1. |
- Hellberg, Sandra, 1986-
(författare)
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Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement.The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment.The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells.This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.
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2. |
- Hellberg, Sandra, et al.
(författare)
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Maintained thymic output of conventional and regulatory T cells during human pregnancy
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - Philadelphia, United States : American Academy of Allergy, Asthma and Immunology. - 0091-6749 .- 1097-6825. ; 143:2, s. 771-775.e7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- During pregnancy, immunological tolerance toward the semiallogeneic fetus needs to be established while at the same time an effective immune defense must be maintained.1 The pregnancy-associated thymic involution reported in rodents2 has been suggested to support maternal immune regulation by reducing the output of potentially harmful TH cells. However, the functional importance of this thymic involution remains unclear and it is not known whether it even occurs in humans.3 In fact, the role of thymus during human pregnancy and in pregnancy-associated tolerance remains largely unknown,4 albeit a role for thymic-derived regulatory T (Treg) cells in pregnancy complications has been suggested,4 supporting a role for thymus in immune regulation during human pregnancy. The aim of this study was to assess the role of thymus in TH-cell regulation during human pregnancy by analyzing the output of different TH-cell populations.
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3. |
- Kempe, Per, et al.
(författare)
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Immune profile in relation to sex steroid cyclicity in healthy women and women with multiple sclerosis
- 2018
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 1:26, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- To prospectively study systemic in vivo immunological effects of sex hormones, using different phases of oral combined hormonal contraceptives (CHC), and the natural menstrual cycles in both healthy women and in women with multiple sclerosis (MS), blood samples from sixty female MS patients and healthy controls with and without CHC were drawn in high and low estrogenic/progestogenic phases. Expression of Th-associated genes in blood cells was determined by qPCR and a panel of cytokines and chemokines was measured in plasma. High hormone level phases were associated with increases in Th1 (TBX21) and Th2 (GATA3) associated markers, as well as the B cell-associated chemokine CXCL13, while the inhibitory regulator CTLA-4 was decreased. These changes were not observed in MS patients, of whom most were treated with immunomodulatory drugs. Our data indicate immune activating properties in vivo of high steroid sex hormone levels during both CHC and normal menstrual cyclicity.
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4. |
- Kempe, Per, et al.
(författare)
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T cell subset-associated transcription factors, cytokines and chemokines in relation to the menstrual cycle and use of combined hormonal contraceptives in women with multiple sclerosis and healthy controls
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Study question: Do peripheral blood levels of cytokines, chemokines, and transcription factors for different T helper (Th) cell subsets change in relation to high and low estrogen/progestogen states in women with multiple sclerosis (MS) and healthy controls with and without combined hormonal contraceptives (CHC)?Summary answer: Our findings indicate a general activation of peripheral blood T cells and B cells during high estrogen/progestogen phases with higher levels of transcription factors associated with both Th1 (TBX21) and Th2 (GATA3) subsets of T cells and the B cell-associated chemokine CXCL13.What is known already: There are some indications that sex steroids may positively affect MS clinically and immunologically.Study design, size, duration: A total of 60 women were included. Paired blood samples were drawn in high and low estrogen/progestogen phases during the same cycle in women using or not using CHC.Participants/materials, setting, methods: Participants were female MS patients and healthy controls with and without CHC. Concentrations of cytokines and chemokines were measured using multiplex bead technology and expression of transcription factors in blood cells was determined by qPCR. Owing to possible differences in cell composition, expression of Th-associated transcription factors were normalized to the T cell-specific transcription factor CD3E.Main results and the role of chance: Sixty women were included but 13 women dropped out, leaving 47 women to the statistical analyses. In healthy controls using CHC, both TBX21, and GATA3 expression was higher in the high estrogen/progestogen phase than in the low estrogen/progestogen phase. TBX21 expression in high estrogen/progestogen phase differed significantly between groups with the highest levels in healthy controls without CHC. In all MS patients as well as in healthy controls using CHC, the concentrations of CXCL13 was significantly higher in the high estrogen/progestogen phase compared to the low estrogen/progestogen phase.Limitations, reasons for caution: The low number of participants. A majority of the MS patients were using immunomodulatory drugs which may have interfered with the results. The study design makes it impossible to differ between estrogenic and progestogenic effects.Wider implications of the findings: Our findings show that high and low levels of estrogens and/or progestogens differently affect immune parameters related to Th cell subsets as well as B cells. The differences between high- and low estrogen/progestogen phases were most obvious in women using CHC indicating that CHC is more potent than 17β-Estradiol/progesterone in inducing immune changes in both MS patients and healthy women.Study funding/competing interest(s): This study was funded by the County Councils of Östergötland and Västernorrland, Sweden. No author have any conflicts of interest to declare.
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5. |
- Papapavlou, Georgia, et al.
(författare)
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Differential effects of estradiol and progesterone on human T cell activation in vitro
- 2021
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Ingår i: European Journal of Immunology. - : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 51:10, s. 2430-2440
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Tidskriftsartikel (refereegranskat)abstract
- Estradiol (E2) and progesterone (P4) are steroid hormones important for the regulation of immune responses during pregnancy. Their increasing levels coincide with an improvement of T cell-mediated diseases such as multiple sclerosis (MS). Although immune-endocrine interactions are involved in this phenomenon, the relative contribution of hormones is not known. We here report a direct comparison of E2- and P4-mediated effects on human CD4+ T cells, key cells in immune regulation. T cells were stimulated to obtain different activation levels and exposed to a broad range of hormone concentrations. Activation level was assessed by CD69/CD25 expression by flow cytometry, and secreted proteins (n = 196) were measured in culture supernatants using proximity extension assay and electrochemiluminescence immunoassay. We found that in low activated cells, pregnancy-relevant E2 concentrations increased activation and the secretion of several immune- and inflammation-related proteins. P4, on the other hand, showed a biphasic pattern, where serum-related concentrations upregulated activation and protein secretion while placenta-relevant concentrations induced a prominent dampening irrespective of the initial activation level. Our results demonstrate the importance of P4 as a major hormone in the immune modulation of T cells during pregnancy and emphasize the need to further evaluate its potency in the treatment of diseases like MS.
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6. |
- Almen-Christensson, Anna, et al.
(författare)
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Prevention of menstrual migraine with perimenstrual transdermal 17-beta-estradiol: a randomized, placebo-controlled, double-blind crossover study
- 2011
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Ingår i: Fertility and Sterility. - : Elsevier Science B.V., Amsterdam.. - 0015-0282 .- 1556-5653. ; 96:2, s. 498-500
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Tidskriftsartikel (refereegranskat)abstract
- he effect of treatment with percutaneous E(2) (100 mu g/24 h) during 2 weeks perimenstrually on the number and severity of menstrual migraine attacks was studied in 27 women in a randomized, placebo-controlled, double-blind, crossover trial. We were not able to demonstrate any difference between E(2) supplementation and placebo on the number or severity of migraine attacks, but both regimens showed significant effects compared with before treatment.
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7. |
- Axelsson, Daniel, et al.
(författare)
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Maternal obesity and the risk of postpartum infections according to mode of delivery
- 2023
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Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa Healthcare. - 1476-7058 .- 1476-4954. ; 36:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the present study was to assess the impact of different maternal Body Mass Index (BMI) classes on the risk of postpartum endometritis, wound infection, and breast abscess after different modes of delivery. Secondly to estimate how the risk of postpartum infection varies with different maternal BMI groups after induction of labor and after obstetric anal sphincter injuries.Methods: A population-based observational study including women who gave birth during eight years (N = 841,780). Data were collected from three Swedish Medical Health Registers, the Swedish Medical Birth Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. Outcomes were defined by ICD-10 codes given within eight weeks postpartum. The reference population was uninfected women. Odds ratios were determined using Mantel-Haenszel technique. Year of delivery, maternal age, parity and smoking in early pregnancy were considered as confounders.Results: There was a dose-dependent relationship between an increasing maternal BMI and a higher risk for postpartum infections. Women in obesity class II and III had an increased risk for endometritis after normal vaginal delivery aOR 1.45 (95% CI: 1.29-1.63) and for wound infections after cesarean section aOR 3.83 (95% CI: 3.39-4.32). There was no difference in how maternal BMI affected the association between cesarean section and wound infection, regardless of whether it was planned or emergent. Women in obesity class II and III had a lower risk of breast abscess compared with normal-weight women, aOR 0.47 (95% CI: 0.38-0.58). The risk of endometritis after labor induction decreased with increasing maternal BMI. The risk of wound infection among women with an obstetrical sphincter injury decreased with increasing BMI.Conclusion: This study provides new knowledge about the impact of maternal BMI on the risk of postpartum infections after different modes of delivery. There was no difference in how BMI affected the association between cesarean section and wound infections, regardless of whether it was a planned cesarean section or an emergency cesarean section.
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8. |
- Axelsson, Daniel, et al.
(författare)
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Postpartum infection in relation to maternal characteristics, obstetric interventions and complications
- 2018
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Ingår i: Journal of Perinatal Medicine. - : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 46:3, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to evaluate the association between maternal characteristics, obstetrical interventions/complications and postpartum wound infections (WI), urinary tract infection (UTI) and endometritis. Furthermore, this study aimed to determine the time from delivery to onset of infections after discharge from the hospital. Three large Swedish Medical Health Registers were scrutinized for the period 2005-2012. A total of 582,576 women had 795,072 deliveries. Women with diagnosis codes for WIs, UTIs or endometritis, from delivery to 8 weeks postpartum, were compared to non-infected women. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Increasing age and body mass index (BMI) were both associated with increasing prevalence of postpartum infections. WIs were most strongly associated with cesarean section (CS) (OR 17.2; 95% CI 16.1-18.3), 3rd and 4th degree tears (OR 10.7%; 95% CI 9.80-11.9) and episiotomy (OR 10.2; 95% CI 8.94-11.5). Endometritis was associated with anemia (OR 3.16; 95% CI 3.01-3.31) and manual placental removal (OR 2.72; 95% CI 2.51-2.95). UTI was associated with emergency CS (OR 3.46; 95% CI 3.07-3.89) and instrumental delivery (OR 3.70; 95% CI 3.29-4.16). For women discharged from the delivery hospital the peak occurrence of UTI was 6 days postpartum, while for WIs and endometritis it was 7 days postpartum.
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9. |
- Axelsson, Daniel, 1974-
(författare)
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Postpartum infections; prevalence, associated obstetric factors and the role of vitamin D
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Postpartum infections are a major cause of maternal mortality and morbidity worldwide. Breast infection, endometritis, urinary tract infection and wound infections are the most common postpartum infections and together they affect almost 20% of women after childbirth. Some risk factors for postpartum infections, for example cesarean section, have been relatively well studied, but other presumable risk factors are yet to be confirmed.The proportion of pregnant women who are overweight or obese is increasing in most parts of the world. Increased maternal body mass index (BMI) is associated with maternal and infant morbidity. The association between overweight / obesity and postpartum infections is incompletely understood. Vitamin D deficiency has in epidemiological studies been shown to increase the risk of various infections. Furthermore, vitamin D is an important factor in the human immune system. Concomitantly, vitamin D supplementation seems protective against some types of infections. Whether vitamin D deficiency is a risk factor for postpartum infections has not been studied.Material and Methods: In a population-based observational study using questionnaires, the prevalences of postpartum wound infections, endometritis, urinary tract infections and mastitis in the southeast region of Sweden were estimated (Paper I). All women giving birth in the region during one year (n=11 124) were asked to participate. Papers II and III were cohort studies based on all deliveries in Sweden during eight years (2005-2012). Data sources were the Swedish Medical Birth Register, the Swedish National Patient Register and the Swedish Prescribed Drugs Register. In paper II all term deliveries were included (n=795 072). Risk factors for postpartum wound infections, endometritis and urinary tract infection were evaluated. Paper III included all deliveries (n=841 780) and examined the impact of BMI on the risk of postpartum wound infections, endometritis and breast abscess after different modes of delivery. Infections were defined as the presence of applicable ICD-10 codes. The Mantel-Haenszel technique was used to calculate adjusted odds ratios. In paper IV the association between vitamin D deficiency and overall postpartum infectious morbidity was analyzed. Serum samples from the Pregnancy Biobank in Linköping, drawn at the time of delivery, were used to determine concentrations of 25-hydroxyvitamin D in 1397 women. ICD-10 codes were extracted from the women’s medical records. The prevalence of vitamin D deficiency was calculated and adjusted odds ratios for postpartum infections were estimated with multivariable logistic regression analysis.Results: More than one out of ten women in southeast Sweden reported wound infections; endometritis, urinary tract infection or mastitis postpartum and 7.5% reported antibiotic treatment for infection. Cesarean section was the strongest risk factor for wound infection, followed by obstetric anal sphincter injuries and episiotomy. For endometritis, the strongest risk factors were anemia, manual placental removal and emergency cesarean section. Urinary tract infection was associated with anemia, instrumental vaginal delivery and emergency cesarean section. There was a dose-dependent increased risk of postpartum infection with higher BMI. For morbidly obese women the risk of infection was over 50% higher than for normal weight women. The risk of endometritis after normal vaginal delivery increased the higher the BMI, as did the risk of wound infection after cesarean section, regardless of the type of cesarean section. For breast abscess, there was an inverse association with BMI.Vitamin D deficiency was present among almost 60% of pregnant women at the time of delivery. No association between vitamin D deficiency and postpartum infections was found.Conclusions: Every tenth Swedish woman acquired an infection postpartum and three quarters of them received antibiotics for infection. Anemia was an important risk factor for postpartum infection, and the strongest risk factor for endometritis and urinary tract infection. Strong efforts should be made to reduce blood loss during and after childbirth. This thesis confirmed cesarean section as a major risk factor for postpartum infection, especially wound infection. The risk increased if the woman was overweight or obese, regardless of whether it was a planned or an emergency cesarean section.Vitamin D deficiency was common among Swedish pregnant women, but it was not found to be associated with postpartum infections.
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10. |
- Axelsson, Daniel, et al.
(författare)
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Vitamin D deficiency at the time of delivery : Prevalence and risk of postpartum infections
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postpartum infections are a common cause of morbidity after childbirth. Vitamin D deficiency has been shown to increase the risk for several infections in a non-pregnant population. Vitamin D deficiency has been described as common in pregnant women.Objective: To investigate whether vitamin D deficiency in pregnant women in labor was associated with an increased risk of overall postpartum infectious morbidity within eight weeks of delivery. A secondary aim was to estimate the prevalence of vitamin D deficiency among pregnant women in Linkoping, Sweden at the time of delivery.Material and methods: Serum vitamin D levels in labor were analyzed for 1397 women. Vitamin D deficiency was defined as serum levels <50 nmol/L. All ICD-10 codes given to the women eight weeks postpartum were reviewed and postpartum infections were defined as the presence of an ICD-10 code suggestive of infection. The prevalence of postpartum infections among women with sufficient vitamin D levels was compared with women with vitamin D deficiency. Adjusted Odds Ratios and 95% confidence intervals for postpartum infections were calculated using multivariate logistic regression analysis.Results: Fifty eight per cent of the women had serum vitamin D levels <50 nmol/L. The proportion of women with vitamin D deficiency varied, as expected, with season. No association between vitamin D deficiency and postpartum infections was found. For vitamin D 25-50 nmol/L the adjusted Odds Ratio was 0.85 (95% confidence interval 0.56-1.29) and for vitamin D <25 nmol/L the adjusted Odds Ratio was 1.15 (95% confidence interval 0.66-2.03). Women who smoked or who had a cesarean section had an increased risk of postpartum infections.Conclusions: Vitamin D deficiency was more common than previously reported in Swedish pregnant women. No association between vitamin D deficiency and postpartum infections was found. Other well-known risk factors for postpartum infection were identified.
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11. |
- Bengtsdotter, H., et al.
(författare)
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Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use
- 2018
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Ingår i: European Journal of Contraception and Reproductive Health Care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 23:1, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- 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 (1.5mg estradiol and 2.5mg 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 -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 -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 -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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12. |
- Berin, Emilia, et al.
(författare)
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Contraceptive knowledge and attitudes among women seeking induced abortion in Kathmandu, Nepal
- 2014
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Ingår i: International Journal of Women's Health. - : Dove Medical Press. - 1179-1411. ; 6:1, s. 335-341
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To map the knowledge about and attitudes toward birth control methods among women in Kathmandu, Nepal, and to compare the results between women seeking an induced abortion and a control group. Method: This was a cross-sectional cohort study with matched controls. Women aged 15-49 years seeking medical care at the Department of Gynecology and Obstetrics at Kathmandu Medical College were included and interviewed. A case was defined as a woman who sought an elective medical or surgical abortion. A control was defined as a woman who sought medical care at the outpatient department or had already been admitted to the ward for reasons other than elective abortion. A questionnaire developed for the study - dealing with different demographic characteristics as well as knowledge about and attitudes toward contraceptives - was filled out based on the interview. Results: A total of 153 women were included: 64 women seeking an abortion and 89 controls. Women seeking an abortion had been pregnant more times than the control group and were more likely to have been informed about contraceptives. Women with higher education were less likely to seek an abortion than women with lower education. There was no significant difference in knowledge about and attitudes toward contraceptives between cases and controls. The women considered highest possible effectiveness to be the most important feature when deciding on a birth control method. Conclusion: Women seeking abortion in Kathmandu had shorter education and a history of more pregnancies and deliveries than women in the control group. Education and counseling on sex and reproduction as well as on contraceptive methods probably need to be improved in Nepal to avoid unwanted pregnancies. Attitudes about contraceptives need to be further investigated to develop better and more effective methods to educate women about family planning in order to increase reproductive health. © 2014 Berin et al.
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13. |
- Birch Tyrberg, Rasmus, et al.
(författare)
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Students’ and teachers’ attitudes towards PBL-curriculum components in a medical programme : a follow-up study
- 2021
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Ingår i: MedEdPublish. - : Association for Medical Education in Europe. - 2312-7996. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to explore students' and teachers' attitudes towards horizontal and vertical integration and other components of the curriculum, and to compare these results with data from a study at our medical school published in 2002.Methods: A questionnaire with 17 questions regarding different components of our curriculum was sent to students and staff at our medical school. They were asked to rate the importance of different components on a Likert scale from 1-6. We compared the answers between the two groups, and also compared them with the results from 2002.Results: Horizontal and vertical integration were rated as very important components (Teachers (n=283) median 5 and 5, Students (n=596) 6 and 5 respectively). Students valued lectures and clinical rotations more highly than teachers. Teachers considered laboratory training, training in searching scientific literature, scientific projects, basic education in ethics, reading and discussion of fictional literature, interprofessional components and examinations as significantly more important than the students did.Conclusions: Attitudes have remained positive towards horizontal and vertical integration despite major changes in the curriculum. The majority of the components of our curriculum were well appreciated, indicating that our curriculum is robust, but some components warrant inspection and possible revision.
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14. |
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15. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Attitudes among students and teachers on vertical integration between clinical medicine and basic science within a problem-based undergraduate medical curriculum
- 2002
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Ingår i: Medical teacher. - : Informa UK Limited. - 0142-159X .- 1466-187X. ; 24:3, s. 286-288
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Tidskriftsartikel (refereegranskat)abstract
- Important elements in the curriculum at the Faculty of Health Sciences in Link÷ping are vertical integration, i.e. integration between the clinical and basic science sections of the curriculum, and horizontal integration between different subject areas. Integration throughout the whole curriculum is time-consuming for both teachers and students and hard work is required for planning, organization and execution. The aim was to assess the importance of vertical and horizontal integration in an undergraduate medical curriculum, according to opinions among students and teachers. In a questionnaire 102 faculty teachers and 106 students were asked about the importance of 14 different components of the undergraduate medical curriculum including vertical and horizontal integration. They were asked to assign between one and six points to each component (6 points = extremely important for the quality of the curriculum, 1 point = unimportant). Students as well as teachers appreciated highly both forms of integration. Students scored horizontal integration slightly but significantly higher than the teachers (median 6 vs 5 points, p=0.009, Mann-Whitney U-test), whereas teachers scored vertical integration higher than students (6 vs 5, p=0.019, Mann-Whitney U-test). Both students and teachers considered horizontal and vertical integration to be highly important components of the undergraduate medical programme. We believe both kinds of integration support problem-based learning and stimulate deep and lifelong learning and suggest that integration should always be considered deeply when a new curriculum is planned for undergraduate medical education.
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16. |
- Brynhildsen, Jan, 1962-
(författare)
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Combined hormonal contraceptives : prescribing patterns, compliance, and benefits versus risks
- 2014
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Ingår i: Therapeutic Advances in Drug Safety. - : Sage Publications. - 2042-0986 .- 2042-0994. ; 5:5, s. 201-213
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Forskningsöversikt (refereegranskat)abstract
- Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the ‘real-life’ efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy.
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17. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? : A prospective study among female soccer players
- 2007
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 7:6, s. 348-353
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Tidskriftsartikel (refereegranskat)abstract
- Female sex hormones have been suggested to affect the risk of low back pain. One reason is the fact that back pain is a very common symptom during pregnancy. It also seems to be a more common problem among female than male athletes, e.g. in soccer. Although there are few scientific data supporting a relationship between female sex hormones, use of oral contraceptives and low back pain, many doctors and physiotherapists advise women with low back pain to avoid oral contraceptives. The aim of this study was to evaluate whether low back pain fluctuated during the menstrual cycle and differed between women using and not using oral contraceptives. A questionnaire was sent to 12 female soccer teams; 261 players answered and 50 players (28 with back pain and 22 controls) fulfilled the prospective study. At baseline the players underwent a thorough clinical examination and then filled in a diary concerning menstrual data, back pain, training and matches during one season. A total of 296 menstrual cycles was analysed. No difference in prevalence or severity of back pain was seen between the different phases of the menstrual cycle or between users and non-users of oral contraceptives. Our data do not support the hypothesis that low back pain is influenced by hormonal fluctuations during the menstrual cycle or by use of oral contraceptives.
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18. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Follow-Up of Patients With Low Back Pain During Pregnancy
- 1998
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Ingår i: Obstetrics and Gynecology. - : American College of Obstetricians and Gynecologists (ACOG). - 0029-7844 .- 1873-233X. ; 91:2, s. 182-186
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify the long-term risk for low back pain among women with previous severe low back pain during pregnancy.Methods: In a previous prospective study, 79 pregnant women developed low back pain severe enough to require sick leave. Twelve years later a questionnaire was sent to 62 of these women and 84 controls who did not develop severe low back pain during pregnancy. The questionnaire asked about occupation, low back pain in general and during later pregnancies, and sick leave due to low back pain. There were also questions regarding use of oral contraceptives and its possible relation to low back pain.Results: The response rate was 84% in the back pain group and 80% among controls. The two groups were similar according to the percentage of women having had another pregnancy (33 of 52 [63%] versus 39 of 67 [58%]) but ten (19%) of the women with previous low back pain stated they had refrained from another pregnancy because of their fear of low back pain compared with only one control. Almost all women (31 of 33) with previous severe low back pain experienced the same symptoms in a subsequent pregnancy, compared with 17 of 39 (44%) controls. Even when they were not pregnant, women with previous low back pain suffered more often and used more sick leave due to low back pain (44 of 52 versus 43 of 67, chi(2) = 5.68, P < .05). The location (sacroiliac joint or lumbar affection) of the previous low back pain did not affect the long-term prognosis. In a logistic regression model, previous low back pain during pregnancy was the only independent risk factor for low back pain during a subsequent pregnancy, whereas an occupation involving physical demand did not affect the results. However, together with previous low back pain during pregnancy, heavy occupation increased the risk for current nonpregnant low back pain.Conclusion: Women with severe low back pain during pregnancy have an extremely high risk for experiencing a new episode of severe low back pain during another pregnancy and when not pregnant.
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19. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Is Hormone Replacement Therapy a Risk Factor for Low Back Pain Among Postmenopausal Women?
- 1998
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Ingår i: Spine. - : Wolters Kluwer. - 0362-2436 .- 1528-1159. ; 23:7, s. 809-813
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Tidskriftsartikel (refereegranskat)abstract
- Study Design: Cross-sectional study with two age cohorts.Objective: To assess whether women receiving hormone replacement therapy after menopause have a higher prevalence of back problems than women who do not receive such treatment.Background: Back pain is a common medical problem: throughout life and especially during pregnancy. Hormonal factors have been proposed as a possible contributor.Patients and Methods: A validated postal questionnaire was sent in early 1995 to all 1324 women of 55 years and 56 years of age residing in Linkoping, Sweden. This questionnaire included questions about current rent hormone replacement treatment, previous and current back problems, medical care for back problems, parity, exercise and smoking habits, and occupation.Results: The questionnaire was returned by 84.7% of the women. There was a significant, albeit weak, positive association between current use of hormone replacement treatment and low back pain. Previous back problems during pregnancy was a strong risk factor for current back pain, whereas neither current smoking nor regular physical exercise was a risk factor according to multiple logistic regression analysis. The interaction of smoking and an occupation involving heavy lifting significantly affected back pain.Conclusions: Women receiving hormone replacement treatment had a slightly, but significantly, higher prevalence of current back pain than nonusers (48% vs. 42%, respectively, P < 0.05), which could not be explained by differences in occupation, smoking habits, or current physical activity. Although the association be-tween hormone replacement therapy and back problems is weak and probably of minor clinical importance, it is speculated that hormonal effects on joints and ligaments may be involved.
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20. |
- Brynhildsen, Jan, et al.
(författare)
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Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers
- 2013
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 102:6, s. 620-624
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Tidskriftsartikel (refereegranskat)abstract
- Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.
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21. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Lipids and clotting factors during low dose transdermal estradiol/norethisterone use
- 2005
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Ingår i: Maturitas. - : Elsevier. - 0378-5122 .- 1873-4111. ; 50:4, s. 344-352
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis.Methods: A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks.Results: In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholestrol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year.Conclusions: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
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22. |
- Brynhildsen, Jan, 1962-
(författare)
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Low back pain in women in relation to different exposures to female sex hormones
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To investigate the effects of increased exposition to female sex hormones and physical strain on the prevalence of low back pain (LBP) in women. To study the etJect of increased exposition to female sex hormones on spinal sagiual mobility.Background: Scientific data and clinical observations suggest an increased prevalence of LBP in women as compared with men, especially in athletes. Estrogen receptors arc present in the musculo-skeletal apparatus and in the central nervous system and female sex hormones have been suggested to affect the stability of the pelvic joints and the perception of pain. The impaired stability together with a hypermobile spine may cause increased isometric muscular work, and as a consequence, pain. Also the perception of pain may be altered by female sex hormones. Because LBP is more common in female athletes than in male athletes, increased exposition to both female sex hormones and physical strain may affect the occurrence of LBP in women. Such an exposition occurs during pregnancy, with a well-known increase in prevalence of LBP.Methods: 28 women with an increased exposition to physical strain (female soccer players) and a history of LBP underwent a clinical examination and were then observed prospectively during 6 months to study variations in the occurence and severity of LBP during the different phases of the menstrual cycle. 716 female elite athletes and 113 controls answered a questionnaire with regard to their use of oral contraceptives (OCs) and the occurrence of LBP. 1103 women, 55 or 56 years old, answered a questionnaire concerning the occurrence and severity ofLBP and use of hormone replacement therapy (HRT). 52 women with and 67 women without a history of disabling LBP during a pregnancy in 1983-84 answered a questionnaire concerning LBP during subsequent pregnancies. 24 young, healthy women were followed prospectively over a period of 12 months to measure spinal sagittal mobility before use of OCs and after 3 and 12 months of OC-use.Results: No differences were observed with regard to occurrence or severity of LBP between the different phases of the menstrual cycle or between OC-users and non-users. LBP was more common in the athletes as compared with the controls. The prevalence ofLBP was slightly increased among the HRT-users (OR 1.30; 95% CI 1.02-1.41) compared with non-users. 94% of the women with previous disabling LBP during pregnancy reported LBP in a subsequent pregnancy compared with 44% of the controls. Also concequenccs of LBP, as sick-leave, were more common in the group of women with disabling LBP during a previous pregnancy. No change in spinal sagittal mobility was observed in the group of women before and after the women began to use OCs.Conclusions: Use of oral contraceptives does not seem to increase the prevalence of LBP. There is nothing in our results to suggest that women with LBP with an unspecific origin should discontinue their use of oral contraceptives. Postmenopausal women who use HRT had a slightly increased prevalence of LBP, but this increase is probably of no clinical significance. Women who had suffered from LBP during a previous pregnancy run a high risk for LBP in the future, both during a subsequent pregnancy and during the non-pregnant state. Increased exposition to exogenously administered female sex hormones does not increase spinal sagittal mobility in young, healthy, nullipareous women.
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23. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Low dose transdermal estradiol/norethisterone acetate treatment over 2 years does not cause endometrial proliferation in postmenopausal women
- 2002
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Ingår i: Menopause. - : Raven Press. - 1072-3714 .- 1530-0374. ; 9:2, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the effects of 2-year transdermal continuous combined estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) (Estragest TTS) on bleeding and on the endometrium. Design: This double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years past menopause with intact uteri. Patients received a transdermal patch delivering either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo. Of the 266 women initially included, 135 (96 Estragest TTS, 39 placebo) completed a second year open follow-up, where all women had the estradiol/norethisterone patch. Endometrial biopsies were performed at weeks 0, 48 (n = 171), and 96 (n =109). Effects on endometrial morphology and uterine bleeding were studied. Results: The overall incidence of endometrial hyperplasia after treatment with the estradiol/norethisterone acetate patch for one year was 0.8% with only one case of atypical hyperplasia. There were no clinically significant changes in endometrial thickness in either treatment group. The proportion of bleed-free patients with the estradiol/norethisterone acetate transdermal system increased from 55% in cycles 1-3 to 83% in cycles 10-12. By the 12th cycle, 92% of patients receiving estradiol/norethisterone acetate patches were bleed-free. No additional hyperplasia was seen during the second year follow-up. Conclusions: A continuous combined transdermal patch delivering 0.025 mg estradiol/day and 0.125 mg norethisterone acetate/day provided good endometrial protection. The dose maintained a consistently high rate of amenorrhea in postmenopausal women.
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24. |
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25. |
- Brynhildsen, Jan, 1962-, et al.
(författare)
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Oral contraceptive use among female elite athletes and age-matched controls and its relation to low back pain
- 1997
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 76:9, s. 873-878
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exogenous and endogenous female sex steroids may influence the risk of low back pain. The fact that back pain is a very common symptom during pregnancy supports this theory. Back pain is also more common among female than male athletes. Oral contraceptives have been suggested to increase the risk of low back pain.Objective: To evaluate whether the prevalence of low back pain is higher among oral contraceptive users than non-users and if it differs between women taking part in different sports.Methods: A questionnaire was sent to female elite athletes in volleyball (n=205), basketball (n=150), and soccer (n=361) as well as to age-matched controls (n=113). The questionnaire comprised questions about age, constitution, occupation, parity and use of contraceptive method as well as previous and current back pain and possible consequences of the back problems.Results: The response rate was 85%. Between 42% and 52% of the women in the different groups used oral contraceptives. The groups were similar in most background variables, except that the volleyball and basketball players were taller. The prevalence of current low back pain was between 21% and 34% in the different athlete groups with an average of 30%, whereas only 18% of the controls suffered from low back pain (p<0.01). The prevalence of low back pain within each group, athletes as well as controls, was similar in women who used, and did not use oral contraceptives.Conclusions: This study does not support the theory that low back pain is affected by the use of oral contraceptives. Instead, constitutional factors and mechanical stress during intense physical activity is probably more important.
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