| 1. |
- Vinnars, Marie-Therese, et al.
(författare)
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Pregnancy-related maternal physiological adaptations and fetal chemical exposure
- 2023
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier. - 0303-7207 .- 1872-8057. ; 578
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal life represents a susceptible window of development during which chemical exposures can permanently alter fetal development, leading to an increased likelihood of disease later in life. Therefore, it is essential to assess exposure in the fetus. However, direct assessment in human fetuses is challenging, so most research measures maternal exposure. Pregnancy induces a range of significant physiological changes in women that may affect chemical metabolism and responses. Moreover, placental function, fetal sex, and pregnancy complications may further modify these exposures. The purpose of this narrative review is to give an overview of major pregnancy-related physiological changes, including placental function and impacts of pregnancy complications, to summarize existing studies assessing chemical exposure in human fetal organs, and to discuss possible interactions between physiological changes and exposures. Our review reveals major knowledge gaps in factors affecting fetal chemical exposure, highlighting the need to develop more sophisticated tools for chemical health risk assessment in fetuses.
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| 2. |
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| 3. |
- Bixo, Marie
(författare)
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Gynekologisk anamnes och undersökningsmetoder
- 2022. - 2
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Ingår i: Problemorienterad gynekologi och obstetrik. - Stockholm : Liber. - 9789147141906 ; , s. 28-43
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Bixo, Marie
(författare)
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Klimakteriebesvär
- 2022. - 2
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Ingår i: Problemorienterad gynekologi och obstetrik. - Stockholm : Liber. - 9789147141906 ; , s. 225-234
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Bixo, Marie
(författare)
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Klimakteriet
- 2022. - 3
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Ingår i: Gynekologi. - Lund : Studentlitteratur AB. - 9789144144191 ; , s. 97-107
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
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| 7. |
- Bäckström, Torbjörn, et al.
(författare)
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A randomized, double-blind study on efficacy and safety of sepranolone in premenstrual dysphoric disorder
- 2021
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- Women with premenstrual dysphoric disorder (PMDD) experience mood symptoms related to the increase in progesterone and the neuroactive steroid allopregnanolone. Our hypothesis is that allopregnanolone is the symptom provoking factor. The rationale for the present study was to treat PMDD patients with the GABAA receptor modulating steroid antagonist, sepranolone (isoallopregnanolone). Patients (n = 206) with PMDD from 12 European centers were randomized in a parallel double-blind study and treated with placebo, sepranolone 10 mg and 16 mg. Patients administered sepranolone subcutaneously every 48 h during the 14 premenstrual days of three consecutive menstrual cycles. After obtaining informed consent, the PMDD diagnosis was confirmed according to DSM-5 and verified with two menstrual cycles of daily symptom ratings using the Daily Record of Severity of Problems (DRSP) scale in an eDiary. Inclusion and exclusion criteria stipulated that the women should be essentially healthy, not pregnant, have no ongoing psychiatric disorder or take interfering medications, and have regular menstrual cycles. The study's primary endpoint was the Total symptom score (Sum21, the score for all 21 symptom questions in the DRSP). In the prespecified statistical analysis the average score of the 5 worst premenstrual days in treatment cycles 2 and 3 were subtracted from the corresponding average score in the two diagnostic cycles. The treatment effects were tested using analysis of variance in a hierarchal order starting with the combined active sepranolone treatments vs. placebo. The prespecified analysis of Sum21 showed a large treatment effect of all three treatments but no statistically significant difference to placebo. However, the ratings of distress showed a significant treatment effect of sepranolone compared to placebo (p = 0.037) and the ratings of impairment showed a trend to greater treatment effect of sepranolone compared to placebo. Many women with PMDD had symptoms during a longer period than the late luteal phase. It has previously been shown that 9 premenstrual days may be more representative for comparison of PMDD symptom periods than the 5 worst premenstrual days. A post hoc analysis was undertaken in the per protocol population investigating the treatment effect during 9 premenstrual days in the third treatment cycle. The Sum21 results of this analysis showed that the sepranolone 10 mg was significantly better than placebo (p = 0.008). Similar significant treatment effects were found for the impairment and distress scores. A significantly larger number of individuals experienced no or minimal symptoms (Sum21 <42 points) with the 10 mg sepranolone treatment compared to placebo (p = 0.020). The results indicate that there is an attenuating effect by sepranolone on symptoms, impairment, and distress in women with PMDD especially by the 10 mg dosage. Sepranolone was well tolerated, and no safety concerns were identified.
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| 8. |
- Bäckström, Torbjörn, et al.
(författare)
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Positive GABAA receptor modulating steroids and their antagonists : Implications for clinical treatments
- 2022
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Ingår i: Journal of neuroendocrinology (Print). - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 34:2
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Forskningsöversikt (refereegranskat)abstract
- GABA is the main inhibitory neurotransmitter in the brain and GABAergic transmission has been shown to be of importance for regulation of mood, memory and food intake. The progesterone metabolite allopregnanolone (Allo) is a positive GABAA receptor modulating steroid with potent effects. In humans, disorders such as premenstrual dysphoric disorder (PMDD), hepatic encephalopathy and polycystic ovarian syndrome are associated with elevated Allo levels and increased negative mood, disturbed memory and increased food intake in some individuals. This is surprising because Allo shares many properties with benzodiazepines and is mainly considered to be anxiolytic and anti-depressant. However, it is well established that, in certain individuals, GABAA receptor activating compounds could have paradoxical effects and thus be anxiogenic in low physiological plasma concentrations but anxiolytic at high levels. We have demonstrated that isoallopregnanolone (Isoallo), the 3β-OH sibling of Allo, functions as a GABAA receptor modulating steroid antagonist (GAMSA) but without any effects of its own on GABAA receptors. The antagonistic effect is noted in most GABAA subtypes investigated in vitro to date. In vivo, Isoallo can inhibit Allo-induced anaesthesia in rats, as well as sedation or saccadic eye velocity in humans. Isoallo treatment has been studied in women with PMDD. In a first phase II study, Isoallo (Sepranolone; Asarina Pharma) injections significantly ameliorated negative mood in women with PMDD compared with placebo. Several GAMSAs for oral administration have also been developed. The GAMSA, UC1011, can inhibit Allo induced memory disturbances in rats and an oral GAMSA, GR3027, has been shown to restore learning and motor coordination in rats with hepatic encephalopathy. In humans, vigilance, cognition and pathological electroencephalogram were improved in patients with hepatic encephalopathy on treatment with GR3027. In conclusion GAMSAs are a new possible treatment for disorders and symptoms caused by hyperactivity in the GABAA system.
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| 9. |
- Comasco, Erika, 1982-, et al.
(författare)
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Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder : A Proof-of-Concept Randomized Controlled Trial
- 2021
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 178:3, s. 256-265
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Premenstrual dysphoric disorder (PMDD) is a common mood disorder, characterized by distressing affective, behavioral, and somatic symptoms in the late luteal phase of the menstrual cycle. The authors investigated continuous treatment with a selective progesterone receptor modulator, ulipristal acetate (UPA), as a potential treatment for PMDD. Methods: The authors conducted an investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial in which women with PMDD (N=95) were treated with either 5 mg/day of UPA or placebo during three 28-day treatment cycles. The primary outcome was the change in premenstrual total score on the Daily Record of Severity of Problems (DRSP) from baseline to end of treatment. DRSP scores were captured by daily ratings using a smartphone application and were analyzed with linear mixed models for repeated measures. Results: The mean improvement in DR SP score after 3 months was 41% (SD=18) in the UPA group, compared with 22% (SD=27) in the placebo group (mean difference 18%; 95% CI = -29, -8). Treatment effects were also noted for the DRSP depressive symptom subscale (42% [SD=22]compared with 22% [SD=32]) and the DRSP anger/irritability subscale (47% ISD=21) compared with 23% (SD=35I), but not for the DRSP physical symptom subscale. Remission based on DRSP score was attained by 20 women in the UPA group (50.0%) and eight women in the placebo group (21.1%) (a statistically significant difference). Conclusions: If these results are replicated, UPA could be a useful treatment for PMDD, particularly for the psychological symptoms associated with the disorder.
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| 10. |
- Dehara, Marina, et al.
(författare)
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Menopausal hormone therapy and risk of sarcoidosis : a population-based nested case–control study in Sweden
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:3, s. 313-322
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Tidskriftsartikel (refereegranskat)abstract
- Sarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case–control study (2007–2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis. Dispensations of MHT were obtained from the Swedish Prescribed Drug Register before sarcoidosis diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression. Ever MHT use was associated with a 25% higher risk of sarcoidosis compared with never use (aOR 1.25, 95% CI 1.13–1.38). When MHT type and route of administration were considered together, systemic estrogen was associated with the highest risk of sarcoidosis (aOR 1.51, 95% CI 1.23–1.85), followed by local estrogen (aOR 1.25, 95% CI 1.11–1.42), while systemic estrogen-progestogen combined was associated with the lowest risk compared to never users (aOR 1.12, 95% CI 0.96–1.31). The aOR of sarcoidosis did not differ greatly by duration of MHT use. Our findings suggest that a history of MHT use is associated with increased risk of sarcoidosis, with women receiving estrogen administered systemically having the highest risk.
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