Progestin implants for female contraception

Four different implants, in the form of capsules or covered rods, that release one of the synthetic progestins levonorgestrel, etonogestrel, Nestorone, or Elcometrine and nomegestrol acetate were reviewed. Biocompatible polymers or copolymers of polydimethyl/polymethylvinyl-siloxanes or ethylvinylacetate are used to hold the steroid crystals and to control the rate of release. Once inserted under the skin, these implants release the corresponding steroid continuously over prolonged periods, a process that can be readily interrupted by implant removal. During long-term use of the implant, the released steroid circulates in blood at a fairly stable level. The physical characteristics of the implants, including drug contents and rate of release, serum levels of the progestin during use, and the duration of their effective life are described. Total steroid loads vary in the range of 50 mg to 216 mg; average release rates are in the range of 30-100 ug/day, and effective lives from 6 months to 7 years.     

Clinical comparative study of oral contraceptives containing 30 microg ethinylestradiol/150 microg levonorgestrel,and 35 microg ethinylestradiol/250 microg norgestimate in Thai women

The study was conducted to compare cycle control, efficacy and side effects of two oral contraceptives containing 30 μg ethinylestradiol (EE)/150 μg levonorgestrel (LNG) and 35 μg ethinylestradiol (EE)/250 μg norgestimate (NGM). An open-label, randomized, comparative study was conducted in which 140 healthy women received the 30 μg EE/150 μg LNG or 35 μg EE/250 μg NGM preparation for six treatment cycles. There were no significant statistical differences between both groups in terms of cycle length and amount of withdrawal bleeding. The mean duration in the 35 μg EE/250 μg NGM group was longer than 30 μg EE/150 μg LNG group with significant statistical difference. More patients in 35 μg EE/250 μg NGM group experienced BTT at each cycle compared with the 30 μg EE/150 μg LNG group, but was not statistically significant. There was no amenorrhea nor pregnancies occurring in either group. No significant changes in body weight or blood pressure were found in both groups. The incidence of adverse events in both groups was low and tended to decrease with time. Statistically significant differences were observed for headache and dizziness, which occurred more in the 30 μg EE/150 μg LNG group. In conclusion, 35 μg EE/250 μg NGM provides reliable contraceptive efficacy. It also provides good cycle control equal to 30 μg EE/150 μg LNG with a lower incidence of minor adverse effects such as headache and dizziness compared to 30 μg EE/150 μg LNG.     

左旋十八甲基炔诺酮新型避孕微胶囊的研制及其药物动力学的评价

本研究用乙交酯丙交酯共聚物（ＰＬＧＡ）为囊材，以左旋十八甲基炔诺酮（ＬＮＧ）为主药，用新工艺合成了几种新型ＬＮＧ微胶囊，并对它们进行了扫描电镜观察、体外释放度及动物（兔）体内释药动力学实验。结果发现，新型ＬＮＧ微胶囊由于其含有一个不含药物的控释层，改变了原来的释药模式，在爆破释放峰后都出现了一个第二释放峰，且这种第二释放峰出现的时相取决于新型微胶囊的粒径即控释层的厚度，它为筛选和控制药物的周期性释放提供了新的模式，展现了广阔前景。     

Prevention of unintended pregnancies by using emergency contraception: the differences between levonorgestrel and ulipristal acetate. A theoretical model using data from a survey on the use of emergency contraception in Spain, 2017

Objective: To estimate the differences in unintended pregnancies avoided using either levonorgestrel (LNG) or ulipristal acetate (UPA) emergency contraception (EC).

Design: Cross-sectional study.

Setting: Survey carried out in Spain.

Participants: 1000 Spanish women reporting unprotected sex in 2017.

Main measurements: EC use, reasons for not using EC, calculation of the number of unintended pregnancies avoided.

Results: 39% of Spanish women having had unprotected sex used EC. 61% of those women did not use EC and 11% did not know the existence of this resource. In 2017 the use of EC prevented 101,271 unintended pregnancies. If instead of using LNG every woman had used UPA another 15,979 additional pregnancies could have been prevented.

Conclusions: If all Spanish women having unprotected sex used EC we could expect a significant decrease in the number of unintended pregnancies and abortions. Using UPA instead of LNG would have a greater impact on that reduction with the corresponding benefit for women and society as a whole.     

复方左旋18甲长效口服避孕药临床观察

1987年7月至1990年7月在北京顺义、丰台、宣武、朝阳四个区县对两种配方的复方长效口服避孕药进行随机分组的临床观察。A组(左旋18甲基炔诺酮6 mg与炔雌醚3 mg配伍)370例,总共服药6560周期;B组(消旋18甲基炔诺酮12 mg与炔雌醚3 mg配伍)362例,总共服药5716周期。二年结果A组的妊娠率3.33/100妇女,累积终止率21.6/100妇女,继续使用率77.79/100妇女。B组妊娠率3.90,累积终止率36.13,继续使用率64.28。在开始服药6月时A组的妊娠率显著低于B组,以后未见明显差异。恶心呕吐、头晕、头疼等副反应的发生率亦明显低于B组。月经周期控制良好。本研究表明左旋18甲基炔诺酮6 mg与CEE 3 mg的配方具有甾体激素总量小、避孕效果肯定、副反应低等优点,可以取代消旋18甲长效避孕药。     

LNG对双室培养的卵巢颗粒细胞和卵泡内膜细胞分泌功能的影响

本文采用羊膜双室培养系统,观察了18甲基炔诺酮(LNG)对猪卵巢颗粒细胞(G-C)和卵泡内膜细胞(T-C)在甾体激素生成过程中的影响。生长在羊膜两侧的G-C和T-C在加入或不加FSH、LH及各种不同浓度LNG的条件下孵育48小时,用RIA测定内、外室培养液中孕酮(P)和雌二醇(E_2)的含量,并与单独培养时的结果相比较。结果表明:①在FSH刺激时,LNG(30、3000nmol/L)明显抑制双室培养的G-C的P和E_2产量:P产量由55.1±3.4μmol/L降为25.8±1.8和20.3±3.8μmol/L;E_2产量由9.35±0.06nmol/L降至5.24±0.64和3.34±0.72nmol/L。但对P和E_2的基础水平无影响。②不论有或无LH刺激,LNG(30、3000nmoL/L)均明显抑制双室培养的T-C的P产量。有LH刺激时,P产量由70.9±6.5μmoL/L分别降为47.1±11.8和4.8±0.5μmol/L;在无LH刺激时,则由26.9±1.7μmol/L分别降至16.9±1.1和5.6±0.9μmol/L。结论:①LNG抑制双室培养中G-C的P和E_2产量,这种抑制作用是通过降低促性腺激素的刺激作用而产生的;②LNG不但抑制T-C的P基础分泌量,而且还表现为降低促性腺激素对P的刺激效应。③双室培养系统模拟了两种卵巢细胞在体时的旁分泌调节作用,与单独培养相比,是研究避孕药对卵巢功能影响的一种更为理想的模型。     

A comparative study of monophasic oral contraceptives containing either drospirenone 3 mg or levonorgestrel 150 microg on premenstrual symptoms

This open-label randomized study compared the effects of two combined oral contraceptives (OCs) containing 3 mg drospirenone (DRSP)/30 microg ethinyl estradiol (EE) with 150 microg levonorgestrel (LNG)/30 microg EE on the prevalence and changes from baseline of premenstrual symptoms after six cycles. The symptoms were measured using the Women's Health Assessment Questionnaire. Subjects receiving DRSP/EE had fewer prevalence of premenstrual symptoms than those receiving LNG/EE after six cycles. A significantly lower score of negative affect category in the premenstrual phase was demonstrated in those receiving DRSP/EE more than LNG/EE. The DRSP/EE group showed a greater improvement of mean scores from baseline in the premenstrual phase compared with those who received LNG/EE on negative affect as seen in the items on anxiety, irritability, feeling sad or blue and weight gain in the category of water retention. In conclusion, OCs containing DRSP have beneficial effects in reducing the prevalence of premenstrual symptoms especially the symptoms of negative affect and weight gain, particularly when compared to LNG/EE. Hence, it should be recommended for women who are susceptible to these adverse symptoms.     

Lipid profile in women over 35 years old using triphasic combined oral contraceptives

Twenty-nine women aged 35 years old or more, using triphasic combined oral contraceptive (COC) were evaluated during six cycles for the following parameters: total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and its subfraction HDL2, triglycerides, apoproteins A and B, Castelli risk index I and II (cholesterol/HDL-C and LDL-C/HDL-C) and apoprotein ratio (apoprotein B/apoprotein A). The same laboratory measurements were done in a control group of 49 non-COC-user women. The results showed that there were no differences on most of the studied parameters between user and nonuser women. There was a significant reduction of HDL-C and HDL2-C, although within the normal range. In addition, it was observed a significant increment of triglycerides and apoprotein B at 6 months of follow-up only in user group (p < 0.05), although within the normal range. It is concluded that the use of levonorgestrel triphasic COC appeared to have no additional adverse impact when used by women aged over 35 years. Further studies are needed to obtain conclusive data.     

Effect of long-term progestin treatment on endometrial vasculature in normal cycling mice

The aim of this study was to develop a mouse model to investigate the effects of long-term progestin-only exposure on endometrial vascular structure. Normal cycling mice received Silastic implants containing either medroxyprogesterone acetate (MPA) or levonorgestrel (LNG) and were dissected after 1, 3 or 6 weeks. Endometrial vascular density increased significantly within 1 week of MPA (482 +/- 40.2 vessels/mm2) or LNG (440 +/- 26.5 vessels/mm2) treatment compared with normal cycling mice (293 +/- 10.5 vessels/mm2). MPA increased stromal cell density within 1 week of treatment (13813 +/- 1450 cells/mm2) compared with normal cycling mice (8256 +/- 928 cells/mm2). However, although LNG significantly increased stromal cell density overall, the increase did not reach significance within the individual weeks examined. There was no significant change in the ratio of vascular to stromal cell density among treated and normal cycling mice. Epithelial cell height significantly decreased within 1 week of LNG (17.6 +/- 1.3 microm) treatment compared with normal cycling mice (23.5 +/- 1.3 microm); epithelial cell height also decreased within 1 week of MPA treatment (16.6 +/- 2.1 microm), although this did not reach statistical significance. VEGF immunostaining increased significantly in luminal epithelium after MPA or LNG treatment, and in glandular epithelium after LNG treatment. These observations are similar to those reported in human endometrium, suggesting that this mouse model may facilitate further investigations into breakthrough bleeding due to long-term progestin use.     

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.