In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on three of the most common unhealthy habits – tobacco, alcohol and drug addiction – and their reported effects on male fertility. Tobacco smoking is remarkably common in most first-world countries; despite a progressive decline in the US, recent reports suggest a prevalence of more than 30% in subjects of reproductive age – a disturbing perspective, given the well-known ill-effects on reproductive and sexual function as well as general health. Alcohol consumption is often considered socially acceptable, but its negative effects on gonadal function have been consistently reported in the last 30 years. Several studies have reported a variety of negative effects on male fertility following drug abuse – a worrying phenomenon, as illicit drug consumption is on the rise, most notably in younger subjects. While evidence in these regards is still far from solid, mostly as a result of several confounding factors, it is safe to assume that cessation of tobacco smoking, alcohol consumption and recreational drug addiction might represent the best course of action for any couple trying to achieve pregnancy.

Background: Considerable interest has been gathered on the relevant impact of preventable factors, including incorrect lifestyle and unhealthy habits, on female fertility. Smoking, alcohol and addictive drugs consumption represent a major concern, given the broad range of diseases which might be favored or exacerbated by these dependable attitudes. Despite the well-characterized effects of prenatal exposure on pregnancy outcomes and fetus health, a substantial proportion of women of reproductive age is still concerned with these habits. At present, the impact of smoke, alcohol and addictive drugs on women fertility, and, particularly, the specific targets and underlying mechanisms, are still poorly understood or debated, mainly due to the scarcity of well-designed studies, and to numerous biases.Objective: The current review will provide a comprehensive overview of clinical and experimental studies in humans and animals addressing the impact of smoke, alcohol and addictive drugs on female fertility, by also embracing effects on ovary, oviduct, and uterus, with particular reference to primary endpoints such as ovarian reserve, steroidogenesis, ovulation and menstrual cycle, oviduct function and uterus receptivity and implantation. A brief focus on polycystic ovary syndrome and endometriosis will be also included.Methods: A Pubmed literature search was performed with selected keywords; articles were individually retrieved by each author. No limitation was set for publication date. Articles in languages other than English were excluded. Additional articles were retrieved from references list of selected manuscripts.Results and conclusions: Currently, the most consistent evidences of a detrimental effect of smoke, alcohol and addictive drugs on specific domains of the female reproductive function are provided by experimental studies in animals. Overall, clinical studies suggest that smoking is associated to decreased fertility, although causal inference should be further demonstrated. Studies addressing the effect of alcohol consumption on female fertility provide conflicting results, although the majority reported lack of a correlation. Extremely scarce studies investigated the effects of addictive drugs on female fertility, and the specific actions of selected drugs have been difficult to address, due to multidrug consumption.

Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.

Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.