[Efficacy and adverse effects of levonorgestrel-releasing intrauterine system in treatment of adenomyosis].

OBJECTIVE: To evaluate the efficacy and adverse effects of levonorgestrel-releasing intrauterine system (Mirena) in the treatment of adenomyosis. METHODS: The clinical data of 75 patients with adenomyosis who had Mirena insertion in Women's Hospital,Zhejiang University School of Medicine from September 2013 to December 2013 were retrospectively analyzed. The patients were followed up to 39 months. The efficacy and adverse effects were assessed. RESULTS: Pictorial Blood Loss Assessment Chart (PBAC) scores were decreased significantly after Mirena insertion both in patients with menorrhea (118±13 vs. 29±33, P<0.01) and normal menstruation (82±15 vs. 14±13, P<0.01); the patients with menorrhea showed a more significant decrease in PBAC score than those with normal menstruation (90±35 vs. 69±19,P<0.01). The visual analogue scale (VAS) score decreased significantly after Mirena insertion compared with pre-treatment[7(6,7) vs. 1(0,2), P<0.01]. The expulsion of Mirena occurred in 18 cases (24.0%); 9 cases (12.0%) had no effect and 28 cases (37.3%) had changes of menstruation patterns. Multivariate Cox regression analysis showed that the expulsion of Mirena was not associated with post-treatment VAS score, PBAC score before and after treatment or menstrual stabilization time (all P>0.05). CONCLUSIONS: Mirena is effective and safe in the long term management of adenomyosis, but about one third patients may require further treatment because of the expulsion or ineffectiveness of Mirena.

Ethinylestradiol and levonorgestrel preparations on the Belgian market: a comparative study.

Preparations formulated as coated or film-coated tablets, containing levonorgestrel and the combination ethinylestradiol/levonorgestrel, were evaluated in a comparative study. This study comprised in vitro dissolution, assay and content uniformity. The analytical methods were previously validated according to international guidelines. All examined products complied with the postulated requirements.

Comparison of Levonorgestrel-releasing Intrauterine System (LNG-IUS) against Laparoscopic Assisted Supracervical Hysterectomy (LASH) for menorrhagia treatment: An economic evaluation.

BACKGROUND: This economic evaluation and literature review was conducted with the primary aim to compare the cost-effectiveness of laparoscopic assisted supracervical hysterectomy (LASH) with NICE's gold-standard treatment of Levonorgestrel-releasing intrauterine system (LNG-IUS) for menorrhagia. MATERIALS AND METHODS: A cost-utility analysis was conducted from an NHS perspective, using data from two European studies to compare the treatments. Individual costs and benefits were assessed within one year of having the intervention. An Incremental Cost-Effectiveness Ratio (ICER) was calculated, followed by sensitivity analysis. Expected Quality Adjusted Life Years (QALYS) and costs to the NHS were calculated alongside health net benefits (HNB) and monetary net benefits (MNB). RESULTS: A QALY gain of 0.069 was seen in use of LNG-IUS compared to LASH. This yielded a MNB between -£44.99 and -£734.99, alongside a HNB between -0.0705 QALYs and -0.106 QALYS. Using a £20,000-£30,000/QALY limit outlined by NICE,this showed the LNG-IUS to be more cost-effective than LASH, with LASH exceeding the upper bound of the £30,000/QALY limit. Sensitivity analysis lowered the ICER below the given threshold. CONCLUSIONS: The ICER demonstrates it would not be cost-effective to replace the current gold-standard LNG-IUS with LASH, when treating menorrhagia in the UK. The ICER's proximity to the threshold and its high sensitivity alludes to the necessity for further research to generate a more reliable cost-effectiveness estimate. However, LASH could be considered as a first line treatment option in women with no desire to have children.

Simultaneous determination of mifepristone and monodemethyl-mifepristone in human plasma by liquid chromatography-tandem mass spectrometry method using levonorgestrel as an internal standard: application to a pharmacokinetic study.

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine mifepristone and monodemethyl-mifepristone in human plasma using levonorgestrel as the internal standard (IS). After solid-phase extraction of the plasma samples, mifepristone, monodemethyl-mifepristone and the IS were subjected to LC-MS/MS analysis using electro-spray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an XTERRA MS C(18) column (150 x 2.1 mm i.d., 5 microm). The method had a chromatographic run time of 4.5 min and linear calibration curves over the concentration ranges of 5-2000 ng/mL for mifepristone and monodemethyl-mifepristone. The recoveries of the method were found to be 94.5-103.7% for mifepristone and 70.7-77.3% for monodemethyl-mifepristone. The method had a lower limit of quantification (LLOQ) of 5.0 ng/mL and a lower limit of detection (LOD) of 1.0 ng/mL for both mifepristone and monodemethyl-mifepristone. The intra- and inter-batch precision was less than 15% for all quality control samples at concentrations of 10, 100 and 1000 ng/mL. These results indicate that the method was efficient with a short run time (4.5 min) and acceptable accuracy, precision and sensitivity. The validated LC-MS/MS method was successfully used in a pharmacokinetic study in healthy female volunteers after oral administration of 25 mg mifepristone tablet.

Emergency Contraception for Adolescents: A Political Battle.

The political debate for adolescents to have access to emergency contraception that is available over the counter has been going on for years. Since 1999, Levonorgestrel, Plan B One Step®, has been used in the United States as an emergency contraception but with a prescription at the time. The FDA has done years of research and testing with Barr Laboratories, the manufacture of Plan B One Step®, to make it safe for females of all ages. In 2003, the FDA recommended the over the counter use of Plan B One Step® for all ages, yet this did not occur. In pharmacies across our nation young women find it impossible to purchase this product whether they be of age or not. Politics is making the choices for our young females, not medical evidence. How long are we going to let this continue?

The levonorgestrel intrauterine system in contraception.

The levonorgestrel intrauterine system (LNG IUS) releases 20 microg/24 h of levonorgestrel from a polymer cylinder mounted on a T-shaped frame and covered with a release rate-controlling membrane. It is approved for 5-year use. The most outstanding features of LNG IUS are its high contraceptive efficacy and reduction of menstrual blood flow. No single mode of action can account for its contraceptive efficacy. The endometrium becomes thin and inactive, and the cervical mucus turns scanty and viscous. Although ovulation may be disturbed to some degree, estradiol production continues normally. The Pearl index for LNG IUS from large clinical trials is 0.1. Extrauterine pregnancies occur in 1 in 5000 users per year. Both the volume of menstrual blood loss and the number of bleeding days are reduced. During the first year of use, 20% of women become amenorrheic. There is an initial increase in the mean number of bleeding and spotting days, but in 3 to 6 months the number of bleeding and spotting days is the same as observed in copper IUD-users. The variation between individuals is wide and unpredictable. There are also additional health benefits secondary to the inactivation of the endometrium: increased hemoglobin, decreased dysmenorrhea, a possible decrease in pelvic inflammatory disease. LNG IUS may also decrease the growth of fibroids. LNG IUS is well accepted by users, with typical annual continuation rates above 80% in clinical studies.

Preliminary experience with Norplant in an inner city population.

Norplant, the five-year subdermal contraceptive system, is the first implantable contraceptive method approved for general use in the United States. We describe the preliminary experiences of 246 U.S. women who accepted Norplant between April, 1991 and September, 1991. Norplant was well accepted among this diverse general population. Intensive counselling about side effects, especially menstrual changes, is crucial for patient satisfaction. Although 48% of acceptors experienced menstrual cycle changes and 70% experienced at least one side effect, phone calls and unscheduled visits for problems were infrequent. Adequate counselling about side effects obviates the need for a routine follow-up visit one month after insertion.

PIP: Between April and October 1991 in Baltimore, Maryland, family planning providers tried to follow 246 13-42 year old women at a clinic at the Francis Scott Key (FSK) Medical Center for 3 months who accepted the levonorgestrel-releasing implant Norplant to evaluate its acceptability and effectiveness among a high-risk population. 56% of the women were Black and 41% White. 69% were single. Most were interval gynecologic patients (109), but many were postabortion patients (97). The providers could only follow 108 women. Reasons for unscheduled visits were insertion site tenderness, amenorrhea, and removal. At 1 month, 70 % had at least 1 side effect. 48% had irregular bleeding 1-2 months after insertion. Other side effects included headache (49%), acne (24%), weight gain (22%), increased appetite (19%), and dizziness (18.5%). The 24-hour telephone hotline had only received 38 problem calls, all of which were from FSK Norplant patients. More than 50% of the calls were about menstruation concerns. Reasons for removal included pressure to receive Norplant, increased acne, headaches and prolonged bleeding, and postinsertion site problems. 1 woman became pregnant, but it occurred before insertion. She underwent an abortion and continued to use Norplant. 78% of the women considered Norplant to be excellent and 14% considered it to be good. 95% would recommend it to others. 69% reported convenience to be the best thing about Norplant and 22% said it was pregnancy prevention. Worst things were irregular bleeding (26%) and progestin-related side effects (e.g., headaches and weight gain) (19%). 35% did not consider anything to be bad about Norplant. 64% had at least some apprehension before insertion, the major reasons being fear of needles (48%) and of pain (37%). Prior to insertion, just 37% were worried about potential side effects. The providers thought that the routine follow-up visit at 1 month was not cost-effective and provided no specific clinical benefit. They advocated adequate counseling about side effects to take the place of the follow-up visit.

Evaluation of the clinical performance of a levonorgestrel-releasing IUD, up to seven years of use, in Campinas, Brazil.

The clinical performance of a levonorgestrel IUD, releasing 20 mcg/day, used by 293 women at the Family Planning Clinic of the State University of Campinas, was evaluated up to the end of the seventh year of use. No pregnancies occurred in 899 women-years of observation. The cumulative removal rate for amenorrhea or severe hypomenorrhea was 15.7 per 100 women at seven years. The expulsion rate was within ranges observed with copper IUDs in the same clinic. The continuation rate was 49.5% at three years and 23.7 at seven years. The cumulative loss to follow-up rate was 13.7% at seven years. The effectiveness, good continuation rate, and reduction of the amount of blood loss make this device appropriate to be offered to Brazilian women, as an additional contraceptive option.

Effectiveness of Norplant implants through seven years: a large-scale study in China.

The effectiveness of Norplant implants over a seven year period of continuous use was studied in a multicenter trial. Pregnancy rates were 0.4 per 100 in both year six and year seven. More than 3,600 women completed 6 years and more than 2,400 women completed 7 years. Pregnancy rates increased with weight (p < .05) and decreased with age, but in years 6 and 7 combined, the pregnancy rate neither reached nor exceeded 1 per 100 woman years in any 5 year age group or in any 10 kg weight group.

PIP: The effectiveness of Norplant implants containing a total of 216 mg of levonorgestrel over a 7-year period of continuous use was studied in a multicenter trial. Enrollment continued from 1984 to 1987 with a cut-off in May 1994, by which time all women had completed 7 years of use. The subjects were 18-40 years old with at least 1 living child. More than 3600 women completed 6 years and more than 2400 women completed 7 years. There were 18 pregnancies in the 6th year and 12 in the 7th year. One of these was ectopic. The annual gross pregnancy rates were 0.40 per 100 in both the 6th and 7th year. For both years there was a significant difference in pregnancy rates among women in the different weight groupings (p 0.05), but not in the different age groupings. In years 6 and 7 combined, the pregnancy rate neither reached nor exceeded 1 per 100 woman years in any 5 year age group or in any 10 kg weight group. Only women under age 30 at admission who then weighed 65 or more kg had a pregnancy rate of 1.31 +or- 0.76 per 100 in the 6th and 7th years. No age-weight group had a pregnancy rate as high as 2.0 per 100 in the 2-year period beyond normal use. Cumulative life table pregnancy rates at the end of 5 years had been 1.53 per 100 for all subjects. At the end of 7 years the cumulative rate had increased by less than 1 per 100 to 2.32 per 100. The highest cumulative pregnancy rates were found among the women under age 25 and those weighing 70 or more kg at acceptance. The former group had a cumulative failure rate of 4.7 and the latter a cumulative rate of 6.6 per 100, respectively. This study provides evidence that Norplant implants remain a highly effective contraceptive method for a period of 7 years of continuous use.

An evaluation of the levonorgestrel-releasing IUD: its advantages and disadvantages when compared to the copper-releasing IUDs.

The levonorgestrel-releasing IUD (LNG-IUD-20), providing a daily dose of 20 ug, has recently been approved for marketing in Finland. The IUD's high efficacy in preventing accidental pregnancy and other numerous positive features make it a promising contraceptive device for worldwide use, just like the currently available T-shaped copper-releasing (TCu) IUDs. This paper reviews published reports comparing the LNG-IUD-20 and the currently used TCu IUDs. The merits and disadvantages of the steroid-releasing IUD are evaluated in terms of its performance and other special features relative to the TCu IUDs. Also, a number of future studies with medical and programmatic importance are proposed. A broader understanding about these two IUD families will facilitate their use in a complementary way for family planning programs.

PIP: This literature review compares the merits and disadvantages of the levonorgestrel-releasing IUD made by Leiras Pharmaceuticals, Turkey, Finland (LNG-IUD-20), with the Nova-T, Copper-T (TCu) and 220C, and Copper-T-38-Ag (TCu-380Ag). This IUD releases 20 mcg levonorgestrel daily from a Silastic sleeve on the vertical shaft containing 52 mg. The plasma level stabilized after a month at about 0.2 ng/ml, about half as high as that seen with Norplant implants. It is identical in size to the Nova-T. The Cu-T IUDs differ with respect to copper wire or sleeves, or silver-cored wire. The chief studies reviewed here were 2 multi-center trails primarily in European countries, and a 2 large multi-center trials in India. Cumulative pregnancy rates were 0.0 to 0.6 per 100 users for the LNG IUD, compared to slightly higher failures for inert or copper IUDs. While removal rates for bleeding, pain and pelvic inflammatory disease were lower for the LNG-IUD-20, removals for oligomenorrhea, amenorrhea and hormonal side effects were higher than for the other IUDS. In the Indian trials, removals for amenorrhea and irregular bleeding were much higher than rates reported in the European studies, resulting in significantly lower continuation rates overall. The results pointed to district benefits for the LNG-IUD-20, such as lower blood loss and anemia, relief of dysmenorrhea and menorrhagia, as well as possible lower risks of ectopic pregnancy in case of failure, less PID (pelvic inflammatory disease), and the claim by the maker that strictly correct placement is not necessary. Disadvantages of the LNG-IUD-20 are more difficult insertion due to the wider diameter; oligomenorrhea, amenorrhea and irregular bleeding; hormonal side effects such as acne, weight gain, nausea, headache and breast tension; and potential risk of functional ovarian cysts. The LNG-IUD-20 is considered comparable to copper IUDs in effectiveness, safety, longevity, and return to fertility after removal. Users should be counseled that the oligomenorrhea or amenorrhea is neither a medical problem or indicative of infertility, is common for the 1st 2 months, is reversible on removal, may signal an improved hemoglobin profile, relief of dysmenorrhea, and may be preferred to heavy bleeding from other IUDS. The program implications of this IUD are potential lower incidence of ectopic pregnancy and PID. The effect of its use on breast feeding, cost-effectiveness compared to Norplant, in-country manufacture, and cultural acceptance need to be determined in specific locales.

Acceptability of Norplant-2 rods as a method of family planning.

The Norplant-2 rod system consists of two silastic rods in which levonogestrel has been incorporated with the polymer. The continuation rate at the end of five year was 62%. No accidental pregnancies occurred throughout the five years of use. The post-removal conception rate in women desiring pregnancy was 70.8% at the end of two years. The majority of acceptors were happy with the rods and 86.8% expressed the desire to have another set of implants inserted following removal of the first set. The study shows the Norplant-2 rod system to be a well accepted method of family planning.

PIP: Physicians from the National University Hospital, Singapore enrolled 100 women between December 1985-March 1986 in a 5 year study of the efficacy, acceptability, and reversibility of Norplant-2 rods. They examined them at 1, 3, 6, and 12 months and 2 times each year thereafter. All women returned. No one had an unintended pregnancy. The leading reason for removal was planning a pregnancy (24 of 38 removals). The 8 removals for menstrual problems occurred during the 1st 2 years. Of the 24 women, 6 changed their minds about having another child and used other family planning methods. 58.3% of the 24 women (77.7% of the 18 women who still wanted to conceive) were pregnant within 3 months after removal. At the end of 2 years, only 1 woman did not become pregnant (70.8% of 24 and 94.4% of 18) probably because she was experiencing subfertility since she was 44 years old. All 17 women gave birth vaginally to healthy full term infants. The physicians removed the rods from the 62 women who still had a Norplant-2 system at the end of 5 years. 87.1% (52) found the Norplant-2 system very favorable. No woman said it was not favorable. Further all 62 women were satisfied with all the information they received about the Norplant-2 system. 74.2% thought Norplant-2's ease of use/convenience was its best attribute and 24.2% said it was the low risk of pregnancy. Moreover 48.4% did not think negatively about Norplant-2. The least liked attribute was menstrual pattern changes (35.5%). 4 women complained about the removal procedure being painful, yet 3 requested a 2nd set of Norplant-2 rods. In fact, 86.8% of the women who intended to use contraception after removal chose Norplant-2 rods. Of the 9 women who did not plan to use contraception, 7 planned to conceive and 2 were widowed. In conclusion, Norplant-2 system is safe and efficient. Further it has an advantage over the Norplant-6 system--ease of insertion and removal.

Efficacy and continuation rates of Norplant in Pakistan.

A total of 265 women who had the Norplant system inserted were followed for 5 years. The present study is based on 11,435 women-months of use, describing the continuation rates and efficacy of Norplant among these women. The 5-year cumulative continuation rate was 45.7 per 100 continuing users. The continuation rates were age-dependent. The women > or = 35 years of age consistently maintained higher continuation rates at all time intervals as compared with those of younger women. During 5 years of follow-up, five women became pregnant. Three pregnancies occurred in year 2, one in year 3, and one in year 5. The 5-year cumulative pregnancy rate was 2.5 per 100 continuing users. The weight of the user did not influence the pregnancy rate. The continuation rates, as well as the pregnancy rates, are comparable to those reported from other countries in the region.

PIP: This article documents a 5-year follow-up of Norplant acceptors. The study was based on the medical records of 265 women who obtained Norplant from the Family Planning Association of Pakistan clinics in Lahore and Karachi during 1988-89 to examine the efficacy and continuation rates of Norplant in Pakistan. The studied sample participated in the introductory trial that were followed up for 5 years. Results revealed that the cumulative continuation rate during the 5-year period was 45.7 per 100 continuing users. The continuation rates were age-dependent, wherein women aged 35 years or older consistently maintained higher continuation rates at all time intervals as compared with younger women. During the 5-year follow-up, 5 women became pregnant (3 in year 2, 1 in year 3, and 1 in year 5). Furthermore, the 5-year cumulative pregnancy rate was 2.5 per 100 continuing users. The user¿s weight did not influence the pregnancy rate. Lastly, the continuation rates, as well as the pregnancy rates, were comparable to those reported from other countries in the region.

Phase II--clinical trial with biodegradable subdermal contraceptive implant Capronor (4.0-cm single implant). Indian Council of Medical Research Task Force on Hormonal Contraception.

The subdermal biodegradable contraceptive implant Capronor (4.0 cm) was implanted in 41 women to observe the efficacy and side effects. Only one pregnancy was reported at 10 months of use, and the life table continuation rate at 12 months was 82.2 per 100 users. No serious clinical side effects were reported during the study period. The menstrual pattern was disrupted during the first 3 months of implant use in two-thirds of the women which improved by the end of 12 months of use. The results of this Phase II study suggest that Capronor is a safe and effective long-acting contraceptive. These findings need to be confirmed in a Phase III clinical trial on a larger sample size.

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants.

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

Assessing the acceptability of Norplant contraceptive in four patient populations.

The object of this study was to review the experience of Norplant implants insertion at the University of Colorado Health Sciences Center with specific attention to the potential impact of source of care and/or clinic site of of insertion. Norplant implants were inserted at four different office sites, namely, adolescent-teen, resident, certified nurse midwife, and faculty physician. The charts of all patients who had Norplant implants inserted between April 1991 and September 1992 were reviewed and we attempted to contact each patient by telephone to assess clinical course and acceptability of Norplant contraceptive. We were able to contact 254 of 414 women (61%) who had Norplant implants inserted. The average length of time since Norplant implants insertion was 13.2 months. The only significant demographic difference between groups was that the adolescent-teen patients were younger, of lower parity, less educated, and were more likely to be single than the other three groups. The overall removal proportion was 14.6%, and removal proportions were not significantly different between any of the four groups. The primary reason for removal was unacceptable bleeding (32% of removers). Only 59% of patients returned for follow-up care. Faculty physician patients were significantly more compliant with follow-up compared to adolescent-teen and resident patients (p < 0.01). Patient retention of Norplant contraceptive is unrelated to age or the clinic setting in which the device was inserted. Since similar side effects are experienced by retainers and removers, it is unclear what other factors prompt women to seek removal. Particularly in the teen and resident groups, follow-up is poor.

PIP: To refine understanding of the acceptability of Norplant in the US on the basis of different target populations and sources of care, the experiences of four groups of clients who had the implants inserted at University of Colorado Health Sciences Center between April 1991 and September 1992 and could be reached for a postinsertion telephone interview were compared. The 254 women interviewed (61% of total acceptors over this period) were drawn from four clinics: adolescent, resident, certified nurse midwife, and faculty physician. The average length of time since insertion was 13.2 months. As expected, adolescent patients were significantly more likely to be younger, single, less educated, and of lower parity than women in the three other groups. The overall removal rate was 14.6%, with no significant difference among groups or in terms of factors such as age, race, or socioeconomic status; the mean time to removal was 10.2 months. The most common reason for removal (32%) was unacceptable bleeding; however, abnormal bleeding was not significantly associated with the decision to discontinue the method. Weight gain and headache were the only side effects reported significantly more frequently by removers than retainers. Only 150 (59%) women returned for a scheduled postinsertion follow-up visit; compliance was lowest among teens (41%) and highest among patients of faculty (77%). 10 of the 37 women who opted for removal had this procedure performed at another clinic site; this finding suggests that clinic-based studies may underestimate the actual Norplant discontinuation rate.

A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant.

To compare the contraceptive efficacy, tolerability, and bleeding patterns, 200 healthy female volunteers received, in an open, comparative, randomized, multicenter study in China, either a single-rod (Implanon) or a six-capsule (Norplant) contraceptive implant for 2 years with an optional extension of up to 4 years. Women were exposed to Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding/spotting days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. Similarly, with Norplant, the median number of bleeding/spotting days decreased from 34.5 to 18.0-23.0 days, respectively. The number of bleeding/spotting episodes during year 1 was 2.0 per 90-day reference period with Implanon and 3.0 per period with Norplant (p < 0.05 for periods 1-4). For the remaining 90-day periods, there was no statistical difference between the two groups. In general, there was less frequent bleeding with Implanon compared with Norplant, whereas the incidences of amenorrhea and infrequent bleeding were higher with Implanon than with Norplant. The mean overall incidence of prolonged bleeding fell markedly during the study, from 66.0% in reference period 1 to 27.3% in period 16 with Implanon and from 69.0% to 21.7% with Norplant, respectively. The most common adverse events were related to disturbed bleeding patterns, which were also the major reasons for discontinuation (Implanon n = 8; Norplant n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Implanon was inserted in a mean time of 0.61 min and Norplant in 3.90 min (p < 0.001). Similarly, the mean time required to remove the implant was significantly shorter for Implanon than for Norplant (2.18 min vs 11.25 min, p < 0.001). The maximum time required for removal of the implant was 10 min for the Implanon group and 60 min for the Norplant group. In both groups, blood pressure and hemoglobin were not affected, whereas body weight tended to increase. It can be concluded that both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Compared with Norplant, there was less frequent bleeding with Implanon, whereas the incidence of infrequent bleeding and amenorrhea was higher. Implanon was significantly quicker to insert and to remove than was the multiple capsule system.

PIP: This study compares the contraceptive efficacy and bleeding patterns of a single-rod (Implanon) and a six-capsule (Norplant) contraceptive implant for 2 years, with an optional extension of up to 4 years, among 200 healthy female volunteers in China. Women were administered with Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. No pregnancies occurred during the study, demonstrating excellent contraceptive efficacy. The median number of bleeding/spotting (B/S) days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. With Norplant, the median number of B/S days decreased from 34.5 to 18.9-23.0 days. There was less frequent bleeding with Implanon than with Norplant. The most common adverse effects were related to disturbed bleeding patterns, which were also the main reasons for discontinuation (Implanon, n = 8; Norplant, n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Lastly, Implanon required less time for insertion and removal as compared to Norplant.

Consensus statement on emergency contraception.

Twenty-four experts from around the world, representing the fields of research, policy, communications, women's advocacy and medicine, gathered at the Rockefeller Foundation Conference Center in Bellagio, Italy, in April 1995 to discuss emergency contraception. The conference was hosted by South-to-South Cooperation in Reproductive Health and co-sponsored by the International Planned Parenthood Federation, Family Health International, the Population Council and the World Health Organization. The conference was supported by the Rockefeller Foundation.

Comparative study on intermittent versus continuous use of a contraceptive pill administered by vaginal route.

A multicenter, international, randomized, comparative trial was conducted to assess the acceptability, efficacy and safety of two different schedules of a contraceptive pill, containing 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol, administered by the vaginal route. One schedule of daily administration for 21 days with a seven-day interruption to allow withdrawal bleeding was compared to daily administration without interruption for bleeding. A total of 900 women were recruited in three countries, Brazil, Egypt and China; 7,090 women-months of vaginal pill use were recorded (3,364 using the pills intermittently and 3,726 continuously). Four undesired pregnancies occurred, one in Egypt and three in China, all four in women using the pills intermittently. There was a statistically significant difference (p = 0.486) in pregnancy rate between the two groups. There were no other significant differences in discontinuation rates despite marked differences in bleeding patterns, amenorrhea predominating in the continuous use group. Hemoglobin levels increased significantly in the two groups but hematocrit was significantly higher in the continuous use group.

PIP: 900 healthy women 16-42 years old were recruited in Brazil, China, and Egypt for a multicenter, randomized, comparative clinical trial to determine the acceptability, efficacy, and safety of two different schedules of a contraceptive pill with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol administered vaginally. The two schedules were: 1) daily vaginal use of the pill for 21 days, followed by withdrawal for regular bleeding, and restarted 7 days later, and 2) use of the pill by the vaginal route nonstop for one year. There were no significant difference in cumulative discontinuation rates between the two groups (total, 15.5 for intermittent group and 14.64 for continuous group), except for unwanted pregnancy. The only unwanted pregnancies occurred to 4 women in the intermittent group (1.04%) (p = 0.0486). Women in the continuous use group were more likely than those in the intermittent group to have spotting at least once (20.6% vs. 4.4%; p 0.001). Women in the continuous group were more likely than those in the intermittent group to have amenorrhea. For example, the mean number of bleeding/spotting days during all time intervals was lower for the continuous group than for the intermittent group (p 0.001; last interval, 0.97 vs. 12.83). Hemoglobin levels increased considerably in both groups between baseline and one year of use (11.61 vs. 11.9 g/dl for intermittent group and 11.54 vs. 11.81 g/dl for continuous use; p 0.001). The mean value of hematocrit at 12 months for the continuous group was higher than that at baseline (38.8% vs. 38.2%; p = 0.011). It did not increase in the intermittent group, however. Women in both groups gained weight during the 12 months of pill use. The weight gain was significant for the continuous group only. These findings suggest that continuous use of vaginal contraceptive pills may be more advantageous than intermittent use oral contraceptives and may benefit anemic women and those who bleed heavily during menstruation.

Levonorgestrel-releasing IUD as a method of contraception with therapeutic properties.

The levonorgestrel-releasing intrauterine device LNg IUD is a new contraceptive method that combines the advantages of both hormonal and intrauterine contraception. It gives users non-contraceptive health benefits and can also be used as an effective therapy for menorrhagia. The local release of LNg within the endometrial cavity results in strong suppression of endometrial growth as the endometrium becomes insensitive to ovarian estradiol. The endometrial suppression is the reason for a significant reduction of menstrual blood loss or amenorrhea, and for the disappearance of dysmenorrhea. The bleeding pattern during the use of the LNg IUD is characterized by reduction of the blood loss and in the number of bleeding days per cycle. During the first two to three months of use, however, irregular spotting is common. The removal of the device results in a quick return of menstrual bleeding and fertility. The failure rate of copper-releasing IUDs, as with other methods of fertility regulation, is higher in young women and decreases with age. The LNg IUD, on the other hand, has the same low pregnancy rate in every age group of the users. The LNg IUD also gives protection against ectopic pregnancy and pelvic inflammatory disease and, by reducing menstrual blood loss, increases the body iron stores. The LNg IUD can be used to effectively treat menorrhagia. This has been demonstrated in studies with quantitative determination of menstrual blood loss. During the first year of use, the LNg IUD reduced menstrual blood loss by 90% from pretreatment levels. Comparative clinical trials with the LNg IUD cover more than 10,000 women-years of follow-up during use over five to seven years. The Pearl pregnancy rate in studies has been 0.0-0.2 per 100 women-years. The overall ectopic Pearl pregnancy rate is 0.02 per 100 woman-years. The LNg IUD is marketed in Denmark, Finland, Norway, Sweden and in the United Kingdom.

PIP: The levonorgestrel-releasing intrauterine device (LNg IUD) is a new contraceptive method which combines the advantages of both hormonal and intrauterine contraception. It confers noncontraceptive health benefits and can also be used as an effective therapy for menorrhagia. The new device is currently being marketed in Denmark, Finland, Norway, Sweden, and the UK. Comparative clinical trials with the LNg IUD cover more than 10,000 women-years of follow-up during use over 5-7 years. The Pearl pregnancy rate has been 0.0-0.2 per 100 women-years and the overall ectopic Pearl pregnancy rate is 0.02 per 100 woman-years. The local release of LNg in the endometrial cavity results in the strong suppression of endometrial growth as the endometrium becomes insensitive to ovarian estradiol. The endometrial suppression is the reason for a significant reduction of menstrual blood loss or amenorrhea, and for the disappearance of dysmenorrhea. Use of the LNg IUD results in the reduction of blood loss and in the number of bleeding days per cycle. Irregular spotting is, however, common during the first two-three months of use. The reduction in menstrual blood loss results in an increased storage of iron in the body. Menstrual bleeding and fertility are quickly restored following removal of the device. Finally, unlike copper-releasing IUDs, the failure rate of the LNg IUD is not dependent upon the user's age, and it protects against ectopic pregnancy and pelvic inflammatory disease.