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  • 1.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Artery Wall Layer Dimensions during Normal Pregnancy: A longitudinal study using non-invasive high-frequency ultrasound2013In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 304, no 2, p. H229-H234Article in journal (Refereed)
    Abstract [en]

    The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

  • 2.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Individual Artery Wall Layer Dimensions Indicate Increased Cardiovascular Risk in Previous Severe Preeclampsia: An investigation using non-invasive high-frequency ultrasound2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563Article in journal (Refereed)
    Abstract [en]

    Preeclampsia, especially severe preeclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media (I/M) ratio indicate an increased cardiovascular risk in women with previous severe PE. The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) (Collagenoson, Meudt, Germany) in 42 women with previous severe preeclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M ratio are signs of a less healthy artery wall. Women with previous severe preeclampsia had a thicker mean CCA intima and a higher I/M ratio than women with previous normal pregnancies (both p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic (ROC) curve analysis, both intima thickness and I/M ratio clearly discriminated between women with and without previous severe preeclampsia [area under the curve (AUC) about 0.95], whereas CCA-IMT did not (AUC 0.52). Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M ratio clearly demonstrated the well known increased cardiovascular risk in women with previous severe preeclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with a history of previous severe preeclampsia.

  • 3.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre-eclampsia2014In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 43, no 6, p. 675-680Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Pre-eclampsia, especially severe pre-eclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media ratio (I/M) indicate an increased cardiovascular risk in women with previous severe pre-eclampsia.

    METHODS: The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) in 42 women with previous severe pre-eclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M are signs of a less healthy artery wall.

    RESULTS: Women with previous severe pre-eclampsia had a thicker CCA intima and a higher I/M than women with previous normal pregnancies, also after adjustment for mean arterial pressure, body mass index and CCA-IMT (all p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic curve analysis, intima thickness and I/M clearly discriminated between women with and without previous pre-eclampsia (c value about 0.95), whereas CCA-IMT did not (c = 0.52).

    CONCLUSIONS: Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M clearly demonstrated the well known increased cardiovascular risk in women with pre-eclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with previous severe pre-eclampsia.

  • 4.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Changes in the Artery Wall Layer Dimensions in Women with Preeclampsia: an investigation using non-invasive high frequency ultrasound2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, no S159, p. 28-28Article in journal (Other academic)
    Abstract [en]

    Background:

    Preeclampsia (PE) is associated with increased risk for cardiovascular disease later in life. Whether, the artery wall layer dimensions differ between PE and normal pregnancy is unclear. The aim of this study was to estimate if women with PE have different common carotid artery wall layer dimensions than women with normal pregnancy, both during pregnancy and about one year postpartum.

    Methods:

    By using high-frequency (22MHz) ultrasound (Collagenoson, Meudt, Germany) separate estimates of the common carotid artery intima and media layers were obtained and the I/M ratio was calculated in women with PE (n=55 during pregnancy and n=48 at postpartum) and with normal pregnancy (n=65 during pregnancy and n=59 at postpartum). Thick intima, thin media and a high intima/media ratio are signs of less healthy artery wall and vice versa.

    Results:

    In women with PE, the intima was thicker (0.18 } 0.03 vs. 0.11 } 0.02; p < .001), the media was thinner (0.47 } 0.12 vs. 0.55 } 0.14; p = .001) and the I/M ratio was higher (0.41 } 0.14 vs. 0.20 } 0.05; p < .001) compared to women with normal pregnancy. Further, for changes from pregnancy to postpartum, both for PE and normal pregnancy, the intima and the I/M ratio had improved but still significantly higher in women with PE than in women with normal pregnancy.

    Conclusion:

    In women with PE, we found a thicker intima, thinner media and a higher I/M ratio compared to women with normal pregnancy, indicating a more negatively affected artery wall layer dimensions. Persisting negative effects of PE on artery wall at postpartum, despite improvement of artery wall layers compared to values during pregnancy, indicates a permanent damage of the vascular system in this group of women.

  • 5.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia2017In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 50, p. 93-99Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

    METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.

    RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.

    CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.

  • 6.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 241, p. 417-422Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).

    METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.

    RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.

    CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.

  • 7.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima-Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia: An investigation using non-invasive high-frequency ultrasound2013In: Circulation Cardiovascular Imaging, ISSN 1941-9651, E-ISSN 1942-0080, Vol. 6, no 5, p. 762-768Article in journal (Refereed)
    Abstract [en]

    Background Preeclampsia (PE) is associated with increased risk of cardiovascular disease later in life. Ultrasound assessment of the common carotid artery intima-media thickness (IMT) during or after PE has not indicated any increased cardiovascular risk. Methods and Results We used high-frequency ultrasound (22 MHz) to estimate the individual common carotid artery IMTs in 55 women at PE diagnosis and in 64 women with normal pregnancies at a similar stage. All were re-examined about 1 year postpartum. A thick intima, thin media, and high intima/media (I/M) ratio are signs of a less healthy artery wall. PE was associated with a significantly thicker mean common carotid artery intima, thinner media, and higher I/M ratio than in normal pregnancy (mean I/M difference, 0.21; 95% confidence interval, 0.17-0.25; P<0.0001). After adjustment for first trimester body mass index and mean arterial pressure, differences in intima thickness and I/M remained significant. About 1 year postpartum, these values had improved in both groups, but group differences remained significant (all adjusted P<0.0001). There were no significant differences in IMT between groups. In receiver-operating characteristic curve analysis, intima thickness and I/M were strongly predictive of prevalent PE (area under the curve, approximate to 0.95), whereas IMT was not (area under the curve, 0.49). Conclusions The arteries of women with PE were negatively affected during pregnancy and 1 year postpartum compared with women with normal pregnancies, indicating increased cardiovascular risk. Estimation of intima thickness and I/M ratio seem preferable to estimation of common carotid artery IMT in imaging cardiovascular risk in PE. Results from this pilot study warrant further confirmation.

  • 8.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 275, p. E69-E70Article in journal (Other academic)
  • 9.
    Al-Saqi, Shahla Hamza
    et al.
    Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Jonasson, Aino Fianu
    Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Uvnäs-Moberg, Kerstin
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women2016In: Post Reproductive Health, ISSN 2053-3691, E-ISSN 2053-3705, Vol. 22, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo.

    STUDY DESIGN: Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks.

    RESULTS: The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04).

    CONCLUSION: Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.

  • 10.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects2014In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, no 8, p. 1105-1111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.

    METHODS:

    A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.

    RESULTS:

    Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).

    CONCLUSIONS:

    S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

  • 11.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikstrom, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Plasma Levels of S100B in Women with Preeclampsia2013In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 20, no S3, p. 115A-115AArticle in journal (Other academic)
  • 12.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Clin Res Ctr, Dalarna, Sweden..
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum2016In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 29, no 12, p. 1374-1379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND There is evidence of cerebral involvement among women with preeclampsia. Levels of the cerebral biomarkers neuron-specific enolase (NSE) and S100B are elevated during pregnancy in women developing preeclampsia. It is although not known if these biomarkers return to normal range postpartum. The aim with this study was to compare levels of S100B and NSE during pregnancy and 1 year postpartum in women who have had preeclampsia to women with normal pregnancies. METHODS This study was a longitudinal study of cases (n = 53) with preeclampsia and controls (n = 58) consisted of normal pregnant women in matched gestational weeks. Plasma samples were collected at inclusion during pregnancy and 1 year postpartum. Plasma samples were analyzed for levels of S100B and NSE by enzyme-linked immunosorbent assays kits. RESULTS Levels of NSE and S100B in women with preeclampsia were higher during pregnancy than in women with normal pregnancies. One year postpartum, women who have had preeclampsia still had a higher median level of both NSE (5.07 vs. 4.28 mu g/l, P < 0.05) and S100B (0.07 vs. 0.06 mu g/l, P < 0.05) compared to women with previous normal pregnancies. High levels of NSE and S100B postpartum remained associated with previous preeclampsia after adjustment for confounding factors. Levels of NSE correlated to S100B during pregnancy and postpartum. CONCLUSIONS Levels of NSE and S100B are still elevated 1 year postpartum in women who have had preeclampsia in contrast to women with previous normal pregnancies. We hypothesize that there might be a persistent cerebral involvement among women with preeclampsia even 1 year postpartum.

  • 13. Damberg, Mattias
    et al.
    Westberg, Lars
    Berggård, Cecilia
    Landen, Mikael
    Sundblad, Charlotta
    Eriksson, Olle
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Naessen, Tord
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Ekman, Agneta
    Eriksson, Elias
    Investigation of transcription factor AP-2beta genotype in women with premenstrual dysphoric disorder.2005In: Neurosci Lett, ISSN 0304-3940, Vol. 377, no 1, p. 49-52Article in journal (Refereed)
  • 14.
    Eriksson, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Landén, Mikael
    Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Sweden.
    Sundblad, Charlotta
    Department of Pharmacology, Institute of Physiology and Pharmacology, Gothenburg University, Sweden.
    Holte, Jan
    Carl von Linné Clinic, Uppsala Science Park, Sweden.
    Eriksson, Elias
    Department of Pharmacology, Institute of Physiology and Pharmacology, Gothenburg University, Sweden.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ovarian morphology in premenstrual dysphoria2012In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 37, no 6, p. 742-751Article in journal (Refereed)
    Abstract [en]

    Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty-two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study.

  • 15.
    Eriksson, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wall, Anders
    Marteinsdottir, Ina
    Ågren, Hans
    Hartvig, Per
    Blomqvist, Gunnar
    Långström, Bengt
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria2006In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 146, no 2, p. 107-116Article in journal (Refereed)
    Abstract [en]

    The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.

  • 16.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood2012In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 16, no 4, p. 385-391Article in journal (Refereed)
    Abstract [en]

    We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.

  • 17.
    Hanrieder, Jörg
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Nyakas, Adrien
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Proteomic Analysis of Human Follicular Fluid Using an Alternative Bottom-Up Approach2008In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 7, no 1, p. 443-449Article in journal (Refereed)
    Abstract [en]

    Human follicular fluid (hFF) is the in vivo environment of oocytes during follicular maturation in the ovaries. It contains a huge variety of compounds such as, e.g., proteins that might play an important role in follicular development and oocyte growth. Previous proteomic studies on follicular fluid have isolated and already identified a certain number of proteins. Nevertheless, only a small part of proteins present in follicular fluid have been covered so far and a large number have still not been identified. Therefore, the need for new, more resolving, and sensitive approaches in proteome research is evident. We utilized a proteomic setup based on in solution isoelectric focusing (IEF) and reversed-phase nanoliquid chromatography coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (nano-LC MALDI TOF/TOF MS) for in depth protein analysis of human follicular fluid samples of patients undergoing controlled ovarian hyper stimulation (COH) for in vitro fertilization therapy (IVF). This approach led to the significant identification of 69 proteins, where 32 have not been reported before to be found in human follicular fluid with proteomic methods. Among these findings, at least two relevant compounds essentially involved in hormone secretion regulation during the folliculogenetic process were identified: sex hormone binding globulin (SHBG) and inhibin A (INHA). To confirm these results, both proteins were further validated by immunoassays.

  • 18.
    Johnsson, Inger W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 12, p. 2152-2157Article in journal (Refereed)
    Abstract [en]

    AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40.

    METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries.

    RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher.

    CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight.

  • 19.
    Kirilovas, Dmitrijus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Chaika, Andrey
    Bergström, Mats
    Bergström-Petterman, Elizabeth
    Carlström, Kjell
    Nosenko, Jelena
    Korniyenko, Svetlana
    Yakovets, Anna
    Mogilevkina, Iryna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Granulosa cell aromatase enzyme activity: Effects of follicular fluid from patients with polycystic ovary syndrome, using aromatase conversion and [11C]vorozole-binding assays2006In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 22, no 12, p. 685-691Article in journal (Refereed)
    Abstract [en]

    The local regulation of ovarian aromatase enzyme in polycystic ovary syndrome (PCOS) was studied with aromatase conversion and [C-11]vorozole-binding assays to analyze aromatase activity, substrate-enzyme affinity and number of aromatase binding sites in non-cultured human granulosa cells (GC) incubated with different sources and preparations of follicular fluid (FF). Incubation with FF from women stimulated in in vitro fertilization cycles with follicle-stimulating hormone yielded higher conversion activity than with FF from healthy women and PCOS patients, paralleled with higher substrate affinity (lower K-d) than with FF from healthy women. In PCOS women, charcoal-pretreated FF yielded higher conversion, whereas the ether-pretreated FF yielded lower conversion activity, than with untreated PCOS FF. Both preparations of FF yielded higher affinity to substrate (lower Kd values) and the ether-pretreated FF a lower number of binding sites (B-max). It seems that steroids with the presence of proteins in PCOS FF reduced aromatase conversion activity through decreased substrate affinity, whereas FF preparations devoid of proteins reduced the aromatase conversion activity mainly through blocking of aromatase active sites. Identification of specific agents responsible for this rapid regulation of aromatase function might help to understand normal regulation of the menstrual cycle and supposed imbalances of inhibitors/activators in PCOS.

  • 20.
    Kirilovas, Dmitrijus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Naessen, Tord
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Bergström, Mats
    Bergström-Petterman, Elizabeth
    Carlström, Kjell
    Långström, Bengt
    Characterization of [11C]vorozole binding in ovarian tissue in rats throughout estrous cycle in association with conversion of androgens to estrogens in vivo and in vitro.2003In: Steroids, ISSN 0039-128X, Vol. 68, no 14, p. 1139-46Article in journal (Refereed)
  • 21.
    Kirilovas, Dmitrijus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schedvins, Kjell
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Von Schoultz, Bo
    Carlström, Kjell
    Conversion of circulating estrone sulfate to 17β-estradiol by ovarian tumor tissue: A possible mechanism behind elevated circulating concentrations of 17β-estradiol in postmenopausal women with ovarian tumors2007In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 23, no 1, p. 25-28Article in journal (Refereed)
    Abstract [en]

    AIM: Elevated serum levels of 17beta-estradiol (E2) are frequently found in postmenopausal women with ovarian tumors not classified as estrogen-producing. Conversion of circulating estrone sulfate (E1S) to E2 is one alternative way of E2 formation in target tissues in postmenopausal women. Our aim was to find out if conversion of circulating E1S to E2 by the tumor tissue could be a reason for elevated serum E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors. METHOD: Serum E2 was measured in 12 postmenopausal women with 'non-estrogen-producing' ovarian tumors (nine benign, three malignant). Total hydrolysis of and [3H]E2 formation from [3H]E1S by the tumor tissue homogenates was studied in vitro. RESULTS: Serum E2 showed significant positive correlations with total hydrolysis of and [3H]E2 formation from [3H]E1S in the total material as well as in the benign tumor subgroup. [3H]E2 formation was the most important independent variable. CONCLUSION: Conversion of circulating E1S to E2 by the tumor tissue could be one important reason for elevated S-E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.

  • 22.
    Kristjansdottir, Jona
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Olsson, Gunilla I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Sundelin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Self-reported health in adolescent girls varies according to the season and its relation to medication and hormonal contraception: A descriptive study2013In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 18, no 5, p. 343-354Article in journal (Refereed)
    Abstract [en]

    Objectives To study seasonal variations in self-rated health and depressive symptoms in adolescent girls and possible differences in reported health with regard to use of medications. Method The SF-36 questionnaire was completed by 1250 girls with a mean age of 17 years, who visited a health centre in the course of one year. From January to July inclusive, depressive symptoms in 453 of the participants were also assessed using MADRS-S. Age and regular medication data were recorded. Results Significantly better mental health and less depressive symptoms were reported during the summer, than in winter months. Seasonality was more related to the SF-36 mental, than physical health subscales. Respondents treated with hormonal contraceptives (HCs) only and those not taking any medication scored better on several SF-36 subscales, than girls on antidepressives and other medications. Respondents taking HCs tended to report better physical health and less depressive symptoms on MADRS-S than those taking no medication. Conclusions Adolescent girls showed seasonal variations in self-reported health and depressive symptoms, with more symptoms during winter months. HC users tended to report better physical health and less depressive symptoms than those on no medication. The high prevalence of suspected depression during the winter months deserves attention.

  • 23.
    Kristjánsdóttir, Jóna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olsson, Gunilla I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Sundelin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Could SF-36 be used as a screening instrument for depression in a Swedish youth population?2011In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 25, no 2, p. 262-268Article in journal (Refereed)
    Abstract [en]

     Objective: Depression among youth is a condition associated with serious long-term morbidity and suicide. The aim of this study was to investigate whether a HRQoL instrument, the short form 36 version 1.0 (SF-36), could be used to screen for depression in a clinical Youth Centre (YC). A second purpose was to describe self-reported health and depression. Setting: A clinical YC at a University hospital. Design: A sample of 660 youths, 14-20 years old was assessed with SF-36 and Montgomery Asberg Depression Rating Scale, self-screening version (MADRS-S). Answers to all the questions in both instruments were given by 79% (519/660; 453 women and 66 men). Mean age in the sample was 17.5 +/- 1.6 years. Results: Strong correlations were found between all the SF-36 subscales and the depression ratio scale MADRS-S. Receiver operating characteristic (ROC) curve analysis confirmed that the SF-36 subscales mental health (MH) and vitality (VT) could correctly predict depression on the individual level with Area Under the ROC Curve values 0.87 and 0.84 in ROC curves. Individuals scoring 48 or lower on MH and 40 or lower on VT should be followed up with a clinical interview concerning possible depressive disorder. Mild to moderate depression was common (35.5%), especially among women (37.5%). Men scored higher than women on all SF-36 subscales except for physical functioning. Conclusions: The SF-36 can be used to screen for suspect depression in a youth population followed by interview. This gives an opportunity to detect and treat emerging depressive symptoms early.

  • 24.
    Kristjánsdóttir, Jóna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Sundelin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Health-related quality of life in young women starting hormonal contraception: a pilot study2018In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 23, no 3, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Objectives: Our purpose was to study whether there is a difference in self-rated health-related quality of life (HRQOL) and changes in HRQOL perception after 3 months of hormonal contraceptive use in adolescents. Seasonal variations in symptoms of depression were also studied. Methods: A test group (T1) (n=193) and a selected control group (n=238) of women aged 14-20 years who were visiting a young person's clinic completed the 36-item short-form health survey (SF-36) and answered additional questions on menstrual history and pattern, need for menstrual pain relief medication, and other regular medication. The test group was reassessed after 3 months of hormonal contraception (T2). Seasonal variations in reported SF-36 scores were studied for the whole group. Results: The selected control group and test group at T1 were similar with regard to age at menarche and menstrual pattern. The duration of bleeding and use of painkillers were significantly reduced and the impact on everyday life was significantly improved after 3 months of hormonal contraception (p=.000, two-tailed). No changes in HRQOL or symptoms of possible depression were found after 3 months of hormonal contraception. The highest prevalence odds ratio for possible depression (SF-36 mental health scale score <= 48), adjusted for group, season and age, for spring vs winter, was 2.15 (95% confidence interval 0.95, 4.85). Conclusions: After 3 months of hormonal contraception both the number of days of menstrual bleeding and the use of medication to relieve menstrual pain were reduced, but there were no significant changes in self-rated HRQOL perception. Seasonal effects on HRQOL were reported.

  • 25.
    Kushnir, Mark M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Uppsala University, Science for Life Laboratory, SciLifeLab. ARUP Inst Clin & Expt Pathol, 500 Chipeta Way, Salt Lake City, UT 84108 USA; Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wånggren, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Hreinsson, Julius
    IVF Sweden, IVF Kliniken Falun, Falun, Sweden.
    Rockwood, Alan L.
    ARUP Inst Clin & Expt Pathol, 500 Chipeta Way, Salt Lake City, UT 84108 USA; Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
    Meikle, A. Wayne
    Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA; Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
    Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment2016In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 162, p. 126-133Article, review/survey (Refereed)
    Abstract [en]

    Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF.

  • 26.
    Kushnir, Mark M.
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wånggren, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Rockwood, Alan L.
    Crockett, David K.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Protein and Steroid Profiles in Follicular Fluid after Ovarian Hyperstimulation as Potential Biomarkers of IVF Outcome2012In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, no 10, p. 5090-5100Article in journal (Refereed)
    Abstract [en]

    Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocy-te retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.

  • 27. Landen, M
    et al.
    Eriksson, O
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Sundblad, C
    Andersch, B
    Naessen, T
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Eriksson, E
    Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.2001In: Psychopharmacology, Vol. 155, p. 292-Article in journal (Refereed)
  • 28.
    Leonard, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus: an investigation by non-invasive high-frequency ultrasound2011In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 40, no 4, p. 279-282Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To determine whether high-frequency ultrasound (US) yielding separate assessments of intima and media thickness gives additional information about the vascular morphology compared with the total common carotid artery intima-media thickness (CCA-IMT).

    METHODS:

    Using a 22 MHz US instrument, we determined the near-wall CCA-IMT, the intima and media layers, and the intima/media (I/M) ratio in 47 premenopausal women with systemic lupus erythematosus (SLE), 20 healthy women, and 17 postmenopausal women (mean ages 37, 40, and 69 years, respectively).

    RESULTS:

    In SLE, the carotid intima was thicker (0.19 ± 0.04 vs. 0.12 ± 0.02 mm), the media thinner (0.45 ± 0.12 vs. 0.68 ± 0.24 mm), the I/M ratio higher (0.45 ± 0.17 vs. 0.20 ± 0.07) (all p < 0.0001), and the CCA-IMT lower (0.64 ± 0.13 vs. 0.80 ± 0.25 mm, p < 0.01) compared to age-matched controls. The SLE patients had a thicker carotid intima compared to the postmenopausal women (0.19 ± 0.04 vs. 0.14 ± 0.03 mm, p < 0.0001) and a similar I/M ratio.

    CONCLUSION:

    Separate assessment of carotid artery wall layers demonstrated a thicker intima, thinner media, and a higher I/M ratio in women with SLE compared to healthy controls and indicated an artery wall status in SLE comparable to 30-years-older healthy women. Separate estimates of carotid intima and media layers may be preferable to CCA-IMT in SLE patients.

  • 29.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Franklin, Karl A.
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Sweden.
    Öhagen, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women2018In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 7, article id zsy099Article in journal (Refereed)
    Abstract [en]

    Study Objectives: Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, especially in women. Recently, it has been suggested that OSA during rapid eye movement (REM) sleep, associated with long apneas and deep desaturations, could have severe cardiometabolic consequences. The aim of this study was to investigate whether OSA during REM sleep is associated with early signs of atherosclerosis in a population-based sample of women.

    Methods: In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements, blood sampling, blood pressure measurement, and answered questionnaires. Ten years later, 201 of the original participants, free of known atherosclerotic disease at baseline and without continuous positive airway pressure treatment for OSA, underwent a high-frequency ultrasound of the common carotid artery to assess the individual thickness of the layers of the artery wall.

    Results: Severe OSA during REM sleep (REM apnea-hypopnea index [AHI] ≥ 30) was associated with a thicker intima. This association was still significant after adjustment for age, body mass index, alcohol, and smoking, as well as for further adjustment for systolic blood pressure, low-density lipoprotein, C-reactive protein, and diabetes (β-coefficient, 0.008; p-value, 0.022). The association between a REM AHI of ≥30 and intima thickness was also seen in women with no or mild OSA and normal non-REM AHI.

    Conclusions: In this study of a community-based sample of women, severe OSA during REM sleep was independently associated with early signs of atherosclerosis.

  • 30.
    Naessen, T
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Rodriguez Macias, KA
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Lithell, H
    Department of Public Health and Caring Sciences.
    Serum lipid profile improved by ultra-low doses od 17-ß estradiol in elderly women.2001In: J Clin Endocrinol Metab, Vol. 6, p. 2757-Article in journal (Refereed)
  • 31.
    Naessen, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Lindmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Lagerström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Larsen, Hans-Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Persson, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Early postmenopausal hormone therapy improves postural balance2007In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 14, no 1, p. 14-19Article in journal (Refereed)
    Abstract [en]

    Objective: Postmenopausal hormone therapy (HT) results in more substantial reductions in the risk of hip fracture when initiated sooner rather than later after menopause. We studied the effects of postmenopausal HT on the postural balance of postmenopausal women, with further assessment according to the time since they achieved menopause.

    Design: One hundred women with a mean age of 52.5 years (91 evaluable) were randomly and blindly assigned to either a sequential estradiol-norethisterone acetate regimen or placebo for 3 months, after which all participants received open HT for a further 3 months. Postural balance was assessed as sway velocity using a force platform.

    Results: After 3 months of HT, sway velocity had improved (decreased) from baseline by 7.0% (P = 0.007 vs baseline and P = 0.038 vs placebo). Continued HT for 6 months further improved sway velocity by 12% from baseline (P < 0.0001) to reach values similar to those historically found in younger women or in postmenopausal women after long-term HT. Closer proximity to menopause and more pronounced increases in serum estradiol values were associated with stronger improvements in sway velocity (P = 0.018 for interaction). HT also improved dizziness (P = 0.016 vs baseline and 0.022 vs placebo). (Nonparametric statistics are used throughout, except for analyses of interaction and dizziness.)

    Conclusions: Initiation of HT soon after menopause rapidly improved postural balance to levels normally seen in young women. We suggest that improved postural balance can contribute to the protection against fractures associated with HT and explain the more substantial reduction in hip fracture risk after HT initiated sooner, compared with later, after menopause. Further study is required to confirm these results.

  • 32.
    Naessen, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lindmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Larsen, Hans Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hormone therapy and postural balance in elderly women2007In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 14, no 6, p. 1020-1024Article in journal (Refereed)
    Abstract [en]

    Objective: Most fractures occur in elderly individuals without osteoporosis, and more than 90% of all hip fractures are associated with a fall. It is unclear whether hormone therapy (HT) can improve postural balance when initiated in elderly women and the effect of endogenous estradiol (E2) levels. Design: Forty healthy women (33 assessable), age 60 years or older, were recruited through advertising in the local media. They were randomly and blindly assigned to receive either estradiol patches (50 μg/24 h) combined with oral medroxyprogesterone acetate (2.5 mg/d) or placebo for 6 months. Postural balance was assessed as sway velocity using a force platform. Results: Low serum E2 levels were associated with greater impairment of sway velocity during the study in the placebo group. After 6 months sway velocity had improved (decreased) in the HT group by 4.3% from baseline and increased in the placebo group by 6.2%. The difference was not significant (1.30 cm/s, 95% CI: -3.0 to 0.4; P = 0.13). However, among women with low serum E2 levels at baseline (less than the median, 35 pmol/L), sway velocity improved in the HT group and deteriorated in the placebo group with a difference of 23% (2.9 cm/s, 95% CI: 0.6-5.1; P = 0.013). There were similar results after adjustment for baseline sway velocity (P = 0.003) and in the intention-to-treat analysis (P = 0.023). There was also a significant interaction between the study group and baseline serum E2 levels with regard to changes in sway velocity (P = 0.014). Conclusions: In elderly women low endogenous serum E2 levels were associated with greater impairment of postural balance function during the study, whereas HT, as compared with placebo, improved postural balance in women with low serum E2 levels.

  • 33.
    Naessen, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rodriguez-Macias, Kenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Menopausal estrogen therapy counteracts normal aging effects on intima thickness, media thickness and intima/media ratio in carotid and femoral arteries: An investigation using noninvasive high-frequency ultrasound2006In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 189, no 2, p. 387-392Article in journal (Refereed)
    Abstract [en]

    Background: Estrogen therapy that is started at the time of menopause seems to protect against the development of atherosclerosis and cardiovascular diseases, in contrast to the initial increased cardiovascular risk when hormone therapy is initiated in older women. With increased aging and degree of atherosclerosis, the thickness of the artery intima increases and that of the media decreases. These changes can be noninvasively estimated using high-frequency ultrasound.

    Methods and results: The thickness of carotid and femoral artery intima and media was assessed, using noninvasive high-frequency ultrasound (25 MHz). Long-term estrogen users (mean treatment duration 20 years) had a significantly thinner mean carotid intima layer (-25%; P=0.0002), a thicker media layer (+74%; P=0.0002) and a substantially lower intima/media thickness ratio (-54%; P < 0.0001) than 17 age-matched nonusers, with values closer to those in 20 premenopausal women. Similar but less pronounced differences between the postmenopausal groups were found for the femoral artery.

    Conclusions: A preserved thin artery wall intima and a low intima/media thickness ratio, at values close to those in young women might be partially responsible for the beneficial cardiovascular effects of estrogen therapy when it is initiated at the time of menopause.

  • 34.
    Naessen, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Samsioe, G
    Hormonbehandling efter menopaus: HRT och hjärtkärlrisk2010Report (Other academic)
  • 35.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Effekter på benmassa och frakturrisk vid hormonell behandling efter menopaus2014In: Klimakteriet - en uppdatering / [ed] Anna-Clara Spetz Holm, Lena Jonasson och Mats Hammar, Studentlitteratur AB, 2014, 1, p. 85-91Chapter in book (Refereed)
  • 36.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hormonbehandling efter menopaus: Behandling av osteoporos - bakgrundsdokumentation2007In: Information från Läkemedelsverket, ISSN 1101-7104, no 4, p. 38-43Article in journal (Other academic)
  • 37.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hormonbehandling efter menopaus: effekter på benmassa/frakturrisk samt andra effekter2008In: Svenska Osteoporossällskapet, p. 146-157Article in journal (Other academic)
  • 38.
    Naessén, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Kushnir, Mark M
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Higher endogenous estrogen levels in 70-year-old women and men: an endogenous response to counteract developing atherosclerosis?2012In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 19, no 12, p. 1322-1328Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Reported associations between endogenous steroid hormone levels and cardiovascular disease in the older population have been contradictory. We evaluated plasma steroid concentrations in terms of the dimensions of the common carotid artery wall layers as a measure of the extent of atherosclerosis.

    METHODS:

    A subgroup of 70-year-old participants (32 women and 50 men) from the Prospective Investigation of the Vasculature in Uppsala Seniors study was investigated. All participants had assessments of common carotid artery wall layer parameters (intima thickness, media thickness, and intima-media thickness [IMT] ratio; measured by high-frequency ultrasound at 22 MHz) and endogenous steroid hormone concentrations (measured by liquid chromatography-tandem mass spectrometry).

    RESULTS:

    Low androgen levels, high aromatase enzyme activity (estrone [E1]/androstenedione and estradiol [E2]/testosterone), high E2/E1 ratio, and high estrogen levels (E1, E2, estriol, and E2/sex hormone-binding globulin) were consistently associated (often significantly) with a more unhealthy artery wall (thick intima, thin media, and high IMT ratio) in both sexes. Consistently strong associations were found between the aromatase index E2/testosterone and intima, media, and the IMT ratio. For IMT ratio, in both men (rs = 0.52) and women (rs = 0.58), P was <0.001 for both and remained significant after adjustment for cardiovascular disease risk factors and the Framingham risk score (both P < 0.01).

    CONCLUSIONS:

    Low androgens, high aromatase enzyme activity, and high estrogen levels are often significantly associated with an unhealthy artery wall on ultrasound. We suggest that the steroid hormone profile of older individuals with higher estrogens most probably reflects an endogenous response to developing atherosclerosis, rather than a cause-and-effect relationship. However, the reverse causality cannot be excluded.

  • 39.
    Naessén, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bergström, I
    Hormonbehandling efter menopaus: effekter på benmassa/frakturrisk2010Report (Other academic)
  • 40.
    Naessén, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kushnir, Mark M.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Chaika, Andrey
    Donetsk State Medical University, Ukraine.
    Nosenko, Jelena
    Donetsk State Medical University, Ukraine.
    Mogilevkina, Iryna
    Donetsk State Medical University, Ukraine.
    Rockwood, Alan L.
    ARUP Institute for Clinical and Experimental Pathology, Utah.
    Carlström, Kjell
    Karolinska Institute.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Kirilovas, Dmitrijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry.2010In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, no 6, p. 2228-2233Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    To compare steroid concentrations and steroid product-to-precursor ratios in ovarian follicular fluid (FF) from women with polycystic ovary syndrome (PCOS) and from regularly menstruating women in their early follicular phase, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polycystic ovary syndrome involves abnormal regulation of the steroidogenic enzymes, leading to arrest of follicle development.

    DESIGN

    Case-control study.

    SETTING

    University hospital clinic.

    PATIENT(S)

    Follicular fluid from size-matched ovarian follicles (5-8 mm) in 27 nonstimulated women with PCOS and in 21 women without PCOS was sampled. Thirteen steroids were quantitated from 40 muL of FF, using LC-MS/MS.

    INTERVENTION(S)

    None.

    MAIN OUTCOME MEASURE(S)

    Concentrations of steroids in the FF and product-to-precursor ratios (enzyme activity) were compared between the groups.

    RESULT(S)

    In women with PCOS, ovarian FF contained higher concentrations of individual and total androgens, lower individual and total estrogens (E), and a lower total E-to-androgen ratio, compared with regularly menstruating women. The product-to-precursor concentration ratios indicated higher CYP17-linked and lower CYP19-linked (aromatase) enzyme activity. Receiver operating characteristic plots indicated the early CYP17 step (17-OH5P/5P) being highly important for the prevalence of PCOS (c = 0.95).

    CONCLUSION(S)

    The women with PCOS had higher ovarian CYP17-linked and lower CYP19-linked (aromatase) enzyme activity, confirming previous data. Multiple steroid assessments from minute volumes including FF from nonstimulated ovaries, using LC-MS/MS, might be useful in research, clinical endocrinology, and in IVF.

  • 41.
    Naessén, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Non-Invasive High-Frequency Ultrasound Using Intima And Intima/Media Thickness Ratio (But Not CIMT), Correctly Monitored Expected Beneficial Vascular Effects Of Menopausal Hormone Therapy2016In: ATHEROSCLEROSIS, ISSN 0021-9150, Vol. 252, p. E192-E193Article in journal (Refereed)
  • 42.
    Naessén, Tord
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Samsioe, Göran
    Jonasson, Lena
    Hormonell behandling och hjärtkärlsjukdom2014In: Klimakteriet - en uppdatering / [ed] Holm, Jonasson, Hammar, Studentlitteratur AB, 2014, 1, p. 75-83Chapter in book (Other academic)
  • 43.
    Nash, Peppi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wentzel, Parri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eriksson, Ulf J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Placental dysfunction in Suramin-treated rats: a new model for pre-eclampsia2005In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 26, no 5, p. 410-418Article in journal (Refereed)
    Abstract [en]

    Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of placental dysfunction and pre-eclampsia. This study was carried out to evaluate if inhibited angiogenesis by Suramin injections in early pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two different Sprague-Dawley strains, U and H, were given intraperitoneal injections of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated on gestational day 20. Suramin injections caused increased blood pressure and decreased renal blood flow in the U rats. In both rat strains Suramin decreased the placental blood flow and caused fetal growth retardation. In both strains the placental concentration of the isoprostane 8-epi-PGF2alpha was increased, indicating oxidative stress. The serum concentration of Endothelin-1 was increased in the U rats. The U strain had a lower basal placental blood flow, and the effects of Suramin were more pronounced in this strain. We conclude, that Suramin injections to pregnant rats cause a state of placental insufficiency, which partly resembles human pre-eclampsia. The induction of this condition is at least partly mediated by oxidative stress, and is subject to varied genetic susceptibility.

  • 44.
    Ormarsdottir, Sif
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Department of Surgical Sciences.
    Naessen, Tord
    Department of Women's and Children's Health.
    Petren-Mallmin, Marianne
    Broome, Ulrika
    Hultcrantz, Rolf
    Lööf, Lars
    Interfaculty Units, Centre for Clinical Research.
    An open, randomized, controlled study of transdermal hormone replacement2004In: Journal of Internal Medicine, Vol. 256, no 1, p. 63-9Article in journal (Refereed)
  • 45.
    Ribom, Eva L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Piehl-Aulin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Six months of hormone replacement therapy does not influence muscle strength in postmenopausal women2002In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 42, no 3, p. 225-31Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Postmenopausal hormone replacement therapy (HRT) has positive effects on fracture incidence before any effects on bone mineral density can be demonstrated. This has been attributed to increased muscle strength by HRT. This study was designed to evaluate the effect of 6 months of HRT on muscle strength in postmenopausal women. METHODS: Forty postmenopausal women, aged 60-78 were included in the study. They were randomly divided in two groups with 20 women in each group. One group received Menorest 50 microg/24 h (estradiol 4.3 mg) and Gestapuran 2.5 mg (medroxyprogesteron) daily and the other group received placebo treatment. The study was conducted as a double blinded, prospective and placebo controlled trial. Hand grip strength, isokinetic knee flexion and extention, and physical activity were measured before treatment, after 3 and 6 months. Physical activity was estimated using a classification system of physical activity. A JAMAR hydraulic hand dynamometer and a Cybex II dynamometer were used to evaluate muscle strength. RESULTS: Hand grip strength in the right hand, increased significantly in both groups (HRT P<0.001 and placebo P<0.01) and in the left hand in the HRT group (P<0.01). However, there were no differences in muscle strength between the two groups. There was no significant change in isokinetic knee flexion or extension after 6 months in either of the groups. The estimated physical activity increased slightly in the placebo group, but there was no significant difference compared to the treatment group. CONCLUSIONS: Our data suggest that 6 months of HRT does not influence muscle strength in postmenopausal women.

  • 46.
    Ribom, Eva L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Svensson, Peter
    Univ Uppsala Hosp, Physiotherapy Ward.
    van Os, Steve
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Low-dose tibolone (1.25 mg/d) does not affect muscle strength in older women2011In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 18, no 2, p. 194-197Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:: More than 50% of all fractures occur in people without osteoporosis. Hormone therapy increases bone density, improves postural balance, and reduces fracture risk in postmenopausal women. It is unclear whether tibolone, a synthetic steroid hormone drug, can improve muscle strength. Thus, the aim of this study was to study the effects of low-dose tibolone therapy on muscle strength in older women. METHODS:: Eighty healthy women (69 completed the study) 60 years or older were recruited through advertising in the local media. They were randomly allocated to receive either tibolone 1.25 mg/day or placebo for 6 months. The stand-up test was used to assess leg muscle strength and balance. Handgrip and leg muscle strength were measured using JAMAR and modified Cybex dynamometers. RESULTS:: Baseline characteristics, including serum estradiol values and muscle strength, were similar in the two groups. Compliance with the therapy regimen was very high, averaging more than 97% in both groups. After 6 months, mean values for handgrip strength, knee extensor strength, and average time to perform 10 stands were improved numerically in both groups compared with values during baseline. However, there were no significant differences in these parameters within or between groups, and differences remained nonsignificant after adjustment for age, serum estradiol, and baseline value. CONCLUSIONS:: Short-term treatment with low-dose tibolone (1.25 mg/d) seems not to affect muscle strength in older women.

  • 47.
    Rodriguez Macias, KA
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Naessen, T
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Berqgvist, D
    Department of Surgical Sciences.
    Validation of in vivo non-invasive high-frequency ultrasonography of the arterial wall layers.2001In: Ultrasound Med Biol, Vol. 27, p. 751-Article in journal (Refereed)
  • 48. Ulrich, L. S. G.
    et al.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elia, D.
    Goldstein, J. A.
    Eugster-Hausmann, M.
    Endometrial safety of ultra-low-dose Vagifem 10 mu g in postmenopausal women with vaginal atrophy2010In: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 13, no 3, p. 228-237Article in journal (Refereed)
    Abstract [en]

    Methods A total of 336 healthy, non-hysterectomized, postmenopausal women (age 59.5 +/- 6.16 years, 9.4 +/- 5.9 years from last menses) were treated with a 10 mu g estradiol vaginal tablet for 12 months (once daily for 2 weeks and then twice weekly for 50 weeks). Endometrial histology was analyzed at baseline and at the end of the trial. Results Of the 336 enrolled subjects, 292 (86.9%) completed the 52-week study. All 336 subjects received an endometrial biopsy at baseline, and 283 had biopsy results at week 52, when 258 out of the 283 biopsy samples were classified as 'atrophic' or 'inactive' endometrium. There were 21 with 'no tissue' despite a repeat biopsy attempt to obtain endometrial tissue, one had insufficient tissue with endometrial thickness > 4 mm, one was 'weakly proliferative' and two revealed polyps. No cases of endometrial hyperplasia or endometrial cancer were reported. The mean endometrial thickness decreased from 2.04 mm (n = 334) from study start to 1.94 mm (n = 293) after 52 weeks, and the estradiol levels remained at the low postmenopausal level. Conclusions After 12 months of treatment with the 10 mu g estradiol vaginal tablet, there was no suggestion of endometrial stimulation and no cases of endometrial hyperplasia or cancer reported. This study provides reassuring data on the endometrial safety of treatment with the 10 mu g estradiol vaginal tablet for 1 year in a large group of postmenopausal, non-hysterectomized women with vaginal atrophy.

  • 49.
    Wide, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eriksson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Effects of 17 beta-oestradiol and norethisterone acetate on sulfonation and sialylation of gonadotrophins in post-menopausal women2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 2, p. 97-106Article in journal (Refereed)
    Abstract [en]

    Background. The number of terminal sialic acid and sulfonated N-acetylgalactosamine (SO3-GalNAc) on gonadotrophins in serum varies during the menstrual cycle and changes at menopause, suggesting that gonadal steroids modify their oligosaccharide synthesis. Our objective was to determine the effects of 17 beta-oestradiol (E-2) and a progestogen, norethisterone acetate (NETA), on the sulfonation and sialylation of gonadotrophins in post-menopausal women. Methods. Serum samples were obtained from eight post-menopausal women treated with 20 mg E-2 implants every 6 months, from four women who in addition were treated daily with 5 mg NETA orally for a 2-week period, and from four women who got this NETA treatment during a 4-week period. Sera from 11 non-treated post-menopausal women served as a reference group. The gonadotrophin serum concentrations, the number of SO3-GalNAc and sialic acid residues per serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) molecule, and the distributions of molecules with 0-1-2-3-4 sulfonated residues were measured. Results. The E-2-treated post-menopausal women had considerably less (P < 0.001) sialic acid and slightly more (P < 0.01) SO3-GalNAc per serum LH and FSH molecule than the non-treated. Two weeks of NETA treatment increased the sulfonation of LH (P < 0.01) and FSH (P < 0.05) concomitantly with decreased (P < 0.05) sialylation of LH. Conclusion. The primary effect of E-2 treatment was a decrease in sialylation and, due to competition for the same substrate, a secondary and consequentially minor increase in sulfonation of LH and FSH. The primary effect of the NETA therapy was an increase in the sulfonation of LH and FSH concomitantly with secondary and consequentially decreases in sialylation of LH.

  • 50.
    Wide, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eriksson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sulfonation and sialylation of gonadotropins in women during the menstrual cycle, after menopause, and with polycystic ovarian syndrome and in men2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 11, p. 4410-4417Article in journal (Refereed)
    Abstract [en]

    Context: More basic isoforms of LH and FSH appear in blood at midcycle and more acidic after menopause. The LH isoforms are more basic in women with polycystic ovarian syndrome (PCOS). These charge alterations may reflect differences in the number of two negatively charged residues on the gonadotropins: sialic acid and sulfonated N-acetylgalactosamine, residues that modulate the half-life of the gonadotropins in blood.

    Objective: The objective of the study was to determine the contributions of sialic acid and sulfonated N-acetylgalactosamine and sialic acid on LH and FSH to the observed alterations in charge.

    Design/Participants: Serum samples were obtained from 59 young women with regular cycles, nine postmenopausal women, 12 women with PCOS, and 40 young men.

    Main Outcome Measures: The number of sulfonated N-acetylgalactosamine and sialic acid residues per LH and FSH molecule in serum and the distributions of molecules with 0-1-2-3-4 sulfonated residues were determined by electrophoretic analyses before and after removal of sialic acid.

    Results: Considerably decreased sulfonation of LH was found at midcycle and in women with PCOS concomitant with slightly increased sialylation. The sulfonation of LH increased in the luteal phase, and the sialylation was highest after menopause for both hormones. The frequencies of sulfonated LH and FSH isoforms were directly related (P < 0.01) to body mass index in women with PCOS.

    Conclusion: The observed variations in sialic acid and sulfonated residues on serum gonadotropins are suggested to reflect alterations in the isoform composition of the hormones secreted by the pituitary, resulting in modulations of their biological properties, such as half-life in blood.

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