Tibolone improves depression in women through the menopause transition: A double-blind randomized controlled trial of adjunctive tibolone

Kulkarni, Jayashri; Gavrilidis, Emorfia; Thomas, Natalie; Hudaib, Abdul Rahman; Worsley, Roisin; Thew, Caroline; Bleeker, Caitlin; Gurvich, Caroline

doi:10.1016/j.jad.2018.04.103

Cited by 30 publications

(18 citation statements)

References 29 publications

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“…In line with this, the synthetic selective agonist of ER-β WAY-200070 was suggested to act as an anxiolytic and antidepressant in mice ( Hughes et al , 2008 ). However, the study of this compound did not progress to the clinical phase, while tibolone, a synthetic steroid acting on ER-β but preferably ER-α and having also progestogenic and androgenic effects, has shown preliminary evidence of improving depressive symptoms during the menopause transition ( Kulkarni et al , 2018 ).…”

Section: Genetic Analysis For Drug Repositioning and Development Of Nmentioning

confidence: 99%

Genetics and major depressive disorder: clinical implications for disease risk, prognosis and treatment

Fabbri

Montgomery

Lewis

et al. 2020

International Clinical Psychopharmacology

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In the post-genomic era, genetics has led to limited clinical applications in the diagnosis and treatment of major depressive disorder (MDD). Variants in genes coding for cytochrome enzymes are included in guidelines for assisting in antidepressant choice and dosing, but there are no recommendations involving genes responsible for antidepressant pharmacodynamics and no consensus applications for guiding diagnosis or prognosis. However, genetics has contributed to a better understanding of MDD pathogenesis and the mechanisms of antidepressant action, also thanks to recent methodological innovations that overcome the challenges posed by the polygenic architecture of these traits. Polygenic risk scores can be used to estimate the risk of disease at the individual level, which may have clinical relevance in cases with extremely high scores (e.g. top 1%). Genetic studies have also shed light on a wide genetic overlap between MDD and other psychiatric disorders. The relationships between genes/pathways associated with MDD and known drug targets are a promising tool for drug repurposing and identification of new pharmacological targets. Increase in power thanks to larger samples and methods integrating genetic data with gene expression, the integration of common variants and rare variants, are expected to advance our knowledge and assist in personalized psychiatry.

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Section: Genetic Analysis For Drug Repositioning and Development Of Nmentioning

confidence: 99%

Genetics and major depressive disorder: clinical implications for disease risk, prognosis and treatment

Fabbri

Montgomery

Lewis

et al. 2020

International Clinical Psychopharmacology

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“…Tibolone is a synthetic steroid with a mixed hormonal profile which has shown benefit in treating perimenopausal depression. 6 Tibolone can cause minor intermenstrual bleeding, but does not cause increased breast density. 6 Bioidentical hormones are compounds synthesised to resemble ovarian hormones.…”

Section: Drug or 'Biological' Treatmentsmentioning

confidence: 99%

“…6 Tibolone can cause minor intermenstrual bleeding, but does not cause increased breast density. 6 Bioidentical hormones are compounds synthesised to resemble ovarian hormones. There are limited safety and dosing data on these compounds which are not recommended by the International Menopause Society.…”

Section: Drug or 'Biological' Treatmentsmentioning

confidence: 99%

Perimenopausal depression - an under-recognised entity

Kulkarni¹

2018

Aust Prescr

Self Cite

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There is a high rate of suicide in women aged 45-54 years. This may be related to the biological changes associated with the menopause. Perimenopausal depression may present with symptoms that differ from those of typical depression. Management can include psychotherapy and other non-drug interventions. If drug treatment is indicated, it may be hormone replacement therapy, an antidepressant or both. anxiety symptoms for the first time in their mid-40s are actually experiencing depression related to the perimenopausal hormone fluctuations. Similarly, women who experience an exacerbation of a previously well-controlled depression may also be experiencing a perimenopausal relapse.

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“…Other studies also found anti-manic effects in women with bipolar disorder after SERM treatment (Amrollahi et al, 2011;Yildiz, Guleryuz, Ankerst, Öngür, & Renshaw, 2008;Zarate et al, 2007). A small number of studies investigating the use of estrogen as an adjunct to antidepressant therapy specifically for perimenopausal women and reported positive results (e.g., Kulkarni et al, 2018; for a review see Worsley et al, 2012).…”

Section: Sex Hormones and Psychosismentioning

confidence: 99%

Antipsychotic effects of sex hormones and atypical hemispheric asymmetries

Hodgetts

Hausmann

2020

Cortex

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Functional cerebral asymmetries (FCAs) are a fundamental principle of brain organisation. While specific patterns of asymmetry are characteristic of healthy human brains, atypical or reduced FCAs have been reported for several psychotic disorders, including schizophrenia and mood disorders. However, it is unclear whether atypical FCAs reflect a predisposition to psychotic disorders or a compensatory neural strategy for the progressive structural and functional changes in the brain associated with psychosis. A separate stream of research has demonstrated the antipsychotic effects of sex hormones in clinical populations. Moreover, modern neuroscience has shown that sex hormones, particularly estrogen and progesterone, can affect FCAs due to their organising effects (e.g. during prenatal development), and also by their activating effects throughout life (e.g. in younger women during the menstrual cycle or in post-menopausal women as a consequence of hormone therapy). By combining these research streams, this narrative literature review explores the relationship between the neuromodulatory properties of estrogen, FCAs and psychotic and psychotic-like symptoms. This research is not only of theoretical interest for the understanding of FCAs and psychotic symptoms, but might also be of clinical relevance for the development of stratified treatment approaches for women and men suffering from psychosis and mood disorders.

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Tibolone improves depression in women through the menopause transition: A double-blind randomized controlled trial of adjunctive tibolone

Cited by 30 publications

References 29 publications

Genetics and major depressive disorder: clinical implications for disease risk, prognosis and treatment

Genetics and major depressive disorder: clinical implications for disease risk, prognosis and treatment

Perimenopausal depression - an under-recognised entity

Antipsychotic effects of sex hormones and atypical hemispheric asymmetries

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