止血凝胶气囊在功能失调性子宫出血中的临床应用

目的探讨止血凝胶气囊压迫止血治疗功能失调性子宫出血的临床效果。方法选择2009年1月～2011年12月治疗的功血患者共94例,试验组50例,在刮宫术后于宫腔内放置止血凝胶气囊压迫止血24h,并从当天起每天口服去氧孕烯炔雌醇片（妈富隆）1片,连服21d停药,对照组44例于刮宫术后同法服用妈富隆,观察两组72h内的阴道流血情况。结果试验组24h及48h出血量明显小于对照组,差异有统计学意义;72h完全止血的患者两组问无统计学意义。结论刮宫术后于宫腔放置止血凝胶气囊短时间内（48h）有明显止血效果,但对于后期止血无明显意义,临床上对于出血量大,贫血症状明显,需要立即止血患者有使用价值。     

Effects of oral contraceptive combinations containing levonorgestrel or desogestrel on serum proteins and androgen binding

The effects of the oral contraceptive combinations 0.125 mg Org 2969 (desogestrel) (13-ethyl-11-methylene-18, 19-dinor-17α-pregn-4-en-20-yn-17—01) + 0.05 mg ethinyloestradiol (EE) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin (SHBG), ceruloplasmin, transcortin and ratio free testosterone over total testosterone (percentage free testosterone) and ratio free 5α-dihydrotestosterone over total 5α-dihydrotestosterone (percentage free 5α-dihydrotestosterone) were compared in healthy female volunteers.

Treatment was randomly distributed over the volunteers; 11 women received Org 2969 + EE and 11 women received levonorgestrel + EE. These combinations induced similar increases in transcortin levels (115 and 140%) and ceruloplasmin levels (115 and 123 %) after 3 months of treatment. However, the combination Org 2969 + EE induced a substantial increase (213%) in SHBG capacity after 3 months of treatment, whereas a smaller increase (80%) was observed with levonorgestrel + EE. A return to pretreatment values was observed 2 months after termination of treatment for all parameters. The difference in the effects of both preparations on SHBG was statistically significant and can be best explained by a difference in the androgenicity of the progestogens. A good correlation was observed between SHBG capacity and the reciprocal value of the percentage free testosterone and the reciprocal value of the percentage free 5α-dihydro-testosterone. These results confirm that SHBG is the major regulator of the biologically active free androgen fraction in women before, during and after combined oral contraceptive treatment.     

口服地索高诺酮联用睾酮皮下埋植抑制精子发生的临床研究

目的　研究口服地索高诺酮 (DSG ,第三代孕激素 )联用睾酮皮下埋植对精子发生的抑制作用。方法　将 36例研究对象随机分成口服DSG 15 0 μg组和 30 0 μg组 ,对象于治疗前期、治疗后 2周、4周以及以后每隔 4周随访 1次 ,测量睾丸体积、血压、体重 ,留取精液、尿液和血标本。性激素、精液的分析每 4周 1次 ,临床生化和血液学筛查每 12周 1次。结果　达到无精子的有效率为 90 % ,两组差异无显著性 ,平均起效时间为 (12 .15± 6 .2 2 )周 ,30 0 μg组起效快 ,停药后精子计数能恢复至正常值范围 ;DSG对睾酮产生有抑制作用 ,但仍在正常值范围 ,停药后睾酮值恢复较慢 ;用药后体重、高密度脂蛋白 (HDL)、总胆固醇 (TC)、低密度脂蛋白 (LDL)均有不同程度的增加 ,无其它明显不良反应。结论　口服地索高诺酮联用睾酮皮埋对精子发生有明显的抑制作用 ,使用中未发现明显的不良反应     

A double-blind study comparing the contraceptive efficacy,acceptability and safety of two progestogen-only pills containing desogestrel 75 μg/day or levonorgestrel 30 μg/day: Collaborative Study Group on the Desogestrel-containing Progestogen-only Pill

Objective To compare the contraceptive efficacy, bleeding pattern, acceptability and safety of desogestrel 75 μg/day (Cerazette®) as a progestogen-only formulation to levonorgestrel 30 μg/day in healthy female subjects.

Methods In a double-blind, randomized, group-comparative, multicenter trial, 989 subjects were randomized to desogestrel 75 μg/day and 331 to levonorgestrel 30 μg/day. The women were observed during 13 consecutive treatment periods of 28 days.

Results The Pearl indices for in-treatment pregnancies, excluding gross non-compliance, were 0.14 (one pregnancy in 727 woman-years) in the desogestrel group and 1.17 (three pregnancies in 257 woman-years) in the levonorgestrel group. Using the 90-day reference period for assessing the bleeding pattern, desogestrel users had a higher incidence of amenorrhea and infrequent bleeding on the one hand, and of frequent bleeding and prolonged bleeding on the other hand, at the beginning of the study period. In contrast to the levonorgestrel group, a tendency towards less bleeding over time was observed in the desogestrel group. The frequency and pattern of adverse experiences were comparable for desogestrel 75 μg/day and levonorgestrel 30 μg/day.

Conclusions Desogestrel 75 μg/day is a reliable and safe progestogen-only pill with a contraceptive efficacy superior to levonorgestrel 30 μg/day. There was a similar overall acceptability of desogestrel 75 μg/day and levonorgestrel 30 μg/day.     

The effects of seven monophasic oral contraceptive regimens on hemostatic variables: conclusions from a large randomized multicenter study

We investigated the effects of ethinylestradiol dose (50, 30 and 20 μg) and progestogen type [desogestrel (DSG), gestodene (GSD), levonorgestrel (LNG) and norgestimate (NGM)] in oral contraceptives on 24 hemostatic variables. In a multicenter, randomized, comparative study, 707 healthy, nonsmoking, nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested. Significantly greater increases in prothrombin fragment 1+2 and factor VII (activity and antigen), were found in the DSG, NGM and GSD groups compared to the LNG group. Similarly, significantly lower levels of protein S (free and total) and increased APC-sr (endogenous thrombin potential based) were found in the same groups compared with the LNG group. In addition, the estradiol dose (50 vs. 30 μg) significantly influenced these parameters. All changes were within the normal range and have not been associated with an increased risk of venous thromboembolic event (VTE). However, raised levels of these variables are associated with prothrombotic states such as pregnancy. The significance of the haemostatic changes found in this study in relation to VTE risk remains to be determined, but results of this study probably cannot explain the differences in risk of VTE between OCs containing different progestogens.     

Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue

BACKGROUND: The aim of this study was to compare in vitro the role of two oral contraceptives, desogestrel (a less androgenic derivative of levonorgestrel) and levonorgestrel--alone and in combination with ethinyl estradiol--on low-density lipoprotein (LDL) receptor regulation by assessing receptor protein expression and functional effectiveness. STUDY DESIGN: Placental tissue and cultured placental cells (JEG-3) were used to study the expression and endocytotic activity of LDL receptor protein. The expression of the receptor was assessed by immunocytochemistry and immunoblot assays with and without contraceptive challenge. Functioning activity of LDL receptor was studied by measuring the rate of uptake of LDL by placental cells. Quantification of LDL was based on the total cholesterol content of the lipoprotein. RESULTS: A combination of desogestrel (20 ng/mL of incubation medium) and ethinyl estradiol (10 ng/mL of incubation medium) maintained the LDL receptor at high level of expression and functioning mode. In contrast, the double-blind preparation of levonorgestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL) had shown much lower expression as well as receptor-mediated LDL uptake. The concentration of contraceptives used in this study was similar to the prevailing concentration of oral contraceptives in clinical use. CONCLUSION: Higher expression of LDL receptor and enhanced rate of LDL uptake by the receptor protein projects the possibility that there might be less atherosclerosis-related disorders from the combination of desogestrol and ethinyl estradiol.     

Coeliac axis thrombosis associated with the combined oral contraceptive pill: a rare cause of an acute abdomen

We report a case of coeliac axis thrombosis and splenic infarction presenting in a girl of 14 years who had been on the oral contraceptive pill (OCP), Marvelon (ethinyloestradiol 30 μg plus desogestrel 150 μg, Organon, Cambridge, UK), for 3 weeks. She had no other risk factors for thrombo-embolism. Diagnosis was made with duplex Doppler ultrasound and confirmed with dynamically-enhanced comput‐ed tomography and magnetic resonance angiography, thus avoiding the need for percutaneous arteriography. Though mesenteric thrombo-embolic disease is recognised in association with use of the combined OCP, it has not previously been reported to affect the coeliac axis. Paediatricians and surgeons should be aware of the risks to young girls on the OCP, and consider it in their differential diagnosis of the acute abdomen. Accepted: 4 April 1997     

Reciprocal coordination of a combination oral contraceptive containing desogestrel+ethinyl estradiol on the expression of LOX-1 and LDLR in placental trophoblast cells

Background

The aim of this study was to assess the consistency of antiatherosclerotic potential of a combination oral contraceptive steroid (ethinyl estradiol+desogestrel) by rating its effect on the differential expression of the low-density lipoprotein receptor (LDLR) and lectin-like oxidized LDL (LOX-1) receptor.

Study Design

Cells from placental trophoblast cell line (JAR) and differentiated primary placental trophoblast cells isolated from term human placentae were used for this study. Expressions of LOX-1 and LDLR were assessed by immunoblot and immunocytochemistry assays. Differential effects of the constituent steroids in the combination of ethinyl estradiol and desogestrel were verified on the expression profile of the receptors.

Results

Desogestrel opposed the effect of ethinyl estradiol on LOX-1 expression, and when used in combination, the combination oral contraceptive reduced the expression of LOX-1 in contrast to LDLR. The characteristic change in the expressions of LOX-1 and LDLR showed an antiatherosclerotic improvisation at the unique combination of ethinyl estradiol (10 ng/mL) and desogestrel (20 ng/mL).

Conclusion

The aforesaid combination of ethinyl estradiol and desogestrel keeps LOX-1 and LDLR reciprocally expressed in antiatherosclerotic mode.     

Effects of an estrogen-free, desogestrel-containing oral contraceptive in women with migraine with aura: a prospective diary-based pilot study

Background

Migraine with aura (MA) is a contraindication to the use of combined oral contraceptives (COCs) because of the increased risk of ischemic stroke. Progestogen-only contraceptive pill (POP) is a safe alternative to COCs and it is preferable in women with cerebrovascular diseases or risk factors for stroke.

Study Design

Prospective diary-based pilot study. Thirty women with MA (n=15 who have never used COCs and n=15 who had previously used COCs were diagnosed according to the International Headache Society criteria. The observational period lasted 9 months during which women filled in a diary with the clinical characteristics of headache attacks. After a 3-month run-in period, each subject received an estrogen-free desogestrel (DSG) (75 mcg/day)-containing OC (Cerazette®; Schering-Plough, formerly NV Organon, Oss, The Netherlands). Follow-up evaluations were planned at the end of the third and sixth month of treatment.

Results

The number (mean±S.D.) of migraine attacks was significantly reduced both in previous COCs users (from 3.9±1.0 to 2.9±0.8; p<.001) and nonusers (from 3.2±0.9 to 2.6±1.3; p<.02) following 6 months of POP use in comparison with the run-in period. Duration of headache pain did not differ significantly in both groups throughout the study. Interestingly enough, a beneficial POP effect on the duration (mean±S.D.) of visual aura (from 16.3±9.5 to 11.4±5.6 min) and on the total duration (mean±S.D.) of neurological symptoms (from 33.6±23.3 to 18.6±18.0 min) was only significantly reported by previous COCs users (p<.001, for both) by the end of the study period. The POP was well tolerated by each woman and the bleeding pattern was variable with a tendency towards infrequent bleeding.

Conclusions

The present study supports the use of the POP containing desogestrel in a population of women with MA and underlines a positive effect on symptoms of aura, especially in MA sensitive to previous use of COCs.     

Randomized, Crossover and Single-Dose Bioquivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 μg) in Healthy Female Volunteers

Despite the increase in the substitution of branded medicinal product with generic drugs, this is a controversial issue for some pharmacological groups (such as contraceptives).The aim of the present clinical trial was to assess the bioequivalence and tolerability of two oral formulations of desogestrel.Thirty-three healthy female volunteers participated in this randomized and two-way crossover study. During two separate experimental periods, with at least four weeks of washout period, women received a single oral dose of 75 μg of desogestrel from each of the formulations (test formulation and reference formulation). Desogestrel bioavailability was determined by the measurement of 3-ketodesogestrel plasma concentration.Pharmacokinetic parameters were comparable and the 90% CI for the ratio of C_max (96.14–114.53%) and AUC_0–t (105.73–123.83%) values for the test and reference formulations fell within the established regulatory interval (80–125%). Both formulations were also comparable in terms of tolerability.From the results of this study it can be concluded that test formulation (desogestrel 75 μg, Cyndea PHARMA S.L.) is bioequivalent to the reference formulation (Cerazet® 75 μg, Organon Española S.A.).