Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a genome-wide association study (GWAS) of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank.

The analysis included 232 993 women aged 39–71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD.

GWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause [top rs77322567, odds ratio (OR) = 0.78, p = 7.7 × 10−15]. Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression (rg = 0.231, s.e. = 0.055, p = 2.8 × 10−5). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications.

These results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3) are effective treatments for hot flashes.

Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression.

Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression.

We found that early life adversity significantly impaired the metabolic response to pioglitazone. Effects on depressive symptoms did not reach significance, but nonetheless suggested that pioglitazone could mitigate the depressant effects of childhood adversity, only among those insulin resistant at baseline.

We conclude that a history of early life adversity may impair the body’s ability to respond to insulin sensitizing pharmacotherapy, and furthermore that its contribution to resistant depression may function in part via the generation of an insulin resistant phenotype.

The aim of this study was to develop a mathematical model of the hypothalamo-pituitary-gonadal axis that would reflect available data in humans.

A model of hormonal relationships at the early follicular and midluteal phases of the human menstrual cycle is proposed.

Two distinct temporal patterns of oscillatory behavior have been demonstrated for both pituitary and gonadal steroids in the early follicular phase: first, rapid oscillations in gonadotropin releasing hormone, follicle stimulating hormone, and luteinizing hormone (Q∼1 hour) that were an immediate consequence of the programmed equations. Second, there were slower, undulating, emergent rhythms in luteinizing hormone and follicle stimulating hormone, and also in estrogen, having oscillatory periods of 2–12 hours. There was also a longer-period (Q2–3 days) emergent rhythm in progesterone. In the mid-luteal phase, estrogen and progesterone rhythms were correlated, and all hormones showed an ∼6-hour periodicity.

To our knowledge, the oscillatory behavior of peripheral sex steroids in the follicular phase has not been previously noted.