Psychological symptoms in perimenopause and early menopause are common. The impact of menopausal hormone therapy (MHT) on menopausal mood symptoms is unclear.

To assess the impact of 17β-oestradiol ± micronised progesterone or the levonorgestrel-releasing intrauterine device, and/or transdermal testosterone, on depressive and anxiety symptoms in peri- and postmenopausal women.

A real-world retrospective cohort study set in the largest specialist menopause clinic in the UK. The Meno-D questionnaire measured mood-related symptoms.

The study included 920 women: 448 (48.7%) perimenopausal, and 435 (47.3%) postmenopausal. Following initiation/optimisation of MHT, mean Meno-D scores decreased by 44.59% (95% CI −46.83% to −42.34%, P < 0.001) after average 107 days follow-up. Mood symptoms significantly improved (P < 0.01 per symptom). Improvement occurred in peri- and postmenopausal women. All MHT regimens improved mental health including both progestogen types (body-identical progesterone and levonorgestrel-releasing intrauterine device), MHT initiation strategy (oestradiol ± a progestogen versus oestradiol ± a progestogen and testosterone, 45.38 v. 48.53%, respectively, P = 0.47) and MHT optimisation strategy (MHT users treated with a higher oestradiol dose versus testosterone added versus both a higher oestradiol dose and testosterone, 34.70, 43.93 and 43.25%, respectively, P = 0.38).

Use of menopausal hormone therapy was associated with significant improvement in mood in peri- and postmenopausal women. Prospective studies and randomised clinical trials are needed to assess the effects of different regimens in different patient populations over longer time periods.

Menopause is an inflection point in the ageing trajectory. Independent of chronological age, menopause is associated with the biological ageing of several body systems. In this review, we highlight the importance of considering the influence of menopause – its types, symptoms and interventions – on brain health. Supplementing the loss of ovarian hormones with menopausal hormone therapy (MHT) may be key for supporting the healthy brain ageing of females. MHT has been associated with reduced risk of several neurodegenerative diseases; however, its benefits are not always observed on brain health.

This narrative review highlights often overlooked MHT factors that influence its effects to produce positive or negative effects on brain health, cognition and neurodegenerative disease risk. These factors include the many varieties of MHT, including formulation, administration route and dosing schedule, as well as individual characteristics, particularly the presence of vasomotor symptoms and apolipoprotein ε4 (APOE4) genotype.

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Menopause factors, including age, abruptness and symptoms, influence brain ageing. MHT influences brain health, with transdermal MHT showing more positive effects on brain ageing, but its effectiveness may depend on individual factors such as genotype, reproductive and lifestyle factors.

To develop effective and individualised MHT treatments, further research is needed. Preclinical models must consider the type of human menopause and MHT. To achieve the greatest dementia prevention in females, more menopause education and care is needed that extends beyond 60 years of age, or 10 years postmenopause.