M. Valeria Bahamondes

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.

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.

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).

Human vaginal histology in long-term users of the injectable contraceptive depot-medroxyprogesterone acetate.

OBJECTIVES Apparently, depot-medroxyprogesterone acetate (DMPA) increases a womans risk of acquiring HIV. The objective of this study was to test whether the vaginal mucosal thickness and Langerhans cell counts were significantly different in long-term DMPA users compared with women users of an intrauterine device (IUD) who had never used DMPA. STUDY DESIGN Cross-sectional study. Twenty-three DMPA users were matched with 23 nonusers controlled for age, body mass index (BMI; kg/m²), and duration of contraceptive use. Four groups of women were evaluated according to the duration of DMPA use: >1, <5; ≥5, <10; ≥10, <15 or ≥15 years. Estradiol (E₂) levels were compared between the two groups. Histologic sections of vaginal mucosal biopsies were evaluated to measure the mean epithelial thickness and S100 immunostained sections were used to count the number of Langerhans cells/mm. RESULTS Mean (±S.D.) E₂ levels were significantly lower in DMPA users (39.4±26.6 pg/mL) compared with nonusers (102.6±60.3 pg/mL) despite similar ages (42.3±7.4 and 42.4±7.4 years, respectively). Mean (±S.D.) vaginal thickness was 232.6±108.1 and 229.7±112.9 in DMPA users and nonusers, respectively. There were no differences in vaginal thickness or Langerhans cell count/mm between users and nonusers even after controlling for DMPA duration of use. CONCLUSIONS Vaginal epithelial thinning or Langerhans cell count was not different between long-term DMPA users and copper-IUD users who had never used DMPA. IMPLICATIONS No differences were found in vaginal epithelial thickness or in Langerhans cell count between long-term users of the injectable contraceptive DMPA and nonusers.

Body weight and composition in users of levonorgestrel-releasing intrauterine system

BACKGROUND There is little information about body weight and body composition (BC) among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). The aim of this study was to evaluate body weight and BC in LNG-IUS users compared to users of the TCu380A intrauterine device (IUD). STUDY DESIGN A prospective study was done with 76 new users of both contraceptive methods. Women were paired by age (±2 years) and body mass index (BMI, kg/m², ±2). Body weight and BC (% lean mass and % fat mass) were evaluated by a trained professional at baseline and at 1 year of contraceptive use. The BC measurements were obtained using Lunar DXA equipment. Weight and BC were evaluated in each woman at baseline and at 12 months and analyzed as the mean change within each woman. Then, the changes in weight and BC for each woman were calculated and then compared between LNG-IUS and TCu380A IUD users (paired data for each woman). The central-to-peripheral fat ratio was calculated by dividing trunk fat by the upper and lower limb fat. RESULTS There were no significant differences at time of IUD insertion between LNG-IUS and TCu380A IUD users regarding age (mean±SD) (34.4±7.5 vs. 33.9±8.0 years), BMI (25.3±4.1 vs. 25.9±4.1) and number of pregnancies (1.9±0.2 vs. 1.7±0.2), respectively. Mean body weight gain of 2.9 kg was observed among LNG-IUS users at 12 months (p=.0012), whereas the body weight of TCu380A IUD users only increased by 1.4 kg (p=.067). There was no significant difference in body weight change between the two groups of users at 12 months. The variation in the central-to-peripheral fat ratio was the same between the two groups (-1.6% vs. -0.2%; p=.364). LNG-IUS users showed a 2.5% gain in fat mass (p=.0009) and a 1.4% loss of lean mass, whereas TCu380A IUD users showed a loss of 1.3% of fat mass (p=.159) and gain of 1.0% of lean mass (p=.120). TCu380A IUD users gained more lean mass than LNG-IUS users (p=.0270), although there was no significant difference between the two groups after 12 months of use. CONCLUSIONS Although an increase in mean fat mass among LNG-IUS users at 12 months of use was observed, it should be noted that an increase of body weight was also observed in both groups after 1 year of insertion of the device. However, a study with a larger number of women and long-term evaluation is necessary to evaluate these body changes.

In vitro assessment of some sperm function following exposure to levonorgestrel in human fallopian tubes

BackgroundThe mechanism of action of levonorgestrel (LNG) as emergency contraception (EC) remains a subject of debate and its effect on sperm function has been only partially explained. The aim of this study was to assess whether LNG at a similar dose to those found in serum following oral intake for EC could affect spermatozoa when exposed to human fallopian tubes in vitro.MethodsFifteen mini-laparotomies were performed, the side on which ovulation occurred was recorded, and both tubes were removed and perfused with a suspension containing 1 × 10(6) motile spermatozoa, with or without LNG. Following 4-hour incubation, the tubes were sectioned to separate the isthmus and the ampulla. Each segment was flushed and the material was evaluated to quantify the number of motile sperm, the number of spermatozoa adhering to the oviductal epithelium and the acrosome reaction (AR) rate.ResultsThe addition of LNG did not significantly alter the number of recovered motile spermatozoa either at the isthmus or at the ampulla, nor did it have any effect on the number of recovered spermatozoa adhered to the human tubal epithelium. Furthermore, LNG did not affect the AR rate. No significant differences were found even when the side on which ovulation occurred was taken into account.ConclusionsIn a similar dose to that observed in serum following oral intake for EC, LNG had no effect on the number of motile spermatozoa recovered from the human fallopian tubes in vitro, on their adhesion to the tubal epithelium, distribution or AR rate. The possible effect of LNG as EC on sperm function remains poorly understood.

Long-term assessment of forearm bone mineral density in postmenopausal former users of depot medroxyprogesterone acetate

BACKGROUND There are many controversies on the association between depot medroxyprogesterone acetate (DMPA) and bone mineral density (BMD). This study reevaluated BMD in postmenopausal women who had used DMPA as a contraceptive until they reached menopause and compared them with non-users. BMD had previously been measured in these women either at 1 year or 2-3 years after menopause and was reassessed in these women 2 years later. Therefore, comparisons were made between the first and third years and between the second to third and fourth to fifth years after menopause. STUDY DESIGN BMD was reevaluated using dual-energy X-ray absorptiometry at two parts of the non-dominant forearm up to 5 years after menopause in 79 women between 46 and 61 years old: 24 former DMPA users and 55 former copper intrauterine device (IUD) users. RESULTS With respect to the former DMPA users, only the BMD measurement at the distal radius in the first year (mean±SEM, 0.425±0.017) was significantly higher than the third-year measurement (0.406±0.017) (p<.015). No significant differences were found at the ultradistal radius. There were no significant differences between the groups of former DMPA and IUD users with respect to BMD measurements either at the distal radius or at the ultradistal radius. There was a direct relationship between higher body mass index (kg/m(2)) and higher BMD at the distal radius between the first and third years. At the ultradistal radius, there was an indirect relationship between older age and lower BMD between the first and third years in both groups. CONCLUSIONS No statistically significant differences were found in forearm BMD measurements between postmenopausal women who had been long-term users of DMPA and those who had been long-term users of an IUD until menopause. Evaluation of BMD after the menopause showed slightly higher values in former DMPA users compared with non-users.