Depression is one of the leading causes of disease-related disability in women, and they are nearly twice as likely as men to suffer from an episode of depression. The difference begins in early life and persists through to mid-life, and as such, these reproductive years have been labelled by some as a 'window of vulnerability'. The prevalence has been reported to be particularly high during the menopausal transition, but there is no consensus supporting a direct association with reproductive status. This may be partly due to methodological limitations and inconsistencies in the available studies, resulting from a large number of confounding factors. In addition, relationships between sex hormones and the neurotransmitters purported to be responsible for depression are complex. What appears to be universally accepted is that treatment, with oestrogen, for low mood in women during midlife years may be beneficial, and should be considered. Key Words Depression MidlifeSexual dimorphism Receptor polymorphisms SearchingAll searches were conducted in PUBMED and EMBASE. The following search terms were combined using Boolean rules: depression, menopause, midlife, women. All searches were updated June 2016.Searching of grey literature or unpublished literature was not undertaken. Papers published in languages other than English were not reviewed.The titles and abstracts of records retrieved by the searches were sifted for relevance, with potentially significant publications obtained in full text.

The hot flush is the most characteristic and often the most distressing symptom of the menopause. It is a unique feature and yet the mechanism and health implications are still not fully understood. This review summarizes some of the current thoughts on factors contributing to flushing, the physiological, vascular and neuroendocrine changes associated with flushing and the possible cardiovascular and other health implications for women experiencing hot flushes. Therapy is not discussed.

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Menopausal symptoms can disrupt a woman's personal and social life. Vasomotor symptoms (hot flushes and night sweats) are the most common symptoms and can be treated very effectively with oestrogen-based hormone therapy. The decision to use oestrogen (often simply termed hormone therapy or hormone replacement therapy or HT) therapy involves balancing the potential benefits against the potential risks. Most agree that short-term oestrogen therapy, using the lowest effective dose, is a reasonable option for recently menopausal women with moderate-to-severe symptoms who are in good cardiovascular health (Martin and Manson. 2008. J. Clin. Endocrinol. Metab. 93, 4567-75). Whilst effective and safe in most instances, HT is not suitable for all women or for all menopause-related symptoms when alternatives are available. The role of HRT in chronic disease prevention is also discussed.

Precis: Flushing postmenopausal women appear to have better vascular responses than non-flushing women but paradoxically, such women appear to have worse (not better) CVD risk factors. 2 ABSTRACTBackground: 70% of postmenopausal women suffer from hot flushes causing significant morbidity in

Background: 70% of postmenopausal women suffer from hot flushes but the pathophysiology is

Vasomotor symptoms are the most common indication for the prescription of hormone replacement therapy since it is effective in over 80% of cases. In 1995, 37% of American women took hormone replacement therapy, principally for this purpose. However, following the publication of results from the Women's Health Initiative, as many as half of these women in the US and in the UK and New Zealand discontinued hormone therapy. Discontinuation of estrogen is often accompanied by a return of vasomotor symptoms; however, only a small number (18%) of women report restarting hormone therapy. Alternatives are available, but limited knowledge on etiology and mechanisms of hot flushing represents a major obstacle for the development of new, targeted, non-hormonal treatments, and no current alternatives are as effective as estrogen.

Hot flushes are the most common indication for the prescription of hormone replacement therapy (HRT) since it is effective in over 80% of cases. In 1995, 37% of American women took HRT, principally for this purpose. However, over the last five years, publications such as those from the Women's Health Initiative (WHI) have caused concern among women since they perceive that the risks outweigh the benefits. Following this publication, half of the women taking HRT in the UK, USA and New Zealand discontinued HRT. With the discontinuation of estrogen many women re-developed hot flushes; however only a small number (18%) of women report restarting hormone therapy. The majority of these (76%) for the recurrence of severe hot flushes or night sweats. Alternatives are available, but limited knowledge on aetiology and mechanisms of hot flushing represents a major obstacle for the development of new, targeted, non-hormonal treatments, and no current alternatives are as effective as estrogen.