Neuroendocrine Changes during Menopausal Transition

Abstract

Menopause is the permanent cessation of menstrual cycles following the loss of ovarian follicular activity. Quality of life of postmenopausal woman is the result of a series of psychobiological transformations, that see in the reduction of sex hormones and steroids the etiopathogenetic determinant moment. Symptoms of menopause range from somatic side such as metabolic changes, increased cardiovascular disease, irregular vaginal bleeding, urogenital symptoms, vaginal dryness, osteoporosis and risk of bones fractures to changes of central nervous system as vasomotor symptoms, sleep disruption, mood changes, migraine, sexual dysfunctions. It is fundamental to know the mechanisms underlying changes in the central nervous system during menopause, related to hypoestrogenism, to be able to create appropriate target therapy for patients, improving their quality of life. In fact, the central nervous system is now one of the major targets of sex steroids that cannot be achieved disregard when dealing with the problem of choice of a particular type of MHT.

Pharmacological, Neurochemical, and Behavioral Mechanisms Underlying the Anxiolytic- and Antidepressant-like Effects of Flavonoid Chrysin

“…Anxiety symptoms in women are associated with a reduction in steroid hormones, such as estradiol and progesterone, and its reduced metabolite allopregnanolone in the peripheral and CNS, which may occur pre-menstruation, post-partum, and during the transition to menopause stage [ 80 , 81 ]. These steroid hormones may modulate several neurotransmission systems, such as the serotoninergic, noradrenergic, dopaminergic, and GABAergic [ 82 ]; therefore, some of these hormones have been proposed as novel groups of anxiolytic drugs for treating particular anxiety and depression disorders associated with reduced concentrations of steroid hormones [ 83 ]. It has recently been proposed that the flavonoid chrysin mimics some of the pharmacological effects of neurosteroids in female rats [ 37 ].…”

Considerations of Timing Post-ovariectomy in Mice and Rats in Studying Anxiety- and Depression-Like Behaviors Associated With Surgical Menopause in Women

“…Ovarian hormones, estradiol, and progesterone, regulate several neurochemical processes in brain structures involved in the physiopathology of anxiety and depression, such as the prefrontal cortex, hypothalamus, amygdala, septal nucleus, and hippocampus (Giannini et al, 2021). Studies among laboratory animals and humans have reported that progesterone and its reduced metabolite allopregnanolone target the GABA A receptor and facilitate the activation of the GABAergic system, which can modulate dopaminergic and serotonergic pathways (Chen et al, 2021), producing anxiolytic-and antidepressant-like effects (Fernández-Guasti and Picazo, 1995;Estrada-Camarena et al, 2002;Frye and Walf, 2002;Rodríguez-Landa et al, 2007).…”

“…Studies among laboratory animals and humans have reported that progesterone and its reduced metabolite allopregnanolone target the GABA A receptor and facilitate the activation of the GABAergic system, which can modulate dopaminergic and serotonergic pathways (Chen et al, 2021), producing anxiolytic-and antidepressant-like effects (Fernández-Guasti and Picazo, 1995;Estrada-Camarena et al, 2002;Frye and Walf, 2002;Rodríguez-Landa et al, 2007). Estrogen appears to mediate anxiety-and depressionlike behavior by stimulating tryptophan hydroxylase, the ratelimiting enzyme in the synthesis of serotonin (Bethea et al, 2000;Giannini et al, 2021). In rats, estrogen also mediates the regulation of the 5-hydroxytryptamine-1A (5-HT 1A ) receptor expression in the dorsal raphe nucleus.…”

“…Both types of menopause in women are characterized by low plasma levels and brain concentrations of estradiol and progesterone, and a marked increase in follicle-stimulating hormone (FSH) levels. This likely affects several brain neurotransmitter systems and some peripheral physiological processes, impacting the quality of life of women (Monteleone et al, 2018;Giannini et al, 2021). In addition, the long-term absence of steroid hormones is associated with physiological changes that predispose women to genitourinary, cardiovascular, osseous, and mood disorders (Giannini et al, 2021).…”

“…This likely affects several brain neurotransmitter systems and some peripheral physiological processes, impacting the quality of life of women (Monteleone et al, 2018;Giannini et al, 2021). In addition, the long-term absence of steroid hormones is associated with physiological changes that predispose women to genitourinary, cardiovascular, osseous, and mood disorders (Giannini et al, 2021). While such changes occur gradually and require a long time to stabilize in natural menopause, they are established in a shorter time in surgical menopause, thereby influencing the severity of symptoms in comparison to natural menopause (Rodríguez-Landa et al, 2015;Kingsberg et al, 2020;Giannini et al, 2021).…”