Plasma brain-derived neurotrophic factor (BDNF) levels are associated with the hormonal status of women. Moreover, the suprachiasmatic nucleus appears to be implicated in the modulation of BDNF central levels. We aimed to investigate whether BDNF circadian rhythms exist in women and if there is a relationship with cortisol circadian rhythmicity. Moreover, we aimed to establish whether the hormonal status influences BDNF diurnal variations. A total of 30 women were studied: 10 fertile ovulatory women, 10 women undergoing oral contraceptive (OC) therapy and 10 post-menopausal women. Basal BDNF and estradiol levels were assayed in blood samples collected after overnight fasting at regular intervals (08:00, 12:00, 16:00, 20:00, 24:00). BDNF and cortisol levels were measured in samples collected during the follicular and luteal phases in ovulatory women and once a month in OC and post-menopausal women. Luteal BDNF levels were significantly higher than follicular levels in fertile women (P < 0.001). In OC women, BDNF levels were similar to the follicular BDNF levels, whereas in post-menopausal women, they were significantly lower (P < 0.001). BDNF showed a diurnal rhythm in the follicular phase and in women undergoing OC, although the diurnal rhythm was blunted in the luteal phase. In post-menopausal women, BDNF and cortisol levels significantly decreased during the day. BDNF has a diurnal variation in women that is somewhat analogous to cortisol variation; however, the amplitude of the variation in BDNF levels appears to be influenced by ovarian function. Interactions between BDNF, the hypothalamus–pituitary–adrenal axis and sex steroids might play a critical role in the human homeostasis and adaptation.

BACKGROUND: Menopausal symptoms can be very distressing and considerably affect a woman’s personal and social life. It is becoming more and more evident that leaving bothersome symptoms untreated in midlife may lead to altered quality of life, reduced work productivity and, possibly, overall impaired health. Hormone therapy (HT) for the relief of menopausal symptoms has been the object of much controversy over the past two decades. At the beginning of the century, a shadow was cast on the use of HT owing to the concern for cardiovascular and cerebrovascular risks, and breast cancer, arising following publication of a large randomized placebo-controlled trial. Findings of a subanalysis of the trial data and extended follow-up studies, along with other more modern clinical trials and observational studies, have provided new evidence on the effects of HT.OBJECTIVE AND RATIONALE: The goal of the following paper is to appraise the most significant clinical literature on the effects of hormones in postmenopausal women, and to report the benefits and risks of HT for the relief of menopausal symptoms.SEARCH METHODS: A Pubmed search of clinical trials was performed using the following terms: estrogens, progestogens, bazedoxifene, tibolone, selective estrogen receptor modulators, tissue-selective estrogen complex, androgens, and menopause.OUTCOMES: HT is an effective treatment for bothersome menopausal vasomotor symptoms, genitourinary syndrome, and prevention of osteoporotic fractures. Women should be made aware that there is a small increased risk of stroke that tends to persist over the years as well as breast cancer risk with long-term estrogen–progestin use. However, healthy women who begin HT soon after menopause will probably earn more benefit than harm from the treatment. HT can improve bothersome symptoms, all the while conferring offset benefits such as cardiovascular risk reduction, an increase in bone mineral density and a reduction in bone fracture risk. Moreover, a decrease in colorectal cancer risk is obtainable in women treated with estrogen–progestin therapy, and an overall but nonsignificant reduction in mortality has been observed in women treated with conjugated equine estrogens alone or combined with estrogen–progestin therapy. Where possible, transdermal routes of HT administration should be preferred as they have the least impact on coagulation. With combined treatment, natural progesterone should be favored as it is devoid of the antiapoptotic properties of other progestogens on breast cells. When beginning HT, low doses should be used and increased gradually until effective control of symptoms is achieved. Unless contraindications develop, patients may choose to continue HT as long as the benefits outweigh the risks. Regular reassessment of the woman’s health status is mandatory. Women with premature menopause who begin HT before 50 years of age seem to have the most significant advantage in terms of longevity.WIDER IMPLICATIONS: In women with bothersome menopausal symptoms, HT should be considered one of the mainstays of treatment. Clinical practitioners should tailor HT based on patient history, physical characteristics, and current health status so that benefits outweigh the risks.