The hypothalamic–pituitary–gonadal axis in mood disorders

Abstract

This article has demonstrated that stress and HPA axis activation affect the reproductive axis. Despite similarities in the HPA axis picture between women with major depression and those with hypothalamic amenorrhea and exercise or nutritional amenorrhea, no abnormalities in LH secretion have been documented in major depression. Lower estradiol in the follicular phase in depressed women and lower testosterone in depressed men however, have been observed [81, 92]. Although PMS would appear to be the best candidate for a mood disorder associated with abnormalities in reproductive hormones, no abnormalities in LH, estradiol or progesterone have been documented in PMS either [62]. Similarly, blockade of progesterone appears to be ineffective as a treatment for PMS [79]. Complete elimination of monthly cycling with leuprolide improves mood, however. No published studies have examined women with major depression to determine whether leuprolide will exacerbate or improve depressive symptoms. Some studies suggest beneficial effects of estrogen on mood in postmenopausal women, but no placebo controlled studies have explored estrogen augmentation in the treatment of major depression in either post- or premenopausal women, although estrogen is beneficial in women with perimenopause-related mood disorders [78].

Antisense Oligodeoxynucleotides for Estrogen Receptor-β and α Attenuate Estradiol's Modulation of Affective and Sexual Behavior, Respectively

“…The lifetime prevalence rates for anxiety and depression disorders among women are approximately twice than that seen in men (Breslau et al, 1995;Earls, 1987;Kessler et al, 1993Kessler et al, , 1994Nolen-Hoeksema, 1987;Schneier et al, 1992; reviewed in Seeman, 1997;Young, 1998;Young and Korszun, 2002). Studies in humans suggest that differences in ER isoform expression in the brain may have some functional importance for affective disorders and efficacy in their treatment (Osterlund and Hurd, 2001;Osterlund et al, 2000Osterlund et al, , 2005.…”

3α-hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors

“…Depression and schizophrenia are often characterized by aberrant stress response and/or diminished activity of the reproductive axis Rupprecht et al, 2001;Seeman 2002;Young and Korszun, 2002). Given that 3α,5α-THP mitigates HPA responses, and there are sex differences in 3α,5α-THP and stress responsiveness, whether 3α, 5α-THP is a neuroendocrine mediator that underlies sex/hormonal differences in responses to behavioral/environmental stimuli is of interest.…”

“…More women than men have mood disorders, which can be linked to hormonal status (Young and Korszun, 2002). Premenstrual syndrome, postpartum depression, and associated psychoses, are defined by psychiatric disturbances with menstruation or parturition (when 3α,5α-THP levels decrease precipitously; Freeman et al, 2002;Young and Korszun, 2002).…”

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

“…A long history of clinical evidence implicates HPA-and HPG-axis dysregulation in the development of mood disorders (Plotsky et al, 1998;Young and Korszun, 2002;Nemeroff et al, 1984). 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).…”