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  • 1.
    Ahangari, Alebtekin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå Neurosteroid Research Center, Umeå University, Umeå, Sweden.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå Neurosteroid Research Center, Umeå University, Umeå, Sweden.
    Innala, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå Neurosteroid Research Center, Umeå University, Umeå, Sweden.
    Andersson, C.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå Neurosteroid Research Center, Umeå University, Umeå, Sweden.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå Neurosteroid Research Center, Umeå University, Umeå, Sweden.
    Acute intermittent porphyria symptoms during the menstrual cycle2015In: Internal medicine journal (Print), ISSN 1444-0903, E-ISSN 1445-5994, Vol. 45, no 7, p. 725-731Article in journal (Refereed)
    Abstract [en]

    Background: Acute intermittent porphyria (AIP), a life-threatening form of the disease, is accompanied by several pain, mental and physical symptoms.

    Aims: In this study, we evaluated the cyclicity of AIP and premenstrual syndrome (PMS) symptoms in 32 women with DNA-diagnosed AIP during their menstrual cycles, in northern Sweden.

    Methods: The cyclicity of AIP symptoms and differences in them between the follicularand luteal phases, and the cyclicity of each symptom in each individual woman indifferent phases of her menstrual cycle were analysed with a prospective daily ratingquestionnaire. PMS symptoms were also evaluated in the patients on a daily rating scale.

    Results: Of the 32 women, 30 showed significant cyclicity in at least one AIP or PMS symptom (P < 0.05–0.001). Back pain (10/32) was the most frequent AIP pain symptomand sweet craving (10/15) was the most frequent PMS symptom. Pelvic pain (F = 4.823,P = 0.036), irritability (F = 7.399, P = 0.011), cheerfulness (F = 5.563, P = 0.025), sexualdesire (F = 8.298, P = 0.007), friendliness (F = 6.157, P = 0.019), breast tenderness (F =21.888, P = 0.000) and abdominal swelling (F = 16.982, P = 0.000) showed significantcyclicity. Pelvic pain and abdominal swelling (rs= 0.337, P < 0.001) showed the strongest correlation. The age of women with latent AIP was strongly correlated with abdominal swelling during the luteal phase (rs= 0.493, P < 0.01).

    Conclusion: Our results suggest that the symptoms of AIP patients change during their menstrual cycles.

  • 2. Ahlborg, Liv
    et al.
    Hedman, Leif
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Murkes, Daniel
    Westman, Bo
    Kjellin, Ann
    Fellander-Tsai, Li
    Enochsson, Lars
    Visuospatial ability correlates with performance in simulated gynecological laparoscopy2011In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 157, no 1, p. 73-77Article in journal (Refereed)
    Abstract [en]

    Objective: To analyze the relationship between visuospatial ability and simulated laparoscopy performed by consultants in obstetrics and gynecology (OBGYN). Study design: This was a prospective cohort study carried out at two community hospitals in Sweden. Thirteen consultants in obstetrics and gynecology were included. They had previously independently performed 10-100 advanced laparoscopies. Participants were tested for visuospatial ability by the Mental Rotations Test version A (MRT-A). After a familiarization session and standardized instruction, all participants subsequently conducted three consecutive virtual tubal occlusions followed by three virtual salpingectomies. Performance in the simulator was measured by Total Time, Score and Ovarian Diathermy Damage. Linear regression was used to analyze the relationship between visuospatial ability and simulated laparoscopic performance. The learning curves in the simulator were assessed in order to interpret the relationship with the visuospatial ability. Results: Visuospatial ability correlated with Total Time (r = -0.62; p = 0.03) and Score (r = 0.57; p = 0.05) in the medium level of the virtual tubal occlusion. In the technically more advanced virtual salpingectomy the visuospatial ability correlated with Total Time (r = -0.64; p = 0.02), Ovarian Diathermy Damage (r = -0.65; p = 0.02) and with overall Score (r = 0.64; p = 0.02). Conclusions: Visuospatial ability appears to be related to the performance of gynecological laparoscopic procedures in a simulator. Testing visuospatial ability might be helpful when designing individual training programs.

  • 3. Ahlborg, Liv
    et al.
    Hedman, Leif
    Nisell, Henry
    Felländer-Tsai, Li
    Enochsson, Lars
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Center for Advanced Medical Simulation and Training (CAMST), Karolinska University Hospital, Stockholm, Sweden; Division of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Simulator training and non-technical factors improve laparoscopic performance among OBGYN trainees2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 10, p. 1194-1201Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate how simulator training and non-technical factors affect laparoscopic performance among residents in obstetrics and gynecology. DESIGN: In this prospective study, trainees were randomized into three groups. The first group was allocated to proficiency-based training in the LapSimGyn(®) virtual reality simulator. The second group received additional structured mentorship during subsequent laparoscopies. The third group served as control group. At baseline an operation was performed and visuospatial ability, flow and self-efficacy were assessed. All groups subsequently performed three tubal occlusions. Self-efficacy and flow were assessed before and/or after each operation. SETTING: Simulator training was conducted at the Center for Advanced Medical Simulation and Training, Karolinska University Hospital. Sterilizations were performed at each trainee's home clinic. POPULATION: Twenty-eight trainees/residents from 21 hospitals in Sweden were included. METHODS/MAIN OUTCOME MEASURES: Visuospatial ability was tested by the Mental Rotation Test-A. Flow and self-efficacy were assessed by validated scales and questionnaires. Laparoscopic performance was measured as the duration of surgery. Visuospatial ability, self-efficacy and flow were correlated to the laparoscopic performance using Spearman's correlations. Differences between groups were analyzed by the Mann-Whitney U-test. RESULTS: No differences across groups were detected at baseline. Self-efficacy scores before and flow scores after the third operation were significantly higher in the trained groups. Duration of surgery was significantly shorter in the trained groups. Flow and self-efficacy correlate positively with laparoscopic performance. CONCLUSIONS: Simulator training and non-technical factors appear to improve the laparoscopic performance among trainees/residents in obstetrics and gynecology.

  • 4. Altmäe, Signe
    et al.
    Stavreus-Evers, Anneli
    Ruiz, Jonatan R
    Laanpere, Margit
    Syvänen, Tiina
    Yngve, Agneta
    Salumets, Andres
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Variations in folate pathway genes are associated with unexplained female infertility2010In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, no 1, p. 130-137Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility.

    DESIGN: An association study.

    SETTING: Hospital-based IVF unit and university-affiliated reproductive research laboratories.

    PATIENT(S): Seventy-one female patients with unexplained infertility.

    INTERVENTION(S): Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements.

    MAIN OUTCOME MEASURE(S): Allele and genotype frequencies of the following polymorphisms: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C/T, 1298A/C, and 1793G/A, folate receptor 1 (FOLR1) 1314G/A, 1816delC, 1841G/A, and 1928C/T, transcobalamin II (TCN2) 776C/G, cystathionase (CTH) 1208G/T and solute carrier family 19, member 1 (SLC19A1) 80G/A, and concentrations of plasma homocysteine, vitamin B12, and serum folate.

    RESULT(S): MTHFR genotypes 677CT and 1793GA, as well as 1793 allele A were significantly more frequent among controls than in patients. The common MTHFR wild-type haplotype (677, 1298, 1793) CAG was less prevalent, whereas the rare haplotype CCA was more frequent in the general population than among infertility patients. The frequency of SLC19A1 80G/A genotypes differed significantly between controls and patients and the A allele was more common in the general population than in infertile women. Plasma homocysteine concentrations were influenced by CTH 1208G/T polymorphism among infertile women.

    CONCLUSION(S): Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility.

  • 5.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Innala, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, no 2, p. 176-183Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. DESIGN: A retrospective population-based study. SUBJECTS: All women aged > or =18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. RESULTS: A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged > or =45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged > or =45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). CONCLUSIONS: About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP.

  • 6.
    Andersson, Liselott
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology.
    Implications of psychiatric disorders during pregnancy and the postpartum period - A population-based study2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Depressive and anxiety disorders are common health problems, affecting women at least twice as often as men. Although some studies have been made on pregnant women or, especially, in the postpartum period, most of these studies have been performed on small samples, mainly specific risk groups such as teenage mothers, women of low socioeconomic status and certain ethnic groups. Also, there is a lack of studies on antenatal and postpartum depression and/or anxiety using diagnostic criteria adhering to the Diagnostic and Statistical Manual of Mental disorders, fourth edition (DSM-IV).

    Aims and methods: The aims were to estimate the point prevalence of mood, anxiety and eating disorders, based on DSM-IV criteria, in an unselected population during the second trimester of pregnancy, and to assess the obstetric and neonatal outcome, as well as the health care consumption during pregnancy, delivery and the early postpartum period among women with a psychiatric disorder, compared to healthy subjects. Finally, we aimed to investigate depression and anxiety, and associated maternal characteristics and events through pregnancy and the postpartum period in the same group of women. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used for assessment of psychiatric disorders during the second trimester of pregnancy and three to six months after delivery. From October 2nd, 2000, to October 1st, 2001 all women attending the second trimester routine ultrasound-screening at two different hospitals in northern Sweden (at Umeå University Hospital and at Sunderby Central Hospital) were approached for participation in the study. After delivery, data were extracted from the medical records of the mothers and their offspring to evaluate obstetric and neonatal outcome. Three to six months after delivery, the women who had an antenatal depression and/or anxiety were contacted for an assessment using the PRIME-MD. The same procedure was made in a control group, consisting of 500 women, randomly selected among those who did not have any psychiatric diagnosis according to the PRIME-MD investigation during the second trimester of pregnancy.

    Results and conclusions: Of the 1555 women in the study population, 220 (14.1%) had one or more PRIME-MD diagnoses. Living single, low socioeconomic status, smoking, multiparity and a body mass index of 30 or more were significantly associated with a psychiatric diagnosis in the second trimester of pregnancy. Women with antenatal depression and/or anxiety more often suffered from nausea and vomiting during pregnancy were more often on sick leave, and they visited their obstetrician more often than healthy subjects, specifically because of fear of childbirth and premature contractions. Also, they were more commonly delivered by elective caesarean section, had an increased use of epidural analgesia and reported a longer self-experienced duration of labor. Severe complications of pregnancy, delivery, and the early postpartum period were not affected by antenatal depression and/or anxiety. There was no significant difference in neonatal outcome depending on antenatal depressive or anxiety disorder. Fewer cases of depressive and/or anxiety disorders were prevalent postpartum, but there was a significant shift from a majority of sub-threshold diagnoses during pregnancy to full DSM-IV diagnoses during the postpartum period. Previous psychiatric disorder and living singly were significantly associated with both a new-onset and a postpartum continuation/recurrence of depression and/or anxiety. Postpartum continuation/recurrence of a psychiatric disorder was additionally associated with smoking, obesity, and adverse obstetric events.

  • 7.
    Andersson, Liselott
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Department of Obstetrics and Gynecology, Sunderby Hospital, Luleå, Sweden.
    Sundström-Poromaa, Inger
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Åström, Monica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Implications of antenatal depression and anxiety for obstetric outcome2004In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 104, no 3, p. 467-476Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the obstetric outcome and health care consumption during pregnancy, delivery, and the early postpartum period in an unselected population-based sample of pregnant women diagnosed with antenatal depressive and/or anxiety disorders, compared with healthy subjects. METHODS: Participants were 1,495 women attending 2 obstetric clinics in Northern Sweden. The Primary Care Evaluation of Mental Disorders was used to evaluate depressive and anxiety disorders in the second trimester of pregnancy. To assess demographic characteristics, obstetric outcome, and complications, the medical records of the included women were reviewed. RESULTS: Significant associations were found between depression and/or anxiety and increased nausea and vomiting, prolonged sick leave during pregnancy and increased number of visits to the obstetrician, specifically, visits related to fear of childbirth and those related to contractions. Planned cesarean delivery and epidural analgesia during labor were also significantly more common in women with antenatal depression and/or anxiety. CONCLUSION: There is an association between antenatal depressive and/or anxiety disorders and increased health care use (including cesarean deliveries) during pregnancy and delivery.

  • 8.
    Andréen, Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Turkmen, Sharuh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    van Wingen, Guido
    F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, The Netherlands.
    Fernández, Guillen
    F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, The Netherlands.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators2009In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 34, no 8, p. 1121-1132Article in journal (Refereed)
    Abstract [en]

    Certain women experience negative mood symptoms as a result of progesterone during the luteal phase of the menstrual cycle, progestagens in hormonal contraceptives, or the addition of progesterone or progestagens in sequential hormone therapy (HT). This phenomenon is believed to be mediated via the action of the progesterone metabolites on the GABA(A) system, which is the major inhibitory system in the mammalian CNS. The positive modulators of the GABA(A) receptor include allopregnanolone and pregnanolone, both neuroactive metabolites of progesterone, as well as benzodiazepines, barbiturates, and alcohol. Studies on the effect of GABA(A) receptor modulators have shown contradictory results; although human and animal studies have revealed beneficial properties such as anaesthesia, sedation, anticonvulsant effects, and anxiolytic effects, recent reports have also indicated adverse effects such as anxiety, irritability, and aggression. It has actually been suggested that several GABA(A) receptor modulators, including allopregnanolone, have biphasic effects, in that low concentrations increase an adverse, anxiogenic effect whereas higher concentrations decrease this effect and show beneficial, calming properties. The allopregnanolone increase during the luteal phase in fertile women, as well as during the addition of progesterone in HT, has been shown to induce adverse mood in women. The severity of these mood symptoms is related to the allopregnanolone serum concentrations in a manner similar to an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. It has also been shown that progesterone/allopregnanolone treatment in women increases the activity in the amygdala (as measured with functional magnetic resonance imaging) in a similar way to the changes seen during anxiety reactions. However, it is evident that only certain women experience adverse mood during progesterone or GABA(A) receptor modulator treatments. Women with premenstrual dysphoric disorder (PMDD) have severe luteal phase related symptoms; in this phase, they show changes in GABA(A) receptor sensitivity and GABA concentrations that are related to the severity of the condition. These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA(A) receptor. CONCLUSION: Progesterone and progestagens induce negative mood, most probably via their GABA(A) receptor active metabolites. In postmenopausal women treated with progesterone and animals treated with allopregnanolone, there is a bimodal association between serum allopregnanolone concentration and adverse mood, resembling an inverted U-shaped curve. In humans, the maximal effective concentration of allopregnanolone for producing negative mood is within the range of physiological luteal phase serum concentrations.

  • 9. Austeng, Dordi
    et al.
    Kallen, Karin
    Hellstrom, Ann
    Jakobsson, Peter
    Lundgren, Pia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tornqvist, Kristina
    Wallin, Agneta
    Holmstrom, Gerd
    Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden - the EXPRESS study2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 4, p. 311-315Article in journal (Refereed)
    Abstract [en]

    Purpose: The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions. Methods: A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004-2007. Screening for ROP was to start at postnatal age 5weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country. Results: The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP. Conclusion: The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.

  • 10. Babula, Oksana
    et al.
    Danielsson, Ingela
    Sjöberg, Inga
    Ledger, William J
    Witkin, Steven S
    Altered distribution of mannose-binding lectin alleles at exon I codon 54 in women with vulvar vestibulitis syndrome2004In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 191, no 3, p. 762-766Article in journal (Refereed)
    Abstract [en]

    Objectives: Mannose-binding lectin (MBL) is active in the innate immune defense against microorganisms. In this study, we determined whether vulvar vestibulitis syndrome, a disorder of unknown etiology, was associated with an altered distribution of MBL alleles.

    Study design: Buccal swabs were obtained from women with vulvar vestibulitis syndrome in New York (62) and from 2 cities in Sweden (60), as well as control women in New York (48) and Sweden (51). DNA was tested for a single nucleotide polymorphism at codon 54 in exon I by polymerase chain reaction, endonuclease digestion, and gel electrophoresis. Blood samples were also obtained from the New York women and tested by ELISA for plasma MBL concentrations. The relationships between genotype, allele frequencies, blood MBL levels, and diagnosis were analyzed by Fisher exact test and one-way analysis of variance.

    Results: The variant MBL allele, MBL*B, was detected in 35.5% and 26.7% of vulvar vestibulitis patients from New York and Sweden, respectively. Only 12.5% of New York controls (P = .007) and 9.8% of Swedish controls (P = .01) were MBL*2-positive. All women, with one exception, who were positive for MBL*B were MBL*A/MBL*B heterozygotes. Women who carried MBL*B had almost a 10-fold reduction in median plasma MBL concentrations (278 ng/mL), as opposed to women who were MBL*A homozygotes (1980 ng/mL) (P < .0001).

    Conclusion: MBL*B carriage and reduced plasma MBL levels are more common in women with vulvar vestibulitis syndrome than in control patients, and may contribute to symptomatology in a subset of patients.

  • 11. Bengtsdotter, Hanna
    et al.
    Lundin, Cecilia
    Gemzell Danielsson, Kristina
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Baumgart, Juliane
    Marions, Lena
    Brynhildsen, Jan
    Malmborg, Agota
    Lindh, Ingela
    Sundström Poromaa, Inger
    Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use2018In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 23, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    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 Δ-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 Δ-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 Δ-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.

  • 12.
    Berglund, Anna-Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    A holistic view of urinary stress incontinence in women1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The present study group consists of 45 women with genuine stress incontinence who were selected for surgical treatment and randomized either to retropubic urethrocystopexy (n=30) or pubococcygeal repair (n=15). The preoperative assessment included medical history, gynecological examination, urine analysis and culture, residual urine, pad test, frequency-continence charts, water urethrocystoscopy, continence test and cystometry with analysis of micturition. Moreover, five semistructured interviews were performed with the women and two with their partner. The following questionnaires were used measuring a) personality characteristics: Karolinska Scales of Personality (KSP), Eysenck Personality Inventory (EPI), b) depression: Beck Depression Inventory (BDI) and c) social support: Interview Schedule for Social Interaction (ISSI).

    The results have shown that there was no difference in the subjective cure rate between the two surgical methods (73% vs. 80 % respectively). The bladder volume had increased in both groups and the intravesical pressure of the bladder filled to maximum had increased in the pubococcygeal repair group. Other urodynamic variables were unchanged by the operation. Pad tests have demonstrated that 67 % of the women in the urethrocystopexy group and 47 % in the pubococcygeal repair group ceased to leak urine. Postoperatively, 63 % of the women in the urethrocystopexy group needed high doses of analgesics compared with only 33 % in the pubococcygeal repair group. Among the women experiencing severe to very severe pain dysphoric subjects were overrepresented. Postoperative residual urine was a minor nursing problem in both groups.

    Women with SUI of long duration scored significantly higher than controls on the KSP scales of somatic anxiety, psychic anxiety, psychasthenia, suspicion and on the EPI lie-scale. There was no significant difference in sexual activity before and after surgery. One or two sexual dysfunctions within the desire, excitement, orgasmic and resolution phase were reported by the majority of women both before and after surgical intervention.

    The cured women reported a higher level of overall activities before surgery than the improved (i.e. not cured) women, whereas post surgery both the cured and the improved women obtained about the same level of activities. Regarding social support, no differences between the cured or improved women occured as concerns attachment. The cured women showed a higher degree of adequacy of social integration compared with the improved women.

    In order to delineate predictive factors for the surgical outcome the following variables were investigated: age of patient, duration of urine leakage, parity, personality, psychological and social factors. The following predictors of the outcome of surgical treatment emerged: duration of stress incontinence, neuroticism and age of patient.

    The results of the present study indicate the ecessity of a multidisciplinary approach to the treatment and nursing of women with SUI.

  • 13.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. EURISTIKOS Excellence Centre for Paediatric Research, University of Granada, Granada, Spain.
    Torres-Espinola, Francisco J.
    Garcia-Valdes, Luz
    Teresa Segura, Ma
    Martinez-Zaldivar, Cristina
    Padilla, Carmen
    Rueda, Ricardo
    Petez Garcia, Miguel
    McArdle, Harry J.
    Campoy, Cristina
    The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring2017In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 118, no 7, p. 533-540Article in journal (Refereed)
    Abstract [en]

    Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI >= 25 kg/m(2)) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113.3 (SD 9.9) v. 117.1 (SD 9.2), P=0.039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114.0 (SD 9.7) v. 121.5 (SD 10.9), P = 0.039) and lower receptive, expressive and composite (99.5 (SD 8.6) v. 107.6 (SD 8.3), P= 0.004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12.3 (SD 2.0) v. 13.0 (SD 2.1), P = 0.037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.

  • 14.
    Bergman, Caroline
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Maternal satisfaction following induction of labour2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 15.
    Bergström, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Persson, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Mogren, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Pregnancy-related low back pain and pelvic girdle pain approximately 14 months after pregnancy - pain status, self-rated health and family situation2014In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 14, p. 48-Article in journal (Refereed)
    Abstract [en]

    Background: Pelvic girdle pain (PGP) in pregnancy is distinct from pregnancy-related low back pain (PLBP). However, women with combined PLBP and PGP report more serious consequences in terms of health and function. PGP has been estimated to affect about half of pregnant women, where 25% experience serious pain and 8% experience severe disability. To date there are relatively few studies regarding persistent PLBP/PGP postpartum of more than 3 months, thus the main objective was to identify the prevalence of persistent PLBP and PGP as well as the differences over time in regard to pain status, self-rated health (SRH) and family situation at 12 months postpartum. Methods: The study is a 12 month follow-up of a cohort of pregnant women developing PLBP and PGP during pregnancy, and who experienced persistent pain at 6 month follow-up after pregnancy. Women reporting PLBP/PGP (n = 639) during pregnancy were followed up with a second questionnaire at approximately six month after delivery. Women reporting recurrent or persistent LBP/PGP at the second questionnaire (n = 200) were sent a third questionnaire at 12 month postpartum. Results: A total of 176 women responded to the questionnaire. Thirty-four women (19.3%) reported remission of LBP/PGP, whereas 65.3% (n = 115) and 15.3% (n = 27), reported recurrent LBP/PGP or continuous LBP/PGP, respectively. The time between base line and the 12 months follow-up was in actuality 14 months. Women with previous LBP before pregnancy had an increased odds ratio (OR) of reporting 'recurrent pain' (OR = 2.47) or 'continuous pain' (OR = 3.35) postpartum compared to women who reported 'no pain' at the follow-up. Women with 'continuous pain' reported statistically significant higher level of pain at all measure points (0, 6 and 12 months postpartum). Non-responders were found to report a statistically significant less positive scoring regarding relationship satisfaction compared to responders. Conclusions: The results from this study demonstrate that persistent PLBP/PGP is a major individual and public health issue among women 14 months postpartum, negatively affecting their self-reported health. However, the perceived relationship satisfaction seems to be stable between the groups.

  • 16. Billfeldt, Nina K.
    et al.
    Borgfeldt, Christer
    Lindkvist, Håkan
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Stjerndahl, Jan-Henrik
    Ankardal, Maud
    A Swedish population-based evaluation of benign hysterectomy, comparing minimally invasive and abdominal surgery2018In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 222, p. 113-118Article in journal (Refereed)
    Abstract [en]

    Objective: The aim was to evaluate surgical routes for benign hysterectomy in a Swedish population, including abdominal and minimally invasive surgery. Study design: Prospectively collected data from the Swedish National GynOp Registry 2009-2015: 13 806 hysterectomy cases were included: abdominal (AH, n = 7485), vaginal (VH, n = 3767), conventional laparoscopic (LH, n = 1539) and robotically-assisted (RAH, n = 1015). Results: The VH group had the shortest operation time at 75 min, AH 97 min and RAH 104 min. LH was longest at 127 min (p < 0.005). The mean estimated blood loss was higher in the AH group (250 ml) compared to all minimally invasive surgery (MIS, 65-172 ml): p < 0.005). Conversion rates were 10% for LH, 4.8% for VH and 1.6% for RAH (p < 0.005). Hospitalization and patient reported time to normal activities of daily living (ADL) were longer for AH compared to MIS (p < 0.005). Time to return to work was eight days longer in the AN group (35 days) compared with the MIS groups (p < 0.005). Complications were fewest in the VH group at 5.4% compared with AH 7.6% and RAH 8.7% (both p < 0.001), but did not significantly differ from the LH group at 6.6%. Overall patient satisfaction was reported to be 86-94% one year after surgery. Conclusion: Women operated on for benign hysterectomy with minimally invasive methods in Sweden 2009-2015 had reduced length of hospitalization, as well as time to resuming normal ADL and return to work, compared to AH. Postoperative outcome measures were improved by minimally invasive methods and MIS should preferably be used.

  • 17.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ovarian steroids in rat and human brain: effects of different endocrine states1987Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain.

    In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated.

    In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex.

    In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5<*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata.

    Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women.

    In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution.

  • 18.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Reply2006In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 13, no 3, p. 538-538Article in journal (Other academic)
  • 19.
    Bixo, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Ekberg, Karin
    Poromaa, Inger Sundstrom
    Hirschberg, Angelica Linden
    Jonasson, Aino Fianu
    Andreen, Lotta
    Timby, Erika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Wulff, Marianne
    Ehrenborg, Agneta
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 46-55Article in journal (Refereed)
    Abstract [en]

    Context: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.

    Objective: The objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.

    Design: This was an explorative randomized, double-blind, placebo-controlled study.

    Setting: Swedish multicentre study with 10 centers.

    Participants: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott’s algorithm.

    Intervention: Subjects were randomized to treatment with UC1010 (10 or 16 mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.

    Outcome measures: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).

    Results: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p = 0.041) and borderline significance (p = 0.051) for the sum of Negative mood score.

    Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n = 60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p = 0.006), and for sum of Negative mood score (p = 0.003) and impairment (p = 0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.

    Conclusions: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

  • 20.
    Bixo, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Johansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Timby, Erika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Michalski, Louise
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder2018In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 30, no 2, article id e12553Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) afflicts 3%-5% of women of childbearing age, and is characterised by recurrent negative mood symptoms (eg, irritability, depression, anxiety and emotional lability) during the luteal phase of the menstrual cycle. The aetiology of PMDD is unknown, although a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone, has been established during the luteal phase. Allopregnanolone is a positive modulator of the GABA(A) receptor: it is sedative in high concentrations but may precipitate paradoxical adverse effects on mood at levels corresponding to luteal phase concentrations in susceptible women. Saccadic eye velocity (SEV) is a measure of GABA(A) receptor sensitivity; in experimental studies of healthy women, i.v. allopregnanolone decreases SEV. Women with PMDD display an altered sensitivity to an i.v. injection of allopregnanolone compared to healthy controls in this model. In functional magnetic resonance imaging (fMRI) studies, women with PMDD react differently to emotional stimuli in contrast to controls. A consistent finding in PMDD patients is increased amygdala reactivity during the luteal phase. Post-mortem studies in humans have revealed that allopregnanolone concentrations vary across different brain regions, although mean levels in the brain also reflect variations in peripheral serum concentrations. The amygdala processes emotions such as anxiety and aggression. This is interesting because allopregnanolone is detected at high concentrations within the region into which marked increases in blood flow are measured with fMRI following progesterone/allopregnanolone administration. Allopregnanolone effects are antagonised by its isomer isoallopregnanolone (UC1010), which significantly reduces negative mood symptoms in women with PMDD when administered s.c. in the premenstrual phase. This was shown in a randomised, placebo-controlled clinical trial in which the primary outcome was change in symptom scoring on the Daily Rating of Severity of Problems (DRSP): the treatment reduced negative mood scores (P<.005), as well as total DRSP scores (P<.01), compared to placebo in women with PMDD. In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms as a result of its ability to antagonise the allopregnanolone effect on the GABA(A) receptor.

  • 21.
    Bixo, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lindén Hirschberg, Angelica
    Ännu inte visat att östradiol och »naturligt« progesteron är säkert2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 11, article id DAXWArticle in journal (Refereed)
  • 22. Bjurberg, Maria
    et al.
    Kjellén, Elisabeth
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Oncology, Lund University Hospital.
    Ohlsson, Tomas
    Bendahl, Pär-Ola
    Brun, Eva
    Prediction of patient outcome with 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography early during radiotherapy for locally advanced cervical cancer2009In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 19, no 9, p. 1600-1605Article in journal (Refereed)
    Abstract [en]

    Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival.

    Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[(18)F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation.

    Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis.

    Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.

  • 23.
    Björn, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Hormone replacement therapy and effects on mood2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: During the past 5 decades, hormone replacement therapy (HRT) has been used, and appreciated for its beneficial effects, by millions of women in their menopause. As treatment for climacteric symptoms, estrogen is outstanding, and effects on hot flushes, vaginal dryness, and insomnia have been widely documented. The increased risks of venous thrombosis and breast cancer, however, restrict the use of estrogen.

    Estrogen treatment in women with a remaining uterus includes a progestin, added to protect the endometrium from hyperplasia and malignancies. The long-standing clinical impression, that progestin addition negatively influences mood, has been discussed in previous studies. Mood deterioration is, however, not mortal, although mood is important to the wellbeing and daily functioning of women treated with hormones. Studies of the mental side effects of HRT add to our understanding of steroid effects in the brain.

    Aims and methods: In our studies, we aimed to establish to what extent negative side effects cause women to discontinue HRT, and find out which drug compounds lead to mood deterioration. The questions asked were whether the type and dose of progestin and the estrogen dose during the progestin addition influence the mood and physical symptoms during sequential HRT.

    Compliance with HRT and reasons for discontinuing the therapy were evaluated in a retrospective longitudinal follow-up study. Treatment effects were studied in three randomized, double-blind, cross-over trials. During continuous estrogen treatment, effects of sequential addition of a progestin were studied by comparing two different progestins, medroxyprogesterone acetate (MPA) andnorethisterone acetate (NETA), comparing different doses of the same progestin, MPA, and comparing two doses of estrogen during addition of the same dose of MPA. The main outcome measure was the daily rating on mood and physical symptoms kept by the participants throughout the studies. The clinical trials were carried out at three gynecological centers in northern Sweden.

    Results and conclusions: Besides fear of cancer and a wish to determine whether climacteric symptoms had meanwhile disappeared, negative side effects was the most common reason or discontinuing HRT. Tension in the breasts, weight gain, a depressed mood, abdominal bloating, and irritability were the most important side effects seen both in women who continued HRT and in women who had discontinued the therapy.

    In our clinical trials, we showed that addition of a progestin to estrogen treatment induces cyclic mood swings characterized by tension, irritability, and depression, as well as increased breast tension, bloatedness, and hot flushes. Women with a history of premenstrual syndrome (PMS) appeared to be more sensitive to the progestin addition and responded with lower mood scores compared with women without previous PMS. In our studies, MPA provoked depressed mood to a lesser extent than did NETA. Surprisingly, the higher dose of MPA (20 mg) enhanced the mood, compared with 10 mg, when added to estrogen treatment. In women continuously treated with 3 mg estradiol, mood and physical symptoms worsened during the progestin addition, as compared with treatment with 2 mg estradiol. The negative side effects seen during sequential HRT have much in common with symptoms seen in the premenstrual dysphoric disorder (PMDD), which is a psychoneuroendocrine disorder with psychiatric expression. Explanations for treatment effects on mood are likely to be found in drug interactions with neurotransmitter systems of the brain.

  • 24.
    Björn, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Strandberg Nöjd, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Collberg, P.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy2002In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 16, p. 1-8Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare adverse mood effects of two different doses of medroxyprogesterone acetate (MPA) during postmenopausal hormone replacement therapy (HRT) in women with and without a history of premenstrual syndrome (PMS). The study was designed as a randomized double-blind cross-over study and included 36 postmenopausal women at three health care areas in northern Sweden. The women received 2 mg estradiol continuously during five 28-day cycles and 10 mg or 20 mg MPA sequentially for 12 days during each cycle. The main outcome measures were mood and physical symptoms noted on a daily rating scale. We found that physical symptoms did not differ between 10 and 20 mg MPA. Both women with a history of PMS and women without responded with more negative mood symptoms with the lower dose of MPA. In women with previous PMS the higher dose of MPA enhanced positive mood symptoms. With respect to mood and physical symptoms, the aim to lower MPA doses in HRT is unwarranted.

  • 25.
    Björn, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Strandberg Nöjd, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Negative mood changes during hormone replacement therapy: a comparison between two progestogens2000In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 183, no 6, p. 1419-1426Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to compare side effects of medroxyprogesterone acetate and norethindrone acetate during postmenopausal hormone replacement therapy in women with and without a history of premenstrual syndrome. Study Design: Fifty-one postmenopausal women were randomly selected in a double-blind crossover study. The women received 2 mg of estradiol continuously during five 28-day cycles and 10 mg of medroxyprogesterone or 1 mg of norethindrone sequentially for 12 days of each cycle. Daily symptom rating scales were kept. Results: The women showed cyclic changes, with negative mood and physical symptoms culminating during the late progestogen phase and positive mood during the estrogen-only phase. Symptoms declined with time but remained after 5 months. Women with a history of premenstrual syndrome responded strongly to both progestogens. Medroxyprogesterone acetate induced less negative and more positive mood symptoms than norethindrone in women with no history of premenstrual syndrome. In both groups medroxyprogesterone caused more physical symptoms than norethindrone. Conclusion: The addition of medroxyprogesterone to estrogen is preferable to norethindrone with respect to mood symptoms in women without a history of premenstrual syndrome.

  • 26.
    Björn, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Drug related negative side effects is a common reason for poor compliance in hormone replacement therapy1999In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 32, no 2, p. 77-86Article in journal (Refereed)
    Abstract [en]

    Objectives: The reasons for poor compliance with hormone replacement therapy (HRT) and, in particular drug-related reasons, have not yet been fully elucidated. In this study, a cohort of peri- or postmenopausal women—mainly workers from a small town and surrounding rural area—was studied. The aim of the study was to investigate why some women never start or discontinue HRT, even when great effort has been made to inform and fulfill the demands of the patient. Methods: All women who were given a HRT prescription at a gynecological practice between September 1991 and December 1992 participated in a longitudinal study. A written questionnaire was mailed to these patients in 1996. Data from the questionnaire was supplemented with information from the medical records. Care of patients included initial information, follow-up within 4 months, yearly visits supplemented with contacts on demand. Results: 356 women received the questionnaire, among which 92% replied. A total of 2% never started HRT. Seventy-five percent continued the therapy for more than 3 years. Reasons for discontinuing HRT were negative side-effects (35%), desire to find out if climacteric symptoms had ended (26%), fear of cancer and thrombosis (25%), weariness of bleeding (19%) and a wish to deal with the problems ‘naturally’ (15%). Conclusions: Compliance with HRT can be high if adequate information is given and follow-ups are made. The main reason for poor compliance was negative side-effects, most likely progestin-related. The results of this study suggest that the future challenge will be to minimize negative side-effects of HRT.

  • 27.
    Björn, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Gunnel
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy2003In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 88, no 5, p. 2026-2030Article in journal (Refereed)
    Abstract [en]

    Previous studies have indicated that the addition of progestinsduring sequential hormonal replacement therapy (HRT)causes negative mood and physical symptoms. History of premenstrualsyndrome, type of progestin, and dose of progestinhave thus far been shown to influence the progestin-inducedadverse mood symptoms during HRT.

    The aim of this study was to compare adverse mood effectsof two different doses of estradiol, in combination with a progestin,during postmenopausal HRT. Twenty-eight perimenopausalwomen were included in this randomized, doubleblind,crossover study comparing 2- or 3-mg continuousestradiol, with an addition of 10 mg medroxyprogesteroneacetate on d 17–28 during each treatment cycle. The mainoutcome measures were mood and physical symptoms kept ona daily rating scale. Together with the progestin, the higherdose of estrogen caused significantly more negative moodsymptoms than the lower dose. Tension, irritability, and depressedmood were all significantly augmented during theprogestin phase of cycles with 3mg estradiol (P<0.001). Physicalsymptoms also increased during the progestin phase of3-mg estradiol cycles (P<0.001), whereas positive mood symptomswere less affected. The only positive mood that changedwith estrogen dose was friendliness, which decreased duringthe progestin phase of high estradiol cycles compared withcycles with lower estradiol (P < 0.05).

    Our conclusion is that an increase of the estrogen doseaccentuates negativemoodand physical symptoms during theprogestin phase of sequential hormonal therapy.

  • 28.
    Blom, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Violence exposure among Swedish youth2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Violence is a global public health problem and violence among youth is a matter of high priority. Adolescence and young adulthood are important periods for the foundation of future health. Youth victimization may have serious health consequences, making it important to address the occurrence and socio-medical context for possible interventions against violence.

    Aims

    To analyze prevalence, risk patterns and gender differences in emotional, physical, sexual, and multiple-violence victimizations and the associations between violence victimization and sexual ill health, sexual risk behaviors and mental health in Swedish youth.

    Methods

    A cross sectional study using two samples, a national sample from nine youth health centers in Sweden and a population-based sample from a middle-sized Swedish city. The questionnaire included standardized instruments addressing violence exposure (NorAQ), socio-demographics, mental and sexual ill-health and sexual risk behaviors, alcohol and substance use. Proportions and crude and adjusted odds ratios with a 95% CI were calculated.

    Results

    A total of 2,250 young women and 920 men, aged 15-23, answered the questionnaire at the youth health centers. In upper secondary school, 1,658 women and 1,589 men, aged 15-22, answered the questionnaire.

    High prevalence rates with gendered differences both in rates and in co-occurrence of different types of violence were found. Women were more often exposed to emotional violence and sexual violence than men, while men were more often physically victimized. For both women and men, violence victimization before the age of 15 was strongly associated with all types of violence victimizations during the past year.

    Strong associations were found between multiple-violence victimization and poor mental health in both genders. Among the sexually experienced students, consistent associations between lifetime multiple-violence victimization and various sexual ill-health and sexual risk behaviors were found in both genders, except for non-contraceptive use.

    Conclusions

    High prevalence of violence victimization in youth and strong associations between victimization, especially multiple victimization, and poor mental and sexual health were found. This needs to be recognized and addressed in social and medical settings.

     

  • 29.
    Blom, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Department of Obstetrics and Gynaecology, Sundsvall Hospital, Sundsvall, Sweden.
    Högberg, Ulf
    Uppsala, Sweden.
    Olofsson, Niclas
    Sundsvall; Linköping, Sweden.
    Danielsson, Ingela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Department of Research and Development, Västernorrland County Council, Sundsvall, Sweden.
    Strong association between earlier abuse and revictimization in youth2014In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 14, no 14, article id 715Article in journal (Refereed)
    Abstract [en]

    Background:  Violence victimization among youth is recognized as a public health problem. The objective was to analyze the risk pattern of emotional, physical, and sexual abuse during the past 12 months by gender, sociodemographic factors, health risk behaviors, and exposure to abuse before the age of 15, among young men and women attending youth health centers in Sweden.

    Methods: A cross-sectional survey was conducted using a nationally representative sample of youth health centers. A total of 2,250 young women and 920 young men aged 15-23 completed a self-administered questionnaire. Odds ratios (OR) and adjusted odds ratios (AOR) with 95% CI were calculated.

    Results: A consistent and strong association was noted between exposure to all types of violence during the past year and victimization before the age of 15 for all types of violence for both women and men. The only exceptions were childhood sexual victimization and sexual violence during the past year for men. Younger age was associated with all violence exposure for the women and with emotional violence for the men. For the women, drug use was associated with all types of violence, while the association with hazardous alcohol use and not living with parents was restricted to physical and sexual violence exposure, present smoking was restricted to emotional and physical violence exposure, and partnership and living in urban areas were restricted to sexual violence. For men, not being partnered, hazardous alcohol consumption, and drug use meant increased risk for physical violence, while smoking and living in urban areas were associated with sexual violence. After adjustment, immigration had no association with violence exposure.

    Conclusions: Violence victimization in young men and women is often not a single experience. Findings underline the importance of early interventions among previously abused youth.

  • 30.
    Bodén, Elisabeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Human papilloma virus: association with vulvovaginitis and genital intra-epithelial neoplasia1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In many women with gynecological complaints such as itching, burning, discharge, and fissures causing dyspareunia, examination of the vulvovaginal mucosa reveals hyperkeratotic and papillomatous changes. Polymerase Chain Reaction (PCR) technique revealed 64% of such lesions to harbour Human Papilloma Virus (HPV)- DNA, whereas Southern blot (SB) technique showed 50% to be positive for HPV- DNA.

    Women with papillomatous lesions were more often HPV-DNA positive than those with/Zat hyperkeratotic lesions. The virus-induced vulvovaginitis described was sometimes the sole cause of atypical Pap-smears. However, papilloma virus infections in vulva and vagina were often accompanied by cervical as well as vaginal and vulval intra-epithelial neoplasia.

    In women with an atypical Pap-smear, signs of HPV were observed by colposcopy in 58% of cases, by cytology in 21%, by histopathology in 53% and by HPV- DNA hybridization techniques in 46%. Colposcopy, cytology and histopathology were more sensitive than SB and Filter In Situ Hybridization (FISH) in detecting HPV in benign epithelium and in mild to moderate dysplasia. The FISH technique, when applied to cell samples and the SB technique for biopsy material proved equally sensitive when benign tissue and mild to moderate dysplasia were analysed. However, in women with severe dysplastic lesions, use of the SB technique on biopsy material proved more sensitive than FISH.

    In lesions with severe dysplasia, HPV-DNA was very often present (67% of CIN III lesions). HPV 16, which is capable of oncogenic transformation, was found in 54% of such tissue.

    At follow-up after laser treatment of genital intra-epithelial neoplasia, HPV-DNA could be detected in 38% of cases. This indicates that HPV may affect the entire mucosa of the lower genital tract, even when not clinically detectable. Thus, to eradicate the virus, systemic therapy would appear to be required.

    Vulvovaginal HPV infection is an entity with characteristic symptoms, morphological changes and oncogenic potential. Certain HPV-types are associated with the development of genital intra-epithelial neoplasia. The diagnostic methods presently available are not, however, sensitive enough for detection of HPV-infection and there is no effective treatment currently available. It would therefore be premature to suggest the introduction of a screening program for certain oncogenic HPV- types. Further study of the natural history of the virus infection is needed before any step can be taken toward using HPV screening in the effort to prevent cervical cancer.7

  • 31. Bohlin, Katja S.
    et al.
    Ankardal, Maud
    Stjerndahl, Jan-Henrik
    Lindkvist, Håkan
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Milsom, Ian
    Influence of the modifiable life-style factors body mass index and smoking on the outcome of hysterectomy2016In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 95, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

    Introduction

    The aim of this study was to study the impact of body mass index (BMI) and smoking on the outcome of hysterectomy and whether effects of these factors vary between abdominal, laparoscopic and vaginal hysterectomy.

    Material and methods

    Pre-, per- and postoperative (8 weeks) data were retrieved from the Swedish National Register for Gynecological Surgery on 28 537 hysterectomies performed because of a benign indication between 2004 and 2013. Multivariable logistic regression analyses were used to identify independent factors affecting the rate of complications, presented as adjusted odds ratios (adjOR) with 95% confidence intervals (CI).

    Results

    Overweight and obesity had the strongest impact on complications in the abdominal hysterectomy group. In women with a BMI 30 an increased adjOR could be seen for bleeding >1000 mL (2.90; 95% CI 2.23-3.77), peroperative complications (1.54; 95% CI 1.26-1.88), operation time >120 min (2.67; 95% CI 2.33-3.03), postoperative complications (1.21; 95% CI 1.08-1.34) and postoperative infections (1.73; 95% CI 1.50-1.99). With vaginal hysterectomy, the effect of BMI 30 could be seen in relation to excessive bleeding >500 mL (1.63; 95% CI 1.22-2.17) and operative time >120 min (2.00; 95% CI 1.60-2.50). With laparoscopic hysterectomy (LH), a BMI 30 had a higher adjOR for prolonged surgery (1.71; 95% CI 1.30-2.26). Smokers had an increased risk of postoperative infection in the abdominal hysterectomy (1.23; 95% CI 1.07-1.40) and vaginal hysterectomy groups (1.21; 95% CI 1.02-1.43) but not in the LH group.

    Conclusions

    Body mass index and smoking had a negative effect with all hysterectomy approaches but to a lesser extent in vaginal and laparoscopic hysterectomies. This should be taken into consideration in advance of surgery to improve outcome.

  • 32. Bohlin, Katja Stenstrom
    et al.
    Ankardal, Maud
    Nüssler, Emil
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lindkvist, Håkan
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Milsom, Ian
    Factors influencing the outcome of surgery for pelvic organ prolapse2018In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 1, p. 81-89Article in journal (Refereed)
    Abstract [en]

    Pelvic organ prolapse (POP) surgery is a common gynecological procedure. Our aim was to assess the influence of obesity and other risk factors on the outcome of anterior and posterior colporrhaphy with and without mesh. Data were retrieved from the Swedish National Register for Gynecological Surgery on 18,554 women undergoing primary and repeat POP surgery without concomitant urinary incontinence (UI) surgery between 2006 and 2015. Multivariate logistic regression analyses were used to identify independent risk factors for a sensation of a vaginal bulge, de novo UI, and residual UI 1 year after surgery. The overall subjective cure rate 1 year after surgery was 80% (with mesh 86.4% vs 77.3% without mesh, p < 0.001). The complication rate was low, but was more frequent in repeat surgery that were mainly mesh related. The use of mesh was also associated with more frequent de novo UI, but patient satisfaction and cure rates were higher compared with surgery without mesh. Preoperative sensation of a vaginal bulge, severe postoperative complications, anterior colporrhaphy, prior hysterectomy, postoperative infections, local anesthesia, and body mass index (BMI) 30 were risk factors for sensation of a vaginal bulge 1 year postsurgery. Obesity had no effect on complication rates but was associated increased urinary incontinence (UI) after primary surgery. Obesity had no influence on cure or voiding status in women undergoing repeat surgery. Obesity had an impact on the sensation of a vaginal bulge and the presence of UI after primary surgery but not on complications.

  • 33.
    Boman, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Endometrial carcinoma: steroid hormones and receptors in relation to proliferation1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The significance of the hormonal milieu for endometrial changes is as well-known as its link with endometrial carcinoma. Unopposed oestradiol treatment is shown to increase the incidence for this cancer. Obesity leads to elevated levels of oestrogens and is a risk factor for endometrial carcinoma. An association between high tumour proliferation and prognosis is a general feature of human cancer. Tumour growth can be expressed as proliferation rate and flow cytometry (FCM) is a sensitive and reproducable method to estimate S-phase fraction (SPF) and ploidy level. Both parameters have been shown to correlate with prognosis. Sex steroid hormone levels were analysed together with clinical parameters, SPF, and receptors in established endometrial carcinoma.

    The study consisted of postmenopausal women with endometrial adeno­carcinoma. H ormones were analysed in 127 patients, 99 were analysed for FCM and 60 for oestrogen and progesterone receptors. RIA technique was used for hormone assay of oestrone, oestradiol, progesterone, androstenedione and testosterone plasma levels. The receptors were analysed with an immunohistochemical method, and SPF and ploidy level by flow cytometry.

    A wide range of oestrogen concentrations was found. Some patients had levels comparable to fertile women. Strong correlations were found between body mass index, weight and depth of uterine cavity. No relations were found between receptors and SPF, apart from oestrogen- receptor positive tumours having a lower SPF when compared with receptor negative tumours. The influence of oestradiol on tumour proliferation expressed as SPF was ambiguous. SPF was increased with higher oestradiol levels in the group of peri-diploid, well-differentiated tumours, while a negative correlation was found for the peri-diploid, moderately differentiated tumours. The aneuploid and poorly differenti­ated tumours had a high SPF regardless of oestradiol concentration. The association between progesterone concentration and SPF was of a more general nature. Progesterone above a threshold level was related to a lower SPF in well-differentiated and moderately differentiated tumours. Thus endogenous progesterone seems to play a role in controlling the tumour’s proliferation activity, in contrast to oestradiol, that had a role which did not appear to relate to proliferation activity in any specific direction. The only stimulative association was seen in well-differentiated tumours, but SPF was still below the mean value for all diploid tumours.

  • 34. Braem, Marieke G. M.
    et al.
    Onland-Moret, N. Charlotte
    Schouten, Leo J.
    Kruitwagen, Roy F. P. M.
    Lukanova, Annekatrin
    Allen, Naomi E.
    Wark, Petra A.
    Tjonneland, Anne
    Hansen, Louise
    Brauner, Christina Marie
    Overvad, Kim
    Clavel-Chapelon, Francoise
    Chabbert-Buffet, Nathalie
    Teucher, Birgit
    Floegel, Anna
    Boeing, Heiner
    Trichopoulou, Antonia
    Adarakis, George
    Plada, Maria
    Rinaldi, Sabina
    Fedirko, Veronika
    Romieu, Isabelle
    Pala, Valeria
    Galasso, Rocco
    Sacerdote, Carlotta
    Palli, Domenico
    Tumino, Rosario
    Bueno-de-Mesquita, H. Bas
    Gram, Inger Torhild
    Gavrilyuk, Oxana
    Lund, Eiliv
    Sanchez, Maria-Jose
    Bonet, Catalina
    Chirlaque, Maria-Dolores
    Larranaga, Nerea
    Barricarte Gurrea, Aurelio
    Quiros, Jose R.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jirstrom, Karin
    Butt, Salma
    Tsilidis, Konstantinos K.
    Khaw, Kay-Tee
    Wareham, Nick
    Riboli, Elio
    Kaaks, Rudolf
    Peeters, Petra H. M.
    Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, p. e37141-Article in journal (Refereed)
    Abstract [en]

    While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

  • 35. Brand, J. S.
    et al.
    Onland-Moret, N. C.
    Eijkemans, M. J. C.
    Tjonneland, A.
    Roswall, N.
    Overvad, K.
    Fagherazzi, G.
    Clavel-Chapelon, F.
    Dossus, L.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg.
    Grote, V.
    Bergmann, M. M.
    Boeing, H.
    Trichopoulou, A.
    Tzivoglou, M.
    Trichopoulos, D.
    Grioni, S.
    Mattiello, A.
    Masala, G.
    Tumino, R.
    Vineis, P.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Redondo, M. L.
    Sanchez, M. J.
    Castano, J. M. Huerta
    Arriola, L.
    Ardanaz, E.
    Duell, E. J.
    Rolandsson, O.
    Franks, P. W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Butt, S.
    Nilsson, P.
    Khaw, K. T.
    Wareham, N.
    Travis, R.
    Romieu, I.
    Gunter, M. J.
    Riboli, E.
    van der Schouw, Y. T.
    Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT2015In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 70, no 8, p. 507-508Article in journal (Other academic)
    Abstract [en]

    The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and <10 years [HR, 1.59; 95% CI, 1.03-2.43]), whereas women with diabetes at age 50 years or older had a later menopause (HR, 0.81; 95% CI, 0.70-0.95). No association with ANM was found for diabetes onset between the ages 20 and 50 years. Strengths of the study include its large sample size and the measurement of a broad set of potential confounders. However, there were several limitations. First, results may have been underestimated because of survival bias. Second, the sequence of menopause and diabetes in women with a late age at diabetes is uncertain, as both events occur in a short period, and both diabetes and menopause status were based on self-report, not verified by medical records. Third, no distinction was made between types 1 and 2 diabetes. Although there is no overall association between diabetes and age at menopause, the data suggest that early-onset diabetes may accelerate menopause. The delaying effect of late-onset diabetes on ANM is not in agreement with other studies suggesting the opposite association.

  • 36. Broeze, KA
    et al.
    Opmeer, BC
    Coppus, SFPJ
    Van Geloven, N
    Alves, MFC
    Anestad, G
    Bhattacharya, S
    Allan, J
    Guerra-Infante, MF
    Den Hartog, JE
    Land, JA
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Van der Linden, PJQ
    Mouton, JW
    Ng, EHY
    Van der Steeg, JW
    Steures, P
    Svenstrup, HF
    Tiitinen, A
    Toye, B
    Van der Veen, F
    Mol, BW
    Chlamydia antibody testing and diagnosing tubal pathology in subfertile women: an individual patient data meta-analysis2011In: Human Reproduction Update, ISSN 1355-4786, E-ISSN 1460-2369, Vol. 17, no 3, p. 301-310Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays.

    METHODS We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction.

    RESULTS We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology.

    CONCLUSIONS In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.

  • 37. Bryman, Inger
    et al.
    Sylven, Lisskulla
    Berntorp, Kerstin
    Innala, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bergström, Ingrid
    Hanson, Charles
    Oxholm, Marianne
    Landin-Wilhelmsen, Kerstin
    Pregnancy Rate and Outcome in Swedish Women With Turner Syndrome EDITORIAL COMMENT2011In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 66, no 12, p. 756-757Article in journal (Refereed)
    Abstract [en]

    The rate of spontaneous pregnancies in women with Turner syndrome (TS) is low (2% to 5%). Oocyte donation is an option for these women and enables many to become pregnant. Some investigators question the use of pregnancy induction in TS because of the high risk for aortic dissection or other serious cardiac events. A cardiac evaluation is recommended before pregnancy is planned in TS. Among patients with TS who use their own oocytes to become pregnant, 45% suffered a miscarriage. The aim of this study was to assess pregnancy rate and outcome in a population of Swedish women with spontaneous pregnancies or who were induced using donated oocytes. Cytogenetic karyotype also was examined; mosaicism was defined as the presence of more than 5% 46, XX cells. The study subjects were 482 women with TS who had participated in a voluntary screening program conducted at Swedish Turner Centers. Among the 482 women with TS, 57 (12%) had pregnancies, including spontaneous pregnancies. The live-born rate was 67 of 124 (54%). The patient's own oocytes were used in 27 (47%) of the pregnancies and oocyte donation in 30 (53%) of pregnancies. Spontaneous pregnancies occurred in 23 of 57 women (40%) with TS. Most pregnancies using the patient's own oocytes occurred in those with 45, X/46, XX mosaic karyotype. The miscarriage rate was 26% after oocyte donation and 45% with the use of the patient's own oocytes. Five liveborns (7%) had birth defects or a serious illness; 4 of these were born after spontaneous pregnancies. Only 1 live-born had coarctation of the aorta.

  • 38. Bryman, Inger
    et al.
    Sylvén, Lisskulla
    Berntorp, Kerstin
    Innala, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bergström, Ingrid
    Hanson, Charles
    Oxholm, Marianne
    Landin-Wilhelmsen, Kerstin
    Pregnancy rate and outcome in Swedish women with Turner syndrome2011In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 95, no 8, p. 2507-2510Article in journal (Refereed)
    Abstract [en]

    Pregnancies occurred in 57 (12%) of 482 Swedish women with Turner syndrome with a liveborn rate of 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40%, mainly in women with 45,X/46,XX mosaicism, and oocyte donation in 53% where miscarriages were less frequent, odds ratio = 0.43 (95% confidence interval 0.17-1.04).

  • 39.
    Bråbäck, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lowe, Adrian
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hjern, Anders
    Elective cesarean section and childhood asthma2013In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 209, no 5, p. 496-496Article in journal (Refereed)
  • 40.
    Buttner, Barbara E.
    et al.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Witthoft, Cornelia M.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effect of type of heat treatment of breastmilk on folate content and pattern2014In: Breastfeeding medicine, ISSN 1556-8253, Vol. 9, no 2, p. 86-91Article in journal (Refereed)
    Abstract [en]

    Background: Breastmilk is the recommended aliment for preterm infants. Milk banks provide donated breastmilk for the neonatal care of preterm infants when mother's own milk is not is available. To avoid pathogen transmission, donated breastmilk is heat-treated according to different procedures before administration. There is varying information on the effect of heat treatment on folate in breastmilk. Sufficient folate intake, however, is essential for normal growth and brain development. This study determined and compared the effects of different heat treatments on breastmilk folate content and pattern of individual folate forms. Materials and Methods: Donated Swedish breastmilk samples were heat-treated according to three procedures: two low temperature treatments (57 degrees C, 23 minutes; 62.5 degrees C, 12 minutes) and a rapid high temperature treatment (heating to 73 degrees C in boiling water). The folate content and pattern were determined before and after treatment by high-performance liquid chromatography. Results: The folate content in 38 untreated Swedish breastmilk samples was 15046nmol/L. Two different folate vitamers were detected: 5-methyltetrahydrofolate (78 +/- 7%) and tetrahydrofolate (22 +/- 7%). Heat treatment affected only tetrahydrofolate stability and decreased folate content by 15-24%; however, the effects on folate content did not differ among the investigated heat treatment procedures. Conclusions: Folate losses during heat treatment of human milk were considered acceptable. Yet, native folate content of heat-treated, non-fortified breastmilk supplied only 25% of the recommended daily intake for preterm infants.

  • 41.
    Bäckström, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Nyberg, Sigrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Ossewaarde, L
    Ragagnin, Gianna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Savic, I
    Strömberg, J
    Timby, Erika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    van Broekhoven, F
    van Wingen, G
    Allopregnanolone and mood disorders2014In: Progress in Neurobiology, ISSN 0301-0082, E-ISSN 1873-5118, Vol. 113, p. 88-94Article in journal (Refereed)
    Abstract [en]

    Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. Conclusion: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.

    (c) 2013 Elsevier Ltd. All rights reserved.

  • 42. Campbell, Jennifer
    et al.
    Pedroletti, Corinne
    Ekhed, Linn
    Nüssler, Emil
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. National Quality Register of Gynecological Surgery, Umeå, Sweden.
    Strandell, Annika
    Patient-reported outcomes after sacrospinous fixation of vault prolapse with a suturing device: a retrospective national cohort study2018In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 6, p. 821-829Article in journal (Refereed)
    Abstract [en]

    Introduction and hypothesis: Innovations in suturing devices have facilitated sacrospinous ligament fixation (SSF) for the correction of vaginal vault prolapse. It is uncertain if outcomes using suturing devices differ from those using a traditional suturing technique. We hypothesize that no difference exists in the efficacy and safety 1 year after SSF for vault prolapse performed with suturing devices or using a traditional technique. The objective was to compare SSF using a suturing device with traditional SSF for the treatment of vault prolapse, regarding symptoms of prolapse recurrence, patient satisfaction, incidence of re-operation, and complications 1 year postoperatively.

    Methods: We carried out a retrospective cohort study using register-based national data from 2006 to 2013. The Swedish Quality Register of Gynecological Surgery includes assessments pre-operatively, at hospital admittance, surgery, discharge, and questionnaires at 8 weeks and 1 year after surgery. Demographic variables and surgical methods were included in multivariate logistic regression analyses.

    Results: In the suturing device group (SDG, n = 353), 71.5% were asymptomatic of recurrence after 1 year compared with 78.7% in the traditional SSF group (TSG, n = 195); risk difference - 7.3% (95%CI -15.2%; 0.7%). Adjusted odds ratio (aOR) for being asymptomatic 1 year postoperatively was 0.56 (95%CI 0.31; 1.02, p = 0.057). Patient satisfaction was similar in SDG and TSG (78.1% vs 78.4%). Reoperation occurred in 7.4% in the SDG compared with 3.6% in the TSG, risk difference 3.8% (95%CI 0.0%; 7.5%), aOR 3.55 (95%CI 1.10; 11.44, p = 0.03).

    Conclusions: Patient satisfaction was similar 1 year after SSF, despite symptoms of recurrence being more likely and reoperation more common after using a suturing device compared with a traditional technique. The methods did not differ with regard to surgical complications.

  • 43. Carrasquilla, German D.
    et al.
    Chiavenna, Chiara
    Bottai, Matteo
    Magnusson, Patrik K.
    Santacatterina, Michele
    Wolk, Alicja
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Engstrom, Gunnar
    Borgfeldt, Christer
    Pedersen, Nancy L.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Berglund, Anita
    Leander, Karin
    The association between menopausal hormone therapy and coronary heart disease depends on timing of initiation in relation to menopause onset. Results based on pooled individual participant data from The Combined Cohorts of Menopausal Women - Studies of Register Based Health Outcomes in Relation to Hormonal Drugs (COMPREHEND) study2015In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 22, no 12, p. 1373-1373Article in journal (Other academic)
  • 44. Chaturvedi, Sarika
    et al.
    Randive, Bharat
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Department of Public Health and Environment, R D Gardi Medical College, Ujjain, India.
    Diwan, Vishal
    De Costa, Ayesha
    Quality of Obstetric Referral Services in India's JSY Cash Transfer Programme for Institutional Births: A Study from Madhya Pradesh Province2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, article id e96773Article in journal (Refereed)
    Abstract [en]

    Background:

    India launched JSY cash transfer programme to increase access to emergency obstetric and neonatal care (EmONC) by incentivising in-facility births. This increased in-facility births from 30% in 2005 to 73% in 2012 however, decline in maternal mortality follows a secular trend. Dysfunctional referral services can contribute to poor programme impact on outcomes. We hence describe inter-facility referrals and study quality of referral services in JSY.

    Methods and Results:

    Women accessing intra natal care (n = 1182) at facilities (reporting >10 deliveries/month, n = 96) were interviewed in a 5 day cross sectional survey in 3 districts of Madhya Pradesh province. A nested matched case control study (n = 68 pairs) was performed to study association between maternal referral and adverse birth outcomes. There were 111 (9.4%) in referrals and 69 (5.8%) out referrals. Secondary level facilities sent most referrals and 40% were for conditions expected to be treated at this level. There were 36 adverse birth outcomes (intra partum and in-facility deaths). After matching for type of complication and place of delivery, conditional logistic regression model showed maternal referral at term delivery was associated with higher odds of adverse birth outcomes (OR-2.6, 95% CI: 1.0-6.6 p = 0.04). Maternal death record review (April 10-March 12) was conducted at the CEmOC facility in one district. Spatial analysis of transfer time from sending to the receiving CEmOC facility among in-facility maternal deaths was conducted in ArcGIS10 applying two hours (equated to 100 Km) as desired transfer time. There were 124 maternal deaths, 55 of which were among mothers referred in. Buffer analysis revealed 98% mothers were referred from <2 hours. Median time between arrival and death was 6.75 hours.

    Conclusions:

    High odds of adverse birth outcomes associated with maternal referral and high maternal deaths despite spatial access to referral care indicate poor quality of referral services.

  • 45.
    Christianson, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Essén, Birgitta
    'Let men into the pregnancy': men's perceptions about being tested for Chlamydia and HIV during pregnancy2013In: Midwifery, ISSN 0266-6138, E-ISSN 1532-3099, Vol. 29, no 4, p. 351-358Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate how to prevent transmission of HIV and Chlamydia trachomatis (CT) by exploring whether screening of men during pregnancy may be an innovative way to reach men, to increase detection, and to avoid the present gendered responsibility.

    DESIGN: An explorative research strategy with in-depth interviews and an analysis informed by grounded theory principles was used.

    SETTING: The northern part of Sweden.

    PARTICIPANTS: Twenty men/becoming fathers in their twenties and early thirties were offered CT and HIV testing and were interviewed about their perceptions about being tested during pregnancy.

    FINDINGS: Six categories emerged that concerned the men's risk perceptions, reasons for not testing men, benefits and negative consequences associated with being tested, incentive measures for reaching men and the optional time for testing men during pregnancy. The majority of the men perceived their own risk for having CT or HIV to be close to zero, trusted their stable partner, and did not see men as transmitters. They did not understand how men could play a role in CT or HIV transmission or how these infections could negatively affect the child. However, few informants could see any logical reasons for excluding men from testing and the majority was positive towards screening men during the pregnancy.

    KEY CONCLUSIONS: Men's sexual health and behaviour on social and biological grounds will affect the health of women and their children during pregnancy and childbirth. As long as expectant fathers do not count in this 'triad', there is a risk that CT and HIV infections in adults and infants will continue to be an unsolved problem.

    IMPLICATIONS FOR PRACTICE: Knowledge from this research can contribute to influencing the attitudes among health-care providers positively, and inspiring policy changes.

  • 46.
    Christianson, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Eriksson, Carola
    Umeå University, Faculty of Medicine, Department of Nursing.
    Myths and misconceptions: Midwives´ perception of the vaginal opening or hymen and virginity2013In: British journal of midwifery, ISSN 0969-4900, E-ISSN 2052-4307, Vol. 21, no 2, p. 108-115Article in journal (Refereed)
    Abstract [en]

    Ideas and misconceptions about the vaginal opening, hymen and virginity are widely held in many societies. The aim of this study was to investigate the perceptions of the vaginal opening, the hymen and its connection with bleeding, sexual intercourse, physical activity and virginity verification among an international group of midwives. An online questionnaire about the topic was emailed to midwives who attended the International Confederation of Midwives' (ICM) Congress in Glasgow. The respondents (n=480) represented five continents with European delegates dominating the attendees. Two thirds (66%) of the respondents believed that girls are born with a covering membrane that breaks during the first vaginal intercourse and 52% thought that the membrane breaks during physical activities. Fifteen percent connected bleeding with the first vaginal intercourse and 21% stated that virginity can be verified by a gynecological examination. Midwives play a significant role in improving the sexual and reproductive health of women, thus in order to challenge long-held biomedical 'truths', midwives must become conscious and knowledgeable about how the myths surrounding the hymen contribute to gender inequalities and health disparities in women. A first step is to implement gender perspectives in midwifery education.

  • 47. Clendenen, Tess V.
    et al.
    Hertzmark, Kathryn
    Koenig, Karen L.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rinaldi, Sabina
    Johnson, Theron
    Krogh, Vittorio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lukanova, Annekatrin
    Zeleniuch-Jacquotte, Anne
    Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study2016In: Hormones & cancer, ISSN 1868-8500, Vol. 7, no 3, p. 178-187Article in journal (Refereed)
    Abstract [en]

    Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case-control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1 = 1.59, 95 % CI = 0.96, 2.64, p = 0.08) and free testosterone (ORT3-T1 = 1.76, 95 % CI = 1.01, 3.07, p = 0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n = 51 cases; ≥55 years, n = 110 cases). Among women who were ≥55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95 % CI = 1.25, 3.44, p = 0.005) for a doubling in testosterone and 1.55 (95 % CI = 1.04, 2.31, p = 0.049) for a doubling in free testosterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged ≥55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted.

  • 48. Clendenen, Tess V
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zeleniuch-Jacquotte, Anne
    Koenig, Karen L
    Berrino, Franco
    Lukanova, Annekatrin
    Lokshin, Anna E
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Krogh, Vittorio
    Sieri, Sabina
    Muti, Paola
    Marrangoni, Adele
    Nolen, Brian M
    Liu, Mengling
    Shore, Roy E
    Arslan, Alan A
    Circulating inflammation markers and risk of epithelial ovarian cancer.2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 5, p. 799-810Article in journal (Refereed)
    Abstract [en]

    Background: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer.

    Methods: We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer.

    Results: We observed a trend across quartiles for IL-2 (ORQ4 vs. Q1: 1.57, 95% CI: 0.98–2.52, P = 0.07), IL-4 (ORQ4 vs. Q1: 1.50, 95% CI: 0.95–2.38, P = 0.06), IL-6 (ORQ4 vs. Q1: 1.63, 95% CI: 1.03–2.58, P = 0.03), IL-12p40 (ORQ4 vs. Q1: 1.60, 95% CI: 1.02–2.51, P = 0.06), and IL-13 (ORQ4 vs. Q1: 1.42, 95% CI: 0.90–2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors.

    Conclusions and Impact: This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.

  • 49. Crawshaw, Marilyn
    et al.
    Adams, Damian
    Allan, Sonia
    Blyth, Eric
    Bourne, Kate
    Bruegge, Claudia
    Chien, Anne
    Clissa, Antonia
    Daniels, Ken
    Glazer, Ellen
    Haase, Jean
    Hammarberg, Karin
    Van Hooff, Hans
    Hunt, Jennie
    Indekeu, Astrid
    Johnson, Louise
    Kim, Young
    Kirkman, Maggie
    Kramer, Wendy
    Lalos, Ann
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lister, Charles
    Lowinger, Phyllis
    Mindes, Erica
    Monach, Jim
    Montuschi, Olivia
    Pike, Sheila
    Powell, Victoria
    Rodino, Iolanda
    Ruby, Alice
    Schrijvers, Anne Margriet
    Semba, Yukari
    Shidlo, Ruth
    Thorn, Petra
    Tonkin, Lois
    Visser, Marja
    Woodward, Julia
    Wischmann, Tewes
    Yee, Samantha
    Zweifel, Julianne E.
    Disclosure and donor-conceived children2017In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 32, no 7, p. 1535-1536Article in journal (Refereed)
  • 50. Cuneo, Bettina
    et al.
    Clur, Sally Ann
    Swan, Heikki
    Ackerman, Michael
    Herberg, Ulrike
    Etheridge, Susan
    Winbo, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Benson, D. Woodrow
    Schwartz, Peter
    Fetal heart rate and arrhythmia profile predicts long QT syndrome (LQTS) genotype: Results of an 8-center international study2018In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 218, no 1, p. S93-S93Article in journal (Other academic)
    Abstract [en]

    Objective: 1. Determine if fetal heart rate (FHR) predicts LQTS across gestational ages (GA). 2. Ascertain genotype specific effects on FHR and rhythm.

    Study Design: FHR and rhythm data were ascertained from fetuses with maternal or paternal LQTS1, LQTS2 or LQTS3 genotype at 8 international centers. We reviewed obstetrical history including maternal beta blocker (BB) use. At each obstetrical visit, FHRs were calculated from an average of 3 heart beats (ultrasound) or 3 10-second periods of FHR auscultation (Doppler monitor) measured during fetal quiescence. Postnatal genetic testing was performed by commercial laboratories. We compared FHR in the 1st, 2nd and 3rd trimesters between fetuses with (LQTS+) and without (LQTS-) the family mutation by t-test. Differences in FHR between LQTS genotypes were compared by ANOVA. Log FHR was analyzed by a linear mixed effect model with GA as the continuous variable and adjusting for maternal BB use. The predictive ability of FHR to discriminate LQTS+ from LQTS- was addressed by ROC analysis, evaluating the magnitude of FHR (intercept) and change in FHR (slope) across GA.

    Results: Data were available on 51 LQTS+ and 27 LQTS-. Mean FHR differed between LQTS+ and LQTS- fetuses in 2nd and 3rd but not in the 1st trimesters (Table). The magnitude of FHR change in 2nd and 3rd trimesters discriminated LQTS + from LQTS- (both, p<0.05); with AUC of 0.81. FHR effect was most pronounced for LQTS1 and differed significantly between genotypes. LQTS3 did not exhibit a FHR effect at any GA. Only LQTS2 had signature LQTS arrhythmias (2◦ AV block and/or torsade de pointes). Maternal BB had no significant effect on FHR.

    Conclusion: In this study with a preponderance of LQTS1, FHR discriminated LQTS+ from LQTS- fetuses in the 2nd and 3rd trimesters. LQTS genotype appears to affect the fetal presentation of LQTS. These findings provide insight into the natural history of LQTS before birth and may facilitate early detection of LQTS1 and LQTS2 fetuses.

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