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.

Menopause is the permanent cessation of menstrual cycles following the loss of ovarian follicular activity. Quality of life of postmenopausal woman is the result of a series of psychobiological transformations, that see in the reduction of sex hormones and steroids the etiopathogenetic determinant moment. Symptoms of menopause range from somatic side such as metabolic changes, increased cardiovascular disease, irregular vaginal bleeding, urogenital symptoms, vaginal dryness, osteoporosis and risk of bones fractures to changes of central nervous system as vasomotor symptoms, sleep disruption, mood changes, migraine, sexual dysfunctions. It is fundamental to know the mechanisms underlying changes in the central nervous system during menopause, related to hypoestrogenism, to be able to create appropriate target therapy for patients, improving their quality of life. In fact, the central nervous system is now one of the major targets of sex steroids that cannot be achieved disregard when dealing with the problem of choice of a particular type of MHT.

Progesterone and allopregnanolone have crucial and different roles in brain development, function and recovery after injury. Pregnancy is characterized by an increased synthesis of progesterone and its neuro-active metabolites by the placenta, maternal and fetal brain. This supports the critical role of these steroids in maternal brain adaptation during pregnancy and development of the fetal brain. Moreover, allopregnanolone may play a brain-protective role during complications of pregnancy, complications of pregnancy, such as preterm delivery or intrauterine growth restriction (IUGR), by reducing the impact of hypoxia and excitotoxic brain damage or impairment myelination. Behavioral consequences of altered progesterone/allopregnanolone fetal brain programming have also been hypothesized, although further evidence is needed. New potential applications of allopregnanolone as a treatment strategy have also been proposed, addressing unmet clinical needs in perinatal care.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin^®. This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin^® in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin^®, an SSRI-‘like’ therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin^® may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine-metabolic disorder among women at reproductive age. The diagnosis is based on the presence of at least two out of three criteria of the Rotterdam criteria (2003). In the last decades, the dysmetabolic aspect of insulin resistance and compensatory hyperinsulinemia have been taken into account as the additional key features in the etiopathology of PCOS, and they have been widely studied. Since PCOS is a complex and multifactorial syndrome with different clinical manifestations, it is difficult to find the gold standard treatment. Therefore, a great variety of integrative treatments have been reported to counteract insulin resistance. PCOS patients need a tailored therapeutic strategy, according to the patient’s BMI, the presence or absence of familiar predisposition to diabetes, and the patient’s desire to achieve pregnancy or not. The present review analyzes and discloses the main clinical insight of such complementary substances.