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The involvement of gonadal hormones in the pathogenesis of schizophrenia has long been suspected because the psychosis differs in women and men and the illness first makes its appearance shortly after puberty. Changes in sex hormones have been linked with increased vulnerability to mood disorders in women, while testosterone have been associated with increased sexual drive and aggressiveness in men as well as women. Some studies have found abnormal levels of estrogens and testosterone in schizophrenia patients, but the results have been inconsistent and sometimes attributed to the hyperprolactinemia effect of antipsychotics, which may interfere with sex hormones production. The purpose of this review is to present the current knowledge on the link between blood levels of sex-hormones in women during the various stages of the female reproductive life (i.e. puberty, menstrual cycle, pregnancy, contraception, and menopause) and the course of schizophrenia. We also attempt to optimize the clinical approach to women with schizophrenia at these different stages.

Abstract Background It has been shown – mostly in animal models - that circadian clock genes are expressed in granulosa cells and in corpora luteum and might be essential for the ovulatory process and steroidogenesis. Objective We sought to investigate which circadian clock genes exist in human granulosa cells and whether their expression and activity decrease during aging of the ovary. Study design Human luteinized granulosa cells were isolated from young (age 18–33) and older (age 39–45) patients who underwent in-vitro fertilization treatment. Levels of clock genes expression were measured in these cells 36 h after human chorionic gonadotropin stimulation. Methods Human luteinized granulosa cells were isolated from follicular fluid during oocyte retrieval. The mRNA expression levels of the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2 were analyzed by quantitative polymerase chain reaction. Results We found that the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2, are expressed in cultured human luteinized granulosa cells. Among these genes, there was a general trend of decreased expression in cells from older women but it reached statistical significance only for PER1 and CLOCK genes (fold change of 0.27 ± 0.14; p = 0.03 and 0.29 ± 0.16; p = 0.05, respectively). Conclusions This preliminary report indicates that molecular circadian clock genes exist in human luteinized granulosa cells. There is a decreased expression of some of these genes in older women. This decline may partially explain the decreased fertility and steroidogenesis of reproductive aging.

Abstract Background Our aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved. Methods An umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken. The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised. The following databases were searched: MEDLINE, EMBASE, Web of Science, CENTRAL, PsycINFO and CINAHL. In addition, reference lists were screened. We included reviews of the effects of MLT on any type of health-related outcome measure. Results Altogether, 195 reviews met the inclusion criteria. Most were of low methodological quality (mean -4.5, standard deviation 6.7). Of those, 164 did not pool the data and were synthesised narratively (qualitatively) whereas the remaining 31 used meta-analytic techniques and were synthesised quantitatively. Seven meta-analyses were significant with P values less than 0.001 under the random-effects model. These pertained to sleep latency, pre-operative anxiety, prevention of agitation and risk of breast cancer. Conclusions There is an abundance of reviews evaluating the effects of exogenous and endogenous MLT on health. In general, MLT has been shown to be associated with a wide variety of health outcomes in clinically and methodologically heterogeneous populations. Many reviews stressed the need for more high-quality randomised clinical trials to reduce the existing uncertainties.

The pineal hormone Melatonin plays an important role in the regulation of the circadian sleep/wake cycle, mood, and perhaps immune functions, carcinogensis and reproduction. The human circadian rhythm of melatonin release from the pineal gland is tightly synchronized with the habitual hours of sleep. Peri- and postmenopausal women often complain of difficulties initiating and/or maintaining sleep, with frequent nocturnal and early morning awakenings. In this review we discuss the pathophysiology of melatonin function as it relates to sleep disorders in menopausal women, highlighting the potential use of exogenous melatonin during the menopausal transition and beyond.