Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: Elevated blood testosterone concentrations compared to normal controls

Baischer, Wolfgan; Koinig, G.; Hartmann, Beda; Huber, Johannes; Langer, Gerhard

doi:10.1016/0306-4530(94)00081-k

Cited by 113 publications

(61 citation statements)

References 16 publications

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“…In conclusion, the findings reported here contribute to identifying the neural substrates associated with the longstanding clinical observation that changes in women's reproductive system are related to mood fluctuations and MDD symptomology (Rabin et al, 1990;Baischer et al, 1995;Rubinow and Schmidt, 1996;Harlow et al, 2003;Payne, 2003;Roca et al, 2003;Spinelli, 2005;Payne et al, 2009). Using a mild visual stress fMRI paradigm that reliably activates stress circuitry, we demonstrated a role for estradiol in modulating stress circuitry activity in healthy women and found evidence for the disruption of this hormone-brain pathway in major depression.…”

Section: Discussionmentioning

confidence: 93%

“…Throughout the lifecourse, changes in women's reproductive status have been associated with increased risk for mood disturbance and MDD (Rabin et al, 1990;Baischer et al, 1995;Schmidt, 1996, 2006;Harlow et al, 2003;Payne, 2003;Roca et al, 2003;Spinelli, 2005;Payne et al, 2009;Freeman et al, 2014). MDD incidence increases with pubertal onset in females (Angold and Costello, 2006), chronic use of oral contraceptives (Young et al, 2007), the postpartum period (Bloch et al, 2000;Brummelte and Galea, 2010), and perimenopause (Schmidt and Rubinow, 2009).…”

Section: Introductionmentioning

confidence: 99%

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17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

Jacobs

Holsen

Lancaster

et al. 2014

Neuropsychopharmacol

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Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17b-estradiol (E 2 ) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E 2 during the menstrual cycle, we conducted a within-person repeatedmeasures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E 2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E 2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E 2 conditions were attenuated under high E 2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

Jacobs

Holsen

Lancaster

et al. 2014

Neuropsychopharmacol

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“…The reason for the gender-specific changes in the high-frequency spindles in the course of depression is not known, but it might be due to the influence of sex steroids as this frequency range is also mainly affected by the menstrual cycle (Driver et al, 1996) and by sex steroids like progesterone (Friess et al, 1997). As alterations in the concentration of sex steroids are observed during depression (Baischer et al, 1995;Toren et al, 1996), an interaction between endocrine chances and sleep-EEG changes in the course of depression seems likely. For SSRIs like paroxetine, it is suggested that their action depends on adaptive changes of 5-HT receptor function, especially a desensitization of pre-and postsynaptic 5-HT 1A -receptors and postsynaptic 5-HT 2 -receptors (De Vry, 1995).…”

Section: Discussionmentioning

confidence: 99%

State Markers of Depression in Sleep EEG: Dependency on Drug and Gender in Patients Treated with Tianeptine or Paroxetine

Murck

Nickel

Künzel

et al. 2003

Neuropsychopharmacol

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Tianeptine enhances while paroxetine inhibits serotonin reuptake into neurons; however, both show an antidepressive action. A subgroup of 38 depressed patients from a drug trial comparing the efficacy of tianeptine with that of paroxetine was studied with regard to their effects on sleep regulation, especially in relation to treatment response. We recorded sleep EEGs at day 7 and day 42 after the start of treatment with either compound, which allows measurement of changes due to the antidepressive medication in relation to the duration of treatment. Spectral analysis of the non-REM sleep EEG revealed a strong decline in the higher sigma frequency range (14-16 Hz) in male treatment responders independent of medication, whereas nonresponders did not show marked changes in this frequency range independent of gender. The patients receiving paroxetine showed less REM sleep and more intermittent wakefulness compared to the patients receiving tianeptine. REM density after 1 week of treatment was a predictor of treatment response in the whole sample. Psychopathological features with regard to the score in single items of the HAMD revealed predictive markers for response, some of which were opposite in the gender groups, especially those related to somatic anxiety. Changes in REM density were inversely correlated to the changes in HAMD in the paroxetine, but not the tianeptine, group. Our data suggest the importance of taking gender into account in the study of the biological effects of drugs. The study further points to the importance of the higher sigma frequency range in the sleep EEG of non-REM sleep and REM density as a marker of treatment response.

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“…25 A perimenopausa é considerada um período de grande variabilidade hormonal. Os níveis de FSH (maiores ou menores) durante esse período podem funcionar como indicador do comprometimento da função ovariana, 26 por vezes precedendo às flutuações estrogênicas.…”

Section: Discussionunclassified

Associação entre depressão na perimenopausa e níveis séricos de estradiol e hormônio folículo-estimulante

Soares

Almeida

2000

Rev. Bras. Psiquiatr.

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Objetivos: A perimenopausa é freqüentemente associada ao surgimento de alterações físicas e emocionais. Estudos prévios indicam uma associação entre variações dos hormônios folículo-estimulante (FSH), luteinizante (LH) bem como de estrógenos e o surgimento de transtornos do humor, particularmente depressão. Este estudo investigou a correlação entre mudanças nos níveis de estradiol (E2) e FSH e a sintomatologia depressiva em mulheres na perimenopausa. Métodos: Cinqüenta mulheres foram recrutadas nos atendimentos de uma clínica de menopausa e de um serviço psiquiátrico para realização de ensaio clínico com uso de 17 b-estradiol ou placebo. Selecionaram-se mulheres em perimenopausa (idade entre 40 e 55 anos, presença de alterações vasomotoras, irregularidade menstrual nos últimos 6 meses e/ou amenorréia há no máximo 12 meses, níveis de FSH>20 UI/L) e com diagnóstico de transtorno depressivo pelo DSM-IV (transtorno depressivo maior, transtorno distímico ou transtorno depressivo sem outra especificação). Dosagens séricas iniciais e finais (semana 12) de FSH e E2, bem como avaliações da sintomatologia depressiva (escores da MADRS) foram analisadas e suas correlações investigadas. Resultados: As pacientes apresentaram mudanças (p<0,05) entre os níveis séricos de FSH e E2 colhidos pré e pós-intervenção (placebo ou 17 b-estradiol). Observou-se, também, mudança significativa na sintomatologia depressiva (p<0,05). Houve correlação significativa entre as mudanças na sintomatologia depressiva e as mudanças nos níveis de E2 (r de Pearson=0,436, p=0,003) e de FSH (r= 0,554, p<0,001), independentemente do tipo de tratamento empregado. Conclusões: Embora limitado pelo tamanho da amostra e a subpopulação estudada, este estudo preliminar identificou uma correlação significativa entre sintomatologia depressiva e níveis séricos de FSH e E2. Seguimentos populacionais prospectivos poderão esclarecer o papel da variabilidade hormonal no surgimento/exacerbação dos transtornos depressivos na perimenopausa.Climatério. Perimenopausa. Depressão. Estrógenos. Diagnóstico. Tratamento. MADRS.Objectives: Previous studies suggest that the perimenopause is a period of increased risk for physical and emotional disturbances. The intense fluctuation in hormone levels during the perimenopause has been associated with the presence of depressive symptoms. The present study investigated the association between levels of estradiol (E2) and follicle-stimulating hormone (FSH) and the severity of depressive symptoms of women in the perimenopause. Methods: Fifty perimenopausal women (age: 40-55 years, all meeting DSM-IV criteria for depressive disorders [major depressive disorder, dysthymia or depressive disorders NOS], with irregular periods and FSH levels > 20 IU/L) were selected from a larger sample of patients attending specialized gynecologic (n=101) and psychiatric (n=75) outpatient services. They were randomized to receive treatment with patches of placebo or 17 b-estradiol for 12 weeks. Serum levels of estradiol and FSH, and scores on the Montgomery-Å...

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Hypothalamic-pituitary-gonadal axis in depressed premenopausal women: Elevated blood testosterone concentrations compared to normal controls

Cited by 113 publications

References 16 publications

17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

State Markers of Depression in Sleep EEG: Dependency on Drug and Gender in Patients Treated with Tianeptine or Paroxetine

Associação entre depressão na perimenopausa e níveis séricos de estradiol e hormônio folículo-estimulante

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