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  • 1. Alexandersson, Olof
    et al.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Högberg, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Evidence-based changes in term breech delivery practice in Sweden.2005Ingår i: Acta Obstet Gynecol Scand, ISSN 0001-6349, Vol. 84, nr 6, s. 584-7Artikel i tidskrift (Refereegranskat)
  • 2.
    Andersson, Liselott
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bondestam, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Åström, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Point prevalence of psychiatric disorders during the second trimester of pregnancy: a population-based study.2003Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 189, nr 1, s. 148-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: This study was undertaken to determine the point prevalence of psychiatric disorders during the second trimester of pregnancy in a population-based sample of pregnant women. STUDY DESIGN: Participants were 1795 consecutive pregnant women attending routine ultrasound screening at two obstetric clinics in Northern Sweden during 1 year. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used for evaluating. RESULTS: Overall, 1734 (96.6%) of the women filled in the PRIME-MD patient questionnaire. Psychiatric disorders were present in 14.1% of the women. Major depression was prevalent in 3.3% of patients and minor depression in 6.9% of patients. Anxiety disorders were encountered in 6.6% of patients. Women with psychiatric disorders displayed significantly more somatic symptoms and more pronounced fear of childbirth. Among diagnosed patients, only 5.5% had some form of treatment. CONCLUSION: The prevalence of mood and anxiety disorders in this unselected population of pregnant women was high and the majority of the women were found to be undiagnosed and untreated.

  • 3.
    Andersson, Liselott
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Åström, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Depression and anxiety during pregnancy and six months postpartum: a follow-up study2006Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, nr 8, s. 937-944Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To investigate the relationship between antenatal and postpartum depression and anxiety and to explore associated maternal characteristics. METHODS: From a population-based sample of 1,555 women attending two obstetric clinics in Sweden, all women with an antenatal psychiatric diagnosis (n = 220) and a random selection of healthy women (n = 500) were contacted for a second assessment three to six months postpartum. The Primary Care Evaluation of Mental Disorders was used for evaluation on both occasions. RESULTS: Fewer cases of depressive and/or anxiety disorders were prevalent postpartum compared with the second trimester screening. Depression and/or anxiety were prevalent in 16.5% of postpartal women versus 29.2% of pregnant women. There was a significant shift from a majority of subthreshold diagnoses during pregnancy to full Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnoses during the postpartum period. A history of previous psychiatric disorder, living single, and obesity were significantly associated with a new-onset postpartum psychiatric disorder. The absence of a previous psychiatric disorder was significantly associated with a postpartum recovery of depression or anxiety. CONCLUSIONS: Depression and anxiety appear to be less common postpartum than during pregnancy.

  • 4.
    Andersson, Liselott
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Department of Obstetrics and Gynecology, Sunderby Hospital, Luleå, Sweden.
    Sundström-Poromaa, Inger
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Åström, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Implications of antenatal depression and anxiety for obstetric outcome2004Ingår i: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 104, nr 3, s. 467-476Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 5.
    Andersson, Liselott
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Åström, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Neonatal outcome following maternal antenatal depression and anxiety: a population-based study.2004Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 159, nr 9, s. 872-881Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to determine neonatal outcomes among women who had depressive and anxiety disorders during the second trimester of pregnancy in a population-based sample. Participants were 1,465 women and their neonates born at two obstetric clinics in Sweden. The inclusion period for the women was October 2, 2000-October 1, 2001. The Primary Care Evaluation of Mental Disorders (PRIME-MD) classification system was used to evaluate mental disorders in the second trimester of pregnancy. For assessment of demographic characteristics, birth statistics, and birth-related complications, the medical records of the included women and their offspring were reviewed after delivery. The study results revealed no differences in neonatal outcome between women with antenatal depressive disorders and/or anxiety disorders and healthy subjects. The authors conclude that neonatal outcome did not deteriorate despite the women's impaired mental health during pregnancy.

  • 6.
    Andréen, Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Progesterone effects during sequential hormone replacement therapy2003Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 148, nr 5, s. 571-577Artikel i tidskrift (Refereegranskat)
  • 7.
    Andréen, Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Andersson, Agneta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Relationship between allopregnanolone and negative mood in postmenopausal women taking sequential hormone replacement therapy with vaginal progesterone.2005Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 30, nr 2, s. 212-224Artikel i tidskrift (Refereegranskat)
  • 8.
    Andréen, Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Allopregnanolone concentration and mood: a bimodal association in postmenopausal women treated with oral progesterone.2006Ingår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 187, nr 2, s. 209-221Artikel i tidskrift (Refereegranskat)
  • 9.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wihlbäck, Anna-Carin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ahokas, Antti
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Allopregnanolone and progesterone in estradiol treated severe postpartum affective disorder2019Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, s. 68-68Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wihlbäck, Anna-Carin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ahokas, Antti
    Mehiläinen Clinic, Helsinki, Finland .
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Allopregnanolone and progesterone inestradiol treated severe postpartumdepression and psychosisManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background

    Postpartum affective disorders may be associated with dysregulation of gonadal steroids. We investigated peripheral levels of allopregnanolone and progesterone in a combined group of women with postpartum onset of severe depression and psychosis who, as previously reported, responded with rapid symptom remission during sublingual estradiol treatment. The aim was to assess differences in allopregnanolone and progesterone between patients and healthy controls at baseline, and hormonal changes during estradiol treatment and symptom remission in patients.

    Methods

    Allopregnanolone and progesterone in serum were analyzed with radioimmunoassay before and four weeks after initiation of sublingual estradiol treatment in ten women with postpartum depression and four women with postpartum psychosis (ICD-10). Twenty-eight healthy postpartum controls were included for baseline comparison.

    Results

    Allopregnanolone declined significantly during estradiol treatment while there was a trend for lower baseline allopregnanolone levels in patients compared with healthy postpartum controls. The ratio between allopregnanolone and progesterone was significantly lower in patients compared with controls and it remained unchanged after clinical recovery.

    Limitations

    This study is a secondary analysis of two estradiol treatment studies based on availability of samples for the analysis of allopregnanolone. Healthy controls were assessed earlier after birth. Data on potential confounders (somatic health, breastfeeding, other medication) were not available.

    Conclusions

    Clinical recovery of severe postpartum depression and psychosis during estradiol treatment does not seem to depend on increasing levels of allopregnanolone. Differences in progesterone metabolism may constitute a risk factor for severe postnatal affective dysregulation.

    Highlights

    - Allopregnanolone decreased during estradiol treatment in postpartum depression and psychosis.

    - The Allopregnanolone/Progesterone ratio was lower in patients compared with controls

    - Change in neurosteroid metabolism may be risk factor for postnatal affective dysregulation

  • 11. Bengtsdotter, Hanna
    et al.
    Lundin, Cecilia
    Gemzell Danielsson, Kristina
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Baumgart, Juliane
    Marions, Lena
    Brynhildsen, Jan
    Malmborg, Agota
    Lindh, Ingela
    Sundström Poromaa, Inger
    Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use2018Ingår i: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 23, nr 1, s. 45-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders.

    Materials and methods: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychiatric Interview was used to collect information on previous or ongoing mental disorders. The primary outcome measure was the total change score in five mood symptoms on the Daily Record of Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment cycle.

    Results: Women with ongoing or previous mood, anxiety or eating disorders allocated to COC had higher total DRSP Δ-scores during the intermenstrual phase of the treatment cycle in comparison with corresponding women randomised to placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without mental health problems, no difference in total DRSP Δ-scores between COC- and placebo users was noted. Women with a risk use of alcohol who were randomised to the COC had higher total DRSP Δ-scores than women randomised to placebo, mean difference 2.1 (CI 95% 1.0-3.2).

    Conclusions: Women with ongoing or previous mental disorders or risk use of alcohol have greater risk of COC-induced mood symptoms. This may be worth noting during family planning and contraceptive counselling.

  • 12.
    Bengtsson, Sara K. S.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hedström, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Zingmark, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jonsson, Bjorn
    Bäckström, Torbjörn
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans2015Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, s. 22-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABA(A) receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.

  • 13.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ovarian steroids in rat and human brain: effects of different endocrine states1987Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

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

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

  • 14.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Reply2006Ingår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 13, nr 3, s. 538-538Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Bixo, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ekberg, Karin
    Poromaa, Inger Sundstrom
    Hirschberg, Angelica Linden
    Jonasson, Aino Fianu
    Andreen, Lotta
    Timby, Erika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wulff, Marianne
    Ehrenborg, Agneta
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial2017Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, s. 46-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

    Setting: Swedish multicentre study with 10 centers.

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

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

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

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

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

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

  • 16.
    Bixo, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Timby, Erika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Michalski, Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder2018Ingår i: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 30, nr 2, artikel-id e12553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 17.
    Bixo, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lindén Hirschberg, Angelica
    Ännu inte visat att östradiol och »naturligt« progesteron är säkert2015Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, nr 11, artikel-id DAXWArtikel i tidskrift (Refereegranskat)
  • 18.
    Björn, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Strandberg Nöjd, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Collberg, P.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy2002Ingår i: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 16, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 19.
    Björn, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Strandberg Nöjd, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Negative mood changes during hormone replacement therapy: a comparison between two progestogens2000Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 183, nr 6, s. 1419-1426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 20.
    Björn, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Gunnel
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy2003Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 88, nr 5, s. 2026-2030Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

  • 21.
    Bäckström, Torbjörn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Andersson, Agneta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Andreén, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Birzniece, Vita
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Björn, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Haage, David
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Isaksson, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Inga-Maj
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lindblad, Charlott
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundgren, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ödmark, Inga-Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Strömberg, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Turkmen, Sahruh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wahlström, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wang, Mingde
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wihlbäck, Anna-Carin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Zhu, Di
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Zingmark, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Pathogenesis in menstrual cycle-linked CNS disorders.2003Ingår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1007, s. 42-53Artikel, forskningsöversikt (Övrigt vetenskapligt)
  • 22.
    Bäckström, Torbjörn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ossewaarde, L
    Ragagnin, Gianna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Savic, I
    Strömberg, J
    Timby, Erika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    van Broekhoven, F
    van Wingen, G
    Allopregnanolone and mood disorders2014Ingår i: Progress in Neurobiology, ISSN 0301-0082, E-ISSN 1873-5118, Vol. 113, s. 88-94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

    (c) 2013 Elsevier Ltd. All rights reserved.

  • 23.
    Bäckström, Torbjörn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Savic, Ivanka
    Increased neurosteroid sensitivity - An explanation to symptoms associated with chronic work related stress in women?2013Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, nr 7, s. 1078-1089Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Work related psychosocial stress can be accompanied by so called burnout syndrome with symptoms of mental exhaustion, physical fatigue, and cognitive dysfunction. Underlying mechanisms for acquiring burnout syndrome are not clear. Animal studies show that chronic stress is associated with altered release of GABA-A receptor modulating steroids (GAMS), altered composition of the GABA-A receptor and altered sensitivity to GAMS. In the present study we investigated if such changes occur in women with burnout syndrome. We further asked whether flumazenil (a benzodiazepine antagonist, but with positive modulating effects on GABA-A receptors with altered subunit composition) can block the effect of the GAMS allopregnanolone. Ten women with occupational psychosocial stress and burnout syndrome were compared with twelve healthy controls in an experimental setting. Saccadic eye velocity (SEV) was measured after an injection of allopregnanolone, followed by an injection of flumazenil and a second injection of allopregnanolone. The sensitivity to allopregnanolone was significantly higher in the patients compared to controls after the first injection (p = 0.04) and the difference increased when the response per allopregnanolone concentration unit was compared ( p = 0.006). Following the flumazenil injection the burnout patients (p= 0.016), but not controls, showed a decrease in SEV and flumazenil acted like a positive modulator that is agonistic. There was no significant difference between the groups after second allopregnanolone injection. In conclusion, patients with work related psychosocial stress and burnout syndrome show a different response to GABA-A receptor modulators than controls suggesting a changed GABA-A receptor function in these patients. More precisely we hypothesize that the alpha 4 and delta subunits are up-regulated elevating the responsiveness to allopregnanolone and change the effect of flumazenil, which provides a potential explanation to the burnout syndrome. Flumazenil does not block the effect of allopregnanolone.

  • 24.
    Bäckström, Torbjörn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Strömberg, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    GABAA Receptor-Modulating Steroids in Relation to Women’s Behavioral Health2015Ingår i: Current Psychiatry Reports, ISSN 1523-3812, E-ISSN 1535-1645, Vol. 17, nr 11, artikel-id 92Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In certain women, increased negative mood relates to the progesterone metabolite, allopregnanolone (allo), during the luteal phase of ovulatory menstrual cycles, the premenstrual dysphoric disorder (PMDD). In anovulatory cycles, no symptom or sex steroid increase occurs but symptoms return during progesterone/allo treatment. Allo is a potent GABA(A) receptor-modulating steroid and as such is expected to be calming and anxiolytic. A relation to negative mood is unexpected. However, this paradoxical effect can be induced by all GABA(A) receptor modulators in low concentrations whereas higher concentrations are calming. The severity of the mood symptoms relate to allo in an inverted U-shaped curve at endogenous luteal-phase serum concentrations. Allo's effects on the GABA(A) receptor can be antagonized by isoallopregnanolone (ISO), an antagonist to allo. ISO has also been used in a preliminary clinical trial on PMDD ameliorating symptoms with good effect in PMDD patients.

  • 25.
    Hedström, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Spigset, Olav
    Zingmark, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women2009Ingår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 203, nr 1, s. 85-98Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rationale  The pharmacokinetics and behavioral effects of isoallopregnanolone (3β-hydoxy-5α-pregnan-20-one) in women are not known. Objectives  Allopregnanolone (3α-hydoxy-5α-pregnan-20-one) is a well-known neurosteroid, acting via the GABAA receptor in the human brain. The naturally occurring progesterone metabolite isoallopregnanolone is the 3β-stereoisomer of allopregnanolone. Prior studies have concluded that isoallopregnanolone has no effect on the GABAA receptor. However, an antagonistic effect of isoallopregnanolone to allopregnanolone on the GABAA receptor has been shown in animal and in vitro studies. The purpose of this study was to evaluate the pharmacokinetics and behavioral effects of isoallopregnanolone in humans.

    Materials and methods  Six healthy women were given three increasing doses of isoallopregnanolone intravenously in the follicular phase. Repeated blood samples for analyses of isoallopregnanolone and allopregnanolone concentrations were drawn. Saccadic eye movement variables, self-rated sedation, and mood rating scales were used during the test day. A Likert scale for prospective symptoms was used to measure daily fluctuations during the ongoing menstrual cycle.

    Results  Exogenously administered isoallopregnanolone produced a dose-dependent increase in the serum concentration of isoallopregnanolone. In parallel, there was also a rise in the allopregnanolone concentration. There was a decrease in saccadic eye movement variables, but no effect was found on self-rated sedation or mood and no changes were seen in prospective symptoms during the menstrual cycle.

    Conclusions  After administration of isoallopregnanolone at a cumulative dose of 0.20 mg/kg, no adverse effects were observed. There is a metabolism of isoallopregnanolone to allopregnanolone, most likely explaining the effects on the saccadic eye movements.

  • 26.
    Hedström, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Turkmen, Sahruh
    Sundsvalls sjukhus, Obstetrik och gynekologi.
    Wang, Mingde
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Does chronic endogenous exposure to neuroactive steroids change receptor sensitivity to allopregnanolone in humans?Manuskript (preprint) (Övrigt vetenskapligt)
  • 27.
    Hedström, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wang, Mingde
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Gideonsson, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Turkmen, Sahruh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Women with polycystic ovary syndrome have elevated serum concentrations of and altered GABA A receptor sensitivity to allopregnanolone2015Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 83, nr 5, s. 643-650Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectiveSeveral studies have reported that -aminobutyric acid (GABA) ergic circuits are involved in the pathophysiology of polycystic ovary syndrome (PCOS). The progesterone metabolite allopregnanolone is a potent GABA(A)-receptor-modulating steroid, and patients may have increased concentrations of allopregnanolone or altered GABA(A) receptor sensitivity. We investigated both of these possibilities in this study. PatientsWe enrolled 9 women with PCOS and 24 age-matched eumenorrhoeic controls, who were divided into two groups by body mass index (BMI) (16 normal weight and 8 overweight). MeasurementsWe investigated the effects of allopregnanolone injection on GABA(A) receptor sensitivity in both groups of women. All women received a single intravenous dose of allopregnanolone (0050mg/kg). GABA(A) receptor sensitivity was assessed with the saccadic eye velocity (SEV) over 30 degrees (SEV30 degrees), the SEV30 degrees/allopregnanolone concentration ([Allo]) ratio, and sedation, which were measured together with serum allopregnanolone at intervals for 180min after injection. The controls were tested in the follicular phase of the menstrual cycle. ResultsBaseline allopregnanolone concentrations were higher in the PCOS women than in the normal-weight (P=0034) and overweight controls (P=0004). The allopregnanolone concentrations after injection were higher in the PCOS women (P=0006) and overweight controls (P=0037) than in the normal-weight controls. All groups showed a decline in the SEV30 degrees/[Allo] ratio after injection. Allopregnanolone had a smaller effect on the SEV30 degrees/[Allo] ratio in the overweight women (PCOS, P=0032; controls, P=0007) than in the normal-weight controls. The sedation score after allopregnanolone injection was lower in the PCOS patients than in the controls, but was not different between the two control groups. ConclusionsPCOS women had elevated baseline allopregnanolone concentrations compared with follicular-phase controls. All overweight women (PCOS and controls) were less sensitive to allopregnanolone than normal-weight controls.

  • 28.
    Hedström, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wang, Mingde
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Allopregnanolone, a GABA-A receptor agonist, decreases gonadotropin levels in healthy fertile women but not in women with polycystic ovary syndromeManuskript (preprint) (Övrigt vetenskapligt)
  • 29.
    Holmberg, Ellinor
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sjöstedt, J.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Malinina, E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Turkmen, Sahruh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ragagnin, Gianna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundqvist, Anette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Löfgren, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jaukkuri, L.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Allopregnanolone involvement in feeding regulation, overeating and obesity2018Ingår i: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 48, s. 70-77Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABA(A) receptors (primarily with alpha 3 and alpha 2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABA(A) receptor (with compensatory > 12-, > 5- and > 1.5-fold increases in alpha 4, gamma 2, and alpha 1, alpha 3 subunits), and increases in the alpha 4, beta x, delta receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.

  • 30.
    Innala, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström Poromaa, Inger
    Women with acute intermittent porphyria have a defect in 5α-steroid production during the menstrual cycleManuskript (preprint) (Övrigt vetenskapligt)
  • 31.
    Innala, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Andersson, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Evaluation of gonadotropin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria2010Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, nr 1, s. 95-100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To describe the benefits and adverse effects of gonadotropin-releasing hormone (GnRH) agonist treatment for prevention of recurrent menstrual attacks in women with acute intermittent porphyria and variegate porphyria. To describe concomitant add-back therapies with estradiol and progesterone and describe their benefits and adverse effects. DESIGN: A retrospective follow-up with questionnaires, interviews and medical records. SETTING: Out-patient care at the Umeå University Hospital in Sweden. POPULATION: Sixteen Caucasian women with DNA-diagnosed porphyria and menstrual-cycle-related porphyria attacks were treated with GnRH agonists during 1984-2000. Fourteen women participated. The mean age when treatment started was 33 years (17-48 years). The duration of treatment varied between 5 months and 9 years. METHODS: GnRH agonists were administered by the intranasal route or by injections. To reduce menopausal symptoms, add-back therapy with low doses of estradiol was administered, and for endometrial protection progesterone was usually administered. MAIN OUTCOME MEASURES: Treatment effects and adverse events as detected in questionnaires, interviews and medical records. RESULTS: Eleven women reported benefits from GnRH agonist treatment with less intense and/or less frequent porphyria attacks, and in four of them attacks almost disappeared. Two women reported no change. One woman had only temporary improvement. Porphyria attacks were triggered by solely estradiol add-back in two women and in five of nine women when progesterone was given. CONCLUSIONS: GnRH agonist treatment can ameliorate menstrual-cycle-related attacks of porphyria. Dose findings for GnRH agonists and add-back regimes especially for progesterone are intricate.

  • 32.
    Innala, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström Poromaa, Inger
    Department of Women's and Children's Health, Uppsala University, Uppsala.
    Andersson, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Department of Clinical Science and Education, Karolinska Institute, Stockholm, Sweden.
    Women with acute intermittent porphyria have a defect in 5 alpha-steroid production during the menstrual cycle2012Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, nr 12, s. 1445-1452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To measure serum concentrations of progesterone, estradiol and 5 alpha- and 5 beta-reduced progesterone metabolites in the follicular and luteal phases of the menstrual cycle in women with latent acute intermittent porphyria and manifest acute intermittent porphyria in comparison with healthy control women. Design. A descriptive study with repeated measurements during a complete, ovulatory menstrual cycle. Setting. University hospital out-patient clinic. Population. Thirty-two women with DNA-diagnosed acute intermittent porphyria and 20 healthy control women. Methods. Blood samples for serum progesterone, estradiol, allopregnanolone and pregnanolone were drawn on predefined menstrual cycle days, twice in the follicular phase and three times in the luteal phase. Serum levels of estradiol and progesterone were analysed with commercial kits. Allopregnanolone and pregnanolone levels were analysed with radioimmunoassay following diethylether extraction and celite column chromatography. Main outcome measures. Changes in serum levels of progesterone, estradiol, allopregnanolone and pregnanolone throughout the menstrual cycle. Results. Women with acute intermittent porphyria displayed lower serum concentrations of allopregnanolone in comparison with healthy control women, the difference being most prominent in the luteal phase (p < 0.001). Levels of pregnanolone did not differ significantly between groups. No significant difference was found between women with latent acute intermittent porphyria and manifest acute intermittent porphyria. Conclusions. Decreased levels of the 5 alpha-reduced progesterone metabolite allopregnanolone were found in the menstrual cycle of women with acute intermittent porphyria. This has not been reported previously and could indicate a reduced 5 alpha-reductase type 1 capacity in the ovary and liver among these women.

  • 33. Lindholm, Asa
    et al.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Obstetrik och gynekologi.
    Björn, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wölner-Hanssen, Pål
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Anders
    Johnson, Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Poromaa, Inger Sundström
    Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.2007Ingår i: Fertil Steril, ISSN 1556-5653Artikel i tidskrift (Refereegranskat)
  • 34.
    Lindholm, Åsa
    et al.
    Department of Obstetrics and Gynecology, Sunderby Hospital, Luleå, Sweden.
    Andersson, Liselott
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Department of Women's and Children's Health, Uppsala University, Sweden.
    Prevalence of symptoms associated with polycystic ovary syndrome2008Ingår i: International Journal of Gynaecology and Obstetrics, ISSN 0020-7292, Vol. 102, nr 1, s. 39-43Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Objective: To establish the prevalence of symptoms associated with polycystic ovary syndrome (PCOS) in a population-based sample of women from Northern Sweden, and to relate symptoms of PCOS to features of metabolic syndrome.

    Methods: A population-based survey of 147 women under 40 years of age sampled from 267 eligible women from the Northern Sweden component of the World Health Organization's MONICA study. The study involved questionnaires, physical examination, and assays of testosterone and sex hormone-binding globulin.

    Results: The estimated prevalence of symptoms associated with PCOS was 4.8% in the study population. Features of metabolic syndrome were more common in women with signs of hyperandrogenism than in healthy controls.

    Conclusion: The estimated prevalence of PCOS in Northern Sweden corresponds with other prevalence studies. A simple questionnaire and analysis of the free androgen index are sufficient to detect the subgroup with the highest risk for metabolic syndrome.

  • 35.
    Lindholm, Åsa
    et al.
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hudecova, Miriam
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Arnadottir, Ragnheidur
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Holte, Jan
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Poromaa, Inger Sundström
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Tissue plasminogen activator and plasminogen activator inhibitor 1 in obese and lean patients with polycystic ovary syndrome2010Ingår i: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 26, nr 10, s. 743-748Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Disturbances in the fibrinolytic system are predictors of future cardiovascular events. The aim of this study was to compare plasminogen activator inhibitor 1 (PAI-1) activity and tissue plasminogen activator (tPA) mass concentration between patients with polycystic ovary syndrome (PCOS) and control subjects.

    DESIGN: One hundred thirty-five patients with PCOS (lean and obese) and 81 healthy controls were recruited for the study. Blood samples for PAI-1 activity and tPA mass were collected together with anthropometric measures.

    RESULTS: Obese patients with PCOS displayed increased tPA mass concentration in comparison with controls (p <0.05), and this finding was consistent regardless of whether patients displayed signs of hyperandrogenism or not. When hyperandrogenism was introduced as a prerequisite for the PCOS diagnosis, obese patients with PCOS displayed increased PAI-1 activity as well, p <0.05. Lean patients with PCOS did not differ in terms of PAI-1 activity or tPA mass concentration in comparison to controls.

    CONCLUSION: Obese women with PCOS have impaired fibrinolysis, in particular if they also display objective biochemical markers of hyperandrogenism.

  • 36. Lindholm, Åsa
    et al.
    Blomquist, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Dahlbom, Ingrid
    Hansson, Tony
    Sundström Poromaa, Inger
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls.2011Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 26, nr 6, s. 1478-85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    UNLABELLED: BACKGROUND; Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue.

    METHODS: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR.

    RESULTS: Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-α (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost.

    CONCLUSIONS: Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.

  • 37.
    Lindh-Åstrand, Lotta
    et al.
    Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University Hospital, Linköping.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hirschberg, Angelica Lindén
    Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm.
    Sundström-Poromaa, Inger
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Hammar, Mats
    Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University Hospital, Linköping.
    A randomized controlled study of taper-down or abrupt discontinuation of hormone therapy in women treated for vasomotor symptoms2010Ingår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 17, nr 1, s. 72-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate whether tapering down of combined estrogen plus progestogen therapy (EPT) reduced the recurrence of hot flashes and resumption of therapy compared with abrupt discontinuation. A secondary aim was to evaluate whether health-related quality of life (HRQoL) was affected after discontinuation of EPT and to investigate the possible factors predicting resumption of EPT.

    METHODS: Eighty-one postmenopausal women undergoing EPT because of hot flashes were randomized to tapering down or abrupt discontinuation of EPT. Vasomotor symptoms were recorded in self-registered diaries, and resumption of hormone therapy (HT) was asked for at every follow-up. The Psychological General Well-being Index was used to assess HRQoL.

    RESULTS: Neither the number nor the severity of hot flashes or HRQoL or frequency of resumption of HT differed between the two modes of discontinuation of EPT during up to 12 months of follow-up. About every other woman had resumed HT within 1 year. Women who resumed HT after 4 or 12 months reported more deteriorated HRQoL and more severe hot flashes after discontinuation of therapy than did women who did not resume HT.

    CONCLUSIONS: Women who initiate EPT because of hot flashes may experience recurrence of vasomotor symptoms and impaired HRQoL after discontinuation of EPT regardless of the discontinuation method used, abrupt or taper down. Because, in addition to severity of flashes, decreased well-being was the main predictor of the risk to resume HT, it seems important to also discuss quality of life in parallel with efforts to discontinue HT.

  • 38. Lovvik, Tone S.
    et al.
    Carlsen, Sven M.
    Salvesen, Oyvind
    Steffensen, Berglind
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Gomez-Real, Francisco
    Lennebotn, Marianne
    Hestvold, Kristin, V
    Zabielska, Renata
    Hirschberg, Angelica L.
    Trouva, Anastasia
    Thorarinsdottir, Solveig
    Hjelle, Sissel
    Berg, Ann Hilde
    Andrae, Frida
    Poromaa, Inger S.
    Molin, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Underdal, Maria
    Vanky, Eszter
    Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial2019Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 7, nr 4, s. 256-266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy complications. Epi-analysis of two previous randomised controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The aim of this third randomised trial (PregMet2) was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS.

    Methods: PregMet2 was a randomised, placebo-controlled, double-blind, multicentre trial done at 14 hospitals in Norway, Sweden, and Iceland. Singleton pregnant women with PCOS aged 18-45 years were eligible for inclusion. After receiving information about the study at their first antenatal visit or from the internet, women signed up individually to participate in the study. Participants were randomly assigned (1: 1) to receive metformin or placebo by computer-generated random numbers. Randomisation was in blocks of ten for each country and centre; the first block had a random size between one and ten to assure masking. Participants were assigned to receive oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1000 mg twice daily or placebo from week 2 until delivery. Placebo tablets and metformin tablets were identical and participants and study personnel were masked to treatment allocation. The primary outcome was the composite incidence of late miscarriage (between week 13 and week 22 and 6 days) and preterm birth (between week 23 and week 36 and 6 days), analysed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit. We also did a post-hoc individual participant data analysis of pregnancy outcomes, pooling data from the two previous trials with the present study. The study was registered with ClinicalTrials. gov, number NCT01587378, and EudraCT, number 2011-002203-15.

    Findings: The study took place between Oct 19, 2012, and Sept 1, 2017. We randomly assigned 487 women to metformin (n=244) or placebo (n=243). In the intention-to-treat analysis, our composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0.50, 95% CI 0.22- 1.08; p = 0.08). We found no significant differences for our secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1.09, 95% CI 0.69-1.66; p=0.75). We noted no substantial between-group differences in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators. In the post-hoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group ]compared with 40 (10%) of 399 women in the placebo group (OR 0.43, 95% CI 0.23-0.79; p=0.004).

    Interpretation: In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes.

  • 39. Lundin, Cecilia
    et al.
    Gemzell Danielsson, Kristina
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Moby, Lena
    Bengtsdotter, Hanna
    Jawad, Izabella
    Marions, Lena
    Brynhildsen, Jan
    Malmborg, Agota
    Lindh, Ingela
    Sundström Poromaa, Inger
    Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle: A double-blind, placebo-controlled randomized trial2017Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 76, s. 135-143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 40. Lundin, Cecilia
    et al.
    Malmborg, Agota
    Slezak, Julia
    Danielsson, Kristina Gemzell
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bengtsdotter, Hanna
    Marions, Lena
    Lindh, Ingela
    Theodorsson, Elvar
    Hammar, Mats
    Sundstrom-Poromaa, Inger
    Sexual function and combined oral contraceptives: a randomised, placebo-controlled trial2018Ingår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 7, nr 11, s. 1208-1216Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The effect of combined oral contraceptives (COCs) on female sexuality has long been a matter of discussion, but placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate if an oestradiol-containing COC influences sexual function.

    Design: Investigator-initiated, randomised, double-blinded, placebo-controlled clinical trial where 202 healthy women were randomised to a combined oral contraceptive (1.5 mg oestradiol and 2.5 mg nomegestrol acetate) or placebo for three treatment cycles.

    Methods: Sexual function at baseline and during the last week of the final treatment cycle was evaluated by the McCoy Female Sexuality Questionnaire. Serum and hair testosterone levels were assessed at the same time points.

    Results: Compared to placebo, COC use was associated with a small decrease in sexual interest (COC median change score: -2.0; interquartile range (IQR): -5.0 to 0.5 vs placebo: -1.0; IQR: -3.0 to 2.0, P=0.019), which remained following adjustment for change in self-rated depressive symptoms (B= -0.80 +/- 0.30, Wald =7.08, P=0.008). However, the proportion of women who reported a clinically relevant deterioration in sexual interest did not differ between COC or placebo users (COC 18 (22.2%) vs placebo 16 (17.8%), P=0.47). Change in other measured aspects of sexual function as well as total score of sexual function did not differ between the two treatments.

    Conclusions: This study suggests that use of oestradiol-based COCs is associated with reduced sexual interest. However, the changes are minute, and probably not of clinical relevance.

  • 41. Malmenström, Malin
    et al.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Björn, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Aström, Monica
    Poromaa, Inger Sundström
    Patients with psychiatric disorders in gynecologic practice--a three year follow-up.2006Ingår i: J Psychosom Obstet Gynaecol, ISSN 0167-482X, Vol. 27, nr 1, s. 17-22Artikel i tidskrift (Refereegranskat)
  • 42.
    Nüssler, Emil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Eskildsen, Jacob Kjaer
    Nüssler, Emil Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Löfgren, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Impact of surgeon experience on routine prolapse operations2018Ingår i: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, nr 2, s. 297-306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction and hypothesis: Surgical work encompasses important aspects of personal and manual skills. In major surgery, there is a positive correlation between surgical experience and results. For pelvic organ prolapse (POP), this relationship has to our knowledge never been examined. In any clinical practice, there is always a certain proportion of inexperienced surgeons. In Sweden, most prolapse surgeons have little experience in performing prolapse operations, 74% conducting the procedure once a month or less. Simultaneously, surgery for POP globally has failure rates of 25-30%. In other words, for most surgeons, the operation is a low-frequency procedure, and outcomes are unsatisfactory. The aim of this study was to clarify the acceptability of having a high proportion of low-volume surgeons in the management of POP.

    Methods: A group of 14,676 exclusively primary anterior or posterior repair patients was assessed. Data were analyzed by logistic regression and as a group analysis.

    Results: Experienced surgeons had shorter operation times and hospital stays. Surgical experience did not affect surgical or patient-reported complication rates, organ damage, reoperation, rehospitalization, or patient satisfaction, nor did it improve patient-reported failure rates 1 year after surgery. Assistant experience, similarly, had no effect on the outcome of the operation.

    Conclusions: A management model for isolated anterior or posterior POP surgery that includes a high proportion of low-volume surgeons does not have a negative impact on the quality or outcome of anterior or posterior colporrhaphy. Consequently, the high recurrence rate was not due to insufficient experience of the surgeons performing the operation.

  • 43.
    Nüssler, Emil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nüssler, Emil Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Löfgren, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Repair of recurrent rectocele with posterior colporrhaphy or non-absorbable polypropylene mesh: patient-reported outcomes at 1-year follow-up.2019Ingår i: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 30, nr 10, s. 1679-1687Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the results of repair of isolated, recurrent, posterior vaginal wall prolapse using standard posterior colporrhaphy versus non-absorbable polypropylene mesh in a routine health care setting.

    METHODS: This cohort study was based on prospectively collected data from the Swedish National Register for Gynaecological Surgery. All patients operated for recurrent, posterior vaginal wall prolapse in Sweden between 1 January 2006 and 30 October 2016 were included. A total of 433 women underwent posterior colporrhaphy, and 193 were operated using non-absorbable mesh. Data up to 1 year were collected.

    RESULTS: The 1-year patient-reported cure rate was higher for the mesh group compared with the colporrhaphy group, with an odds ratio (OR) of 2.06 [95% confidence interval (CI) 1.03-4.35], corresponding to a number needed to treat of 9.7. Patient satisfaction (OR = 2.38; CI 1.2-4.97) and improvement (OR = 2.13; CI 1.02-3.82) were higher in the mesh group. However, minor surgeon-reported complications were more frequent with mesh (OR = 2.74; CI 1.51-5.01). Patient-reported complications and re-operations within 12 months were comparable in the two groups.

    CONCLUSIONS: For patients with isolated rectocele relapse, mesh reinforcement enhances the likelihood of success compared with colporrhaphy at 1-year follow-up. Also, in our study, mesh repair was associated with greater patient satisfaction and improvement of symptoms, but an increase in minor complications. Our study indicates that the benefits of mesh reinforcement may outweigh the risks of this procedure for women with isolated recurrent posterior prolapse.

  • 44. Poromaa, Inger Sundstrom
    et al.
    Comasco, Erika
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jensen, Peter
    Frokjaer, Vibe G.
    Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age2019Ingår i: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, artikel-id 2767Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Allopregnanolone is a metabolite of the sex hormone progesterone, with suggested relevance for female mood disorders. While allopregnanolone and serotonin are known to influence psychological well-being, the molecular and psychological specifics of their relationship are to date poorly understood, especially in women of fertile age who experience regular fluctuations of progesterone across the menstrual cycle. Availability of serotonin in the synaptic cleft is regulated by the serotonin transporter (SERT), which can be imaged in the living human brain by use of positron emission tomography (PET) and the radiotracer [C-11]DASB. To evaluate sex-specific allopregnanolone-SERT interactions, the present study investigated the relationship between cerebral SERT availability, serum allopregnanolone levels and psychological well-being in women of fertile age. Brain imaging data, self-reported symptoms of mental distress and emotion regulation, and biobank material from ninety healthy women were available from the Center for Integrated Molecular Brain Imaging (CIMBI) database. Age, BMI, and daylight minutes were included as covariates in the analyses and SERT genotype (5-HTTLPR) was considered a potential confounder. Lower serum allopregnanolone levels were associated with higher SERT binding in the prefrontal cortex. Moreover, allopregnanolone levels were negatively associated with measures of alertness, although this finding was not mediated by prefrontal cortex SERT binding. These findings suggest a link between the typical psychological well-being experienced in the follicular phase when allopregnanolone levels are low and higher SERT in the prefrontal cortex, a region for higher cognitive functions and top-down regulation of emotions.

  • 45.
    Segebladh, Birgitta
    et al.
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Bannbers, Elin
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Kask, Kristiina
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Heimer, Gun
    Uppsala Univ, Natl Ctr Knowledge Mens Violence Women, Uppsala, Sweden. Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Sundström-Poromaa, Inger
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
    Prevalence of violence exposure in women with premenstrual dysphoric disorder in comparison with other gynecological patients and asymptomatic controls2011Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, nr 7, s. 746-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of the present study was to estimate prevalence rates of physical, emotional and sexual abuse in women with premenstrual dysphoric disorder (PMDD) in comparison with gynecological outpatients and asymptomatic healthy control subjects.

    DESIGN: Cross-sectional study.

    SETTINGS: Departments of obstetrics and gynecology in three different Swedish hospitals.

    POPULATION: Fifty-eight women meeting strict criteria for PMDD, a control group of 102 women seeking care at the gynecological outpatient clinic (ObGyn controls) and 47 asymptomatic healthy control subjects were included in this study.

    METHODS: The Swedish version of the Abuse Assessment Screen was used to collect information on physical and sexual abuse, and the screening instrument was administered as a face-to-face interview.

    MAIN OUTCOME MEASURES: Previous and ongoing physical and sexual abuse.

    RESULTS: Any lifetime abuse (physical, emotional or sexual) was reported by 31.0% of PMDD patients, by 39.2% of ObGyn controls and by 21.3% of healthy controls. The ObGyn controls reported physical and/or emotional abuse significantly more often than PMDD patients as well as healthy controls (p<0.05). Lifetime sexual abuse was reported significantly more often by ObGyn controls than by healthy controls (p<0.05).

    CONCLUSIONS: Patients with PMDD appear not to have suffered physical, emotional or sexual abuse to a greater extent than other gynecological patients or healthy control subjects. However, exposure to violence was common in all groups of interviewed women, and for the individual patient these experiences may contribute to their experience of symptoms.

  • 46. Segebladh, Birgitta
    et al.
    Bannbers, Elin
    Moby, Lena
    Nyberg, Sigrid
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Poromaa, Inger Sundstrom
    Allopregnanolone serum concentrations and diurnal cortisol secretion in women with premenstrual dysphoric disorder2013Ingår i: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 16, nr 2, s. 131-137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most prior studies in patients with premenstrual dysphoric disorder (PMDD) indicate a blunted hypothalamus-pituitary-adrenal axis function. However, the relationship between neuroactive progesterone metabolites, such as allopregnanolone, and hypothalamus-pituitary-adrenal (HPA) axis function in PMDD patients is relatively sparsely studied. The primary aims of this study were to assess diurnal variation in circulating cortisol and low-dose dexamethasone suppression in PMDD patients and healthy controls, and the relationship between these two HPA axis indices and allopregnanolone serum concentrations. Twenty-six women with prospectively defined PMDD and 30 healthy controls were recruited. Participants underwent diurnal sampling for cortisol serum concentrations and a low-dose dexamethasone suppression test. In addition, morning allopregnanolone serum concentrations were determined. There was no difference in diurnal secretion of cortisol and degree of dexamethasone suppression of cortisol between PMDD patients and healthy controls. However, PMDD patients with high allopregnanolone levels displayed blunted nocturnal cortisol levels in comparison with healthy controls who had low allopregnanolone serum concentrations. In women with PMDD, diurnal secretion of cortisol may be influenced by allopregnanolone levels of the luteal phase. This finding may be attributed to timing of blood sampling in the late luteal phase as well as the individual level of allopregnanolone but could potentially explain the discrepancies in results between studies examining HPA axis function in women with PMDD.

  • 47.
    Segebladh, Birgitta
    et al.
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Borgström, Anna
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder2009Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 201, nr 2, s. 139.e1-139.e8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy.

    STUDY DESIGN: Three different add-back hormone replacement treatments were evaluated in a randomized, double-blinded, cross-over clinical trial in 27 patients premenstrual dysphoric disorder. The add-back treatments consisted of 1.5 mg estradiol and 400 mg progesterone, 1.5 mg estradiol and placebo, and 0.5 mg estradiol and 400 mg progesterone. The primary outcome measure was daily symptom ratings for mood and physical symptoms.

    RESULTS: The highest dose of estradiol in combination with progesterone was associated with the most pronounced symptom recurrence, both in comparison with a lower dose of estradiol together with progesterone and estradiol-only treatment.

    CONCLUSION: Based on the findings of the present study, long-cycle add-back treatment to avoid frequent progestagen use appears to be most beneficial for patients with premenstrual dysphoric disorder.

  • 48.
    Segebladh, Birgitta
    et al.
    Department of Women's and Children's Health, University Hospital, Uppsala University, Uppsala, Sweden.
    Borgström, Anna
    Department of Women's and Children's Health, University Hospital, Uppsala University, Uppsala, Sweden.
    Odlind, Viveca
    Department of Women's and Children's Health, University Hospital, Uppsala University, Uppsala, Sweden.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, Inger
    Department of Women's and Children's Health, University Hospital, Uppsala University, Uppsala, Sweden.
    Prevalence of psychiatric disorders and premenstrual dysphoric symptoms in patients with experience of adverse mood during treatment with combined oral contraceptives2009Ingår i: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 79, nr 1, s. 50-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Negative mood symptoms remain one of the major reasons for discontinuation of combined oral contraceptive pills (COCs). The primary aim of this study was to compare the prevalence of mood and anxiety disorders in women with different experience of COCs.

    STUDY DESIGN: Thirty women currently on COCs with no report of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 33 women who had discontinued COC use due to adverse mood effects and 27 women who had discontinued COC use for reasons other than adverse mood symptoms were included. Ongoing psychiatric disorders were evaluated by a structured psychiatric interview and prevalence rates of premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) were assessed by daily prospective ratings on the Cyclicity Diagnoser scale.

    RESULTS: Women with ongoing or past experience of COC-induced adverse mood, more often suffered from mood disorders than women with no reports of adverse mood while on COC. The prevalence of prospectively defined PMS or PMDD did not differ between prior users with positive or negative experience. Women who had discontinued COC use due to adverse mood symptoms more often had had a legal abortion in the past.

    CONCLUSION: Women with ongoing or past self-reported adverse mood effects from COCs had a significantly increased prevalence of mood disorders.

  • 49. Skalkidou, Alkistis
    et al.
    Bixo, Marie
    Sköldebrand Sparre, Ann-Charlotte
    Strandell, Annika
    Lindén Hirschberg, Angelica
    Filipsson Nyström, Helena
    Hypotyreos under graviditet riskerar barnets neurokognitiva utveckling: Nya riktlinjer och kvarstående kunskapsluckor2016Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, artikel-id DTWAArtikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Thyroid abnormalities are common during pregnancy and can affect pregnancy outcome. In 2012, the working group for endocrinology was assigned by SFOG to develop evidence based guidelines for their management. There is high quality evidence that untreated clinical hypothyroidism increases the risk of pregnancy and fetal complications. Subclinical hypothyroidism is associated with pregnancy complications. The presence of TPO-antibodies is linked to miscarriage and premature birth. It is uncertain whether subclinical hypothyroidism/maternal TPO-antibodies adversely affect the child's neurocognitive development. Reference intervals for TSH among pregnant women in Sweden need to be established.

  • 50.
    Sundström, I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nyberg, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, M
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hammarbäck, S
    Bäckström, T
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist in a low dose regimen1999Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 78, nr 10, s. 891-899Artikel i tidskrift (Refereegranskat)
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