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Bixo, Marie
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Publications (10 of 61) Show all publications
Bendix, M., Bixo, M., Wihlbäck, A.-C., Ahokas, A. & Jokinen, J. (2019). Allopregnanolone and progesterone in estradiol treated severe postpartum affective disorder. Paper presented at 49th Annual Conference of the International-Society-of-Psychoneuroendocrinology - 50 Years of Psychoneuroendocrinology - Returning to Where It All Began, AUG 29-31, 2019, Milan, ITALY. Psychoneuroendocrinology, 107, 68-68
Open this publication in new window or tab >>Allopregnanolone and progesterone in estradiol treated severe postpartum affective disorder
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2019 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, p. 68-68Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2019
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-164512 (URN)10.1016/j.psyneuen.2019.07.195 (DOI)000483655400194 ()
Conference
49th Annual Conference of the International-Society-of-Psychoneuroendocrinology - 50 Years of Psychoneuroendocrinology - Returning to Where It All Began, AUG 29-31, 2019, Milan, ITALY
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2019-11-20Bibliographically approved
Poromaa, I. S., Comasco, E., Bäckström, T., Bixo, M., Jensen, P. & Frokjaer, V. G. (2019). Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age. Frontiers in Psychology, 9, Article ID 2767.
Open this publication in new window or tab >>Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age
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2019 (English)In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, article id 2767Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
allopregnanolone, brain, mood, PET, serotonin transporter, women, 5HTT
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-155960 (URN)10.3389/fpsyg.2018.02767 (DOI)000455554400001 ()
Funder
Swedish Research Council, VR: 2015-00495
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved
Nüssler, E., Granåsen, G., Nüssler, E. K., Bixo, M. & Löfgren, M. (2019). Repair of recurrent rectocele with posterior colporrhaphy or non-absorbable polypropylene mesh: patient-reported outcomes at 1-year follow-up.. International Urogynecology Journal, 30(10), 1679-1687
Open this publication in new window or tab >>Repair of recurrent rectocele with posterior colporrhaphy or non-absorbable polypropylene mesh: patient-reported outcomes at 1-year follow-up.
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2019 (English)In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 30, no 10, p. 1679-1687Article in journal (Refereed) Published
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.

Keywords
Colporrhaphy, National register data, Non-absorbable mesh, Patient-reported outcome, Rectocele
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-164738 (URN)10.1007/s00192-018-03856-y (DOI)000490733000012 ()30627830 (PubMedID)
Available from: 2019-10-30 Created: 2019-10-30 Last updated: 2019-10-30Bibliographically approved
Lovvik, T. S., Carlsen, S. M., Salvesen, O., Steffensen, B., Bixo, M., Gomez-Real, F., . . . Vanky, E. (2019). Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial. The Lancet Diabetes and Endocrinology, 7(4), 256-266
Open this publication in new window or tab >>Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial
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2019 (English)In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 7, no 4, p. 256-266Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Obstetrics, Gynecology and Reproductive Medicine Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-157946 (URN)10.1016/S2213-8587(19)30002-6 (DOI)000461788900013 ()30792154 (PubMedID)
Available from: 2019-04-18 Created: 2019-04-18 Last updated: 2019-04-18Bibliographically approved
Holmberg, E., Sjöstedt, J., Malinina, E., Johansson, M., Turkmen, S., Ragagnin, G., . . . Bäckström, T. (2018). Allopregnanolone involvement in feeding regulation, overeating and obesity. Frontiers in neuroendocrinology (Print), 48, 70-77
Open this publication in new window or tab >>Allopregnanolone involvement in feeding regulation, overeating and obesity
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2018 (English)In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 48, p. 70-77Article, review/survey (Refereed) Published
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.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Allopregnanolone, GABA, GABA(A) receptor, Satiety, Hunger, Obesity, Overeating
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-145173 (URN)10.1016/j.yfrne.2017.07.002 (DOI)000424316800008 ()28694181 (PubMedID)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2019-05-06Bibliographically approved
Bixo, M., Johansson, M., Timby, E., Michalski, L. & Bäckström, T. (2018). Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder. Paper presented at 9th International Meeting on Steroids and Nervous System, FEB 11-15, 2017, Torino, ITALY. Journal of neuroendocrinology (Print), 30(2), Article ID e12553.
Open this publication in new window or tab >>Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder
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2018 (English)In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 30, no 2, article id e12553Article in journal (Refereed) Published
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.

Keywords
GABA, neuroactive steroids, premenstrual dysphoric disorder
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-145601 (URN)10.1111/jne.12553 (DOI)000425521300018 ()
Conference
9th International Meeting on Steroids and Nervous System, FEB 11-15, 2017, Torino, ITALY
Available from: 2018-03-29 Created: 2018-03-29 Last updated: 2018-06-09Bibliographically approved
Nüssler, E., Eskildsen, J. K., Nüssler, E. K., Bixo, M. & Löfgren, M. (2018). Impact of surgeon experience on routine prolapse operations. International Urogynecology Journal, 29(2), 297-306
Open this publication in new window or tab >>Impact of surgeon experience on routine prolapse operations
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2018 (English)In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 2, p. 297-306Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
pelvic organ prolapse, national register data, patient-reported outcome, surgical outcome, quality control, learning curve
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-144825 (URN)10.1007/s00192-017-3353-0 (DOI)000423154300017 ()28577172 (PubMedID)
Note

Errata: Nüssler, E., Eskildsen J. K., Nüssler, E. K., Bixo, M., Löfgren, M. Impact of surgeon experience on routine prolapse operations. International Urogynecology Journal 2018;29:2. DOI: 10.1007/s00192-017-3525-y

Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-10-30Bibliographically approved
Bengtsdotter, H., Lundin, C., Gemzell Danielsson, K., Bixo, M., Baumgart, J., Marions, L., . . . Sundström Poromaa, I. (2018). Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use. European journal of contraception & reproductive health care, 23(1), 45-51
Open this publication in new window or tab >>Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use
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2018 (English)In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 23, no 1, p. 45-51Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
randomised controlled trial, combined oral contraceptives, anxiety, depression, alcohol
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-146240 (URN)10.1080/13625187.2017.1422239 (DOI)000427062900007 ()29323577 (PubMedID)
Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2019-08-26Bibliographically approved
Lundin, C., Malmborg, A., Slezak, J., Danielsson, K. G., Bixo, M., Bengtsdotter, H., . . . Sundstrom-Poromaa, I. (2018). Sexual function and combined oral contraceptives: a randomised, placebo-controlled trial. Endocrine Connections, 7(11), 1208-1216
Open this publication in new window or tab >>Sexual function and combined oral contraceptives: a randomised, placebo-controlled trial
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2018 (English)In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 7, no 11, p. 1208-1216Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Bioscientifica, 2018
Keywords
combined oral contraceptive, McCoy Female Sexuality Questionnaire, placebo, randomised clinical ial, sexual function, sexual interest, testosterone
National Category
Pharmacology and Toxicology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-156337 (URN)10.1530/EC-18-0384 (DOI)000456843800012 ()30352399 (PubMedID)
Available from: 2019-02-13 Created: 2019-02-13 Last updated: 2019-02-13Bibliographically approved
Lundin, C., Gemzell Danielsson, K., Bixo, M., Moby, L., Bengtsdotter, H., Jawad, I., . . . Sundström Poromaa, I. (2017). 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 trial. Psychoneuroendocrinology, 76, 135-143
Open this publication in new window or tab >>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 trial
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2017 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 76, p. 135-143Article in journal (Refereed) Published
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.

Keywords
Randomized clinical trial, Combined oral contraceptives, Estrogen, Progestagen, Depression, Anxiety, ritability
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-132304 (URN)10.1016/j.psyneuen.2016.11.033 (DOI)000393723600019 ()27923181 (PubMedID)
Available from: 2017-04-11 Created: 2017-04-11 Last updated: 2018-06-09Bibliographically approved
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