Hormone Replacement Therapy in the Treatment of Perimenopausal Depression

Abstract

The menopause transition is associated with a two to fourfold increased risk in major depressive disorder (MDD) and clinical elevations in depressive symptoms. While the pathophysiological mechanisms underlying this increased risk remain uncertain, ovarian hormone fluctuation is believed to play a role. To the extent that this is the case, hormone replacement therapy (HRT), through its hormone-stabilizing effects, represents a viable antidepressant treatment. The current review summarizes the most recent literature evaluating the efficacy of HRT in treating MDD in peri- and postmenopausal women. In addition, to provide a clinical context in which to interpret this research, the endocrinology and clinical phenomenology related to depression with onset in the menopause transition (D-MT) are discussed. The available evidence suggests that HRT, specifically involving estrogen delivered through a skin patch, is a promising intervention in the treatment of D-MT. However, HRT of any form is an ineffective antidepressant in women who are well into the postmenopausal period.

Arterial stiffness is associated with depression in middle-aged men — the Maastricht Study

“…A possible explanation for the interaction might be that in women aged 60 years or younger, hormonal fluctuations, as seen during the menstrual cycle and perimenopause, rather than aortic stiffness could predispose them to depression. 34 Reproductive hormones are also thought to have a protective effect on the vasculature, especially before menopause, 15,16 thus further diminishing the association between cfPWV and depression in women. Exogenous hormone supplementation, such as hormone replacement therapy or contraception, could also be a confounder; however, in our study use of such medication was infrequent and did not affect the observed associations.…”

Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population

“…The review did not include intervention studies, neuroendocrine studies, animal models, or studies of postmenopausal women. These domains are clearly important for understanding the development of depression around menopause but are beyond the range of this review and are examined elsewhere [14,[21][22][23][24][25][26][27][28][29].…”

Why is depression more prevalent in women?

“…19 Emerging evidence indicates that hormone replacement therapy, particularly during the perimenopausal period, can be effective in the prevention of postmenopausal depression in women. 20 Another study involving female macaques examined relocation stress-sensitive alterations in their menstrual cycles and showed depressionrelated behaviours and reductions in the function of the brain serotonin system. 21 In this light, a recent study has indicated that women who reported using an oral contraceptive (especially monophasic contraceptives) showed reduced rates of major depression and anxiety compared with nonusers, 22 suggesting that moderating the cycling of estrogen may be protective.…”