Ximena Espejo-Arce

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.

Length of the endometrial cavity as measured by uterine sounding and ultrasonography in women of different parities.

BACKGROUND In view of current controversies regarding the need for new, shorter intrauterine devices (IUDs) that would reduce expulsion rates in nulligravida, endometrial cavity length was measured in women of different parities using uterine sounding and ultrasonography. STUDY DESIGN A cross-sectional descriptive study was performed including 570 women of 17-52 years of age, 260 of whom were nulligravida and 310 parous. RESULTS The difference in mean length between measurements taken by uterine sounding and ultrasonography was 0.28 cm. Mean endometrial cavity length was 3.84+/-0.03 cm (mean+/-S.E.M.) in nulligravida and 4.25+/-0.03 cm in parous women according to uterine sounding (p<.001) and 3.70+/-0.03 cm and 3.84+/-0.03 cm, respectively, according to ultrasonography (p=.006). CONCLUSIONS By either technique, mean length of the endometrial cavity was >3.6 cm, the length of the most common IUDs, the TCu380A and the levonorgestrel-releasing intrauterine system. Therefore, the issue appears controversial for developing new, shorter IUDs, since current models fit most women, including nulligravida, albeit one third of the women of our sample showed endometrial length shorter than 3.2 cm.

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.

A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants

BackgroundThe aim of this study was to evaluate bone mineral density (BMD) at baseline and at 18 and 36 months of use of etonogestrel (ENG)-and levonorgestrel (LNG)-releasing contraceptive implants. This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use.MethodsA total of 111 women, 19–43 years of age, wererandomly allocated to use one of the two implants. At 36 months of follow-up, only 36 and 39 women were still using the ENG- and LNG-releasing implants, respectively. BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry.ResultsThere was no difference in the BMD of users of either implant at 18 and at 36 months. BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values; however, no difference was found at the ultra-distal radius.ConclusionWomen 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values; however, no difference was found at the ultra-distal radius.

Effect of vaginal administration of misoprostol before intrauterine contraceptive insertion following previous insertion failure: a double blind RCT

STUDY QUESTION Is pretreatment with misoprostol useful in insertion of intrauterine contraceptives (IUCs) after insertion failure at the first attempt? SUMMARY ANSWER Pretreatment with intravaginal administration of 200 mcg of misoprostol after IUC insertion failure 10 and 4 h before the second attempt of IUC placement was significantly better than placebo at facilitating the insertion of an IUC. WHAT IS KNOWN ALREADY One of the reasons for low use of IUCs is the concept that insertion is difficult. Misoprostol was used in several randomized clinical trials (RCT) before IUC insertion to facilitate the insertion. In general, the results showed no significant differences when compared with placebo. However, most previous studies have been carried out among unselected women whereas the present study is among women with previous insertion failure. STUDY DESIGN, SIZE, DURATION This was a double blind RCT conducted between February 2013 and October 2014. Participants were 104 women who requested an insertion of an IUC and the insertion failed at the first attempt. After insertion failure, the women received a sealed envelope with misoprostol or placebo. The randomization system (1: 1) in one block size was computer-generated. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was conducted at a tertiary care centre. The women were instructed to insert vaginally one tablet of misoprostol 200 µg (Prostokos, Hebron, Cariacica, PE, Brazil) or placebo 10 and 4 h before the woman returned to the clinic for a new insertion attempt. The outcomes were successful IUC insertion and the use of a cervical dilator immediately prior to the insertion procedure. MAIN RESULTS AND THE ROLE OF CHANCE A total of 2639 women requested the insertion of an IUC during the study period. The IUC was inserted at the first attempt in 2535 women (96%) and 104 women in whom we were unable to insert the device were eligible to participate in the RCT. Four women declined and 100 women were randomized (55 for the misoprostol group and 45 for the placebo group). From the 100 participating women, the levonorgestrel-releasing intrauterine system (LNG-IUS) was chosen by 55 and 37 women and the TCu380A intrauterine device (Cu-IUD) was chosen by none and 8 women in the misoprostol and placebo group, respectively. Seven and three women allocated to misoprostol and placebo, respectively, never returned to the clinic after randomization. We placed the IUC in 42 (87.5%) out of the 48 women and in 26 (61.9%) out of the 42 women randomized to misoprostol and placebo, respectively (P = 0.0066). Regarding the Evaluable Population the relative risk (RR) of successful insertions was 1.41 (95% confidence interval (CI) for absolute difference (8.2, 43.0), P = 0.0066); in the Intent-to-Treat Population the RR (95% CI) was 1.32 (0.3, 36.9). Multiple regression analysis showed that the significant variables associated with the insertion failure were the number of Caesarean section ≥1 (P = 0.020) and the use of placebo (P = 0.026). Dilators were used in 21 (43.7%) out of the 48 and 21 (50%) out of the 42 women randomized to misoprostol and placebo, respectively (P = 0.804). LIMITATIONS, REASONS FOR CAUTION The limitations were that the majority of the women chose the LNG-IUS, and consequently the data for the Cu-IUD were limited, and there was a small number of nulligravidas. WIDER IMPLICATIONS OF THE FINDINGS The results show that IUC insertion difficulties and failures are not common. Pretreatment with intravaginal misoprostol facilitated IUC insertion after failure of insertion at the first attempt, and insertion failure was associated with number of Caesarean sections. STUDY FUNDING/COMPETING INTERESTS This study received partial financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant # 2012/10085-0, and from the National Research Council (CNPq), grant #573747/2008-3. All the TCu380A IUDs were donated by Injeflex, São Paulo, Brazil, and all the LNG-IUS were donated by the International Contraceptive Access Foundation (ICA), Turku, Finland. Both donations were provided in the form of unrestricted grants. The authors declare that there are no conflicts of interest associated with this study. TRIAL REGISTRATION NUMBER ClinicalTrial.gov NCT01754649.

Users' Perspectives on Bleeding Patterns after Two Years of Levonorgestrel-Releasing Intrauterine System Use

The demand for intrauterine devices (IUDs) has increased over recent years because they represent one of the most cost-effective reversible methods of contraception.[1] However, IUD use still causes concern for women, especially those with heavy menstrual bleeding, because of the risk of anaemia.[2] Hormone-medicated IUDs, such as the 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena®1, Leiras Oy, Turku, Finland), are associated with a reduction in the amount of blood loss during the menstrual period. Because of this property, the LNG-IUS has been used for the treatment of menorrhagia.[3,4] From 50–70% of women using LNG-IUS became amenorrhoeic after 1 year of use in one study.[5] However, modification of the menstrual pattern, including amenorrhoea, is one of the leading causes of discontinuation among women using the device for contraception.[6,7] The perception of what is ‘normal’ menstrual bleeding differs widely between different populations, and is influenced by sociocultural aspects and by the counselling women receive. The perception of menstrual patterns in LNG-IUS users varies among different populations. However, these differences could, in part, result from the woman’s interpretation, the service provider’s opinion regarding bleeding patterns, or the system of evaluation. Hence, when a new contraceptive method that is associated with changes in menstrual patterns, like the LNG-IUS, is introduced it is important to inform the potential user what changes she may expect to experience in her bleeding pattern. It is probable that this counselling would directly influence the continuation rate. The objective of this study was to evaluate the perspectives of users of the LNG-IUS in Campinas, Brazil, after 1 year of use, regarding bleeding patterns and their opinion on whether amenorrhoea induced by the device has health consequences.