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  1. 1
    396173
    Peer Reviewed

    Ecological study on the use of hormonal contraception, abortions and births among teenagers in the Nordic countries.

    Hognert H; Skjeldestad FE; Gemzell-Danielsson K; Heikinheimo O; Milsom I; Lidegaard O; Lindh I

    BMJ Open. 2018 Oct 30; 8(10):e022473.

    OBJECTIVES: Compare hormonal contraceptive use, birth and abortion rates among teenagers in the Nordic countries. A secondary aim was to explore plausible explanations for possible differences between countries. DESIGN: Ecological study using national registry data concerning births and abortions among all women aged 15-19 years residing in Denmark, Finland, Iceland, Norway and Sweden 2008-2015. Age-specific data on prescriptions for hormonal contraceptives for the period 2008-2015 were obtained from national databases in Denmark, Norway and Sweden. SETTING: Denmark, Finland, Iceland, Norway and Sweden. PARTICIPANTS: Women 15-19 years old in all Nordic countries (749 709) and 13-19 years old in Denmark, Norway and Sweden (815 044). RESULTS: Both annual birth rates and abortion rates fell in all the Nordic countries during the study period. The highest user rate of hormonal contraceptives among 15-19-year-olds was observed in Denmark (from 51% to 47%) followed by Sweden (from 39% to 42%) and Norway (from 37% to 41%). Combined oral contraceptives were the most commonly used methods in all countries. The use of long-acting reversible contraceptives (LARC), implants and the levonorgestrel-releasing intrauterine systems, were increasing, especially in Sweden and Norway. In the subgroup of 18-19-year-old teenagers, the user rates of hormonal contraceptives varied between 63% and 61% in Denmark, 56% and 61% in Norway and 54% and 56% in Sweden. In the same subgroup, the steepest increase of LARC was seen, from 2% to 6% in Denmark, 2% to 9% in Norway and 7% to 17% in Sweden. CONCLUSIONS: Birth and abortion rates continuously declined in the Nordic countries among teenagers. There was a high user rate of hormonal contraceptives, with an increase in the use of LARC especially among the oldest teenagers. (c) Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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  2. 2
    396082

    Sexual function and combined oral contraceptives - a randomised, placebo-controlled trial.

    Lundin C; Malmborg A; Slezak J; Gemzell-Danielsson K; Bixo M; Bengtsdotter H; Marions L; Lindh I; Theodorsson E; Hammar M; Sundstrom-Poromaa I

    Endocrine Connections. 2018 Sep 1;

    OBJECTIVE: The effect of combined oral contraceptives (COC) on female sexuality has long been a matter of discussion, but placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate if an estradiol-containing COC influences sexual function. DESIGN: Investigator-initiated, randomised, double-blinded, placebo-controlled clinical trial where 202 healthy women were randomized to a combined oral contraceptive (1.5 mg estradiol and 2.5 mg nomegestrol acetate) or placebo for three treatment cycles. METHODS: Sexual function at baseline and during the last week of the final treatment cycle was evaluated by the McCoy Female Sexuality Questionnaire. Serum and hair testosterone levels were assessed at the same time points. RESULTS: Compared to placebo, COC use was associated with a small decrease in sexual interest (COC median change score: -2.0; interquartile range (IQR): -5.0-0.5 vs. placebo: -1.0; IQR: -3.0-2.0, p = 0.019), which remained following adjustment for change in self-rated depressive symptoms B = -0.80 +/- 0.30, Wald = 7.08, p = 0.008. However, the proportion of women who reported a clinically relevant deterioration in sexual interest did not differ between COC or placebo users (COC 18 (22.2%) vs. placebo 16 (17.8%), p = 0.47). Change in other measured aspects of sexual function as well as total score of sexual function did not differ between the two treatments. CONCLUSIONS: This study suggests that use of estradiol-based combined oral contraceptives is associated with reduced sexual interest. However, the changes are minute, and probably not of clinical relevance.
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  3. 3
    392987
    Peer Reviewed

    Health-related quality of life in young women starting hormonal contraception: a pilot study.

    Kristjansdottir J; Sundelin C; Naessen T

    European Journal of Contraception and Reproductive Health Care. 2018 Jun; 23(3):171-178.

    OBJECTIVES: Our purpose was to study whether there is a difference in self-rated health-related quality of life (HRQOL) and changes in HRQOL perception after 3 months of hormonal contraceptive use in adolescents. Seasonal variations in symptoms of depression were also studied. METHODS: A test group (T1) (n = 193) and a selected control group (n = 238) of women aged 14-20 years who were visiting a young person's clinic completed the 36-item short-form health survey (SF-36) and answered additional questions on menstrual history and pattern, need for menstrual pain relief medication, and other regular medication. The test group was reassessed after 3 months of hormonal contraception (T2). Seasonal variations in reported SF-36 scores were studied for the whole group. RESULTS: The selected control group and test group at T1 were similar with regard to age at menarche and menstrual pattern. The duration of bleeding and use of painkillers were significantly reduced and the impact on everyday life was significantly improved after 3 months of hormonal contraception (p = .000, two-tailed). No changes in HRQOL or symptoms of possible depression were found after 3 months of hormonal contraception. The highest prevalence odds ratio for possible depression (SF-36 mental health scale score
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  4. 4
    392546
    Peer Reviewed

    Hormonal contraception increases the risk of psychotropic drug use in adolescent girls but not in adults: A pharmacoepidemiological study on 800 000 Swedish women.

    Zettermark S; Perez Vicente R; Merlo J

    PloS One. 2018; 13(3):e0194773.

    The burden of depression and anxiety disorders is greater in women, and female sex hormones have been shown to affect mood. Psychological side effects of hormonal contraception (HC) are also a common complaint in the clinic, but few previous studies have investigated this subject. We therefore wanted to investigate whether use of HC was associated with adverse psychological health outcomes, and whether this association was modified by age. All women aged 12-30 years on 31 December 2010, residing in Sweden for at least four years and with no previous psychiatric morbidity (n = 815 662), were included. We followed the women from their first HC use (or 31 December 2010, if they were non-users) at baseline, until a prescription fill of psychotropic drugs or the end of the one-year follow-up. We performed age-stratified logistic regression models and estimated odds ratios (OR) to measure the association between different HC methods and psychotropic drug use, as well as the area under the receiver operating curve to estimate discriminatory accuracy of HC in relation to psychotropic drugs. Overall, we found an association between HC and psychotropic drugs (adjusted OR 1.34, 95% confidence interval [CI] 1.30-1.37). In the age-stratified analysis, the strongest association was found in adolescent girls (adjusted OR 3.46, 95% CI 3.04-4.94 for age 12 to 14 years), while it was non-existent for adult women. We conclude that hormonal contraception is associated with psychotropic drug use among adolescent girls, suggesting an adverse effect of HC on psychological health in this population.
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  5. 5
    391428
    Peer Reviewed

    Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.

    Hognert H; Kopp Kallner H; Cameron S; Nyrelli C; Jawad I; Heller R; Aronsson A; Lindh I; Benson L; Gemzell-Danielsson K

    Human Reproduction. 2016 Nov; 31(11):2484-2490.

    STUDY QUESTION: Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? SUMMARY ANSWER: A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. WHAT IS ALREADY KNOWN: The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. STUDY DESIGN SIZE, DURATION: This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. MAIN RESULTS AND THE ROLE OF CHANCE: Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the +/-5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. LIMITATIONS, REASONS FOR CAUTION: For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. WIDER IMPLICATIONS OF THE FINDINGS: Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials number NCT01920022. TRIAL REGISTRATION DATE: 06 August 2013. DATE OF FIRST PATIENT'S ENROLMENT: 13 October 2013. (c) The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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  6. 6
    391403
    Peer Reviewed

    Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use.

    Bengtsdotter H; Lundin C; Gemzell Danielsson K; Bixo M; Baumgart J; Marions L; Brynhildsen J; Malmborg A; Lindh I; Sundstrom Poromaa I

    European Journal of Contraception and Reproductive Health Care. 2018 Feb; 23(1):45-51.

    PURPOSE: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders. MATERIALS AND METHODS: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychiatric Interview was used to collect information on previous or ongoing mental disorders. The primary outcome measure was the total change score in five mood symptoms on the Daily Record of Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment cycle. RESULTS: Women with ongoing or previous mood, anxiety or eating disorders allocated to COC had higher total DRSP Delta-scores during the intermenstrual phase of the treatment cycle in comparison with corresponding women randomised to placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without mental health problems, no difference in total DRSP Delta-scores between COC- and placebo users was noted. Women with a risk use of alcohol who were randomised to the COC had higher total DRSP Delta-scores than women randomised to placebo, mean difference 2.1 (CI 95% 1.0-3.2). CONCLUSIONS: Women with ongoing or previous mental disorders or risk use of alcohol have greater risk of COC-induced mood symptoms. This may be worth noting during family planning and contraceptive counselling.
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  7. 7
    390484
    Peer Reviewed

    Can voluntary pooled procurement reduce the price of antiretroviral drugs? a case study of Efavirenz.

    Kim SW; Skordis-Worrall J

    Health Policy and Planning. 2017 May 1; 32(4):516-526.

    Purpose: : A number of strategies have aimed to assist countries in procuring antiretroviral therapy (ARV) at lower prices. In 2009, as the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) commenced a voluntary pooled procurement scheme, however, the impact of the scheme on ARV prices remains uncertain. This study aims to estimate the effect of VPP on drug prices using Efavirenz as a case study. Methods: This analysis uses WHO Global price report mechanism (GPRM) data from 2004 to 2013. Due to the highly skewed distribution of drug Prices, a generalized linear model (GLM) was used to conduct a difference-in-difference estimation of drug price changes over time. Results: These analyses found that voluntary pooled procurement reduced both the ex-works price of generic Efavirenz and the incoterms price by 16.2 and 19.1%, respectively ( P < 0.001) in both cases). The year dummies were also statistically significant from 2006 to 2013 ( P < 0.001), indicating a strong decreasing trend in the price of Efavirenz over that period. Conclusion: Voluntary pooled procurement significantly reduced the price of 600 mg generic Efavirenz between 2009 and 2013. Voluntary pooled procurement therefore offers a potentially effective strategy for the reduction in HIV drug prices and the improvement of technical efficiency in HIV programming. Further work is required to establish if these findings hold also for other drugs.
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  8. 8
    390413
    Peer Reviewed

    Midwifery-led antenatal care models: mapping a systematic review to an evidence-based quality framework to identify key components and characteristics of care.

    Symon A; Pringle J; Cheyne H; Downe S; Hundley V; Lee E; Lynn F; McFadden A; McNeill J; Renfrew MJ; Ross-Davie M; van Teijlingen E; Whitford H; Alderdice F

    BMC Pregnancy and Childbirth. 2016 Jul 19; 16(1):168.

    BACKGROUND: Implementing effective antenatal care models is a key global policy goal. However, the mechanisms of action of these multi-faceted models that would allow widespread implementation are seldom examined and poorly understood. In existing care model analyses there is little distinction between what is done, how it is done, and who does it. A new evidence-informed quality maternal and newborn care (QMNC) framework identifies key characteristics of quality care. This offers the opportunity to identify systematically the characteristics of care delivery that may be generalizable across contexts, thereby enhancing implementation. Our objective was to map the characteristics of antenatal care models tested in Randomised Controlled Trials (RCTs) to a new evidence-based framework for quality maternal and newborn care; thus facilitating the identification of characteristics of effective care. METHODS: A systematic review of RCTs of midwifery-led antenatal care models. Mapping and evaluation of these models' characteristics to the QMNC framework using data extraction and scoring forms derived from the five framework components. Paired team members independently extracted data and conducted quality assessment using the QMNC framework and standard RCT criteria. RESULTS: From 13,050 citations initially retrieved we identified 17 RCTs of midwifery-led antenatal care models from Australia (7), the UK (4), China (2), and Sweden, Ireland, Mexico and Canada (1 each). QMNC framework scores ranged from 9 to 25 (possible range 0-32), with most models reporting fewer than half the characteristics associated with quality maternity care. Description of care model characteristics was lacking in many studies, but was better reported for the intervention arms. Organisation of care was the best-described component. Underlying values and philosophy of care were poorly reported. CONCLUSIONS: The QMNC framework facilitates assessment of the characteristics of antenatal care models. It is vital to understand all the characteristics of multi-faceted interventions such as care models; not only what is done but why it is done, by whom, and how this differed from the standard care package. By applying the QMNC framework we have established a foundation for future reports of intervention studies so that the characteristics of individual models can be evaluated, and the impact of any differences appraised.
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  9. 9
    389606
    Peer Reviewed

    Knowledge and utilization of sexual and reproductive healthcare services among Thai immigrant women in Sweden.

    Akerman E; Ostergren PO; Essen B; Fernbrant C; Westerling R

    BMC International Health and Human Rights. 2016 Oct 10; 16(1):25.

    BACKGROUND: Migration from Thailand to Sweden has increased threefold over the last 10 years. Today Thailand is one of the most common countries of origin among immigrants in Sweden. Since the year 2000, new HIV cases are also more prevalent among Thai immigrants compared to other immigrant nationalities in Sweden. The purpose of this study was to investigate the association between knowledge and utilization of sexual and reproductive healthcare services, contraceptive knowledge and socio-demographic characteristics and social capital among Thai immigrant women in Sweden. METHODS: This is a cross-sectional study using a postal questionnaire to all Thai women (18-64) in two Swedish regions, who immigrated to the country between 2006 and 2011. The questionnaire was answered by 804 women (response rate 62.3 %). Bivariate and multivariate logistic regression analyses were used. RESULTS: The majority (52.1 %) of Thai women had poor knowledge of where they should turn when they need sexual and reproductive healthcare services. After controlling for potential confounders, living without a partner (OR = 2.02, CI: 1.16-3.54), having low trust in others (OR = 1.61, CI: 1.10-2.35), having predominantly bonding social capital (OR = 1.50, CI: 1.02-2.23) and belonging to the oldest age group (OR = 2.65, CI: 1.32-5.29) were identified as risk factors for having poor knowledge. The majority (56.7 %) had never been in contact with healthcare services to get advice on contraception, and about 75 % had never been HIV/STI tested in Sweden. Low utilization of healthcare was associated with poor knowledge about healthcare services (OR = 6.07, CI: 3.94-9.34) and living without a partner (OR = 2.53, CI: 1.30-4.90). Most Thai women had knowledge of how to prevent an unwanted pregnancy (91.6 %) and infection with HIV/STI (91.1 %). CONCLUSIONS: The findings indicate that social capital factors such as high trust in others and predominantly bridging social capital promote access to knowledge about healthcare services. However, only one-fourth of the women had been HIV/STI tested, and due to the HIV prevalence among Thai immigrants in Sweden, policy makers and health professionals need to include Thai immigrants in planning health promotion efforts and healthcare interventions.
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  10. 10
    389365
    Peer Reviewed

    High birth rates despite easy access to contraception and abortion : a cross-sectional study.

    Hognert H; Skjeldestad FE; Gemzell-Danielsson K; Heikinheimo O; Milsom I; Lidegaard O; Lindh I

    Acta Obstetricia et Gynecologica Scandinavica. 2017 Dec; 96(12):1414-1422.

    INTRODUCTION: The aim was to describe and compare contraceptive use, fertility, birth and abortion rates in the Nordic countries. MATERIAL AND METHODS: National data on births, abortions, fertility rate (1975-2013), redeemed prescriptions of hormonal contraceptives and sales figures of copper intrauterine devices (2008-2013) among women 15-49 years of age in the Nordic countries were collected and analysed. RESULTS: Use of hormonal contraceptives and copper intrauterine devices varied between 31-44%. The highest use was in Denmark (39-44%) and Sweden (40-42%). Combined hormonal contraception followed by the levonorgestrel-releasing intrauterine system were the most common methods. During 1975-2013 abortion rates decreased in Denmark (27-15/1000 women aged 15-44) and Finland (20-10), remained stable in Norway ( approximately 16) and Sweden ( approximately 20) and increased in Iceland (6 -15). Birth rates remained stable around 60/1000 women aged 15-44 in all countries except for Iceland where the birth rate decreased from 95-65. Abortion rates were highest in the age group 20-24 years. In the same age group Sweden had a lower contraceptive use (51%) compared to Denmark (59%) and Norway (56%) and a higher abortion rate 33/1000 compared to Denmark (25/1000) and Norway (27/1000). CONCLUSIONS: In contrast to the declining average fertility and birth rates in Europe, rates in the Nordic countries remain high and stable despite high contraceptive use and liberal access to abortion on womens' request. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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  11. 11
    389131
    Peer Reviewed

    Perfect-use and typical-use Pearl Index of a contraceptive mobile app.

    Berglund Scherwitzl E; Lundberg O; Kopp Kallner H; Gemzell Danielsson K; Trussell J; Scherwitzl R

    Contraception. 2017 Dec; 96(6):420-425.

    OBJECTIVES: The Natural Cycles application is a fertility awareness-based contraceptive method, which uses dates of menstruation and basal body temperature to inform couples whether protected intercourse is needed to prevent pregnancies. Our purpose with this study is to investigate the contraceptive efficacy of the mobile application by evaluating the perfect- and typical-use Pearl Index. STUDY DESIGN: In this prospective observational study, 22,785 users of the application logged a total of 18,548 woman-years of data into the application. We used these data to calculate typical- and perfect-use Pearl Indexes, as well as 13-cycle pregnancy rates using life-table analysis. RESULTS: We found a typical-use Pearl Index of 6.9 pregnancies per 100 woman-years (95% CI: 6.5-7.2), corrected to 6.8 (95% CI: 6.4-7.2) when truncating users after 12months. We estimated a 13-cycle typical-use failure rate of 8.3% (95% CI: 7.8-8.9). We found that the perfect-use Pearl Index was 1.0 pregnancies per 100 woman-years (95% CI: 0.5-1.5). Finally we estimated that the rate of pregnancies from cycles where the application erroneously flagged a fertile day as infertile was 0.5 (95% CI: 0.4-0.7) per 100 woman-years. We estimated a discontinuation rate over 12months of 54%. CONCLUSIONS: This study shows that the efficacy of a contraceptive mobile application is higher than ususally reported for traditional fertility awareness-based methods. The application may contribute to reducing the unmet need for contraception. IMPLICATIONS: The measured typical- and perfect-use efficacy of the mobile application Natural Cycles are important parameters for women considering their contraceptive options as well as for the clinicians advising them. The large available dataset in this paper allows for future studies on acceptability, e.g. by studying the efficacy for different cohorts and geographic regions. Copyright (c) 2017. Published by Elsevier Inc.
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  12. 12
    388750

    Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study.

    Orellana C; Saevarsdottir S; Klareskog L; Karlson EW; Alfredsson L; Bengtsson C

    Annals of the Rheumatic Diseases. 2017 Nov; 76(11):1845-1852.

    OBJECTIVES: To study whether oral contraceptive (OC) use or breastfeeding (BF) influence the risk of rheumatoid arthritis (RA), stratifying the cases by presence/absence of anticitrullinated protein antibodies (ACPA), and whether these factors interact with known risk factors in the development of ACPA-positive RA. METHODS: Women aged >/=18 years, participants in the population-based case-control Swedish Epidemiological Investigation of RA study (2641 cases/4251 controls), completed an extensive questionnaire regarding OC, BF and potential confounders. We calculated ORs, with 95% CIs, adjusted for age, residential area, smoking and alcohol consumption. Attributable proportion due to interaction (AP) was estimated to evaluate presence of interaction. RESULTS: Compared with never users, ever and past OC users had a decreased risk of ACPA-positive RA (OR=0.84 (95% CI 0.74 to 0.96); OR=0.83 (95% CI 0.73 to 0.95), respectively). No significant associations were found for ACPA-negative RA. Long duration of OC use (>7 years vs never use) decreased the risk of both ACPA-positive (p=0.0037) and ACPA-negative RA (p=0.0356).A history of long BF decreased the risk only of ACPA-positive RA in a dose-dependent manner (p=0.0086), but this trend did not remain after adjustments. A significant interaction was observed between the lack of OC use and smoking (AP=0.28 (95% CI 0.14-0.42)) on the risk of ACPA-positive RA. No interactions were found for BF. CONCLUSIONS: OC decreased the risk of RA, especially ACPA-positive RA, where an interaction with smoking was observed. A long duration of OC use decreased the risk of both disease subsets. We could not confirm an association between BF and a decreased risk of either ACPA-positive or ACPA-negative RA.
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  13. 13
    388748
    Peer Reviewed

    Contraceptive pill is linked to lower risk of rheumatoid arthritis, study finds.

    Iacobucci G

    BMJ. 2017 Aug 17; 358:j3925.

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  14. 14
    388352

    Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.

    Engman J; Poromaa IS; Moby L; Wikstrom J; Fredrikson M; Gingnell M

    Neuropsychopharmacology. 2018 Feb; 43(3):555-563.

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9+/-4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 mug ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time-point targeted the mid-luteal phase in placebo users and steady state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdale-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared to the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity. EU Clinical Trials Register: Neuroanatomical and functional abnormalities in patients with aversive effects from oral contraceptives; https://www.clinicaltrialsregister.eu/; 2008-003123-24.Neuropsychopharmacology accepted article preview online, 25 July 2017. doi:10.1038/npp.2017.157.
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  15. 15
    388218
    Peer Reviewed

    Unintended Consequences of Gender Equality Promotion in Swedish Multicultural Contraceptive Counseling: A Discourse Analysis.

    Arousell J; Carlbom A; Johnsdotter S; Larsson EC; Essen B

    Qualitative Health Research. 2017 Aug; 27(10):1518-1528.

    In this article, we explore how reproductive health care providers in Sweden, a country often described as one of the most gender-equal countries in the world, incorporate gender equality ideals in multicultural contraceptive counseling. In the tension between gender equality promotion on one hand and respect for cultural diversity and individualized care on the other, we will demonstrate that values of gender equality were often given priority. This is not necessarily undesirable. Nevertheless, our proposal is that the gender equality ideology may inhibit providers' ability to think differently about issues at stake in contraceptive counseling, which may negatively influence women's possibilities to obtain adequate support. At the end of the article, we suggest how health care providers' reflexivity might be used as a working tool for increased awareness about the taken-for-granted cultural norms that exist in their clinical milieu.
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  16. 16
    379822
    Peer Reviewed

    Midwives' experiences of providing contraception counselling to immigrant women.

    Kolak M; Jensen C; Johansson M

    Sexual and Reproductive Healthcare. 2017 Jun; 12:100-106.

    OBJECTIVE: To describe midwives' experiences of providing contraception counselling to immigrant women. METHODS: The study was conducted with a qualitative design, based on interviews followed by inductive content analysis. Ten midwives were interviewed, working at midwife-led prenatal clinics in immigrant-dense areas in southern Sweden. RESULTS: Midwives require knowledge and understanding of cultures and religions in order to provide contraception counselling to immigrant women. It is important for the midwives to be aware that women have different values regarding sexual and reproductive health. The challenge for the midwives is to understand and to be curious about every woman's lifeworld perspective, culture and religion. The midwives knowledge and understanding of cultures and religions is acquired through experience and shared between them. Knowledge makes a midwife confident in her role as the contraception counselling provider to immigrant women. CONCLUSION: Cultural and religious factors affect contraception counselling. According to the midwives, knowledge and awareness of these factors is crucial and leads to improved understanding of midwives providing contraception counselling, better compliance, fewer unwanted pregnancies and improved sexual and reproductive health among women. Copyright (c) 2017 Elsevier B.V. All rights reserved.
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  17. 17
    379503
    Peer Reviewed

    A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial.

    Zethraeus N; Dreber A; Ranehill E; Blomberg L; Labrie F; von Schoultz B; Johannesson M; Hirschberg AL

    Fertility and Sterility. 2017 May; 107(5):1238-1245.

    OBJECTIVE: To determine whether there is a causal effect of oral contraceptive (OC) treatment on general well-being and depressed mood in healthy women. DESIGN: Double-blind, randomized, and placebo-controlled trial. SETTING: University hospital. PATIENT(S): Three hundred and forty healthy women aged 18-35 years randomized to treatment, of whom 332 completed the data collection at follow-up evaluation. INTERVENTION(S): A combined OC (150 mug levonorgestrel and 30 mug ethinylestradiol) or placebo for 3 months of treatment. MAIN OUTCOME MEASURE(S): Primary outcome measures: global score of Psychological General Well-Being Index (PGWBI) and the Beck Depression Inventory (BDI); secondary outcome measures: six separate dimensions of the PGWBI. RESULT(S): The OC treatment statistically significantly decreased general well-being compared with placebo -4.12 (95% CI, -7.18 to -1.06). Furthermore, OC decreased the following PGWBI dimensions compared with placebo: positive well-being -3.90 (95% CI, -7.78 to -0.01), self-control -6.63 (95% CI, -11.20 to -2.06), and vitality -6.84 (95% CI, -10.80 to -2.88). The effect of OC on depressive symptoms and on the PGWBI dimension depressed mood were not statistically significant. CONCLUSION(S): This study demonstrates a statistically significant reduction in general well-being by a first-choice OC in comparison with placebo in healthy women. We found no statistically significant effects on depressive symptoms. A reduction in general well-being should be of clinical importance. Copyright (c) 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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  18. 18
    376958
    Peer Reviewed

    Current status of a unique vaccine preventing pregnancy.

    Talwar GP; Nand KN; Gupta JC; Bandivdekar AH; Sharma RS; Lohiya NK

    Frontiers In Bioscience. 2017 Jun 01; 9:321-332.

    The ability of a vaccine linking beta hCG to a carrier to generate antibodies against hCG, its reversibility and safety was established by Phase I clinical trials conducted in India, Finland, Sweden, Chile and Brazil. Employing a hetero-species dimer (beta hCG-alphaoLH) linked to tetanus toxoid further improved the immunogenicity of the vaccine. Phase II clinical trials showed that anti-hCG titres above 50 ng/ml prevented pregnancy of sexually active fertile women without derangement of ovulation and menstrual regularity. On decline of antibodies, women conceived again to give birth to normal progeny. A genetically engineered vaccine consisting of beta hCG linked to B subunit of heat labile enterotoxin of E. coli has been made. It is expressed as DNA as well as protein. Priming with DNA followed by protein version of the vaccine generates very high titres against hCG in mice. Extensive toxicology studies in 2 species of rodents, and marmosets have shown complete safety of the vaccine. The vaccine is cleared for Clinical trials by the National Review committee on Genetic Manipulation and Drugs Controller General of India.
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  19. 19
    376527
    Peer Reviewed

    Global maternal health and newborn health: Looking backwards to learn from history.

    Bergstrom S

    Best Practice and Research. Clinical Obstetrics and Gynaecology. 2016 Oct; 36:3-13.

    The late appearance of the 'M' on the international health agenda - in its own right and not just as a carrier of the intrauterine passenger - is thought-provoking. The 'M' was absent for decades in textbooks of 'tropical medicine' until the rhetoric question was formulated: 'Where is the "M" in MCH?' The selective antenatal 'high-risk approach' gained momentum but had to give way to the fact that all pregnant women are at risk due to unforeseeable complications. In order to provide trained staff to master such complications in impoverished rural areas (with no doctors), some countries have embarked on training of non-physician clinicians/associate clinicians for major surgery with excellent results in 'task-shifting' practice. The alleged but non-existent 'human right' to survive birth demonstrates that there have been no concrete accountability and no 'legal teeth' to make a failing accountability legally actionable to guarantee such a right. Copyright (c) 2016. Published by Elsevier Ltd.
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  20. 20
    378643
    Peer Reviewed

    Cultural change after migration: Circumcision of girls in Western migrant communities.

    Johnsdotter S; Essen B

    Best Practice and Research. Clinical Obstetrics & Gynaecology. 2016 Apr; 32:15-25.

    This paper reviews the current knowledge on cultural change after migration in the practice of female circumcision, also named genital cutting or mutilation. Explorative studies show trends of radical change of this practice, especially the most extensive form of its kind (type III or the 'Pharaonic' type). The widespread interpretation that Islam would require circumcision of girls is questioned when, for example, Somalis meet other Muslim migrants, such as Arab Muslims, who do not circumcise their daughters. The few criminal court cases for circumcision of girls that have taken place in Western countries corroborate the conclusion that substantial change in the practice has occurred among migrants. In this literature review, an absence of reports is identified from healthcare providers who have witnessed circumcision after migration. Concurrently, a substantial knowledge exists on how to take care of already circumcised women and girls, and there is a system of recommendations in place regarding best practices for prevention. There is a great potential for healthcare providers to encourage this development towards general abandonment of circumcision of girls. The challenge for the future is how to incorporate culturally sensitive efforts of prevention on the one hand, and the examination of suspicious cases of illegal circumcision on the other. We recommend using--in a cautious way--the existing routines for identifying child abuse in general. Experiences from African contexts show that failure to generate significant change of the harmful practices/tradition may be due to the lack of multidisciplinary collaboration in different sectors of the society. In Western societies, the tendency toward abandonment of the practice could be reinforced by professionals who work toward better inclusion of men and women originally from countries where circumcision is practised. Copyright (c) 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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  21. 21
    378617
    Peer Reviewed

    Contraceptive non-use and emergency contraceptive use at first sexual intercourse among nearly 12 000 Scandinavian women.

    Guleria S; Juul KE; Munk C; Hansen BT; Arnheim-Dahlstrom L; Liaw KL; Nygard M; Kjaer SK

    Acta Obstetricia Et Gynecologica Scandinavica. 2016 Dec 28;

    INTRODUCTION: To describe recent patterns of contraceptive use at first sexual intercourse (FSI) and to examine whether selected factors are associated with non-use and emergency contraceptive pill (ECP) use at FSI, among 18-26-year-old women from Denmark, Norway and Sweden. MATERIAL AND METHODS: This was a population-based, questionnaire study of randomly chosen 18-26-year-old Scandinavian women. The prevalence of contraception methods used at FSI was calculated. Factors associated with contraceptive non-use and ECP use at FSI were determined using log binomial models. RESULTS: The prevalence of contraceptive non-use and ECP use was lowest in Denmark (9.6% % and 2.1%, respectively) compared with Norway (14.1% and 4.4%) and Sweden (16.6% and 4.5%). The risk of contraceptive non-use increased in women who had FSI at or before 14 years of age (13-14 years: PR 1.40; 95% CI 1.24-1.58). The risk of both non-use and ECP use increased when the partner at FSI was 20 years or older and with increasing age difference between the partner and the woman at her FSI. Smoking initiation prior to FSI increased risk of contraceptive non-use (PR 1.70; 95% CI 1.50-1.92), while alcohol initiation prior to FSI increased risk of ECP use at FSI (PR 1.95; 95% CI 1.49-2.54). CONCLUSIONS: Contraceptive non-use at FSI was strongly associated with early age at FSI. ECP and contraceptive non-use at FSI were both strongly associated with increasing partner age and an increasing difference in age between the woman and her partner. Hence, young women should be educated to negotiate contraceptive use with their partners. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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  22. 22
    378406
    Peer Reviewed

    Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries.

    Neogi U; Haggblom A; Singh K; Rogers LC; Rao SD; Amogne W; Schulter E; Zazzi M; Arnold E; Sarafianos SG; Sonnerborg A

    Journal of Antimicrobial Chemotherapy. 2016 Feb; 71(2):367-71.

    OBJECTIVES: The use of the NNRTI rilpivirine in low- and middle-income countries (LMICs) is under debate. The main objective of this study was to provide further clinical insights and biochemical evidence on the usefulness of rilpivirine in LMICs. PATIENTS AND METHODS: Rilpivirine resistance was assessed in 5340 therapy-naive and 13,750 first-generation NNRTI-failed patients from Europe and therapy-naive HIV-1 subtype C (HIV-1C)-infected individuals from India (n = 617) and Ethiopia (n = 127). Rilpivirine inhibition and binding affinity assays were performed using patient-derived HIV-1C reverse transcriptases (RTs). RESULTS: Primary rilpivirine resistance was rare, but the proportion of patients with >100,000 HIV-1 RNA copies/mL pre-ART was high in patients from India and Ethiopia, limiting the usefulness of rilpivirine as a first-line drug in LMICs. In patients failing first-line NNRTI treatments, cross-resistance patterns suggested that 73% of the patients could benefit from switching to rilpivirine-based therapy. In vitro inhibition assays showed approximately 2-fold higher rilpivirine IC50 for HIV-1C RT than HIV-1B RT. Pre-steady-state determination of rilpivirine-binding affinities revealed 3.7-fold lower rilpivirine binding to HIV-1C than HIV-1B RT. Structural analysis indicated that naturally occurring polymorphisms close to the NNRTI-binding pocket may reduce rilpivirine binding, leading to lower susceptibility of HIV-1C to rilpivirine. CONCLUSIONS: Our clinical and biochemical findings indicate that the usefulness of rilpivirine has limitations in HIV-1C-dominated epidemics in LMICs, but the drug could still be beneficial in patients failing first-line therapy if genotypic resistance testing is performed. (c) The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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  23. 23
    387620
    Peer Reviewed

    Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle-A double-blind, placebo-controlled randomized trial.

    Lundin C; Danielsson KG; Bixo M; Moby L; Bengtsdotter H; Jawad I; Marions L; Brynhildsen J; Malmborg A; Lindh I; Sundstrom Poromaa I

    Psychoneuroendocrinology. 2016 Nov 29; 76:135-143.

    OBJECTIVE: Ever since the introduction of combined oral contraception (COC), one of the major reasons for discontinuing the pill use has been mood-related side effects. Moreover, women who discontinue the pill turn to less effective methods whereby the probability of an unintended conception increases. Approximately 4-10% of COC users complain of depressed mood, irritability or increased anxiety, but drug-related causality has been difficult to prove. Given the lack of randomized controlled trials in this area, we aimed to prospectively estimate the severity of adverse mood in COC users that would be as representative of general users as possible. METHODS: This investigator-initiated, multi-center, randomized, double-blinded, placebo-controlled study included 202 healthy women. Women were randomized to a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo for three treatment cycles. Main outcome measure was the Daily Record of Severity of Problems (DRSP), which was filled out daily during one baseline cycle and the final treatment cycle. RESULTS: Results from 84 women in the COC group and 94 women in the placebo group were analysed. COC use was associated with small, but statistically significant, increases in mean anxiety (0.22; 95% CI: 0.07-0.37, p=0.003), irritability (0.23; 95% CI: 0.07-0.38, p=0.012), and mood swings scores (0.15; 95% CI: 0.00-0.31, p=0.047) during the intermenstrual phase, but a significant premenstrual improvement in depression (-0.33; 95% CI: -0.62 to -0.05, p=0.049). Secondary analyses showed that women with previous adverse hormonal contraceptive experience reported significantly greater mood worsening in the intermenstrual phase in comparison with healthy women, p<0.05. The proportion of women who reported a clinically relevant mood deterioration did not differ between those allocated to COC (24.1%) or placebo (17.0%), p=0.262. CONCLUSION: COC use is associated with small but statistically significant mood side effects in the intermenstrual phase. These findings are driven by a subgroup of women who clearly suffer from COC-related side effects. However, positive mood effects are noted in the premenstrual phase and the proportion of women with clinically relevant mood worsening did not differ between treatment groups. Copyright A(c) 2016 Elsevier Ltd. All rights reserved.
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  24. 24
    387577
    Peer Reviewed

    Contraceptive use in the Nordic countries.

    Lindh I; Skjeldestad FE; Gemzell-Danielsson K; Heikinheimo O; Hognert H; Milsom I; Lidegaard O

    Acta Obstetricia Et Gynecologica Scandinavica. 2016 Nov 12;

    INTRODUCTION: The aim was to compare contraceptive use in the Nordic countries and to assess compliance with recommendations from the European Medicines Agency regarding the use of combined oral contraceptives (COC) containing low dose estrogen and levonorgestrel, norethisterone or norgestimate MATERIAL AND METHODS: Data on hormonal contraceptive prescriptions and sales figures for copper intrauterine devices (Cu-IUD) were obtained from national databases and manufacturers in Denmark, Finland, Iceland, Norway and Sweden 2010-2013 RESULTS: Contraceptive use was highest in Denmark (42%) and Sweden (41%), followed by Finland (40%). COC were the most used method in all countries with the highest use in Denmark (26%). The second most used method was the levonorgestrel-releasing intrauterine system (LNG-IUS) with highest use in Finland (15%) and approximately 10% in the other countries. Cu-IUDs (7%) and the progestin-only pill (7%) were most often used in Sweden. COC use decreased with increasing age and LNG-IUS and progestin-only pills use increased. The use of long acting reversible methods of contraception (= LNG-IUS, Cu-IUD, and implants) increased by time and was highest in Sweden (20%) and Finland (18%). The highest use of European Medicines Agency recommended COC was in Denmark, increasing from 13 - 50% between 2010 - 2013. In Finland the recommended COC remained below one per cent CONCLUSION: Contraceptive use was highest in Denmark and Sweden, LNG-IUS use was highest in Finland and all long acting methods were most common in Sweden. The use of COC recommended by the European Medicines Agency was highest in Denmark. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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  25. 25
    373526

    Urinary steroid profile in females -the impact of menstrual cycle and emergency contraceptives.

    Mullen JE; Thorngren JO; Schulze JJ; Ericsson M; Garevik N; Lehtihet M; Ekstrom L

    Drug Testing and Analysis. 2016 Oct 18;

    Today's doping tests involving longitudinal monitoring of steroid profiles are difficult in women. Women have more complex hormonal fluctuations than men and commonly take drugs such as hormonal contraceptives that are shown to affect biomarkers used in these doping tests. In this study we followed six women's urinary steroid profile during one menstrual cycle, including both glucuronides and sulfate conjugated fractions. Additionally, we studied what happens to the steroidal module of the athlete biological passport (ABP) after administration of an emergency contraceptive (levonorgestrel, NorLevo(R)). The study shows that there are large individual variation in all metabolites included in the ABP and that the administration of emergency contraceptives may lead to suspicious steroid profile findings in the ABP. Urinary epitestosterone concentration increased during the menstrual cycle, leading to a decrease in the testosterone/epitestosterone ratio. The ratios followed in the ABP varied widely throughout the menstrual cycle, the coefficient of variation (CV) ranging from 4 to 99%. There was a 3-fold decrease in epitestosterone 24 hours post administration of the emergency contraceptive pill and also androsterone, etiocholanolone, and 5beta- androstan-3alpha,17beta-diol concentrations decreased about 2-fold. When analyzed with the ABP software, one of the six women had an atypical profile after taking the emergency contraceptive. Furthermore, we could not find any alterations in excretion routes (i.e. if the metabolites are excreted as glucuronide or sulfate conjugates) during the menstrual cycle or after administration of emergency contraceptive, indicating no direct effect on phase II enzymes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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