Maria Valeria Bahamondes

Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women.

Objective:Data on the interaction between the etonogestrel (ENG) implant and antiretroviral therapy are lacking. We evaluated the effect of 2 highly active antiretroviral therapy (HAART) regimens (1 including efavirenz and the other ritonavir-boosted lopinavir) on the pharmacokinetic (PK) parameters of an ENG-releasing implant in HIV-positive women. Design:Prospective nonrandomized PK study. Methods:Forty-five HIV-positive women who desired to use ENG implants were included: 15 had received zidovudine/lamivudine + lopinavir/ritonavir for ≥3 months (LPV/r-based HAART group), 15 had received zidovudine/lamivudine + efavirenz for ≥3 months (EFV-based HAART group), and 15 had not received HAART (non-HAART group). PK parameters were measured using ultra-performance liquid chromatography–mass spectrometry at baseline and 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks after implant placement. Results:The EFV-based HAART regimen was associated with a reduction in the bioavailability of ENG, which showed decreases of 63.4%, 53.7%, and 70% in the area under the curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) of ENG, respectively, compared with the non-HAART group. The LPV/r-based HAART regimen was associated with an increase in ENG bioavailability, which showed 52%, 60.6%, and 33.8% increases in the ENG AUC, Cmax, and Cmin, respectively, compared with the non-HAART group. Conclusions:The coadministration of EFV decreased the bioavailability of ENG released from the implant, which could impair contraceptive efficacy. However, the coadministration of LPV/r increased the bioavailability of ENG released from the implant, which suggests that this antiretroviral combination does not impair the ENG implant efficacy.

New and emerging contraceptives: a state-of-the-art review.

Background The first hormonal contraceptive was introduced onto the market in several countries 50 years ago; however, the portfolio of contraceptive methods remains restricted with regards to their steroid composition, their cost, and their ability to satisfy the requirements of millions of women/couples in accordance with their different reproductive intentions, behaviors, cultures, and settings. Methods A literature review was conducted using Medline, Embase, and Current Contents databases, up to September 1, 2013 to identify publications reporting new contraceptives in development using combinations of the search terms: contraception, contraceptives, oral contraceptives, patch, vaginal ring, implants, intrauterine contraceptives, and emergency contraception (EC). Also, several experts in the field were also consulted to document ongoing projects on contraception development. Additionally, the Clinicaltrial.gov website was searched for ongoing studies on existing contraceptive methods and new and emerging female contraceptives developed over the past 5 years. Information was also obtained from the pharmaceutical industry. Results Early sexual debut and late menopause means that women may require contraception for up to 30 years. Although oral, injectable, vaginal, transdermal, subdermal, and intrauterine contraceptives are already available, new contraceptives have been developed in an attempt to reduce side effects and avoid early discontinuation, and to fulfill women’s different requirements. Research efforts are focused on replacing ethinyl-estradiol with natural estradiol to reduce thrombotic events. In addition, new, less androgenic progestins are being introduced and selective progesterone receptor modulators and new delivery systems are being used. In addition, research is being conducted into methods that offer dual protection (contraception and protection against human immunodeficiency virus transmission), and contraceptives for use “on demand.” Studies are also investigating non-hormonal contraceptive methods that have additional, non-contraceptive benefits. Conclusion The most pressing need worldwide is, first, that the highly effective contraceptive methods already available should be affordable to most of the population and also that these methods should fulfill the needs of women of different ages and with different reproductive requirements. The development of new contraceptive methods should also take advantage of the knowledge obtained over the past 30 years on gamete physiology and gamete interaction to avoid the use of steroid compounds.

Levonorgestrel-releasing intrauterine system: uses and controversies.

This article provides a perspective on the use of the levonorgestrel-releasing intrauterine system as a contraceptive method and as therapy in different situations, as well as presenting the corresponding controversies and unresolved issues. All studies have reported high contraceptive efficacy, an improvement in menstrual blood loss in women with idiopathic menorrhagia, menorrhagia due to thrombophilic diseases and fibroids, and excellent endometrial protection during postmenopausal estrogen therapy. Moreover, the device is able to reduce pelvic pain and dysmenorrhea as well as improve the staging of endometriosis and adenomyosis, and to control, albeit partially, endometrial hyperplasia. The expectation is that in years to come the number of hysterectomies and female sterilizations will fall due to increased use of the device, including use by patients with endometriosis and HIV-positive women. It would also be desirable to develop a smaller device for postmenopausal women and nulligravidas.

Variação de peso em usuárias de sistema intra-uterino liberador de levonorgestrel, DIU T-cobre e acetato de medroxiprogesterona no Brasil

BACKGROUND: Assess weight variations in Brazilian users of the 20 µg/day levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena®) for comparison with a cohort of users of the TCu 380A intrauterine device (IUD) and a cohort of users of the injectable contraceptive, depot-medroxyprogesterone acetate (DMPA) over a period of five years. METHODS: A total of 163 users of the LNG-IUS, who had the device inserted in 1998, were admitted to the study. At the time of enrollment, each woman was matched by weight (± 1kg) and age (± 1year) to a woman using a TCu 380A IUD and to another woman using DMPA. All women were followed up for a period of five years. Each year weight was measured and the body mass index (BMI, kg/m2) was calculated. RESULTS: Age of the LNG-IUS users was 27.0 ± 6.7 years (mean ± SD), while age of the copper IUD users was 28.0 ± 6.6 years and that of DMPA users was 26.9 ± 6.5 years. Weight recorded at the onset of the study was 62.9 ± 0.8 kg, 62.8 ± 0.8 kg, and 62.5 ± 0.9 kg (Mean ± SD) for users of the LNG-IUS, the copper IUD, and DMPA, respectively. The BMI of women was initially 25.0 (±0.3), 26.4 (±0.3), and 25.5 (±0.4), (Mean ± SD), for users of the LNG-IUS, copper IUD, and DMPA, respectively. Weight increases of 3.1 kg, 4.9kg and 8.2kg were observed at the end of the fifth year among users of the LNG-IUS, copper IUD, and DMPA, respectively (p = 0.009). Increase of the BMI was also observed among all groups (final BMI was 26.3 ± 0.7, 28.5 ± 0.8 and 28.7 ± 1.3 for users of the LNG-IUS, copper IUD and DMPA, respectively). Multivariate analysis showed that there was a significant association between weight increase and length of use of the contraceptive method and of the DMPA. CONCLUSION: The use of a LNG-IUS during five years caused no significant weight increase and the difference in weight was of the same magnitude as that of copper IUD users.

Associated factors with discontinuation use of combined oral contraceptives

PURPOSE Due to the scarce information available in Brazil in relation to the number of women who initiated the use of combined oral contraceptives and prematurely discontinued, the objective was to assess the reasons for discontinuation of the use of several combined oral contraceptives among Brazilian women living in urban areas. METHODS A cross-sectional study with 400 gynecologists registered withy the Brazilian Federation of Obstetricians and Gynecologists. Each physician interviewed 10 non-pregnant, not breastfeeding, not amenorrheic women aged 18 to 39 years who consulted requesting combined oral contraceptive (COC) with a questionnaire at the beginning of use and at six months later. The questionnaire included sociodemographic data, type of COC chosen or prescribed and reasons for discontinuation when it occurred during follow-up. The strategy of selection allowed the inclusion of women from different socioeconomic strata, however, only those attended at private or insurance offices. The sample size was estimated at 1,427 women. RESULTS A total of 3,465 interviews were conducted at the first visit and 1,699 six months later. The women were 20 to 29 years old, 57.3% were single and an equal proportion of 45.0% attended high school or college. Most (60.7%) were nulligravidas and among those who had used some contraceptive before, 71.8% had used a COC. Among the more prescribed or chosen COC the most prevalent were monophasic with ethynil estradiol (20 µg) and regarding progestin the most prevalent was with gestodene (36.5%) followed by a COC with drosperinone (22.0%). At six months 63.5% still used COC. Among those who discontinued the main reasons were wishing to become pregnant (36.5%) and side effects (57.3%) and the most prevalent were headache (37.6%), weight gain (16.6%) and irregular bleeding (23.6%). CONCLUSIONS The continuation rate of COC was low at six months and this study could contribute to a better counseling on the part of physicians of patients who initiate COC about side-events that are rare, minimal and temporary and about the benefits of COC use.

Estimated disability-adjusted life years averted by free-of-charge provision of the levonorgestrel-releasing intrauterine system over a 9-year period in Brazil

Background The objective was to analyse the contribution of the provision at no cost to users of the 20 µg/day levonorgestrel-releasing intrauterine system (LNG-IUS) towards disability-adjusted life years (DALY) averted over a 9-year period. Methods We analysed data from 15 030 new users of the LNG-IUS who had the device inserted at 26 Brazilian teaching hospitals between January 2007 and December 2015. The devices came from the International Contraceptive Access Foundation (ICA), a not-for-profit foundation that donates the devices to developing countries for use by low-income women who desire long-term contraception and who freely choose to use this device. Estimation of the DALY averted included live births averted, maternal morbidity and mortality, child mortality and unsafe abortions averted. Results A total of 15 030 women chose the LNG-IUS as a contraceptive method during the study period. Over the 9 years of evaluation, the estimated cumulative contribution of the Brazilian program in terms of DALY averted consisted of 486 live births, 14 cases of combined maternal mortality and morbidity, 143 cases of child mortality and 410 unsafe abortions. Conclusions Provision of the LNG-IUS at no cost to low-income Brazilian women reduced unwanted pregnancies and probably averted maternal mortality and morbidity, child mortality and unsafe abortions. Family planning programs, policymakers and stakeholders based in low-resource settings could take advantage of the information that the provision of this contraceptive at no cost, or at affordable cost to a publicly-insured population, is an effective policy to help promote women’s health.

Body composition and weight gain in new users of the three-monthly injectable contraceptive, depot-medroxyprogesterone acetate, after 12 months of follow-up

Abstract Objectives To evaluate weight gain and body composition (BC) in new users of depot-medroxyprogesterone acetate (DMPA) as a contraceptive. Methods This cohort study followed up 20 DMPA users and 20 copper intrauterine device (TCu380A IUD) users, paired for age (± 1 year) and body mass index (BMI ± 1 kg/m2), during 12-months. Healthy, non-obese women aged 18 to 40 years, unaffected by conditions that could influence their body weight, were enrolled. Socio-demographic variables, habits, weight, BMI, BC using dual-energy X-ray absorptiometry, circumferences, skinfold thickness, body fat percentage and waist-to-hip ratio were evaluated. All participants were encouraged to adopt healthy habits. Results At baseline, median age was 29 and 30.5 years, and mean BMI was 24.8 and 24.5 kg/m2 in the DMPA and IUD groups, respectively. At 12 months, an increase was observed in waist and hip circumference in the DMPA users and 8/20 of them had a weight gain ≥ 5% (mean 4.6 kg) with accumulation of fat centrally. Conclusions There were no differences in weight gain or in BC measurements between the groups; nevertheless 40% of women in the DMPA group had larger weight gain and accumulation of fat centrally. The duration of follow-up may have been insufficient to detect differences between the groups. Chinese Abstract 摘要 目的 研究应用长效甲羟孕酮避孕对体重和身体成分的影响 方法 分别选取20名妇女开始使用长效甲羟孕酮避孕（DMPA组）以及20名开始使用含铜宫内节育器避孕（IUD组）进行队列研究，并按照年龄( ±1 岁)、体重指数（BMI± 1 kg/m2 ）进行配对。40名18-40岁的健康、体重适宜、没有其他可能影响体重因素的妇女入选。记录研究对象的社会人口学特征、生活习惯、体重、体重指数、应用X线骨密度仪测量身体成分、手臂、腰、臀以及大腿的周径、皮肤褶皱的厚度、体脂的百分比以及腰臀比的数据。鼓励所有的研究对象选取健康的生活方式及饮食习惯。 结果 入选时两组妇女的平均年龄分别为29岁及30.5岁，体重指数分别为24.8kg/m2以及24.5 kg/m2。12个月后DMPA组的妇女有腰围和臀围的增加，8/20的妇女体重增加≥5%（平均4.6kg）伴有中央性脂肪蓄积的特点。 结论 使用DMPA以及使用含铜IUD12个月后的两组妇女在体重增加以及身体成分上的变化没有差异，但是DMPA组有40%的妇女有更多的体重增加以及体脂的中央性蓄积。研究可能需要更长的随访时间来发现两组的差异。

Exploratory study of the effect of lifestyle counselling on bone mineral density and body composition in users of the contraceptive depot-medroxyprogesterone acetate

Abstract Objectives To compare variations in bone mineral density (BMD) and body composition (BC) in depot-medroxyprogesterone acetate (DMPA) users and nonusers after providing counselling on healthy lifestyle habits. Methods An exploratory study in which women aged 18 to 40 years participated: 29 new DMPA users and 25 new non-hormonal contraceptive users. All participants were advised on healthy lifestyle habits: sun exposure, walking and calcium intake. BMD and BC were assessed at baseline and 12 months later. Statistical analysis included the Mann-Whitney test or Students t-test followed by multiple linear regression analysis. Results Compared to the controls, DMPA users had lower BMD at vertebrae L1 and L4 after 12 months of use. They also had a mean increase of 2 kg in total fat mass and an increase of 2.2% in body fat compared to the non-hormonal contraceptive users. BMD loss at L1 was less pronounced in DMPA users with a calcium intake ≥ 1 g/day compared to DMPA users with a lower calcium intake. Conclusions DMPA use was apparently associated with lower BMD and an increase in fat mass at 12 months of use. Calcium intake ≥ 1 g/day attenuates BMD loss in DMPA users. Counselling on healthy lifestyle habits failed to achieve its aims. Chinese Abstract 摘 要 目的 比较健康生活习惯指导对长效醋酸甲羟孕酮应用者和不用者骨密度和体成分影响的差异。 方法 一项针对年龄在18岁至40岁妇女的探索性研究：29名用长效醋酸甲羟孕酮，25名用非激素类避孕。建议所有的参与者都养成健康的生活习惯：晒太阳，散步和摄入钙。在开始和12个月后评估骨密度和体成分。统计分析包括Mann-Whitney检验或多元线性回归分析后行t-检验。 结果 与对照组相比，用长效醋酸甲羟孕酮12个月后，脊椎L1和L4的骨密度较低。与非激素避孕药使用者比，他们的平均总脂肪增加了2kg，并且体内的脂肪增加2.2%；每天摄入1g钙的长效醋酸甲羟孕酮组与较低钙摄入的长效醋酸甲羟孕酮组比，两组L1的骨密度丢失不太明显。 结论 醋酸甲羟孕酮的使用与骨密度降低明显相关，并且用药12个月后脂肪含量增加。使用醋酸甲羟孕酮时，每天摄入1克钙会抑制骨质丢失。健康生活习惯的建议未能实现其目标。

Prevalence of Chlamydia trachomatis infection among women candidates for in vitro fertilization at a public institution of the State of São Paulo, Brazil

PURPOSE: To evaluate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among women candidates to in vitro fertilization (IVF) in a reference public service in southeastern Brazil. METHODS: Women who were referred for IVF from April 1st, 2008 to December 31st, 2009 were enrolled sequentially in the study. A ginecological-obstetrical background questionnaire was applied and endocervical swab samples were obtained to search for CT and NG using hybrid capture and PCR. The variables studied were: age, color, education, duration of infertility, number of pregnancies and living children, history of miscarriage, ectopic pregnancy, number of sex partners, pelvic inflammatory disease (PID), pelvic surgery, manipulation of the uterine cavity, smoking, and illicit drug use. The women were distributed according to the presence/absence of confirmed chlamydia infection and descriptive analysis was employed. RESULTS: Among 176 women tested the prevalence of CT infection was 1.1% and there was no NG infection. Two thirds of the women were >30 years old, with schooling >8 years and <5 years of infertility, and 56.2% had no children. The main background data were pelvic surgery (77.8%), manipulation of the uterine cavity (62.5%) and PID (27.8%). The tubal factor was the most prevalent, 73.3% of women (from 129), 37.5% had been sterilized, 35.8% had not been sterilized, and other factors had a prevalence <30%. CONCLUSIONS: CT and NG infections had a low prevalence in this sample. Studies at other centers in the country are needed to confirm the prevalence of infection in this particular group of infertile women.

Bleeding patterns of HIV-infected women using an etonogestrel-releasing contraceptive implant and efavirenz-based or lopinavir/ritonavir-based antiretroviral therapy.

Abstract Objectives: The use of progestogen-only contraceptives may cause a change in bleeding pattern, which is a common cause of discontinuation of these methods. Co-administration with some antiretroviral therapies (ART) changes the bioavailability of the etonogestrel (ENG)-releasing contraceptive implant, possibly affecting the bleeding pattern. Bleeding patterns were evaluated in HIV-positive users of the ENG implant co-administered with two common ART regimens. Methods: Forty-five HIV-positive women who wished to use an ENG implant were included in this study: 15 had received zidovudine/lamivudine (AZT/3TC) + lopinavir/ritonavir (LPV/r) for ≥3 months (LPV/r-based ART group), 15 had received AZT/3TC + efavirenz (EFV) for ≥3 months (EFV-based ART group), and 15 had not received ART (non-ART group). Bleeding patterns were evaluated at 3 and 6 months after implant placement using a standard bleeding calendar. Results: Amenorrhoea and infrequent bleeding rates were higher in the LPV/r-based ART group (50% and 36%, respectively) than in the other groups (non-ART group, 36% and 29%, respectively; EFV-based ART group, 7% and 14.5%, respectively; p = 0.01). The EFV-based ART group more frequently had regular bleeding (71.5%) compared with the other groups (LPV/r-based ART group, 7%; non-ART group, 21%; p = 0.01). The proportions of women with frequent and prolonged bleeding were similar (p > 0.05) in the three groups. Conclusions: The co-administration of EFV-based or LPV/r-based ART with the ENG implant affected the expected bleeding patterns during use of the implant, although unfavourable bleeding (frequent and prolonged) was not associated with the medications under evaluation.