Post-marketing Surveillance And Evaluation Of Contraceptives Among Rural Women In Jangsu Province

Contraceptives are a special series of drugs and medical devices used for contraception (interference or blocking pregnancy process) in order to birth control, and oral contraceptives (OCs) and intrauterine devices (IUD) are the most widely used two types of contraceptives. Compared with other drugs and devices, contraceptives have the following characteristics: the first is healthy women use, the second is a big population of use, and the third is long-time use. The use of contraceptives is intended to prevent pregnancy, presents a potential for risk to the health at the same time. Pre-marketing studies have some common problems such as short study time, few cases, narrow subjects, selection bias, so some long-term effects of a product could only be found after it was marketed and used for a long time among a large population.To decrease the related adverse reactions and adverse effects, the researchers at home and abroad have developed some highly effective and safe contraceptives. The third generation oral contraceptives containing desogestrel (DSG) - Marvelon combined oral contraceptive (COC), and two new types copper-bearing indomethacin-releasing intrauterine device Yuan-gong 220 and Yuan-gong 365 are the representatives. Marvelon was first marketed in Netherlands in 1981, and was introduced to China in the 1980s. The currently available data performed with Marvelon are almost clinical trials caORied out within urban women , and we haven't retrieved any literature reported on the safety and acceptability of using Marvelon among Chinese rural women. Yuangong-220 and Yuangong-365 are independently developed in China,and were marketed as new generation of copper-bearing indomethacin-releasing intrauterine device in 2000 and 2002 respectively, yet few post-marketing surveillance studies to date are reported on the safety and efficacy of the two new types copper-bearing indomethacin-releasing intrauterine device.The acceptability of contraceptives is largely affected by the safety and efficacy of the specific methods, which is also influenced by their impact on the users' quality of life. And there is no study to date are reported on the acceptability of Mavelon and the two new types copper-bearing indomethacin-releasing intrauterine device among Chinese rural women from psycologicial perspective.The objective of this post-marketing surveillance study was to evaluate the safety and acceptability of Marvelon and the two new types copper-bearing indomethacin-releasing intrauterine device among rural women in Jiangsu Province, and to analyze the possible factors affected the safety and acceptability to provide evidenced-based guidances for the contraceptive informed choice and the quality care in family planning. Part I Post-marketing Surveillance and Evaluation of the DSG-containing Combined Oral Contraceptive Marvelon^? among rural women in Jiangsu ProvinceSeveral large-scale clinical trials carried out within foreigners indicate that Marvelon provides optimal contraceptive efficacy and a reliable safety profile, although its use is associated with the common side effects and bleeding irregularities. Researches show that concern about weight gain can deter the initiation of combination contraceptive use and cause early discontinuation among users. Weight gain was the most frequently cited reason for oral contraceptive discontinuation in a national study of adult women in the United States. Egarter prove that taking COC had influence on the quality of life in users. the acceptability of contraceptives is largely affected by two important factors , including the side effects and the impact on the quality of life. An active post-marketing surveillance were carried out among 870 women taking Marvelon to collect the base-line data, and to record the side effects, the value of weight and blood pressure, the discontinuation reasons and the time of occurrence, and the changes of the items in the self-administrated quality of life questionnaire among those clients whose education were middle school or higher. Follow-up visits were scheduled for 1-3, 6 and 12 months after treatment began. We took the copper-bearing indomethacin-releasing intrauterine device Yuan-gong 220 users as control group to determine the safety and acceptability of Marvelon among rural women in Jiangsu Province. The main results were as follows:1. Marvelon had good compliance rural women in Jiangsu Province (97.65% - 99.31%), the miss use mainly happened during the first 3 months(3^rd month: 2.35%, 6^th month: 1.12%, 12^th month: 0.69%), the miss rates showed a decrease trend over time(trend test P<0.05) .This study proved that Marvelon was effective(the PI was 0.26, and the two pregnant women both had histories of miss use). 2. During the study period of 12 months, the overall rate of side effects of Marvelon users was 24.02%. The overall rate of side effects of Marvelon users showed a decrease trend over time(trend test P<0.05). The three most frequent side effects were gastrointestinal disorder, bleeding/spotting and chloasma. The rates of gastrointestinal disorder and bleeding/spotting both decreased over time, but the rate of chloasma showed an opposite trend.3. During the study period of 12 months, the use of Marvelon didn't increasethe risk of weight gain>5kg compared with the IUD users(3^rd month: adjusted OR=1.22, 95%CI: 0.42-3.57, 6^th month: adjusted OR=1.60, 95%CI: 0.64-4.00, 12^th month: adjusted OR= 1.05, 95%CI: 0.57-1.91). The Marvelon users had less risk of hypertension than that in the control group during the first 3 months(adjusted OR=0.09, 95%CI: 0.03-0.30).4. The gross cumulative continuation rate for Marvelon users was 83.14%during the study period of 12 months, which was lower than that in the control group,the most common medical reason for discontinuation of treatment was gastrointestinal disorder. Lower educational level was found to be a risk factor for premature discontinuation for Marvelon users (adjusted HR=0.71, P=0.0195).5. The mean scores of 7 items of self-administrated quality of life questionnaire significantly increased after Marvelon intake, but the degree of improvement of 8 items in the questionnaire among the Marvelon users were less than that in the control group.Conclusion: DSG-containing COC Marvelon^? had good compliance among rural women of Jiangsu Province, this study proved that Marvelon was effective was effective. And Marvelon brought fewer side effects, had minor influence on weight gain and blood pressure, but was less acceptable than Yuangong-220 IUD when applied in rural women of Jiangsu Province. We suggest that follow-up services should be regulated during the first 3 months, and more attention should be paid to let the users with lower educational level know the safety of COC Marvelon^?.Part II Post-marketing Surveillance and Evaluation of Two new types Copper-bearing Indomethacin-releasing Intrauterine Device among rural women in Jiangsu ProvinceTo solve the problems after IUD insertion such as bleeding and pain, Chinese experts developed copper-bearing indomethacin-releasing intrauterine device. Researches show that those women using indomethacin-releasing intrauterine device had lower incidence rate of menorrhagia and similar contraceptive efficacy compared with other IUD users. The pre-marketing studies indicate that indomethacin could inhibit the synthesis of prostaglandin, so this kind of IUD could decrease the occurrence of bleeding, the removal rate was below 2% in one year.Expulsion is thought to be an important factor affecting the safety and efficacy. Researches show that women using copper-bearing indomethacin-releasing Yuan-gong IUD had lower incidence rate of expulsion compared with TCu220C users.An active post-marketing surveillance were carried out among 1119 women using copper-bearing indomethacin-releasing intrauterine device Yuan-gong 220 to collect the base-line data, and to record the side effects, the discontinuation reasons and the time of occurrence. Follow-up visits were scheduled for 1-3, 6 and 12 months after IUD insertion. The users of the two new types IUD from gaoyou and jianhu areas were considered as the control group of each other with the aim to compare the occurrence of side effects and adverse effects of the two types IUD users. The main results are as follows:1. The two most frequent side effects were bleeding and pain. During the study period of 12 months, the overall rates of spotting, prolonged bleeding, irregular menstrual cycles , menorrhagia and pain were 8.58%, 13.40%, 1.79%, 2.41% and 10.72% respectively. Expulsion and extraction for bleeding were the two most frequently cited adverse effects, the cumulative incidence of whose were 2.71% and 2.17% respectively during the study period of 12 months.2. The overall rates of side effects of Yuan-gong 220 IUD showed a decrease trend over time (trend test P<0.05). We didn't find any effect of the possible risk factors previously reported by others on the expulsion rate such as age, time of insertion and so on.3. During the first 3 months, the incidence rate of all side effects, spotting, prolonged bleeding and pain among Yuan-gong 220 IUD users were significantly higher than that in Yuan-gong 365 IUD users. During the study period of 12 months, the overall rate of adverse events among Yuan-gong 220 IUD users was 4.75%, which was significantly higher than that in Yuan-gong 365 IUD users (2.23%), especially the rates of partial expulsion(220IUD: 2.38%, 365 IUD: 0.56%, P<0.001).Conclusion: Compared with Yuan-gong 220 IUD, Yuan-gong 365 IUD bringsfewer side effects and lower adverse events rate. We propose to promote theuse of Yuan-gong 365 IUD and reform the process of Yuan-gong 220 IUD.We suggest that follow-up services should be stressed during the first 3months, and timely treatment should be given to those having side effects todecrease the incidences of adverse effects.