| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- Turkmen, Sahruh, et al.
(författare)
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Neurosteroid involvement in threatened preterm labour
- 2020
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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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| 10. |
- 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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