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| 3. |
- Bendix, Marie, 1971-, et al.
(author)
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Allopregnanolone and progesterone in estradiol treated severe postpartum depression and psychosis : Preliminary findings
- 2019
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In: Neurology, psychiatry and brain research. - : Elsevier. - 0941-9500. ; 34, s. 50-57
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Journal article (peer-reviewed)abstract
- Background: Postpartum affective disorders may be associated with dysregulation of gonadal steroids. We investigated peripheral levels of allopregnanolone and progesterone in a combined group of women with postpartum onset of severe depression and/or psychosis who, as previously reported, responded with rapid symptom remission during sublingual estradiol treatment. The aim was to assess differences in allopregnanolone and progesterone between patients and healthy controls at baseline, and hormonal changes during estradiol treatment and symptom remission in patients.Methods: Allopregnanolone and progesterone in serum were analyzed with radioimmunoassay before and four weeks after initiation of sublingual estradiol treatment in ten women with postpartum depression and four women with postpartum psychosis (ICD-10). Twenty-eight healthy postpartum controls were included for baseline comparison.Results: Allopregnanolone declined significantly during estradiol treatment while there was a trend for lower baseline allopregnanolone levels in patients compared with healthy postpartum controls. The ratio between allopregnanolone and progesterone was significantly lower in patients compared with controls and it remained unchanged after clinical recovery.Limitations: This study is a secondary analysis of two estradiol treatment studies based on availability of samples for the analysis of allopregnanolone. Healthy controls were assessed earlier after delivery. Data on potential confounders (somatic health, breastfeeding, other medication) were not available.Conclusions: These preliminary findings suggest that clinical recovery of severe postpartum depression and psychosis during estradiol treatment does not seem to depend on increasing levels of allopregnanolone. Differences in progesterone metabolism may constitute a risk factor for severe postnatal affective dysregulation.
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| 4. |
- Bendix, Marie, 1971-
(author)
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Neuroendocrine studies in patients with affective disorders
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Background: Affective disorders are common and a major cause for increased disability and mortality worldwide. Exogenous stressors and biological variables, including neuroendocrine factors, are assumed to contribute to an increased vulnerability to mood dysregulation. Affective disorders are highly heterogeneous and different neuroendocrine systems may play differential roles in the phenotypic expression of affective disorders in men and women.Aims: The overall aim of this thesis was to study three neuroendocrine systems in relation to underlying behavioral endophenotypes (personality traits, self-directed and interpersonal violence, and psychiatric symptoms) in patients with affective disorders.Methods: In Study I oxytocin plasma levels were assessed in 101 general psychiatric outpatients and followed-up in 36 patients after one month. Patients underwent diagnostic, symptomatic, and personality trait assessments.In Study II insulin and glucagon levels in plasma and cerebrospinal fluid (CSF) were assessed in 28 patients hospitalized after a recent suicide attempt and 19 healthy controls. Study persons were assessed regarding lifetime violence expression, psychiatric diagnoses and symptoms.In Study III serum levels of allopregnanolone, progesterone and estradiol were assessed in 14 women with severe postpartum depression and psychosis who, as previously reported, responded with rapid symptom remission during sublingual estradiol treatment. Hormonal and symptomatic assessment were performed before and after 4 weeks of estradiol treatment. 28 healthy postpartum controls were included for baseline comparison.Results: I) Plasma oxytocin levels were positively associated with personality traits of impulsiveness (monotony avoidance) and negative emotionality (psychic anxiety) with potential gender differences.II) Patients after suicide attempt had higher insulin (plasma and CSF) and lower glucagon levels (CSF) than healthy controls. Insulin levels (plasma and CSF) were higher and glucagon levels (plasma) were lower in patients and controls with higher levels of prior violence expression.III) Serum allopregnanolone decreased in women with postpartum depression and psychosis during estradiol treatment. The ratio between allopregnanolone and progesterone was significantly lower in patients than in healthy controls at baseline and it remained unchanged after symptom remission.Conclusion: Behavioral endophenotypes, rather than categorical diagnoses, of affective disorders were associated with neuroendocrine variation in three different cohorts of patients with affective disorder. Hormonal variation pointed towards an association with trait, rather than state like facets of affective behavior, constituting potential vulnerability markers for affective dysregulation.
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| 5. |
- Bergendahl, Sandra, et al.
(author)
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Lateral episiotomy or no episiotomy in vacuum assisted delivery in nulliparous women (EVA) : multicentre, open label, randomised controlled trial
- 2024
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In: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 385, s. e079014-
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Journal article (peer-reviewed)abstract
- Objective: To assess the effect of lateral episiotomy, compared with no episiotomy, on obstetric anal sphincter injury in nulliparous women requiring vacuum extraction. Design: A multicentre, open label, randomised controlled trial.Setting: Eight hospitals in Sweden, 2017-23.Participants: 717 nulliparous women with a single live fetus of 34 gestational weeks or more, requiring vacuum extraction were randomly assigned (1:1) to lateral episiotomy or no episiotomy using sealed opaque envelopes. Randomisation was stratified by study site.Intervention: A standardised lateral episiotomy was performed during the vacuum extraction, at crowning of the fetal head, starting 1-3 cm from the posterior fourchette, at a 60° (45-80°) angle from the midline, and 4 cm (3-5 cm) long. The comparison was no episiotomy unless considered indispensable.Main outcome measures: The primary outcome of the episiotomy in vacuum assisted delivery (EVA) trial was obstetric anal sphincter injury, clinically diagnosed by combined visual inspection and digital rectal and vaginal examination. The primary analysis used a modified intention-to-treat population that included all consenting women with attempted or successful vacuum extraction. As a result of an interim analysis at significance level P<0.01, the primary endpoint was tested at 4% significance level with accompanying 96% confidence interval (CI).Results: From 1 July 2017 to 15 February 2023, 717 women were randomly assigned: 354 (49%) to lateral episiotomy and 363 (51%) to no episiotomy. Before vacuum extraction attempt, one woman withdrew consent and 14 had a spontaneous birth, leaving 702 for the primary analysis. In the intervention group, 21 (6%) of 344 women sustained obstetric anal sphincter injury, compared with 47 (13%) of 358 women in the comparison group (P=0.002). The risk difference was -7.0% (96% CI -11.7% to -2.5%). The risk ratio adjusted for site was 0.47 (96% CI 0.23 to 0.97) and unadjusted risk ratio was 0.46 (0.28 to 0.78). No significant differences were noted between groups in postpartum pain, blood loss, neonatal outcomes, or total adverse events, but the intervention group had more wound infections and dehiscence.Conclusions: Lateral episiotomy can be recommended for nulliparous women requiring vacuum extraction to significantly reduce the risk of obstetric anal sphincter injury. Trial registration: ClinicalTrials.gov NCT02643108.
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| 8. |
- Bäcklund, Nils, 1987-, et al.
(author)
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Salivary cortisol and cortisone can circumvent confounding effects of oral contraceptives in the short synacthen test
- 2024
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In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 109:7, s. 1899-1906
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Journal article (peer-reviewed)abstract
- Context: Adrenal insufficiency (AI) is usually diagnosed by low plasma cortisol levels following a short Synacthen test (SST). Most plasma cortisol is bound to corticosteroid-binding globulin, which is increased by estrogen in combined estrogen-progestin oral contraceptives (COCs). Women with AI using COCs are therefore at risk of having an apparently normal plasma cortisol level during SST, which would not adequately reflect AI.Objective: To test whether salivary cortisol or cortisone during SST is more robust against the COC effect and to calculate the lower reference limits (LRLs) for these to be used as tentative diagnostic cutoffs to exclude AI.Methods: Forty-one healthy women on COCs and 46 healthy women without exogenous estrogens performed an SST with collection of plasma and salivary samples at 0, 30, and 60 min after Synacthen injection. The groups were compared using regression analysis with age as covariate and the LRLs were calculated parametrically.Results: SST-stimulated plasma cortisol levels were significantly higher in the COC group versus controls, while mean salivary cortisol and cortisone levels were slightly lower in the COC group. Importantly, COC use did not significantly alter LRLs for salivary cortisol or cortisone. The smallest LRL difference between groups was seen for salivary cortisone.Conclusion: Salivary cortisol and especially salivary cortisone are considerably less affected by COC use than plasma cortisol during SST. Due to similar LRLs, a common cutoff for salivary cortisol and cortisone during SST can be used to exclude AI in premenopausal women irrespective of COC use.
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| 11. |
- N-Wihlbäck, Anna-Carin, et al.
(author)
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[Basic investigation of infertility]
- 2004
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:45, s. 3525-3529
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Journal article (peer-reviewed)
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| 12. |
- Timby, Erika, 1974-
(author)
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Allopregnanolone effects in women : clinical studies in relation to the menstrual cycle, premenstrual dysphoric disorder and oral contraceptive use
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Background: Premenstrual dysphoric disorder (PMDD) affects 3–8% of women in fertile ages. Combined oral contraceptives (OCs) are widely used and some users experience adverse mood effects. The cyclicity of PMDD symptoms coincides with increased endogenous levels of allopregnanolone after ovulation. Allopregnanolone enhances the effect of γ-aminobutyric acid (GABA) on the GABAA receptor, the principal inhibitory transmitter system in the brain. The sensitivity to other GABAA receptor agonists than allopregnanolone (i.e. benzodiazepines, alcohol and the 5 β epimer to allopregnanolone, pregnanolone) has been reported to depend on menstrual cycle phase and/or PMDD diagnosis. Isoallopregnanolone, the 3 β epimer to allopregnanolone, has previously been used to verify specific allopregnanolone GABAA receptor effects. Saccadic eye velocity (SEV) is a sensitive and objective measurement of GABAA receptor function. Aims: To study the pharmacological effects, and any effect on gonadotropin release, of intravenous allopregnanolone in healthy women. A second aim was to explore whether allopregnanolone sensitivity differs over the menstrual cycle or during OC use in healthy women, and thirdly in PMDD patients. Methods: Ten women were challenged with a cumulative dose of intravenous allopregnanolone in the follicular phase of the menstrual cycle. The effect on FSH and LH was compared to women exposed to isoallopregnanolone. A single dose of allopregnanolone was administered once in the follicular phase and once in the luteal phase in another ten healthy women and in ten PMDD patients, and additionally in ten women using OCs. Repeated measurements of SEV, subjectively rated sedation and serum concentrations after allopregnanolone injections were performed in all studies. Results: Allopregnanolone dose-dependently reduced SEV and increased subjectively rated sedation. Healthy women had a decreased SEV response in the luteal phase compared to the follicular phase. By contrast, PMDD patients had a decreased SEV response and subjectively rated sedation response to allopregnanolone in the follicular phase compared to the luteal phase. There was no difference in the SEV response to allopregnanolone between women using oral contraceptives and healthy naturally cycling women. Allopregnanolone decreased serum levels of FSH and LH whereas isoallopregnanolone did not affect FSH and LH levels. Conclusion: Intravenous allopregnanolone was safely given and produced a sedative response in terms of SEV and subjectively rated sedation in women. The sensitivity to allopregnanolone was associated with menstrual cycle phase, but in the opposite direction in healthy women compared to PMDD patients. The results suggest mechanisms of physiological tolerance to allopregnanolone across the menstrual cycle in healthy women and support that PMDD patients have a disturbed GABAA receptor function. In addition, one of our studies suggests that allopregnanolone might be involved in the mechanism behind hypothalamic amenorrhea.
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| 14. |
- Timby, Erika, 1974-, et al.
(author)
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Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls — a pilot study
- 2016
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 233:11, s. 2109-2117
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Journal article (peer-reviewed)abstract
- In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABA(A) receptor, enhancing the effect of gamma-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABA(A) receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls.This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients.Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABA(A) receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data.There was a highly significant group x phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018).The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.
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| 15. |
- Wiberg-Itzel, Eva, et al.
(author)
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Lactate in Amniotic Fluid : Predictor of Labor Outcome in Oxytocin-Augmented Primiparas' Deliveries
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
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Journal article (peer-reviewed)abstract
- BACKGROUND: One of the major complications related to delivery is labor dystocia, or an arrested labor progress. Many dystocic deliveries end vaginally after administration of oxytocin, but a large numbers of women with labor dystocia will undergo a long and unsafe parturition. As a result of the exertion required in labor, the uterus produces lactate. The uterine production of lactate is mirrored by the level of lactate in amniotic fluid (AFL).OBJECTIVES: To evaluate whether the level of AFL, analysed in a sample of amniotic fluid collected vaginally at arrested labor when oxytocin was needed, could predict labor outcome in nulliparous deliveries.METHODS: A prospective multicentre study including 3000 healthy primiparous women all with a singleton pregnancy, gestational age 37 to 42 weeks and no maternal /fetal chronic and/or pregnancy-related conditions. A spontaneous onset of labor, regular contractions and cervical dilation ≥ 3 cm were required before the women were invited to take part in the study.RESULTS: AFL, analysed within 30 minutes before augmentation, provides information about delivery outcome. Sensitivity for an acute cesarean section according to high (≥10.1mmol/l) or low (< 10.1mmol/l) AFL values was 39.0% (95% CI; 27-50), specificity 90.3% (95% CI; 87-93) PPV 37.3% (95% CI; 27-48) and NPV was 91.0% (95% CI; 88-93). The overall percentage of correct predictions of delivery outcome when the AFL level was used was 83.7%. Deliveries with a high AFL-level correlated with delivery time >12h (p = 0.04), post-partum fever (>38°C, p = 0.01) and post-partum haemorrhage >1.5L (p = 0.04).CONCLUSION: The AFL is a good predictor of delivery outcome in arrested nulliparous deliveries. Low levels of AFL may support the decision to continue a prolonged vaginal labor by augmentation with oxytocin. A high level of AFL correlates with operative interventions and post-partum complications.
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| 16. |
- Wiberg-Itzel, Eva, et al.
(author)
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Level of lactate in amniotic fluid and its relation to the use of oxytocin and adverse neonatal outcome
- 2014
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley-Blackwell. - 0001-6349 .- 1600-0412. ; 93:1, s. 80-85
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Journal article (peer-reviewed)abstract
- ObjectiveTo assess whether the frequency of adverse neonatal outcome at delivery is related to the level of lactate in amniotic fluid and to the use of oxytocin. DesignProspective observational study. SettingSoder Hospital, Stockholm, Sweden. PopulationSeventy-four women in active labor with a gestational age 36weeks and mixed parity. MethodsLevels of lactate in amniotic fluid were analyzed bedside from an intrauterine catheter every 30min during labor. Deliveries were divided into groups with and without oxytocin. Main outcome measuresThe frequency of adverse neonatal outcome at delivery. ResultOf the deliveries 13.5% (10/74) concluded with an adverse neonatal outcome. The levels of lactate in amniotic fluid increased during labor, more so in deliveries where oxytocin was used. In the group with an adverse neonatal outcome, the level of lactate in amniotic fluid was significantly higher in the final sample before delivery (p=0.04). In 18 deliveries, stimulation with oxytocin was temporarily halted for at least 30min due to overly stimulated labor contractions. A decreasing level of lactate in amniotic fluid was shown within a median 5%/30min. In the group where the administration of oxytocin was halted, there was no adverse neonatal outcome. ConclusionThe frequency of adverse neonatal outcome was associated with the level of lactate in amniotic fluid and with the use of oxytocin. The level of lactate in amniotic fluid may be an additional valuable tool when oxytocin is administered during labor.
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| 17. |
- Wiberg-Itzel, Eva, et al.
(author)
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The association between dystocic labors and circadian signals
- 2013
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In: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 208:1, s. S139-S140
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Journal article (other academic/artistic)abstract
- Objective: Human deliveries commonly occur during the dark period of the day. Melatonin hormone is released as a circadian signal from the human brain, and has been shown to have a synergistic effect together with oxytocin in facilitating the uterine contractions during labor. Melatonin is inhibited by light and energized by dark. During winter the numbers of light hours per day in Sweden are few, but during the summer they are numerous. In Tanzania there is no season difference.Study Design: In 2011,452 Tanzanian and 919 Swedish healthy primiparas with a normal pregnancy and a spontaneous onset of labor were included in the study. Time and date together with the length and outcome of delivery were studied, and a statistical comparison was made.Results: 47% of the Swedish deliveries started in early morning, and 48% ended at midnight. The median time of active labor was significantly longer during the summer season (May to August vs. November to February, p=0.05). The frequency of labor dystocia was increased during summer season, and significantly more in the region on Sweden with midnight sun (29 vs. 40%, p=0.03).48% of Tanzania labors started at midnight, and 41% ended at lunch time. Among Tanzanian women, no difference in median time of active delivery (p=0.5) or the frequency of dystocic labors was shown, according to season of the year (13.7 vs. 14.1 %, p=0.8).Oxytocin was used in 68% of the Swedish deliveries, and the use was higher during the summer season. Oxytocin was used in 31% of the Tanzanian deliveries. No difference in use of oxytocin was shown according to season.Conclusion: In this project a variation of labor dystocia according to season of the year has been studied. A significant overrepresentation of prolonged and dystocic deliveries were shown during the summer season in Sweden. This new knowledge may be of a great importance, when handling a dysfunctional labor.
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| 18. |
- Wiberg-Itzel, Eva, et al.
(author)
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The dysfunctional labor study
- 2014
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 210:1, s. S328-S329
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Journal article (other academic/artistic)
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| 19. |
- Wihlbäck, Anna-Carin, et al.
(author)
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Allopregnanolone serum concentrations and neurosteroid sensitivity during withdrawal from postmenopausal hormone therapy
- 2007
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In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 23:10, s. 590-596
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Journal article (peer-reviewed)abstract
- BACKGROUND: We have previously compared the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during sequential treatment with estradiol-only (E2-only) and estradiol together with progesterone (E2 + P) in postmenopausal women. The aim of the present study was to evaluate the pharmacodynamic response to pregnanolone during withdrawal from E2-only treatment and during withdrawal from treatment with E2 + P. METHOD: Twenty-six postmenopausal women were administered hormone therapy (HT) in a randomized, double blinded, placebo-controlled, crossover study. The women received 2 mg oral estradiol continuously during two 28-day cycles and 800 mg vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle. The pharmacodynamic response to pregnanolone was assessed during the last week of the last treatment cycle and 48 h after termination of the last treatment cycle (withdrawal) by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye movements. RESULTS: During E2-only withdrawal the pregnanolone sensitivity was reduced compared with E2-only treatment. Pregnanolone sensitivity remained unaltered between the combined E2 + P treatment regimen and the withdrawal from these steroids. CONCLUSION: The study indicates that withdrawal from E2-only treatment might change neurosteroid sensitivity, whereas the immediate withdrawal from E2 + P results in unchanged neurosteroid sensitivity.
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| 22. |
- Wihlbäck, Anna-Carin
(author)
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Kroppsklåda och hudförändringar
- 2022. - 2
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In: Problemorienterad gynekologi och obstetrik. - Stockholm : Liber. - 9789147141906 ; , s. 330-339
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Book chapter (other academic/artistic)
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| 23. |
- Wihlbäck, Anna-Carin, 1962-
(author)
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Ovarian hormones and effects in the brain : studies of neurosteroid sensitivity, serotonin transporter and serotonin2A receptor binding in reproductive and postmenopausal women
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Background: Estrogen has been reported to enhance well-being and quality of life during the climacteric phase. In women with an intact uterus estrogen treatment is always combined with progestins in order to protect the endometrium from hyperplasia and malignancies. However, in certain women the addition of progestins causes cyclicity in negative mood symptoms and physical symptoms similar to those encountered during ovulatory cycles in women with premenstrual dysphoric disorder (PMDD). The ovarian hormones estradiol and progesterone have profound effects on a number of neurotransmitter systems in the brain, such as the gamma aminobutyric acid (GABA) system and the serotonergic system. Progesterone metabolites, such as allopregnanolone and pregnanolone (also referred to as neurosteroids) modify the GABAA receptor in the central nervous system (CNS) and enhance GABAergic inhibitory transmission. Neurosteroid sensitivity in human studies can be studied by saccadic eye movement measurements using pharmacodynamic challenges with pregnanolone. Altered neurosteroid sensitivity has been suggested as a possible contributory factor to the progesterone/progestin-induced adverse mood effects of hormone replacement therapy (HRT). There is also evidence of estrogen treatment affecting the serotonergic system in postmenopausal women, although progestin addition has been less well studied. Aims and method: The aim was to investigate whether the negative mood symptoms experienced during the progestin or progesterone phase of HRT were associated with changes in neurosteroid sensitivity, or changes in platelet serotonin uptake site (transporter) and serotonin2A (5-HT2A) receptor binding. The intention was also to investigate whether hormonal changes during the normal menstrual cycle affect these peripheral serotonergic parameters. Postmenopausal women with climacteric symptoms were given HRT in two randomized, double-blinded, placebo-controlled crossover studies. The women received 2 mg estradiol (E2) continuously during 28- day cycles. Synthetic progestins or natural progesterone were added sequentially during the last 14 days, and compared to a placebo addition. Before treatment, as well as during the last week of each treatment cycle the pharmacodynamic response to pregnanolone was assessed using saccadic eye movement measurements. Throughout the studies daily symptom ratings were made. In the study regarding synthetic progestins, platelet serotonin transporter and 5-HT2A receptor binding were assayed before entering the study, as well as during the last week of each treatment cycle. In the study on reproductive women, blood samples were collected for analysis of platelet serotonin transporter and 5-HT2A receptor binding at six different points in time during the menstrual cycle. Results and conclusion: The addition of synthetic progestins to estrogen treatment increased negative mood symptoms and physical symptoms, whereas positive symptoms decreased. The addition of progestins also increased the sensitivity to pregnanolone. The addition of natural progesterone to estrogen treatment increased the sensitivity to pregnanolone. However, in this study the pregnanolone sensitivity was enhanced also during estrogen treatment. Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity. Thus, it is evident that mood deterioration during HRT is associated with altered neurosteroid sensitivity. Platelet serotonin transporter and 5-HT2A receptor binding did not change during the different treatment conditions in HRT. Thus, we were unable to explain the negative mood changes of HRT by use of these peripheral serotonergic parameters. In the study on reproductive women however, it was clear that the serotonergic variables did change during the menstrual cycle. Binding to the serotonin transporter was higher in the late follicular phase than in the ovulatory, early luteal or mid-luteal phases. Binding to the 5-HT2A receptor was higher in the early follicular phase and the early luteal phase than in the mid-luteal phase. These findings may provide a link between the ovarian steroids, and the GABAergic and serotonergic neurotransmitter systems, which in turn, could explain part of the specific vulnerability that women have for the development of adverse mood effects during HRT, mood and anxiety disorders and for the deterioration of mood so frequently seen during the luteal phase.
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| 24. |
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