| 1. |
- Ahangari, Alebtekin, et al.
(författare)
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Acute intermittent porphyria symptoms during the menstrual cycle
- 2015
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Ingår i: Internal medicine journal (Print). - : Wiley. - 1444-0903 .- 1445-5994. ; 45:7, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute intermittent porphyria (AIP), a life-threatening form of the disease, is accompanied by several pain, mental and physical symptoms.Aims: In this study, we evaluated the cyclicity of AIP and premenstrual syndrome (PMS) symptoms in 32 women with DNA-diagnosed AIP during their menstrual cycles, in northern Sweden.Methods: The cyclicity of AIP symptoms and differences in them between the follicularand luteal phases, and the cyclicity of each symptom in each individual woman indifferent phases of her menstrual cycle were analysed with a prospective daily ratingquestionnaire. PMS symptoms were also evaluated in the patients on a daily rating scale.Results: Of the 32 women, 30 showed significant cyclicity in at least one AIP or PMS symptom (P < 0.05–0.001). Back pain (10/32) was the most frequent AIP pain symptomand sweet craving (10/15) was the most frequent PMS symptom. Pelvic pain (F = 4.823,P = 0.036), irritability (F = 7.399, P = 0.011), cheerfulness (F = 5.563, P = 0.025), sexualdesire (F = 8.298, P = 0.007), friendliness (F = 6.157, P = 0.019), breast tenderness (F =21.888, P = 0.000) and abdominal swelling (F = 16.982, P = 0.000) showed significantcyclicity. Pelvic pain and abdominal swelling (rs= 0.337, P < 0.001) showed the strongest correlation. The age of women with latent AIP was strongly correlated with abdominal swelling during the luteal phase (rs= 0.493, P < 0.01).Conclusion: Our results suggest that the symptoms of AIP patients change during their menstrual cycles.
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| 2. |
- Birzniece, Vita, et al.
(författare)
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GABA(A) receptor changes in acute allopregnanolone tolerance
- 2006
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 535:1-3, s. 125-134
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Tidskriftsartikel (refereegranskat)abstract
- To study acute tolerance, rats were anesthetized with interrupted i.v. allopregnanolone infusions where the "silent second" in the electroencephalogram (EEG) was the target. Animals were killed either directly at the first silent second or at the silent second level after 30 or 90 min of anaesthesia. Acute tolerance was demonstrated at 90 min of anaesthesia as earlier shown. In situ hybridization showed a decreased expression of the gamma-aminobutyric acid(A) (GABA(A)) receptor subunit alpha4mRNA amount in the thalamus ventral-posteriomedial nucleus of the tolerant rats. A parallel change in the abundance of the alpha4 subunit was detected with immunohistochemistry. The increase in maintenance dose rate (MDR) was significantly negatively correlated with the alpha4mRNA in the thalamus ventral-posteriomedial nucleus, and positively correlated with alpha2mRNA in different hippocampal subregions. There was also a positive relationship between the alpha1mRNA amounts in the different hippocampal subregions, with significant differences between groups. These changes in GABA(A) receptor subunits mRNA expression and protein (alpha4) might be of importance for the development of acute tolerance to allopregnanolone.
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| 3. |
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| 4. |
- Bäckström, Torbjörn, et al.
(författare)
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Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
- 2011
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Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
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Forskningsöversikt (refereegranskat)abstract
- Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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| 5. |
- Bäckström, Torbjörn, 1948-, et al.
(författare)
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Pathogenesis in menstrual cycle-linked CNS disorders.
- 2003
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1007, s. 42-53
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Bäckström, Torbjörn, et al.
(författare)
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The GABA system, a new target for medications against cognitive impairment—Associated with neuroactive steroids
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:3, s. 281-294
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Forskningsöversikt (refereegranskat)abstract
- The prevalence of cognitive dysfunction, dementia, and neurodegenerative disorders such as Alzheimer's disease (AD) is increasing in parallel with an aging population. Distinct types of chronic stress are thought to be instrumental in the development of cognitive impairment in central nervous system (CNS) disorders where cognitive impairment is a major unmet medical need. Increased GABAergic tone is a mediator of stress effects but is also a result of other factors in CNS disorders. Positive GABA-A receptor modulating stress and sex steroids (steroid-PAMs) such as allopregnanolone (ALLO) and medroxyprogesterone acetate can provoke impaired cognition. As such, ALLO impairs memory and learning in both animals and humans. In transgenic AD animal studies, continuous exposure to ALLO at physiological levels impairs cognition and increases degenerative AD pathology, whereas intermittent ALLO injections enhance cognition, indicating pleiotropic functions of ALLO. We have shown that GABA-A receptor modulating steroid antagonists (GAMSAs) can block the acute negative cognitive impairment of ALLO on memory in animal studies and in patients with cognitive impairment due to hepatic encephalopathy. Here we describe disorders affected by steroid-PAMs and opportunities to treat these adverse effects of steroid-PAMs with novel GAMSAs.
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| 7. |
- Danielsson, C., et al.
(författare)
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Management and outcomes of preterm premature rupture of the membranes
- 2018
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Ingår i: CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY. - : I R O G CANADA, INC. - 0390-6663. ; 45:3, s. 419-424
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of investigation: To compare the maternal and neonatal outcomes of preterm premature rupture of the membranes (PPROM) between two management strategies. Materials and Methods: This retrospective cohort study involved 153 pregnant women who presented with PPROM at a gestational age of 28+0 to 36+6 weeks to evaluate the effects of expectant management (EM; labor > 36 hours) and active management (AM; labor < 36 hours) on maternal and neonatal outcomes. The EM and AM groups were also compared independently of gestational age and after being divided into two subgroups: early PPROM (gestational age 28+0 to 33+6 weeks) and late PPROM (34+0 to 36+6 weeks). Results: There were no differences between the AM and EM groups in the rates of maternal infection or placental abruption, or in neonatal outcomes, including low Apgar scores, respiratory distress syndrome, or the need for continuous positive airway pressure (CPAP). In the early PPROM subgroup, arterial umbilical blood base excess levels were more negative in the AM group (p = 0.007). In the late PPROM subgroup, the change in systolic blood pressure between admission to the maternity care center and membrane rupture was greater in the AM group (p = 0.049). Conclusions: There were no clinically significant differences in the maternal and neonatal outcomes of PPROM between AM and EM.
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| 8. |
- Ekholm, Ulla-Britt, et al.
(författare)
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Sexuality and androgens in women with cyclical mood changes and pre-menstrual syndrome
- 2014
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 93:3, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study the relation between androgen levels and sexual interest in women with different kinds of pre-menstrual syndrome (PMS). Design Causal comparative study. Setting Swedish university hospital outpatient clinic. Population Seventy women with cyclical mood changes. Methods Pre-menstrual syndrome patients were divided into those with and those without preovulatory symptoms. In 37 women, early follicular phase blood samples were analyzed for androstenedione, testosterone, sex hormone-binding globulin (SHBG), progesterone and estradiol, using radioimmunoassay. The participants were divided into subgroups depending on whether the levels of androgens and SHBG were above or below the median. In 33 of them it was possible to compare the cyclicity in sexual parameters between these subgroups. Main outcome measures Daily ratings of sexual parameters and hormonal analyses. Results Plasma testosterone was significantly lower and SHBG significantly higher in women with luteal phase symptoms compared with those with additional follicular phase symptoms. ANOVA showed significant cyclicity for all sexual parameters consistently. For the “sexual feelings” and “pleasant sexual thoughts” parameters, cyclicity was the same whether or not the hormonal levels were “high” or “low.” Conclusions The “Pure-PMS” group and the “pre-menstrual-exacerbation” groups differed in their androgen and SHBG levels. Women suffering from PMS with higher neuroticism Eysenck Personality Inventory scores or “low” levels of androgens and SHBG would be more likely to have a decreased sexual interest pre-menstrually than would women with a high level.
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| 9. |
- Hautala, Laura, et al.
(författare)
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Performance of Variables in Screening for Gestational Diabetes
- 2019
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Ingår i: European Endocrinology. - : Touch Medical Media. - 1758-3780. ; 15:2, s. 101-105
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. The strategies used to screen for GDM vary both internationally and nationally. Therefore, we investigated the performance of the capillary random plasma glucose (RPG) test, maternal body mass index (BMI) and maternal age in predicting GDM.Methods: In a retrospective cohort study, we included pregnant women without pre-existing diabetes or metabolic disease who gave birth in Västernorrland County, Sweden, in 2015–2016. Values for RPG in gestational weeks 23–28 were obtained from obstetric medical records for each pregnancy. The development of GDM was confirmed by evaluating data in the obstetric records. The ability of RPG, maternal BMI, and age to predict GDM was assessed with receiver-operating characteristic curves.Results: In total, 4,698 pregnancies were included in the final statistical analysis. RPG was fairly effective in screening (area under the curve [AUC] 0.73; 95% confidence interval [CI] 0.66–0.80), and BMI performed slightly better (AUC 0.75; 95% CI 0.68–0.82), whereas maternal age performed poorly (AUC 0.61; 95% CI 0.53–0.68). Combining RPG ≥7 and BMI ≥27.9 yielded the best overall sensitivity (75.4%), specificity (70.1%), and AUC (0.75; 95% CI 0.68–0.82).Conclusions: Our results show that the sensitivity of capillary RPG alone in predicting GDM is fair. The combination of RPG with maternal BMI or age showed greater sensitivity. However, none of the screening factors (RPG, BMI, and maternal age), alone or combined, showed sufficiently good performance in predicting GDM.
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| 10. |
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| 11. |
- Hedström, Helena, et al.
(författare)
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Women with polycystic ovary syndrome have elevated serum concentrations of and altered GABA A receptor sensitivity to allopregnanolone
- 2015
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 83:5, s. 643-650
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
- Holmberg, Ellinor, et al.
(författare)
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Allopregnanolone involvement in feeding regulation, overeating and obesity
- 2018
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Ingår i: Frontiers in neuroendocrinology (Print). - : Academic Press. - 0091-3022 .- 1095-6808. ; 48, s. 70-77
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 13. |
- Klevedal, Charlotta, et al.
(författare)
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Fetal-maternal outcomes and complications in pregnant women with polycystic ovary syndrome
- 2017
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Ingår i: Minerva Ginecologica. - Turin : Edizioni Minerva Medica. - 0026-4784 .- 1827-1650. ; 69:2, s. 141-149
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Earlier studies have shown that polycystic ovary syndrome (PCOS) is associated with cardiovascular disease as well as pregnancy complications. We examined whether women with PCOS have an increased risk of complications in pregnancy compared with healthy women, and if there are any correlations between complications and clinical/demographic variables before and/or in early pregnancy.METHODS: This retrospective cohort study comprised 37 women with PCOS and 126 healthy women whose birth was recorded at Sundsvall County Hospital, Sweden, from 2009 to 2014. Medical records were searched to identify pregnancy complications, maternal outcomes, and neonatal outcomes.RESULTS: Compared with healthy women, the women with PCOS were more likely to have a history of miscarriage (42.9% vs. 19.8% P=0.005) and undergo caesarean section (41.2% vs. 21.4%, P=0.019). They were also at increased risk of developing a complication (odds ratio 2.38, 95% CI: 1.05-5.38) or having multiple concurrent complications (odds ratio 8.27, 95% CI: 1.45-47.3). The rates of premature birth, birth weight and Apgar score at 5 min were similar between the two groups. The preconception serum testosterone concentration was positively correlated with the complication rate and negatively correlated with gestational age.CONCLUSIONS: We found that women with PCOS are at greater risk of complications during pregnancy than healthy women, consistent with the results of earlier studies. High testosterone concentrations could be an aggravating factor in the risk of complications. Therefore, women with PCOS may require more careful monitoring during pregnancy than healthy women.
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| 14. |
- Löfgren, Magnus, 1979-, et al.
(författare)
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Withdrawal effects from progesterone and estradiol relate to individual risk-taking and explorative behavior in female rats
- 2009
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Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384 .- 1873-507X. ; 96:1, s. 91-97
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Tidskriftsartikel (refereegranskat)abstract
- Withdrawal from progesterone and estradiol has been used as an animal model of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). In the clinical population individual sensitivity to sex steroid hormones, personality and heredity influence PMS/PMDD. Understanding the phenotypic risk factors of PMS/PMDD and drug development requires an animal model which incorporates individual steroid sensitivity. The main objective of this study was to investigate whether the individual trait of risk-taking and exploration influence the severity of PEWD in female rats. Thirty-two female Wistar rats in their diestrus phase were tested in the open field (OF) and divided into high responders (HR) and low responders (LR). Injections were given i.p. twice daily for 6 days, either 5 mg/kg progesterone combined with 10 mu g/kg 17 beta-estradiol, or vehicle (sesame oil). After a 24-hour withdrawal the animals were tested in the elevated plus maze (EPM). Blood samples for CORT analysis were collected after both behavioral tests. The HR rats withdrawn from progesterone and estradiol, spent less time on the EPM open arms and had lower CORT levels than the HR controls. The LR group showed no differences in EPM behavior and CORT levels during PEWD. The controls showed a stable trait of risk-taking and exploration. indicated by behavioral and CORT level correlations between the OF and EPM tests. These findings show that female rats with the trait of risk-taking and explorative behavior (HR) are more affected by PEWD.
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| 15. |
- Persson, Sofia, et al.
(författare)
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Fecundity among women with polycystic ovary syndrome (PCOS)-a population-based study
- 2019
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 34:10, s. 2052-2060
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Does the long-term fecundity of women with polycystic ovary syndrome (PCOS) differ from those without PCOS?SUMMARY ANSWER: Cumulative probability of childbirth is similar between women with and without PCOS.WHAT IS KNOWN ALREADY: PCOS is the main cause of anovulatory infertility in women after menarche. Previous studies indirectly suggest that fecundity in women with PCOS over the longer term may not be lower than in women without PCOS.STUDY DESIGN, SIZE, DURATION: This is a population-based study using four linked Swedish national registries. A total of 45 395 women with PCOS and 217 049 non-PCOS women were included. Follow-up began at the age of 18 years and continued for a maximum of 26 years, from 1989 to the end of 2015. Childbirth was the main outcome, as identified from the Medical Birth Register.PARTICIPANTS/MATERIALS, SETTING, METHODS: All women born between 1971 and 1997 who were identified with a PCOS diagnosis in the Swedish Patient Registry between 1 January 2001 and 31 December 2016 were included in the study population. Five controls per women with PCOS were randomly drawn from the Total Population Registry. The control women were born in the same year and living in the same municipality as the patient. The fecundity ratio (FR) was calculated by clustered Cox regression using a robust variance, adjusted for maternal birth period, country of birth and level of education.MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative probability of childbirth was 80.2% (95% CI, 79.5–80.9%) in women with PCOS and 78.2% (95% CI, 77.9–78.5%) in those without PCOS. Adjusted FR was 0.81 (95% CI, 0.80–0.82) for first childbirth and 0.58 (95% CI, 0.57–0.60) for first childbirth following a spontaneous pregnancy. The FR for second childbirth was 0.79 (95% CI, 0.77–0.80). Women with PCOS had more than one child less frequently than the comparison group. Within the PCOS group, early age at diagnosis, later birth year, Nordic country of origin and low educational level positively influenced the FR.LIMITATIONS, REASONS FOR CAUTION: Results are not adjusted for BMI, and time from intention to conceive to first childbirth could not be captured. Data on pregnancies, miscarriages or abortions and fertility treatment are unknown for women who did not give birth during the study period. Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes.WIDER IMPLICATIONS OF THE FINDINGS: While cumulative probability of childbirth is similar between groups, women with PCOS need longer time to achieve their first childbirth. Women with PCOS have a lower FR and give birth to fewer children per woman than women without PCOS. Early diagnosis of and information about PCOS may improve affected women’s reproductive potential.STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Swedish Society of Medicine. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests.
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| 16. |
- Persson, Sofia, et al.
(författare)
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Higher risk of type 2 diabetes in women with hyperandrogenic polycystic ovary syndrome
- 2021
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Ingår i: Fertility and Sterility. - : Elsevier. - 0015-0282 .- 1556-5653. ; 116:3, s. 862-871
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype.Design: Population-based cohort study.Setting: Data from six Swedish national registers, with participants being followed for a maximum of 19 years.Patient(s): All women with an International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of PCOS, androgen excess, or anovulatory infertility born between 1950 and 1999 (n = 52,535) were identified in the Patient Register. The HA PCOS phenotype was defined by two filled prescriptions for anti-androgenic drugs. For each woman with PCOS, five control women (n = 254,624) were randomly chosen from the Total Population Register, matched for age and geographic area.Intervention(s): No interventions were performed.Main Outcome Measure(s): International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of T2D or prescription of antidiabetic treatment other than metformin.Result(s): The cumulative incidence rates of T2D were 1.3%, 4.4%, and 14.2% in controls (non-PCOS women) and women with normoandrogenic (NA) and HA PCOS, respectively. After adjustment for BMI, women with PCOS had a twofold higher rate of T2D than non-PCOS women (adjusted hazard ratio, 2.52 [95% confidence interval, 2.15–2.96]). Women with HA PCOS had a higher rate of T2D than those with NA PCOS (adjusted hazard ratio, 3.86 [95% confidence interval, 3.16–4.72]).Conclusion(s): Polycystic ovary syndrome is an independent risk factor for T2D, even after adjustment for BMI. Women with the HA PCOS phenotype face an even higher risk of T2D than those with the NA PCOS phenotype.
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| 17. |
- Persson, Sofia, et al.
(författare)
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Hyperandrogenic symptoms are a persistent suffering in midlife women with pcos; a prospective cohort study in sweden
- 2023
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women, and the majority suffers from hyperandrogenism. Hyperandrogenism causes psychological morbidity and impaired quality of life in women with PCOS during the reproductive years, but data on prevalence and impact during midlife are lacking. Thus, this study aimed to address whether hyperandrogenism persists into midlife and, if so, what impact it has on quality of life. In order to answer this question, we performed a multicenter prospective cohort study, where we included women already diagnosed with PCOS who had reached the age of 45 years or more and age-matched controls. All participants underwent a physical exam, structured medical interview, biochemical testing and filled out self-assessment questionnaires. More than 40% of the women with PCOS and 82% of those who presented with the hyperandrogenic phenotype at the diagnostic work-up still suffered from hirsutism. Circulating testosterone levels were similar between women with PCOS and controls while free androgen index was higher in women with PCOS, independent of weight. Women with hyperandrogenic PCOS expressed persisting concerns regarding hirsutism at the follow-up assessment. In conclusion, women with PCOS who present with hyperandrogenic symptoms at the time they are diagnosed with PCOS have a higher risk of persistent androgenic symptoms and impaired quality of life in midlife.
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| 18. |
- Persson, Sofia, 1985-, et al.
(författare)
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Hypertension and dyslipidaemia in women with polycystic ovary syndrome: a population based register study in Sweden
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Context: Polycystic ovary syndrome (PCOS) is an established risk factor for insulin resistance and the metabolic syndrome.Objective: To study the impact of PCOS and the hyperandrogenic PCOS phenotype on hypertension and dyslipidemia.Design: National register-based cohort study. Setting: Sweden, January 1, 1997 to December 31, 2016.Patients or Other Participants: Women with PCOS born between 1950-1999 residing in Sweden, compared with a matched cohort of non-PCOS women.Interventions: Exposure was defined as having a PCOS diagnosis. Exposed individuals were classified into having hyperandrogenic (HA) or normoandrogenic (NA) phenotypes.Main Outcome Measure (s): Multivariable adjusted Cox regression-derived hazard ratios (HRs) for hypertension or dyslipidemia. The outcomes were defined either by their ICD-10 diagnoses or by prescribed drugs.Results: A total of 50 969 women with PCOS and 246 246 non-PCOS women were included. Women with the HA PCOS phenotype exhibited a 6-fold higher risk of hypertension compared to non-PCOS women [aHR 5.91 (95% CI 5.09-6.86) and aHR 5.51 (4.97-6.10) adjusted for body mass index (BMI) or obesity]. Among NA- PCOS women, the hypertension risk was almost 2-fold [aHR 1.77 (1.63, 1.94) and 1.94 (1.83, 2.07), respectively]. Regarding dyslipidemia, NA-PCOS women had an aHR 2.47 (95% CI 2.04-3.00) and HA-PCOS women an aHR 7.32 (95% CI 5.28-10.16) when adjusted for BMI. Conclusions: PCOS is an independent risk factor for the development of hypertension and dyslipidemia with the risk being higher among women with the hyperandrogenic PCOS phenotype.
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| 19. |
- Persson, Sofia, 1985-
(författare)
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Polycystic ovary syndrome : Long-term health aspects
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age, affecting many aspects of women’s health such as fertility, cardiovascular health and quality of life. However, less is known about later life stages, as well as the impact of hyperandrogenism and PCOS itself, apart from risks associated with excess body weight. The overall aim with this thesis was therefore to study how PCOS, and its hyperandrogenic phenotype, is associated with general health, with focus on diabetes, hypertension, dyslipidaemia and fertility at a longer span of time than during the fertile period.Studies I-III were register-based cohort studies, linking six Swedish national registers. In total, >50 000 women with PCOS and ≈ 250 000 controls were included and followed up for up to 20 years. Study IV was a clinical cross-sectional study including 124 women with PCOS and 74 controls.The main results were that PCOS has a great impact on women’s lives extending beyond the fertile period. While women with PCOS achieve a first childbirth as often as non-PCOS women, they have fewer children overall and give birth at a later age. In addition, PCOS is a moderate risk factor for type 2 diabetes, hypertension and dyslipidaemia, regardless of body weight. The risk appears to be more pronounced in those with the hyperandrogenic phenotype. Finally, hyperandrogenism persists largely in midlife for women with PCOS, both through ongoing symptoms such as hirsutism and by having a negative impact on the women’s quality of life.In conclusion, women with PCOS should be informed that they have a good chance of conceiving, but that some may need assisted reproduction. We suggest that PCOS in general and the hyperandrogenic phenotype in particular be included as independent risk factors when counselling women on their likelihood to suffer from cardiovascular disease and its risk factors in particular such as type 2 diabetes, hypertension and dyslipidaemia.
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| 20. |
- Rexelius, Niklas, et al.
(författare)
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Sexuality and mood changes in women with persistent pelvic girdle pain after childbirth : a case-control study
- 2020
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Ingår i: BMC Women's Health. - : BioMed Central. - 1472-6874. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pelvic girdle pain is a common problem during pregnancy. For most women, the symptoms cease within the first 3-6months of giving birth, but in some women the pain persists. In this study we investigate the sexuality and frequency of depressive symptoms in women with persistent pelvic girdle pain after childbirth and in healthy women.Methods: We conducted a case-control study of women with persistent pelvic girdle pain after childbirth and a control group of healthy women. The frequency of depressive symptoms and sexuality were measured using the self-rating version of the Montgomery-Asberg Depression Rating Scale and the McCoy Female Sexuality Questionnaire.Results: Forty-six women with persistent pelvic girdle pain and thirty-nine healthy women were enrolled. The frequency of depressive symptoms and the total score on female sexuality did not differ between the groups. However, pain during intercourse was more frequent (P<0.001) in women with persistent pelvic girdle pain and caused them to avoid sexual intercourse frequently (P<0.001). In multiple linear regression a higher frequency of depressive symptoms was reversely correlated with a lower score on female sexuality (beta (=)-0,41, p<0,001 95% CI -0,6 - -0,22) This association remained after adjusting for obstetric variables and individual characteristics.Conclusion: Depressive symptoms and female sexuality were similar between women with persistent pelvic girdle pain after childbirth and healthy controls. However, pain during intercourse and avoidance of sexual intercourse were more frequent among women with pelvic girdle pain.
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| 21. |
- Sandström, Anton, et al.
(författare)
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Altered GABAA receptor function in women with endometriosis : a possible pain-related mechanism
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:10, s. 1316-1322
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relationship between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women.Material and methods: 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.Results: Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.Conclusions: Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist.
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| 22. |
- Sandström, Anton, et al.
(författare)
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Effect of hysterectomy on pain in women with endometriosis : a population-based registry study
- 2020
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 127:13, s. 1628-1635
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess pain symptoms before and after hysterectomy in women with endometriosis.Design: A population-based registry study.Setting: Sweden.Population: Women aged 18-45 years who underwent hysterectomy for endometriosis between 2010 and 2015.Methods: Pain symptoms before hysterectomy and 12 months after surgery were collected from the Swedish National Quality Register for Gynaecological Surgery (GynOp). Pain symptoms were also assessed by follow-up surveys after a median follow-up period of 63 months.Main outcome measures: Pelvic or lower abdominal pain after hysterectomy.Results: The study included 137 women. The proportion of women experiencing pain of any severity decreased by 28% after hysterectomy (P < 0.001). The proportion of women with severe pain symptoms decreased by 76% after hysterectomy (P < 0.001). The majority of women (84%) were satisfied with the surgical result. Presence of severe pain symptoms after the hysterectomy was associated with less satisfaction (P < 0.001). Pain symptoms after surgery, patient satisfaction and the patient's perceived improvement were not significantly different between women whose ovarian tissue was preserved and women who underwent bilateral oophorectomy.Conclusions: We observed a significant, long-lasting reduction in pain symptoms after hysterectomy among women with endometriosis. Hysterectomy, with the possibility of ovarian preservation, may be a valuable option for women with endometriosis who suffer from severe pain symptoms.Tweetable abstract: Hysterectomy is a valuable option for women with endometriosis and severe pain symptoms.
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| 23. |
- Tawhid Söderholm, Nora, et al.
(författare)
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Impact of Epidural Analgesia in Labour onNeonatal and Maternal Outcomes
- 2018
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Ingår i: Open Journal of Obstetrics and Gynecology. - : Scientific Research Publishing. - 2160-8792 .- 2160-8806. ; 8, s. 767-779
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate the effect of epidural analgesia during labour on neonatal-maternal outcomes. Methods: A retrospective cohort study of nulliparous parturients who gave birth in Vasternorrland County, Sweden, over a 2-year period between 2015 and 2016. Neonatal outcomes (Apgar score at 5 min and umbilical cord arterial blood gases), maternal outcomes (perineal injury, total bleeding volume and maternal satisfaction with birth) and labour parameters (mode of delivery and the durations of labour and postpartum hospital stay) were evaluated. Results: The study cohort consisted of 1449 women with singleton pregnancies. Patients were divided into two groups according to whether during labour they were administered epidural analgesia using bupivacaine and sufentanil (EDA group, n = 615) or not (non-EDA group, n = 834). The rate of assisted vaginal delivery was significantly higher in the EDA group than in the non-EDA group (15.6% and 11.3%, respectively, p < 0.05), whereas the rates of caesarean section were similar. The duration of the active phase of labour was significantly longer in the EDA group than in the non-EDA group (489 ± 217 min versus 371 ± 210 min, respectively, p < 0.001). The Apgar score at 5 min and umbilical cord blood pH were lower and the base deficit greater in the EDA group (p < 0.001, p < 0.001 and p < 0.01, respectively). Bleeding volume was similar between the groups after adjusting for gestational age. Women in the EDA group were more satisfied with their labour experience, as measured by the visual analogue scale (p < 0.05). Conclusion: The results of this study suggest that EDA affects delivery and neonatal-maternal outcomes negatively, but increases the mother’s satisfaction with labour.
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| 24. |
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| 25. |
- Turkmen, Sahruh, et al.
(författare)
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3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone.
- 2004
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 20:6, s. 1604-1612
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Tidskriftsartikel (refereegranskat)abstract
- Allopregnanolone is a progesterone metabolite and GABA-A receptor modulator with benzodiazepine like effects, including decreased learning and memory. In vitro 3beta-hydroxypregnane steroids antagonize allopregnanolone-induced effects, but no antagonism has been shown in vivo. Our purpose was to evaluate 3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) as a blocker of allopregnanolone-induced effects in vivo and in vitro in rats. We tested adult male Wistar rats in the Morris water maze 8 min after daily injections (i.v.) of allopregnanolone 2 mg/kg (n = 21); allopregnanolone : UC1011 2 : 6 (n = 7), 2 : 8 (n = 7), 2 : 20 (n = 14) mg/kg; UC1011 20 mg/kg (n = 14); or vehicle (10% 2-hydroxypropyl-beta-cyclodextrin, n = 4). Studies of chloride ion uptake into cortical and hippocampal membrane preparations were performed. The latency to find the hidden platform was still high in the allopregnanolone-injected group on day 6. Day 3-6 rats injected with allopregnanolone and UC1011 (2 : 20 mg/kg) had lower latency (P < 0.05), compared to the allopregnanolone-injected group. The group that only received UC1011 learned the location of the platform as fast as the controls. There was no significant difference in swim speed between groups. The time spent swimming close to the pool wall was in the allopregnanolone : UC1011 group (2 : 20 mg/kg) significantly decreased (P < 0.05, day 3-6), compared to the allopregnanolone-injected group. The increased chloride ion uptake induced by increasing dosage of allopregnanolone in the presence of 10 micro m GABA was significantly decreased with UC1011 (P < 0.01), in both cortical and hippocampal homogenates. In conclusion, UC1011 can via antagonism at the GABA-A receptor reduce the negative allopregnanolone effect on learning in the water maze.
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| 26. |
- Turkmen, Sahruh, et al.
(författare)
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Effects of Roux-en-Y gastric bypass surgery on eating behaviour and allopregnanolone levels in obese women with polycystic ovary syndrome
- 2015
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Ingår i: Gynecological Endocrinology. - : Informa Healthcare. - 0951-3590 .- 1473-0766. ; 31:4, s. 301-305
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is associated with abnormal eating habits. We examined whether surgical treatment affected allopregnanolone levels and eating behaviour in nine women with PCOS who qualified for Rou-en-Y gastric bypass surgery. Blood samples were obtained to measure sex-hormone-binding globulin, total testosterone, progesterone, and allopregnanolone, and eating behaviour was evaluated using the Three-Factor Eating Questionnaire before surgery and at 6 and 12 months after surgery. Body mass index and total testosterone levels decreased, and progesterone and sex-hormone-binding globulin levels increased after bariatric surgery compared with pre-surgical values. In patients with anovulatory menstrual cycles, both the serum allopregnanolone level and the allopregnanolone/progesterone ratio were unchanged after surgery. The patients had high uncontrolled and emotional eating scores, and low cognitive restraint scores before surgery, and these scores had improved significantly at 6 and 12 months after surgery. The presurgical allopregnanolone levels were significantly correlated with uncontrolled eating. In conclusion, these results suggest that allopregnanolone appear to be part of the mechanism underlying the abnormal eating behaviour of obese PCOS patients by causing the loss of control over food intake. Roux-en-Y gastric bypass surgery can improve eating behaviour and clinical symptoms, and may facilitate weight loss in obese women with PCOS.
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| 27. |
- Turkmen, Sahruh, et al.
(författare)
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Foetal Macrosomia and Foetal-Maternal Outcomes at Birth
- 2018
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Ingår i: Journal of Pregnancy. - : Hindawi Publishing Corporation. - 2090-2727 .- 2090-2735.
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Tidskriftsartikel (refereegranskat)abstract
- To investigate how macrosomia affects foetal-maternal birth outcomes, we conducted a retrospective cohort study of singleton pregnant women who gave birth at gestational age >= 37+0 weeks. The patients were divided into three groups according to birth weight: "macrosomia" group, >= 4500 g, n=285; "upper-normal" group, 3500-4499 g, n=593; and "normal" group, 2500-3499 g, n=495. Foetal-maternal and delivery outcomes were compared among the three groups after adjustment for confounders. Caesarean section was more frequent in the macrosomia group than in upper-normal and normal groups. The duration of labour (p < 0.05) and postpartum care at the hospital (p < 0.001) were the highest in the macrosomia group. Increased birth weight was associated with higher risks of shoulder dystocia (p < 0.001), increased bleeding volume (p < 0.001), and perineal tear (p < 0.05). The Apgar score at 5 minutes (p < 0.05), arterial cord pH (p < 0.001), and partial pressure of O2 (p < 0.05) were lower, while the arterial cord partial pressure of CO2 was higher (p < 0.001), in the macrosomia group. Macrosomia has potentially serious impacts for neonate and mother as a result of a complicated and occasionally traumatic delivery.
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| 28. |
- Turkmen, Sahruh
(författare)
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Genitala infektioner
- 2022. - 3
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Ingår i: Gynekologi. - Lund : Studentlitteratur AB. - 9789144144191 ; , s. 305-326
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 29. |
- Turkmen, Sahruh
(författare)
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Maternal and neonatal outcomes in vacuum-assisted delivery with the Kiwi OmniCup and Malmstrom metal cup
- 2015
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Ingår i: Journal of obstetrics and gynaecology research. - : Wiley. - 1341-8076 .- 1447-0756. ; 41:2, s. 207-213
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Tidskriftsartikel (refereegranskat)abstract
- AimTo evaluate the effects of different types of vacuum cups on maternal and neonatal outcomes following assisted vaginal delivery.MethodsA retrospective cohort study was undertaken of all vacuum-assisted deliveries performed over a period of 2years. Patients were divided into two groups according to whether a Kiwi OmniCup (n=230) or Malmstrom metal cup (n=98) was used. Maternal outcomes included maternal genital tract injury and total blood loss. Neonatal outcomes included Apgar score, umbilical cord blood gases, neonatal scalp injury and time spent in the neonatal unit.ResultsMaternal or neonatal outcomes and failure rates did not differ between the two groups, however, the duration of the procedure and the fundal pressure maneuver was more frequent in the Malmstrom group.ConclusionThe results of this study suggest that the Kiwi OmniCup and Malmstrom metal cup vacuum extractors are safe and functionally effective for vacuum-assisted delivery.
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| 30. |
- Turkmen, Sahruh, et al.
(författare)
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Neurosteroid involvement in threatened preterm labour
- 2021
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Ingår i: Endocrinology, Diabetes & Metabolism. - Sussex : John Wiley & Sons. - 2398-9238. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABAA receptor. Whether neurosteroid levels and the function of the GABAA receptor are involved in the risk of preterm labour in pregnant women is unknown.Methods: Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABAA receptor function in both groups was measured with a saccadic eye velocity test (SEVT).Results: Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p = .021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: −3.2, 95% confidence interval (CI): −5.5 to −0.9, p = .012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00–1.04, p = .038). SEVT showed that the women in both groups had similar GABAA receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r = .34, p = .044) and negatively with allopregnanolone (r = −.41, p = .013).Conclusions: Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABAA receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABAA receptor agonist.
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| 31. |
- Türkmen, Sahruh, et al.
(författare)
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Persistence of tolerance to the anaesthetic effect of allopregnanolone in male rats.
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 592:1-3, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Both acute and chronic tolerance can develop to allopregnanolone-a gamma-aminobutyric acid (GABA)-modulatory progesterone metabolite. Here we investigated if acute tolerance to allopregnanolone persisted for 1 or 2 days after the induction and thus could be the initial part of chronic tolerance. Male rats were anaesthetised with allopregnanolone (i.v) to the deep anaesthesia level of the silent second (SS), which is an EEG burst suppression of 1 s or more. They were divided into four groups: SS1-anaesthesia to the first silent second; LAn (long anaesthesia)-90 min anaesthesia at the SS level; SS2;D1-90 min anaesthesia and SS induction 1 day later; SS2;D2-90 min anaesthesia and SS induction 2 days later. Allopregnanolone concentrations in tissue and serum were analysed. Levels of the GABAA receptor alpha2, alpha4, gamma2(S+L) and delta subunits mRNAs were analysed by in situ hybridisation. Acute tolerance was induced during the 90 min anaesthesia. Tolerance persisted for 1 day, since the dose of allopregnanolone needed to induce a new SS anaesthesia was increased after 1 day. The level of alpha4 subunit mRNA expression in the ventral posteriomedial nucleus of thalamus was negatively related to the tolerance parameters, the SS dose of allopregnanolone and DeltaSS (SS dose difference between days). Allopregnanolone threshold anaesthesia lasting 90 min induces acute tolerance that persisted for at least 1 day, which could be used as the start of a chronic tolerance. The alpha4 subunit may be involved in allopregnanolone caused effects in the brain.
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| 32. |
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| 33. |
- Turkmen, Sahruh, et al.
(författare)
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Post-partum duration of satisfaction with childbirth
- 2018
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Ingår i: Journal of obstetrics and gynaecology research. - : Blackwell Publishing. - 1341-8076 .- 1447-0756. ; 44:12, s. 2166-2173
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Satisfaction with childbirth has become increasingly important among healthcare providers. We evaluated whether satisfaction levels change with time (up to 3 months after delivery).METHODS: A prospective study of nulliparous women was designed to evaluate their levels of satisfaction with childbirth and care during birth in the maternity unit of a county hospital in Sundsvall, Sweden. Patient satisfaction with birth and health care was measured twice, during the first week after birth and 3 months later, with the Childbirth Experience Questionnaire (CEQ). Maternal and labor information were collected with a form filled in by the patients and completed with information from the patients' records.RESULTS: A total of 78 primiparous women participated in the study and answered the questionnaire in the first week after labor, and 63 of them completed the study by answering the same questionnaire 3 months after delivery. The total CEQ score did not change after 3 months, but the scores for the subscales 'professional support' and 'participation' decreased 3 months after labor (P = 0.008 and P = 0.001, respectively). A visual analogue scale predicted the total CEQ scores at both 1 week (P < 0.001) and 3 months (P = 0.003).CONCLUSION: Our results indicate that satisfaction with labor and birth among primiparous women was unchanged 3 months after labor.
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| 34. |
- Turkmen, Sahruh, et al.
(författare)
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Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone : a comparative pilot study.
- 2004
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Ingår i: Gynecological Endocrinology. - 0951-3590 .- 1473-0766. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary.
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| 35. |
- Turkmen, Sahruh, et al.
(författare)
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Roux-en-Y Gastric Bypass Surgery in Patients with Polycystic Ovary Syndrome and Metabolic Syndrome
- 2016
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 26:1, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to evaluate the impact of Roux-en-Y gastric bypass (RYGB) surgery on metabolic syndrome-related variables in obese women with polycystic ovarian syndrome (PCOS).METHODS: Thirteen obese women with PCOS (Rotterdam criteria) who met the International Diabetes Federation criteria for metabolic syndrome and who qualified for RYGB were enrolled. Clinical examinations included ovarian ultrasonography and measurement of waist, hip, body mass index and blood pressure. Venous blood samples were taken at the visit before surgery to measure triglyceride, high-density lipoprotein, low-density lipoprotein, fasting glucose, glycated haemoglobin (HbA1c), serum progesterone, allopregnanolone, total testosterone and sex hormone-binding globulin (SHBG) levels. Six months after surgery, patients underwent the same examinations and provided blood samples to analyse the same variables.RESULTS: At 6 months after surgery, the metabolic syndrome-related variables improved in all patients, except in six patients with anovulatory menstrual cycles who still satisfied the criteria for metabolic syndrome. The metabolic variables normalised and serum progesterone and allopregnanolone levels increased in seven patients with ovulatory cycles. Testosterone and SHBG normalised in all patients at 6 months after surgery. Serum HDL and diastolic blood pressure did not change after surgery. Correlations were found among testosterone, progesterone, allopregnanolone, lipoproteins, triglyceride, fasting glucose and HbA1c levels, which was interpreted as progesterone and its metabolite allopregnanolone may contribute to metabolic abnormalities.CONCLUSIONS: In PCOS patients, normalisation of metabolic dysfunction may be incomplete by 6 months after RYGB surgery, and the start of ovulatory menstrual cycles may indicate normalisation of metabolic dysfunction.
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| 36. |
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| 37. |
- Turkmen, Sahruh, 1961-
(författare)
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Tolerance and antagonism to allopregnanolone effects in the rat CNS
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many studies have suggested a relationship between sex steroids and negative mental and mood changes in women. Allopregnanolone, a potent endogenous ligand of the GABA-A receptor and a metabolite of progesterone, is one of the most accused neuroactive steroids. Variations in the levels of neuroactive steroids that influence the activity of the GABA-A receptor cause a vulnerability to mental and emotional pathology. In women, there are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone probably develops. We have evaluated the 3β-hydroxy pregnane steroid UC1011 as a functional antagonist to allopregnanolone-induced negative effects in rats. In vivo, we used the Morris Water Maze (MWM) test of learning and, in vitro, we studied chloride ion uptake into cortical and hippocampal membrane preparations. The steroid UC1011 reduces the allopregnanolone-induced learning impairment in the MWM and the increase in chloride ion uptake induced by allopregnanolone. To detect whether chronic tolerance develops to an allopregnanolone-induced condition, male rats were pretreated with allopregnanolone injections for three or seven days. These rats were then tested in the Morris Water Maze for five days and compared with relevant controls. Rats with seven days’ allopregnanolone pretreatment experienced improved performance compared with the acutely allopregnanolone-exposed group, reflecting chronic tolerance development. To study the GABA-A receptor changes in acute allopregnanolone tolerance, we used the silent second (SS) anaesthesia threshold method. At acute tolerance, 90 minutes of anaesthesia, the abundance of the GABA-A receptor α4 subunit and the expression of the α4 subunit mRNA in the thalamus ventral-posteriomedial (VPM) nucleus were reduced. There was also a significant negative correlation between the increase in the allopregnanolone dose needed to maintain anaesthesia and the α4 mRNA in the VPM nucleus. We also investigated whether allopregnanolone tolerance was still present one or two days after the end of the anaesthesia-induced acute tolerance. Tolerance persisted to one day, but not two days, after the treatment and the α4 subunit mRNA expression in the VPM nucleus was negatively related to the allopregnanolone doses needed after one day. In conclusion, the current thesis shows that the substance UC1011 can reduce the allopregnanolone-induced negative effects in the water maze test. Chronic allopregnanolone tolerance can develop to the effects of allopregnanolone. Allopregnanolone tolerance persists one day after the induction of acute allopregnanolone tolerance. The GABA-A receptor α4 subunit in the thalamus might be involved in the development and persistence of acute tolerance to allopregnanolone.
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| 38. |
- Türkmen, Sahruh, et al.
(författare)
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Tolerance development to Morris water maze test impairments induced by acute allopregnanolone
- 2006
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Ingår i: Neuroscience. - : Elsevier Inc.. - 0306-4522 .- 1873-7544. ; 139:2, s. 651-659
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Tidskriftsartikel (refereegranskat)abstract
- The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.
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| 39. |
- Turkmen, Sahruh, et al.
(författare)
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Tolerance to allopregnanolone with focus on the GABA-A receptor
- 2011
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Ingår i: British Journal of Pharmacology. - : Wiley-Blackwell. - 0007-1188 .- 1476-5381. ; 162:2, s. 311-327
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Tidskriftsartikel (refereegranskat)abstract
- Many studies have suggested a relationship between stress, sex steroids, and negative mental and mood changes in humans. The progesterone metabolite allopregnanolone is a potent endogenous ligand of the γ-amino butyric acid -A (GABA-A) receptor, and the most discussed neuroactive steroid. Variations in the levels of neuroactive steroids that influence the activity of the GABA-A receptor cause a vulnerability to mental and emotional pathology. There are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high and continuous allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone may develop. We have shown that both acute and chronic tolerances can develop to the effects of allopregnanolone. Following the development of acute allopregnanolone tolerance, there is a decrease in the abundance of the GABA-A receptor α4 subunit and the expression of the α4 subunit mRNA in the ventral-posteriomedial (VPM) nucleus of the thalamus. Little is known about the mechanism behind allopregnanolone tolerance and its effects on assembly of the GABA-A receptor composition. The exact mechanism of the allopregnanolone tolerance phenomena remains unclear. The purpose of this review is to summarize certain aspects of current knowledge concerning allopregnanolone tolerance and changes in the GABA-A receptors.
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| 40. |
- Turkmen, Sahruh
(författare)
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Vulvasmärta
- 2022. - 2
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Ingår i: Problemorienterad gynekologi och obstetrik. - Stockholm : Liber. - 9789147141906 ; , s. 120-124
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 41. |
- Åström, Evelina, et al.
(författare)
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Obstetric outcomes after cervical loop electrosurgical excision procedure
- 2023
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Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to investigate whether a history of loop electrosurgical excision procedure (i.e., conisation) affects obstetric and neonatal outcomes.Methods: A retrospective cohort study was carried out in Västernorrland county, Sweden. 57 nulliparous women with singleton pregnancies and previous conisation were compared with 100 age-matched pregnant controls without history of conisation.Results: There was significantly lower gestational age by delivery (p = 0.036), however, the premature delivery rate was not different. Caesarean section was also less frequent (OR: 0.29, 95% CI: 0.081–1.04, p = 0.047) in the conisation group than those in the control group. There were no differences in neonatal outcomes.Conclusions: Previous conisation does not affect the risk of prematurity or cervical dilatation during the first stage of labour. Women with history of conisation had a lower rate of caesarean section, and lower gestational age by delivery.
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- Öfverman, Charlotte, 1970-, et al.
(författare)
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The progesterone metabolite isoallopregnanolone is a subunit-selective antagonist of the GABA-A receptor
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Allopregnanolone is a progesterone metabolite that can negatively affect learning and induce anaesthesia in rats. It also impairs episodic memory in women. Allopregnanolone levels are elevated during the luteal phase of the menstrual cycle, during pregnancy, and during stress. Allopregnanolone is a strong positive modulator of the GABAA receptor. The subunit composition of the GABAA receptor is of importance for effects of modulators, and GABAA receptors including the α5-subunit are of significance for learning, while receptors with other subunits are involved in e.g. anesthesia. Isoallopregnanolone, a natural 3β-epimer of allopregnanolone, has been shown to antagonize allopregnanolone-induced anesthesia in rats. We tried to block the allopregnanolone-induced impairment of learning in rats in the Morris water maze test, using isoallopregnanolone (4–32 mg/kg). We also determined steroid concentrations in blood and brain tissue, and with whole-cell patch clamp we studied the effects of isoallopregnanolone and tetrahydrodeoxycorticosterone (a neurosteroid similar to allopregnanolone) on HEK-293 cells expressing the human α5β2γ2L GABAA receptor. Isoallopregnanolone did not block the negative effects of allopregnanolone (2 mg/kg) in the Morris water maze test. Our presumed antagonist actually had an agonistic effect on the tetrahydrodeoxycorticosterone-mediated potentiation of the GABA effect on the α5β2γ2L GABAA receptor. The baseline shift induced by tetrahydrodeoxycorticosterone alone was not reversed by isoallopregnanolone. A bidirectional epimerisation between allopregnanolone and isoallopregnanolone was also identified in the rat. The lack of antagonistic effect at the α5β2γ2L GABAA receptor together with the epimerisation of isoallopregnanolone to allopregnanolone would probably explain the lack of effect of our proposed antagonist on the allopregnanolone-induced impairment of learning
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