Ilza Monteiro

Levonorgestrel-Releasing Intrauterine System or Medroxyprogesterone for Heavy Menstrual Bleeding A Randomized Controlled Trial

OBJECTIVE: To compare the efficacy and safety of the levonorgestrel-releasing intrauterine system and oral medroxyprogesterone acetate in the treatment of idiopathic heavy menstrual bleeding. METHODS: In this multicenter, randomized, controlled study, women aged 18 years or older with heavy menstrual bleeding (menstrual blood loss 80 mL or more per cycle) were randomly assigned to six cycles of treatment with either levonorgestrel-releasing intrauterine system or oral medroxyprogesterone acetate (10 mg daily for 10 days beginning on day 16 of each cycle). The primary efficacy variables were the absolute change in menstrual blood loss from baseline to end of study and the proportion of women with successful treatment (defined as menstrual blood loss less than 80 mL and a 50% or greater reduction in menstrual blood loss from baseline). RESULTS: Of 807 women screened, 165 were randomly assigned to treatment (levonorgestrel-releasing intrauterine system n=82, oral medroxyprogesterone acetate n=83). At the end of the study, the absolute reduction in median menstrual blood loss was significantly greater in the levonorgestrel-releasing intrauterine system group (−128.8 mL, range −393.6 to +1242.2 mL) than in the medroxyprogesterone acetate arm (−17.8 mL, range −271.5 to +78.6 mL, P < .001), and the proportion of women with successful treatment was significantly higher for the levonorgestrel-releasing intrauterine system (84.8%) than for medroxyprogesterone acetate (22.2%, P < .001). CONCLUSION: In women with idiopathic heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system reduces menstrual blood loss more effectively and has a higher likelihood of treatment success than oral medroxyprogesterone acetate. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00360490. LEVEL OF EVIDENCE: I

Therapeutic use of levonorgestrel-releasing intrauterine system in women with menorrhagia: a pilot study

The objective of this study was to evaluate the efficacy and performance, for up to 1 year, of an intrauterine system releasing 20 microg/day of levonorgestrel (LNG-IUS, Mirena) in the treatment of women with menorrhagia. It was a descriptive, prospective, non-comparative study. A 20 microg/day LNG-releasing-IUS was inserted on any day during bleeding to 44 women (between 24 and 49 years of age) who presented with menorrhagia after medical therapies had failed. Menstrual patterns were assessed, and hemoglobin concentrations were measured before LNG-IUS was inserted and at 3, 6, 9, and 12 months of use. The most common bleeding pattern at 3 months after insertion was spotting, and after 6, 9, and 12 months the majority of women presented with amenorrhea or oligomenorrhea. Three women requested removal of the LNG-IUS because of spotting, and six women expelled it spontaneously. Hemoglobin levels were improved from 102 g/L to 123 and 128 g/L at 3 and 12 months, respectively, after insertion of the LNG-IUS (p < 0.01). At 12 months 79.5% of participants continued the use of LNG-IUS. In conclusion, LNG-IUS was an effective treatment for three out of four women with menorrhagia and could be an alternative treatment for women with menorrhagia who are either contraindicated for or refuse hysterectomy or endometrial ablation.

Ease of insertion and clinical performance of the levonorgestrel-releasing intrauterine system in nulligravidas

BACKGROUND Despite the high contraceptive efficacy and the additional noncontraceptive benefits of the levonorgestrel-releasing intrauterine system (LNG-IUS), concerns persist with respect to its use in nulligravidas. The objective of this study was to evaluate the ease of insertion and clinical performance of the LNG-IUS in nulligravida women up to 1 year after insertion. METHODS Two cohorts were formed after LNG-IUS insertion, one consisting of 159 nulligravidas and the other of 477 parous women. Each nulligravida women was paired with three parous women who had an LNG-IUS inserted on the same day. Insertion was classified as easy or difficult, and when classified as difficult, the use of Hegar dilators and/or misoprostol and insertion failure were additional factors recorded. RESULTS In almost 80% of cases, no difficulty was encountered during insertion, and dilators and misoprostol were seldom required; however, when necessary, dilator use was almost threefold higher in nulligravida women. Insertion failed in one nulligravida women and in two parous women. Contraception was the most common reason for insertion, although some of the women received the LNG-IUS for both contraceptive and therapeutic purposes, including heavy menstrual bleeding, hematologic diseases, warfarin use, endometriosis-associated pain and following kidney or liver transplantation. The clinical performance of the device showed zero pregnancy rate, expulsion rates of ∼4/100 women-year and 1-year continuation rate of over 90% in both groups. CONCLUSIONS The LNG-IUS is suitable for use by nulligravidas. It is simple to insert, and its clinical performance in nulligravidas is similar to that found in parous women.

Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system.

BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) is a contraceptive method approved for five years of use. However, there is some evidence that its life span may be longer. The aim of the study was to evaluate serum levonorgestrel (LNG) and estradiol (E(2)) levels and endometrial thickness every 6 months from 7 to 8 1/2 years after insertion. STUDY DESIGN At the end of the approved 5-year life span, no replacement devices were available; therefore, 86 women were allowed to retain the same device for a further 2 years. At the 7-year follow-up visit, the women who consented were again allowed to retain the same device for a further 18 months and were followed-up at six-monthly intervals. At each visit, vaginal sonography was performed to measure endometrial thickness, and a blood sample was taken to measure LNG and E(2). RESULTS Eighty-four months after insertion, 67 women aged 34.3+/-0.8 years (mean+/-SEM) (range, 25-49 years) returned for follow-up. Mean+/-SEM LNG levels decreased from an initial 253+/-27 pg/mL (range, 86-760) during the first 2 months following insertion to 137+/-12 (range, 23-393) at 84 months and 119+/-9 pg/mL (range, 110-129) at 102 months of use (+/-SEM). At 84 months of use, mean+/-SEM endometrial thickness was 2.8+/-0.1 mm, increasing to 3.8+/-0.5 mm at 102 months of use. The incidence of amenorrhea decreased from 41.8% at 84 months to 31.5% at 102 months of use. No correlation was found between LNG levels and bleeding patterns; however, a weak correlation was found between high body mass index (kg/m(2)), high weight, and low serum LNG levels. E(2) levels were similar to those of the follicular phase of the menstrual cycle of regularly menstruating women. CONCLUSIONS During extended use of the LNG-IUS, serum LNG levels were nearly half those found in the first 2 months of use (Wilcoxon signed rank test); serum E(2) levels were normal. Despite the very thin endometrium, menstrual bleeding was reinstated in many cases. At the end of its 5-year life span, there is a window for changing the LNG-IUS, and physicians and users should not be concerned about delaying replacement of the device for a short time beyond the approved life span; however, maintaining the same device long after its approved life span cannot be recommended.

Follow-up of users of intrauterine device with and without bacterial vaginosis and other cervicovaginal infections

This study aimed to assess the prevalence of bacterial vaginosis (BV) and other cervicovaginal infections, as well as the incidence of complications among new users of IUD, 1 and 6 months after its insertion, in the City of Campinas, Brazil. A total of 223 women who had a TCu-380A IUD inserted from May through November 2001, were included in the study. After the IUD insertion all women were scheduled to two additional visits: after 1 month and after 6 months, when they were interviewed and a pelvic examination was performed, along with a collection of specimens from the vagina and the endocervix for laboratory testing. The Nugents criterion was used for the BV diagnosis. They were also evaluated with regard to presence of complications possibly related to IUD insertion and use, i.e., abnormal bleeding, dysmenorrhea, expulsion and pelvic inflammatory disease. The prevalence of cervicovaginal infections was 29.1%, BV being the most frequent (19.7%). Dysmenorrhea was more frequent among women with BV than among women without BV (p = 0.03). A trend of abnormal bleeding being more frequent among women with BV was also found. In conclusion, BV after 1 month of IUD insertion was not associated with IUD complications, with the exception of dysmenorrhea.

Return of fertility after discontinuation of the once-a-month injectable contraceptive Cyclofem®

The objective of this study was to evaluate the return of fertility in women who used Cyclofem as a contraceptive method during the introductory studies conducted in Brazil, Chile, Colombia, and Peru. From these four cohorts, 101 women were eligible for the study. Thirty-one were not included in the study either because they refused to be interviewed, had initiated another contraceptive method the month after discontinuation, or were unable to be contacted. A total of 70 women were included in the study. Our results showed that the return to fertility rate after the discontinuation of Cyclofem was 1.4 per 100 women at the end of the first month and reached 82.9 at one year. More than 50% were pregnant at 6 months. Fifty-one (94.4%) pregnancies ended in a live birth, two were spontaneous first trimester abortions, and one was a hydatidiform mole. Return of fertility was not related to the womans age at the time of discontinuation, her weight, or the number of Cyclofem injections. In conclusion, fertility is restored by 1 month following Cyclofem discontinuation. Users and potential users should be counseled regarding the rapid return of fertility after discontinuing this method of contraception.

Acceptability and performance of the levonorgestrel-releasing intrauterine system (Mirena®) in Campinas, Brazil

The objectives of this study were to evaluate the acceptability of the LNG-IUS Mirena(R), when offered as an additional option in a free choice context, and to evaluate the possibility of using this method in women with increased bleeding wanting an IUD and in copper IUD users requesting removal of the device for bleeding problems. A total of 256 women chose Mirena and were accepted into the study during the enrollment period. This represents 23.3% of all new acceptors of contraceptive methods in the clinic during the same period. Discontinuations were fairly evenly distributed among expulsion, bleeding changes, pain, and personal reasons. Bleeding changes were decreased bleeding, oligomenorrhea or amenorrhea. Comparing the performance in the group of women who chose the LNG-IUS as a first option with those having heavy bleeding, the only difference found was a higher expulsion rate in the group with bleeding problems. No pregnancies occurred and continuation rate was slightly over 75% in the total sample and in both groups. The characteristics of the LNG-IUS (Mirena) allow predicting that this method can effectively contribute to the increase in contraceptive options when introduced to family planning programs in Brazil.

Prospective study of the forearm bone mineral density of long-term users of the levonorgestrel-releasing intrauterine system

BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) induces amenorrhoea, and its effect on bone mineral density (BMD) may constitute a concern. This study evaluated BMD in long-term users of the LNG-IUS or intrauterine device (IUD). METHODS BMD was evaluated at the midshaft of the ulna and ultra-distal radius using dual-energy X-ray absorptiometry in 37 women at 7 or 10 years of use following placement of a second LNG-IUS. The groups were paired for duration of use, age, body mass index (BMI), ethnicity and number of pregnancies. RESULTS The mean age of both LNG-IUS and IUD users at the 7th and 10th year was approximately 34 and 38 years, respectively. Mean BMI was approximately 25 in both groups, increasing to approximately 26 at the 10th year. Amenorrhoea occurred in 51.4 and 91.9% of LNG-IUS users at the 7th and 10th year, respectively. Estradiol levels in LNG-IUS users were normal at both evaluations. There were no differences in BMD (g/cm(2)) at the midshaft of the ulna nor ultra-distal radius between LNG-IUS and IUD users or between the 7th and 10th years of use in LNG-IUS users. A Z-score below -2SD at the ultra-distal radius was observed in only one LNG-IUS user and in none of the IUD users at the 10th year. Higher BMI and BMD at the seventh year and amenorrhoea were predictors of higher BMD at the 10th year. CONCLUSIONS BMD at the midshaft of the ulna and ultra-distal radius in LNG-IUS users were similar to that of IUD users and remained unchanged between the 7th and the 10th years of use.

Estimated disability-adjusted life years averted by long-term provision of long acting contraceptive methods in a Brazilian clinic

STUDY QUESTION What is the contribution of the provision, at no cost for users, of long acting reversible contraceptive methods (LARC; copper intrauterine device [IUD], the levonorgestrel-releasing intrauterine system [LNG-IUS], contraceptive implants and depot-medroxyprogesterone [DMPA] injection) towards the disability-adjusted life years (DALY) averted through a Brazilian university-based clinic established over 30 years ago. SUMMARY ANSWER Over the last 10 years of evaluation, provision of LARC methods and DMPA by the clinic are estimated to have contributed to DALY averted by between 37 and 60 maternal deaths, 315-424 child mortalities, 634-853 combined maternal morbidity and mortality and child mortality, and 1056-1412 unsafe abortions averted. WHAT IS KNOWN ALREADY LARC methods are associated with a high contraceptive effectiveness when compared with contraceptive methods which need frequent attention; perhaps because LARC methods are independent of individual or couple compliance. However, in general previous studies have evaluated contraceptive methods during clinical studies over a short period of time, or not more than 10 years. Furthermore, information regarding the estimation of the DALY averted is scarce. STUDY DESIGN, SIZE AND DURATION We reviewed 50 004 medical charts from women who consulted for the first time looking for a contraceptive method over the period from 2 January 1980 through 31 December 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Women who consulted at the Department of Obstetrics and Gynaecology, University of Campinas, Brazil were new users and users switching contraceptive, including the copper IUD (n = 13 826), the LNG-IUS (n = 1525), implants (n = 277) and DMPA (n = 9387). Estimation of the DALY averted included maternal morbidity and mortality, child mortality and unsafe abortions averted. MAIN RESULTS AND THE ROLE OF CHANCE We obtained 29 416 contraceptive segments of use including 25 009 contraceptive segments of use from 20 821 new users or switchers to any LARC method or DMPA with at least 1 year of follow-up. The mean (± SD) age of the women at first consultation ranged from 25.3 ± 5.7 (range 12-47) years in the 1980s, to 31.9 ± 7.4 (range 16-50) years in 2010-2011. The most common contraceptive chosen at the first consultation was copper IUD (48.3, 74.5 and 64.7% in the 1980s, 1990s and 2000s, respectively). For an evaluation over 20 years, the cumulative pregnancy rates (SEM) were 0.4 (0.2), 2.8 (2.1), 4.0 (0.4) and 1.3 (0.4) for the LNG-IUS, the implants, copper IUD and DMPA, respectively and cumulative continuation rates (SEM) were 15.1 (3.7), 3.9 (1.4), 14.1 (0.6) and 7.3 (1.7) for the LNG-IUS, implants, copper IUD and DMPA, respectively (P < 0.001). Over the last 10 years of evaluation, the estimation of the contribution of the clinic through the provision of LARC methods and DMPA to DALY averted was 37-60 maternal deaths; between 315 and 424 child mortalities; combined maternal morbidity and mortality and child mortality of between 634 and 853, and 1056-1412 unsafe abortions averted. LIMITATIONS, REASONS FOR CAUTION The main limitations are the number of women who never returned to the clinic (overall 14% among the four methods under evaluation); consequently the pregnancy rate could be different. Other limitations include the analysis of two kinds of copper IUD and two kinds of contraceptive implants as the same IUD or implant, and the low number of users of implants. In addition, the DALY calculation relies on a number of estimates, which may vary in different parts of the world. WIDER IMPLICATIONS OF THE FINDINGS LARC methods and DMPA are highly effective and women who were well-counselled used these methods for a long time. The benefit of averting maternal morbidity and mortality, child mortality, and unsafe abortions is an example to health policy makers to implement more family planning programmes and to offer contraceptive methods, mainly LARC and DMPA, at no cost or at affordable cost for the underprivileged population. STUDY FUNDING/COMPETING INTERESTS This study received partial financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant # 2012/12810-4 and from the National Research Council (CNPq), grant #573747/2008-3. B.F.B., M.P.G., and V.M.C. were fellows from the scientific initiation programme from FAPESP. Since the year 2001, all the TCu380A IUD were donated by Injeflex, São Paulo, Brazil, and from the year 2006 all the LNG-IUS were donated by the International Contraceptive Access Foundation (ICA), Turku, Finland. Both donations are as unrestricted grants. The authors declare that there are no conflicts of interest associated with this study.

Length of the endometrial cavity and intrauterine contraceptive device expulsion

To evaluate the correlation between endometrial cavity length and expulsion rate in acceptors of the TCu380A intrauterine device (IUD) or the levonorgestrel‐releasing intrauterine system (LNG‐IUS).