Menopause and depression: a review of psychologic function and sex steroid neurobiology during the menopause

Abstract

The purpose of this review is threefold. The first objective is to assess from current literature the extent to which depressive symptoms may be associated with peri- and postmenopausal states. Although there have been many studies published addressing this topic, there remains much controversy as to whether there is a true positive correlation of increased depressive symptomatology with the peri- and postmenopausal periods. Second, sex steroid neurobiology will be reviewed. In recent years, improved technology has allowed for much more detail in investigations of the central mechanisms of action of the sex hormones. Ultimately, estrogen appears to play an excitatory role in the central nervous system, whereas progesterone has been shown to be inhibitory. The third objective is to determine whether sex steroids have been shown to clinically affect mood and psychologic function, and if so, how such information might relate to regimens for peri- and postmenopausal hormone replacement. Currently, only large, pharmacologic doses of estrogen have been shown to improve mood in clinically depressed patients. Estrogen has been shown to potentiate the effects of some antidepressants; therefore menopausal women with major depressive disorders may respond to lower doses of antidepressant medications when estrogen replacement is added to the treatment regimen. The psychological and physiological manifestations in depressive illnesses of the post-menopausal age period are of great complexity and not clearly understood. In view of the obscurity of the etiological factors it is important to isolate and study the effect of one such possible factor at a time. 1 Many symptoms and signs of various mood disturbances have been attributed to estrogen deficiency during the climacteric, yet it has been argued that there are no psychological symptoms specific to the menopause. The literature concerning psychological symptoms accompanying menopause is confusing. 2 Taken from studies published more than 50 years apart, these quotes describe the long-standing difficulty investigators have faced in evaluating psychologic function during the menopause. From the 1930s to the present, ongoing debate has surrounded issues of depression associated with the peri- and postmenopausal periods: whether there is an association at all and if so, what the cause might be and how might it be treated. Investigators continue to add new information to this debate, driven by the common understanding that issues relating to menopause and the postmenopausal period have become increasingly important. Not only are greater numbers of women approaching menopause, but these women are now expected to live greater than one third of their lives after menopause. 3 The purpose of this review is first to assess from the literature the extent to which depressive symptoms may be associated with peri- and postmenopausal states. Second, in an attempt to explain or define causes of proposed changes in psychologic function during menopause, sex steroid neurobiology will be reviewed. The last objective is to determine from the literature whether sex steroids as used in hormone replacement therapy have been shown to clinically affect mood and psychological function and if so, how such information might relate to regimens for peri- and postmenopausal hormone replacement.