| 1. |
- Hellgren, Charlotte, et al.
(författare)
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Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy
- 2014
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 69:3, s. 147-153
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Tidskriftsartikel (refereegranskat)abstract
- Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has inhibitory function through interaction with the GABAA receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy co-vary with concurrent self-rated symptoms of depression and anxiety. Ninety-six women in pregnancy weeks 37 - 40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory (STAI-S and STAI–T). Their serum allopregnanolone was analyzed by celite chromatography and radioimmunoassay. Ten women had elevated depression scores (MADRS-S ≥ 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the lower range (39.0 ± 17.9 nmol/l vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson’s correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. In conclusion, high allopregnanolone serum concentrations may protect against depressed mood during pregnancy.
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| 2. |
- Kocoska-Maras, L., et al.
(författare)
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Cognitive function in association with sex hormones in postmenopausal women
- 2013
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Ingår i: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 29:1, s. 59-62
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.
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| 3. |
- Lundqvist, Anette, 1963-
(författare)
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Nutritional aspects of behaviour and biology during pregnancy and postpartum
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundA well-balanced nutritious diet is important for the pregnant woman and the growing fetus, as well as for their future health. Poor nutrition results from both over-consumption of energy-rich foods which can lead to a higher weight gain than is healthy and under-nutrition of essential nutrients. Food intake is regulated in complex biological systems by many factors, where steroid hormone is one factor involved.The overall aim of this thesis is to describe dietary intake, vitamin D levels, dietary information and dietary changes, and to study the relation between allopregnanolone and weight gain during pregnancy and postpartum.Methods Study I was a qualitative study with focus group interviews with 23 pregnant women. The text was analysed with content analysis. Study II was a quantitative cross-sectional study conducted in early pregnancy (n=209) with a reference group (n=206). Self-reported dietary data from a questionnaire was analysed using descriptive comparative statistics and a cluster analysis model (Partial Least Squares modelling). Study III had a quantitative longitudinal design. Vitamin D concentrations were analysed in 184 women, collected on five occasions during pregnancy and postpartum. Descriptive comparative statistics and a linear mixed model were used. Study IV was a quantitative longitudinal study with 60 women. Concentrations of allopregnanolone were analysed in gestational week 12 and 35. Descriptive and comparative statistics as well as Spearman’s correlation (rho) were used to describe the relationship between weight gain and allopregnanolone concentrations. Results The focus group interviews showed that women wanted to know more about different foods to reduce any risk for their child but the information about foods was partly up to themselves to find out. They expressedfeelingsof insecurityand guiltif they accidentallyate something“forbidden”. The recommendationswere followedas best as possiblealong withcommon sense todeal with dietchanges. The main themes were “Finding out by oneself”, “Getting professional advice when health problems occur”, “Being uncertain” and “Being responsible with a pinch of salt”. Some differences in the dietary patterns were found among the pregnant women compared to references, with less, vegetables (47 g/day), potatoes/rice/pasta (31 g/day), meat/fish (24 g/day) and intake of alcohol and tobacco/snuff but a higher intake of supplements. Bothpregnant women and referenceshad intakes offolatethrough diet45% (pregnant) and 22% (references) lower than current recommendations(500vs400g/day). Vitamin Dintake was34% lower than the recommendationsof 10mg/day. At least a third of the participants had insufficient plasma levels below 50 nmol/L of vitamin D. Season was a strong factor influencing the longitudinal pattern. Gestational week, season, total energy intake, dietary intake of vitamin D, and multivitamin supplementation over the previous 14 days were factors related to vitamin D levels. A correlation betweenallopregnanoloneconcentrations ingestationalweek 35and weight gainin weeks12–35was seen (p = 0.016). Therewas alsoa correlation betweenthe increase inallopregnanolone(weeks12–35) andweight gain(see above) (p = 0.028). ConclusionsDietary recommendations were described as contradictory and confusing and the dietary advice felt inadequate. The women faced their diet changes and sought information on their own but would have wished for more extensive advice from the midwife. The intake of vitamins essential for pregnancy was lower than recommended, which is also confirmed by low plasma levels of vitamin D in at least one third of the pregnant women. Vitamin D levels peaked in late pregnancy. Aside from gestational week and season which were related to plasma levels, intake from foods and supplements also affected the levels. Reasons for weight gain are complex and depend on many factors. Allopregnanolone is a factor that was seen to relate to the weight gain of the studied pregnant women.
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| 4. |
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| 5. |
- Ossewaarde, Lindsey, et al.
(författare)
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Menstrual cycle-related changes in amygdala morphology are associated with changes in stress sensitivity
- 2013
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 34:5, s. 1187-1193
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual increases in negative mood are thought to arise from changes in gonadal hormone levels, presumably by influencing mood regulation and stress sensitivity. The amygdala plays a major role in this context, and animal studies suggest that gonadal hormones influence its morphology. Here, we investigated whether amygdala morphology changes over the menstrual cycle and whether this change explains differences in stress sensitivity. Twenty-eight young healthy women were investigated once during the premenstrual phase and once during the late follicular phase. T1-weighted anatomical images of the brain were acquired using magnetic resonance imaging and analyzed with optimized voxel-based morphometry. To measure mood regulation and stress sensitivity, negative affect was assessed after viewing strongly aversive as well as neutral movie clips. Our results show increased gray matter volume in the dorsal part of the left amygdala during the premenstrual phase when compared with the late follicular phase. This volume increase was positively correlated with the premenstrual increase in stress-induced negative affect. This is the first study showing structural plasticity of the amygdala in humans at the macroscopic level that is associated with both endogenous gonadal hormone fluctuations and stress sensitivity. These results correspond with animal findings of gonadal hormone-mediated neural plasticity in the amygdala and have implications for understanding the pathogenesis of specific mood disorders associated with hormonal fluctuations. Hum Brain Mapp, 2013. (c) 2011 Wiley Periodicals, Inc.
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| 6. |
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| 7. |
- Boman, Karin, 1946-
(författare)
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Endometrial carcinoma : steroid hormones and receptors in relation to proliferation
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The significance of the hormonal milieu for endometrial changes is as well-known as its link with endometrial carcinoma. Unopposed oestradiol treatment is shown to increase the incidence for this cancer. Obesity leads to elevated levels of oestrogens and is a risk factor for endometrial carcinoma. An association between high tumour proliferation and prognosis is a general feature of human cancer. Tumour growth can be expressed as proliferation rate and flow cytometry (FCM) is a sensitive and reproducable method to estimate S-phase fraction (SPF) and ploidy level. Both parameters have been shown to correlate with prognosis. Sex steroid hormone levels were analysed together with clinical parameters, SPF, and receptors in established endometrial carcinoma.The study consisted of postmenopausal women with endometrial adenocarcinoma. H ormones were analysed in 127 patients, 99 were analysed for FCM and 60 for oestrogen and progesterone receptors. RIA technique was used for hormone assay of oestrone, oestradiol, progesterone, androstenedione and testosterone plasma levels. The receptors were analysed with an immunohistochemical method, and SPF and ploidy level by flow cytometry.A wide range of oestrogen concentrations was found. Some patients had levels comparable to fertile women. Strong correlations were found between body mass index, weight and depth of uterine cavity. No relations were found between receptors and SPF, apart from oestrogen- receptor positive tumours having a lower SPF when compared with receptor negative tumours. The influence of oestradiol on tumour proliferation expressed as SPF was ambiguous. SPF was increased with higher oestradiol levels in the group of peri-diploid, well-differentiated tumours, while a negative correlation was found for the peri-diploid, moderately differentiated tumours. The aneuploid and poorly differentiated tumours had a high SPF regardless of oestradiol concentration. The association between progesterone concentration and SPF was of a more general nature. Progesterone above a threshold level was related to a lower SPF in well-differentiated and moderately differentiated tumours. Thus endogenous progesterone seems to play a role in controlling the tumour’s proliferation activity, in contrast to oestradiol, that had a role which did not appear to relate to proliferation activity in any specific direction. The only stimulative association was seen in well-differentiated tumours, but SPF was still below the mean value for all diploid tumours.
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| 8. |
- Löfgren, Magnus, 1979-
(författare)
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Behavioral effects of female sex steroid hormones : models of PMS and PMDD in Wistar rats
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors. Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids. Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA). Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior. Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.
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| 9. |
- Timby, Erika, 1974-, et al.
(författare)
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Allopregnanolone, a GABA-A receptor agonist, decreases gonadotropin levels in women : a preliminary study
- 2011
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Ingår i: Gynecological Endocrinology. - : Informa Healthcare. - 0951-3590 .- 1473-0766. ; 27:12, s. 1087-1093
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABAA) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABAA receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63, p=0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABAA receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolon.
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| 10. |
- 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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