Weekly contraception with mifepristone.

OBJECTIVE: The study investigated the contraceptive effect of weekly administration of mifepristone. SUBJECTS AND METHODS: A double-blind, randomized clinical trial with weekly doses of 25 or 50 mg of mifepristone was carried out in three centers in China. Women were assigned to either of two groups. We defined each study cycle as 28 days. All bleeding data were derived from women's menstrual cards. The outcome measures were contraceptive efficacy, changes of menstrual pattern and side effects. RESULTS: Eighty-three women were enrolled and the outcome was known in 76 women: 39 in the 25-mg group and 37 in the 50-mg group. No pregnancy occurred in both groups in 456 women-months of use accumulated. There were no significant differences in mean bleeding days and no bleeding days between the two groups in the first three study cycles. In the fourth, fifth and sixth cycles, mean bleeding days in the 50-mg group (0.86, 1.05 and 0.62, respectively) were significantly less than those in the 25-mg group (3.5, 2.87 and 2.4 respectively); mean no bleeding days in the 50-mg group (26.07, 25.95 and 26.11, respectively) were significantly more than those in the 25-mg group (22.93, 23.23 and 23.51, respectively), and the percentage of women who had no bleeding in a 28-day study cycle in the 50-mg group (22.3%, 25% and 21.1%, respectively) was significantly more than those in the 25-mg group (2.6%, 3.9% and 3.9%, respectively). Side effects, such as nausea and breast distension, were uncommon and mild. CONCLUSION: Once weekly administration with 25-mg mifepristone is a potentially effective method for regular contraception.

Expanded clinical trial of emergency contraception with 10 mg mifepristone.

We conducted a clinical single-arm trial to evaluate the effectiveness of 10 mg mifepristone for emergency contraception (EC) in a large population in China. The participating centers were 31 family-planning clinics and hospitals in the following 19 provinces or municipalities in China: Beijing, Shanghai, Tianjin, Harbin, Changchun, Shengyang, Shijiazhuang, Zhengzhou, Taiyuan, Nanjing, Jinan, Hangzhou, Guangzhou, Wuhan, Changsha, Chongqing, Guiyang, Chengdu, Kunming. A total of 4945 women requesting EC within 120 h after a single act of unprotected intercourse were recruited and treated with 10 mg mifepristone. A total of 28 women were lost to follow-up, and 4917 women were included in the analysis, of whom, 69 became pregnant. The combined pregnancy rate was 1.4 [95% confidence interval (CI): 1.0-1.9] and the percentage of pregnancies prevented was 82.2% (95% CI: 77.5-86.2%). There was a significant inverse trend in pregnancy rate with body mass index that disappeared when adjusted for other variables. The pregnancy risk was double among nulliparous women compared to parous women (2.3% compared to 1.0%), and it increased by a factor of 1.5 when the treatment was administered at 25-48 h and at 49-72 h compared to administration within 24 h, although this association was not significant. The risk of pregnancy was higher if intercourse took place during the follicular or preovulatory phase of the cycle. Women having repeated intercourse after treatment without any contraceptive methods had a dramatic increase in the risk of pregnancy, while those who used contraceptives had similar risk to those without acts. Side effects were mild and present in only small proportions of women: nausea and vomiting in 9% and other side effects in 2-3%. Delay of menstruation of 7 days or more occurred in 6.5% of women. The expanded study confirmed the high efficacy and safety of 10 mg mifepristone for EC.

Luteal phase treatment with mifepristone and misoprostol for fertility regulation.

Emergency contraception (EC) with 10 mg mifepristone can prevent pregnancy up to 5 days after a single act of unprotected intercourse. No methods have been shown to be effective when treatment is administered more than 5 days after a single unprotected act or after several unprotected acts. Therefore, we tested, among 699 Chinese women requesting EC and exposed to the risk of pregnancy described, the potential of 100 mg mifepristone followed 2 days later by 0.4 mg misoprostol orally, when administered in the luteal phase of the cycle. At the time of treatment urinary pregnancy test had to be negative. Despite treatment, 25 women (2.7%) became pregnant. Among women with treatment delayed more than 5 days, the pregnancy rate was related to the number of acts of intercourse before treatment, being 1.4% with one episode and increasing to 6.5% when the number of episodes was two or more (relative risk = 4.62, 95% CI: 1.06-20.18). Side effects within a week after treatment were mild, and most women (57.2%) had menstruation within 3 days as expected. An occasional treatment with mifepristone in combination with misoprostol could provide an option for preventing unwanted pregnancies in women who are late for EC.

Menstrual induction with mifepristone and misoprostol.

Menstrual induction refers to early uterine evacuation without laboratory confirmation of pregnancy in women with delayed menses. Mechanical aspiration is the method used in many countries but, as suggested by a pilot study, mifepristone followed by a prostaglandin analogue could also be effective. We launched the present study to evaluate the efficacy and side effects of 150 mg of mifepristone, followed 2 days later by 0.4 mg misoprostol vaginally, for menstrual induction among women with a menstrual delay of up to 7 days. The outcome of treatment was uterine evacuation, which could mean menstruation or termination of early pregnancy. A total of 720 women were recruited. The mean delay of menstruation at recruitment was 4.9 (SD = 1.7) days. Retrospective analysis of human chorionic gonadotropin from serum samples taken at admission showed that 492 (68.3%) women were pregnant at admission, and 228 (31.7%) women had delayed menstruation without pregnancy. One nonpregnant woman was lost to follow-up. Bleeding was induced in 479 (97.4%) pregnant women and in 222 (97.8%) nonpregnant women. Among the pregnant women, 455 (92.5%) had complete abortion, 12 (2.4%) had incomplete abortion and pregnancy continued in 25 (5.1%) women, including one ectopic pregnancy. Side effects were mild and uncommon. We conclude that 95.8% of the women treated had the expected outcome. Further research is needed to compare the efficacy, safety and acceptability of the medical regimen to vacuum aspiration. A rather high continuing pregnancy rate in this study is a concern.

[Effects of mifepristone of different doses on emergency contraception, a randomized double-blind study].

OBJECTIVE: To compare the effects of mifepristone of different doses on emergency contraception. METHODS: 3,052 healthy women with regular menstrual cycle who visited the 10 family planning institutes and hospitals in Beijing, Shanghai, Shangdong, Sichuan, Tianjin, Guangdong, and Liaoning for emergency contraception within the period of 120 hours after a single act of unprotected sex were given a single dose of 10 mg or 25 mg mifepristone randomly and double-blindly. They were asked to record the vaginal hemorrhage that would occur and not to have unprotected sex until the next menstrual onset when they were followed up. The trial for a specific subject ended when she menstruated. If the menstruation was irregular or a specific subject failed to menstruate on time a blood or urine human chorionic gonadotropin (hCG) test was made. If the hCG test was negative, an appointment was made to follow up once one week later. If the hCG test was positive ultrasound examination was made to detect pregnancy. If the subject still failed to menstruate and the hCG test was still negative follow-up for this subject could be finished. RESULTS: Twenty-two of the 3,052 subjects were lost to follow up. Among the remaining 3,030 women 1,516 were in the 10 mg group and 1 514 in the 25 mg group. Seventeen pregnancies occurred in each group, with a pregnancy rate of 1.1% for both groups. The relative risk of pregnancy of treatment of 25 mg mifepristone in comparison with treatment of 10 mg mifepristone was 1.0 (95% CI: 0.51-1.95). Both doses prevented about 85% approximately 86% of the anticipated pregnancy if no measure had been adopted. The pregnancy rate nearly doubled in the women who had unprotected sex after treatment of mifepristone. The efficacy of mifepristone decreased along with the delay of mifepristone administration. Side effects were uncommon and mild. Delay of 7 days or more in the onset of next menstruation occurred in 9%-10% of the women. CONCLUSION: Mifepristone of the dose of 10 mg is safe and effective for emergency contraception. Earlier administration is preferable, although the method can be used effectively up to five days after the unprotected sex.

Therapeutic effects of the levonorgestrel-releasing intrauterine system in the treatment of idiopathic menorrhagia.

OBJECTIVE: To investigate the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of idiopathic menorrhagia. DESIGN: Measurements of menstrual blood loss (MBL), hemoglobin, and serum ferritin before and after LNG-IUS insertion. SETTING: National Research Institute for Family Planning and Beijing Gynecology and Obstetrics Hospital, Beijing, People's Republic of China. PATIENT(S): Thirty-four patients with MBL over 80 mL. INTERVENTION(S): Insertion of the LNG-IUS on cycle days 5-7 and follow-up at 3-month intervals for 3 years. MAIN OUTCOME MEASURE(S): Measurement of MBL, serum ferritin, and hemoglobin for evaluation of efficacy of treatment. RESULT(S): A significant reduction of MBL to 23.4 mL (78.7% decrease), 26.4 mL (83.8% decrease), 2.7 mL (97.7% decrease), and 13.7 mL (85.0% decrease) at 6, 12, 24, and 36 months, respectively. After 6 months, one-third of the patients experienced amenorrhea, and one-fourth, spotting. Hemoglobin increased significantly from 121.5 g/L preinsertion to 135.5 g/L after 36 months, while serum ferritin levels increased significantly from 21.9 ng/mL before insertion to 92.8 ng/mL after 36 months. In women using the LNG-IUS for 3-4 years, the E2 levels in 20 samples were 239.4 pmol/L, P levels were 11.1 nmol/L, and serum LNG levels were maintained at an average of 511 pmol/L. CONCLUSION(S): The significant reduction of MBL and the increase in hemoglobin and serum ferritin levels in the treatment of menorrhagia with the LNG-IUS has great implications for women's reproductive health, particularly in developing countries.