts remained, cyst aspiration guided by ultrasonography was indicated. After 3 extra months, the women were submitted to a new USG examination and in those whose cysts still remained, surgery was performed. All the patients were followed for one year. Results: There was no significant difference among the groups of hormonal treatment. The use of medication promoted a significant influence in the treatment outcomes. We also noted that the cyst aspiration was effective in reducing the size of the cysts after 9 months of follow up. Seven per cent (7%) of the patients have had immediate indication for surgery. Among those who was submitted to cyst aspiration, 19.3% had to be resubmitted to treatment because of re-incidence of the cyst, whereas, 73.2% avoid the need for surgery. Conclusions: The proportion of subjects treated with hormones and/or cyst aspiration, with no need for surgery, was of 73.2%...

Clinical observation of effect of mifepristone combined with norethindrone in treating dysfunctional uterine bleeding of peri-menopause / 中国基层医药

Objective To analyze the efficiency of mifepristone combined with norethindrone in treating dysfunctional uterine bleeding of peri-menopause. Methods 56 patients with dysfunctional uterine bleeding of peri-menopause were randomly divided into two groups, the study group(30 cases) and the comparision group(26 cases). The patients in the study group were treated with mifepristone in small doses combined with norethindrone. And the patients in the comparision group were treated only with norethindrone. Before treating, all the patients were observed and measured symptom of dysfunctional uterine bleeding, blood routine,the function of liver and ren.the en-dometrial thickness and pelvic by ultrasonography. Through hysteroscopy or uterine curettage of diagnosis, en-dometriums were measured by pathology. Results 26 cases in the study group were evaluated as effective,2 cases as obviously effective,and 2 cases as no effective. In the comparision group, 10 patients were evalutated as effective,8 patients as obviously effective,8 patients as no effective. The total effective rates of study group was significantly higher than those of comparison group(P

Long-term Effects of Low-dose Combined Norethisterone and Combined 18-metayl-Norethisterone on Lipid Metabolism in Healthy Women / 中华妇产科杂志

Objective To assess the long term effects of combined oral contraceptive pills use on the mean of serum TG, TC, HDL C, LDL C, ApoA1, ApoB and Lp(a). Methods The study was carried out in 446 women grouped as combined norethisterone containing ethinylestradiol (EE) 35 ?g and norethisterone 625 ?g; combined 18 metayl norethisterone (norgestrel) containing EE 30 ?g and 18 metayl norethisterone 300 ?g for using 5～25 years, and control subjects wearing IUD for the corresponding period. The three groups were similar in age, body mass index (BMI), continued period of contraceptives use and income. Results The data showed that changes of varying degree of lipid and lipoprotein parameters were obvious in women of long term taking low dose combined norethisterone and norgestrel, compared with the control. The mean of TG, HDL C, ApoA1 were significantly increased simultaneously ( P