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Nyberg, S
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Publications (10 of 34) Show all publications
Timby, E., Bäckström, T., Nyberg, S., Stenlund, H., Wihlbäck, A.-C. N. & Bixo, M. (2016). Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls — a pilot study. Psychopharmacology, 233(11), 2109-2117
Open this publication in new window or tab >>Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls — a pilot study
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2016 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 11, p. 2109-2117Article in journal (Refereed) Published
Abstract [en]

In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABA(A) receptor, enhancing the effect of gamma-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABA(A) receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls.

This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients.

Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABA(A) receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data.

There was a highly significant group x phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018).

The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.

Keyword
Neurosteroid, GABA, Premenstrual dysphoric disorder, Saccadic eye velocity, Menstrual cycle
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-50057 (URN)10.1007/s00213-016-4258-1 (DOI)000376102100009 ()
Note

Originally included in thesis in manuscript form

Available from: 2011-11-24 Created: 2011-11-24 Last updated: 2017-12-08Bibliographically approved
Bengtsson, S. K. S., Nyberg, S., Hedström, H., Zingmark, E., Jonsson, B., Bäckström, T. & Bixo, M. (2015). Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans. Psychoneuroendocrinology, 52, 22-31
Open this publication in new window or tab >>Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans
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2015 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, p. 22-31Article in journal (Refereed) Published
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.

Keyword
Allopregnanolone, Isoallopregnanolone, Saccadic eye velocity, GABA(A) receptor, Sedation, Premenstrual dysphoric disorder
National Category
Endocrinology and Diabetes Neurosciences
Identifiers
urn:nbn:se:umu:diva-100765 (URN)10.1016/j.psyneuen.2014.10.025 (DOI)000349271000004 ()25459890 (PubMedID)
Available from: 2015-04-26 Created: 2015-03-09 Last updated: 2018-01-11Bibliographically approved
Bäckström, T., Bixo, M., Johansson, M., Nyberg, S., Ossewaarde, L., Ragagnin, G., . . . van Wingen, G. (2014). Allopregnanolone and mood disorders. Progress in Neurobiology, 113, 88-94
Open this publication in new window or tab >>Allopregnanolone and mood disorders
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2014 (English)In: Progress in Neurobiology, ISSN 0301-0082, E-ISSN 1873-5118, Vol. 113, p. 88-94Article in journal (Refereed) Published
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.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-87179 (URN)10.1016/j.pneurobio.2013.07.005 (DOI)000331508100007 ()
Available from: 2014-03-31 Created: 2014-03-24 Last updated: 2017-12-05Bibliographically approved
Bäckström, T., Bixo, M., Nyberg, S. & Savic, I. (2013). Increased neurosteroid sensitivity - An explanation to symptoms associated with chronic work related stress in women?. Psychoneuroendocrinology, 38(7), 1078-1089
Open this publication in new window or tab >>Increased neurosteroid sensitivity - An explanation to symptoms associated with chronic work related stress in women?
2013 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 7, p. 1078-1089Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Pergamon Press, 2013
Keyword
Allopregnanolone challenge, Burnout syndrome, Saccadic velocity
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-78957 (URN)10.1016/j.psyneuen.2012.10.014 (DOI)000320412400013 ()
Funder
Swedish Research Council, 4X-11198
Note

This study was funded by grants from Swedish research council, project number 4X-11198, and the EU structural fund, objective 1, Svenska läkaresallskapet, Visare Norr, Umea University Foundations and ALE rnedel from Västerbottens Läns Landsting.

Available from: 2013-07-29 Created: 2013-07-29 Last updated: 2017-12-06Bibliographically approved
Nyberg, S. (2013). Mood and physical symptoms improve in women with severe cyclical changes by taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl estradiol. Contraception, 87(6), 773-781
Open this publication in new window or tab >>Mood and physical symptoms improve in women with severe cyclical changes by taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl estradiol
2013 (English)In: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 87, no 6, p. 773-781Article in journal (Refereed) Published
Abstract [en]

Background: The purpose of this study was to investigate how women without and with different severity of premenstrual symptoms react to treatment with a combined oral contraceptive containing 250-mcg norgestimate/35-mcg ethinyl estradiol (EE). Focus was placed on mood and physical symptoms. Study Design: This open, prospective study evaluated 24 women using norgestimate/EE for three cycles in a 21/7 regimen. Symptoms and bleeding pattern were captured by daily ratings on the Cyclicity Diagnoser scale. Results: Women with severe premenstrual mood symptoms improved in summarized negative mood (p<.001) and summarized positive mood (p<.05), as well as in swelling (p<.05) and effect on daily life (p<.05). Women with no or mild or moderate symptoms did not show any significant improvement or deterioration in any symptom after 3 months of treatment. Conclusions: Norgestimate 250 mcg/EE 35 mcg significantly improved premenstrual summarized negative mood symptoms during 3 treatment months compared to pretreatment in women with severe premenstrual symptoms, together with improvement in positive symptoms, swelling and effect on daily life. (C) 2013 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2013
Keyword
Premenstrual symptoms, Combined oral contraceptive pills, Norgestimate, Mood, Menstrual cycle
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-76251 (URN)10.1016/j.contraception.2012.09.024 (DOI)000319550100011 ()
Available from: 2013-07-08 Created: 2013-07-08 Last updated: 2017-12-06Bibliographically approved
Lundell, I. W., Öhman, S. G., Frans, Ö., Helström, L., Högberg, U., Nyberg, S., . . . Svanberg, A. S. (2013). Posttraumatic stress among women after induced abortion: a Swedish multi-centre cohort study. BMC Women's Health, 13, Article Number: 52
Open this publication in new window or tab >>Posttraumatic stress among women after induced abortion: a Swedish multi-centre cohort study
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2013 (English)In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 13, p. Article Number: 52-Article in journal (Refereed) Published
Abstract [en]

Background: Induced abortion is a common medical intervention. Whether psychological sequelae might follow induced abortion has long been a subject of concern among researchers and little is known about the relationship between posttraumatic stress disorder (PTSD) and induced abortion. Thus, the aim of the study was to assess the prevalence of PTSD and posttraumatic stress symptoms (PTSS) before and at three and six months after induced abortion, and to describe the characteristics of the women who developed PTSD or PTSS after the abortion. Methods: This multi-centre cohort study included six departments of Obstetrics and Gynaecology in Sweden. The study included 1457 women who requested an induced abortion, among whom 742 women responded at the three-month follow-up and 641 women at the six-month follow-up. The Screen Questionnaire-Posttraumatic Stress Disorder (SQ-PTSD) was used for research diagnoses of PTSD and PTSS, and anxiety and depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS). Measurements were made at the first visit and at three and six months after the abortion. The 95% confidence intervals for the prevalence of lifetime or ongoing PTSD and PTSS were calculated using the normal approximation. The chi-square test and the Student's t-test were used to compare data between groups. Results: The prevalence of ongoing PTSD and PTSS before the abortion was 4.3% and 23.5%, respectively, concomitant with high levels of anxiety and depression. At three months the corresponding rates were 2.0% and 4.6%, at six months 1.9% and 6.1%, respectively. Dropouts had higher rates of PTSD and PTSS. Fifty-one women developed PTSD or PTSS during the observation period. They were young, less well educated, needed counselling, and had high levels of anxiety and depressive symptoms. During the observation period 57 women had trauma experiences, among whom 11 developed PTSD or PTSS and reported a traumatic experience in relation to the abortion. Conclusion: Few women developed PTSD or PTSS after the abortion. The majority did so because of trauma experiences unrelated to the induced abortion. Concomitant symptoms of depression and anxiety call for clinical alertness and support.

Place, publisher, year, edition, pages
BioMed Central, 2013
Keyword
Induced abortion, Posttraumatic stress disorder, Anxiety disorders, Mental health
National Category
Public Health, Global Health, Social Medicine and Epidemiology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-85793 (URN)10.1186/1472-6874-13-52 (DOI)000329240600001 ()
Funder
Marianne and Marcus Wallenberg Foundation
Available from: 2014-02-12 Created: 2014-02-10 Last updated: 2017-12-06Bibliographically approved
Lundell, I. W., Poromaa, I. S., Frans, O., Helstrom, L., Hogberg, U., Moby, L., . . . Svanberg, A. S. (2013). The prevalence of posttraumatic stress among women requesting induced abortion. European journal of contraception & reproductive health care, 18(6), 480-488
Open this publication in new window or tab >>The prevalence of posttraumatic stress among women requesting induced abortion
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2013 (English)In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 18, no 6, p. 480-488Article in journal (Refereed) Published
Abstract [en]

Objectives To describe the prevalence and pattern of traumatic experiences, to assess the prevalence of posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS), to identify risk factors for PTSD and PTSS, and to analyse the association of PTSD and PTSS with concomitant anxiety and depressive symptoms in women requesting induced abortion. Methods A Swedish multi-centre study of women requesting an induced abortion. The Screen Questionnaire - Posttraumatic Stress Disorder was used for research diagnoses of PTSD and PTSS. Anxiety and depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS). Results Of the 1514 respondents, almost half reported traumatic experiences. Lifetime-and point prevalence of PTSD were 7% (95% confi dence interval [CI]: 5.8-8.5) and 4% (95% CI: 3.1-5.2), respectively. The prevalence of PTSS was 23% (95% CI: 21.1-25.4). Women who reported symptoms of anxiety or depression when requesting abortion were more likely to have ongoing PTSD or PTSS. Also single-living women and smokers displayed higher rates of ongoing PTSD. Conclusions Although PTSD is rare among women who request an induced abortion, a relatively high proportion suffers from PTSS. Abortion seeking women with trauma experiences and existing or preexisting mental disorders need more consideration and alertness when counselled for termination.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keyword
Abortion, Posttraumatic stress disorder, Posttraumatic stress, Depression, Anxiety
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-84510 (URN)10.3109/13625187.2013.828030 (DOI)000327484700008 ()
Funder
Marianne and Marcus Wallenberg Foundation
Available from: 2014-01-15 Created: 2014-01-08 Last updated: 2017-12-06Bibliographically approved
Lundell, I. W., Frans, O., Helstrom, L., Hogberg, U., Moby, L., Nyberg, S., . . . Svanberg, A. S. (2012). Post-traumatic stress disorder among women requesting induced termination of pregnancy: a Swedish multi-centre study. Paper presented at the 2012 FIAPAC Congress "Unwanted pregnancy ‐ a fact of life" 19th‐20th October 2012, Edinburgh, UK. British Journal of Obstetrics and Gynecology, 119(SI, Suppl 2), 2-2
Open this publication in new window or tab >>Post-traumatic stress disorder among women requesting induced termination of pregnancy: a Swedish multi-centre study
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2012 (English)In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 119, no SI, Suppl 2, p. 2-2Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Hoboken, NJ: Wiley-Blackwell, 2012
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-61354 (URN)10.1111/j.1471-0528.2012.03507.x (DOI)000309750000006 ()
Conference
the 2012 FIAPAC Congress "Unwanted pregnancy ‐ a fact of life" 19th‐20th October 2012, Edinburgh, UK
Note

Special Issue: Abstracts from the 2012 FIAPAC Congress "Unwanted pregnancy ‐ a fact of life" 19th‐20th October 2012, Edinburgh, UK.

Available from: 2012-11-21 Created: 2012-11-12 Last updated: 2017-12-07Bibliographically approved
Timby, E., Hedström, H., Bäckström, T., Sundström-Poromaa, I., Nyberg, S. & Bixo, M. (2011). Allopregnanolone, a GABA-A receptor agonist, decreases gonadotropin levels in women: a preliminary study. Gynecological Endocrinology, 27(12), 1087-1093
Open this publication in new window or tab >>Allopregnanolone, a GABA-A receptor agonist, decreases gonadotropin levels in women: a preliminary study
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2011 (English)In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 27, no 12, p. 1087-1093Article in journal (Refereed) Published
Abstract [en]

Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABAA) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABAA receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63, p=0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABAA receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolon.

Place, publisher, year, edition, pages
Informa Healthcare, 2011
Keyword
FSH, LH, GABA, allopregnanolone, isoallopregnanolone
National Category
Obstetrics, Gynecology and Reproductive Medicine Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-49369 (URN)10.3109/09513590.2010.540603 (DOI)000296777700026 ()
Note

Fulltext publiceras 2012-12-01

Available from: 2011-11-14 Created: 2011-11-10 Last updated: 2017-12-08Bibliographically approved
Nyberg, S. (2011). How to determine symptom severity in premenstrual syndrome: a combination of daily symptom ratings and interviews.. Sexual and reproductive healthcare, 2(4), 161-168
Open this publication in new window or tab >>How to determine symptom severity in premenstrual syndrome: a combination of daily symptom ratings and interviews.
2011 (English)In: Sexual and reproductive healthcare, ISSN 1877-5764, Vol. 2, no 4, p. 161-168Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate how premenstrual symptoms are experienced and affect daily life, and to see if there is an agreement in reported symptom severity based on interviews compared to ratings on a symptom rating scale.

STUDY DESIGN: Twenty-two women with different degree of premenstrual symptoms were interviewed about their symptoms. Based on the luteal-phase interviews, they were categorized in four different severity groups: severe (n=5), moderate (n=3), mild (n=8), and no symptoms/cyclicity (n=6). The interviews were then compared with rated symptom scores, number of expressed symptoms per day, number of days with symptoms, and daily life impairment.

MAIN OUTCOME MEASURES: Agreement between rated symptom scores and reported symptoms in the interviews.

RESULTS: Comparing seven days in luteal phase scorings with interview data the group with no symptoms/cyclicity showed high agreement between severities reported in the interviews and daily rated scores. Among women who reported severe symptoms, an agreement was seen in three out of five. In the mild/moderate group, the agreement was less conclusive. The day of interview there was a high agreement between data from the reported symptom ratings and symptoms reported in the interview.

CONCLUSION: Rated symptom scores the day of interview reflects well symptoms reported in the interviews. Mean symptom scores for seven luteal phase days showed an agreement between symptom ratings and symptoms expressed in interviews among women with severe symptoms and no symptoms/cyclicity. In the group with mild/moderate symptoms, data was less conclusive.

Place, publisher, year, edition, pages
Elsevier, 2011
Keyword
Premenstrual symptoms, Menstrual cycle, Symptom severity, Symptom rating scales
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-52221 (URN)10.1016/j.srhc.2011.07.001 (DOI)22055985 (PubMedID)
Available from: 2012-02-14 Created: 2012-02-14 Last updated: 2012-05-09Bibliographically approved
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