Effects of hormone therapy on cognition and mood

Abstract

Objective Results of the Women’s Health Initiative (WHI) and Women’s Health Initiative Memory Study (WHIMS) suggested that hormone therapy (HT) may be detrimental to cognitive health. This article reviews clinical studies which address issues relevant to those results. Design A search of PubMed and Web of Science was conducted using the search terms HT and cognition, HT and mood. Clinical and observational studies were selected if they were published after the year 2000. Theories of HT mechanisms of action, pharmacology, biology, and observational and clinical trials are discussed. Results While observational and clinical trials show conflicting findings, methodological considerations must be acknowledged. HT formulation and dose, route of administration, timing of initiation, length of treatment, and health of participants all contribute to inconsistencies in results. Transdermal estradiol and micronized progesterone administered at time of menopause are generally associated with cognitive and affective benefit. Conclusions At the present time, results from existing studies are equivocal regarding the benefits of HT on cognition and affect. Future studies, such as the Kronos Early Estrogen Prevention Study (KEEPS) should address methodological inconsistencies in order to provide clearer answers to this important question.

Estrogen- and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging

“…However, another study of 210 post-menopausal women that measured serum estradiol levels and used manual tracing to quantify hippocampal volume also failed to find an association between estrogen and hippocampal size or memory performance (den Heijer et al 2003). Overall, despite multiple studies, the effects of aging, menopause, and HRT on cognition and memory remain controversial (Fischer et al 2014). In part this may be due to the particular difficulty of disentangling the confounding factors of menopausal status and age.…”

Pharmacological blockade of the aromatase enzyme, but not the androgen receptor, reverses androstenedione-induced cognitive impairments in young surgically menopausal rats

“…Indeed, this work could generate new insight into the already immensely complex relationship between the loss of ovarian hormones in menopause and memory changes (Weber & Mapstone, 2009; Weber et al, 2013; Fischer et al, 2014). Cognitive effects likely depend on an individual's menopause status, including whether they have intact ovaries (Nappi et al, 1999), what phase of the menopause transition they are in (Weber et al, 2013), circulating levels of androstenedione, as well as other steroid hormones and gonadotropins (Acosta et al, 2009b), and prior hormone exposure history (Bimonte-Nelson et al, 2010).…”

Distinct cognitive effects of estrogen and progesterone in menopausal women

“…However, hormones are still commonly prescribed on and off-label for non-cognitive indications, and some hormone formulations may impart a cognitive benefit for some women. There is emerging evidence that progestins and progesterone do not equivalently influence neurobiological mechanisms of cognitive function, and that progesterone is likely to be more beneficial and carry fewer risks than its synthetic counterparts(Fischer et al, 2014; Jodhka et al, 2009; Maki, 2012; Singh and Su, 2013a). Despite this distinction, there is currently little evidence on the cognitive effects of progesterone in postmenopausal women.…”