Lifestyles and sexuality in men and women: the gender perspective in sexual medicine.

Sexual health is strictly related with general health in both genders. In presence of a sexual dysfunction, the expert in sexual medicine aims to discover the specific weight of the physical and psychological factors can cause or con-cause the sexual problem. At the same time, a sexual dysfunction can represent a marker of the future development of a Non-communicable diseases (NCDss) as cardiovascular or metabolic diseases.In the evaluation phase, the sexual health specialist must focus on these aspects, focusing especially on the risk and protective factors that could impact on both male and female sexuality.This article presents a review of researches concerning healthy and unhealthy lifestyles and their contribute in the development of sexual quality of life in a gender-dependent manner.Among the unhealthy lifestyle, obesity contributes mostly to the development of sexual dysfunctions, due to its negative impact on cardiovascular and metabolic function. Tobacco smoking, alcohol - substance abuse and chronic stress lead to the development of sexual dysfunction in a med-long term.In order to guarantee a satisfying sexual quality of life, sexual health specialists have the responsibility to guide the patient through the adoption of healthy lifestyles, such as avoiding drugs, smoke and excessive alcohol, practicing a regular physical activity, following a balanced diet and use stress-management strategies, even before proposing both pharmaco- and/or psychotherapies.

Challenges to treat hypogonadism in prostate cancer patients: implications for endocrinologists, urologists and radiotherapists.

The literature suggests that the serum testosterone level required for maximum androgen receptor (AR) binding may be in the range of nanomolar and above this range of concentrations; this sexual hormone may not significantly affect tumour biology. This assumption is supported by clinical studies showing that cell proliferation markers did not change when serum T levels increased after exogenous T treatment in comparison to subjects treated with placebo. However, a considerable part of the global scientific community remains sceptical regarding the use of testosterone replacement therapy (TRT) in men suffering from hypogonadism and prostate cancer (Pca). The negative attitudes with respect to testosterone supplementation in men with hypogonadism and Pca may be justified by the relatively low number of clinical and preclinical studies that specifically dealt with how androgens affect Pca biology. More controversial still is the use of TRT in men in active surveillance or at intermediate or high risk of recurrence and treated by curative radiotherapy. In these clinical scenarios, clinicians should be aware that safety data regarding TRT are scanty limiting our ability to draw definitive conclusions on this important topic. In this review we critically discuss the newest scientific evidence concerning the new challenges in the treatment of men with hypogonadal condition and Pca providing new insights in the pharmacological and psychological approaches.

Platelet-derived growth factor regulation of type-5 phosphodiesterase in human and rat penile smooth muscle cells.

INTRODUCTION: Relaxation of cavernous smooth muscle cells (SMCs) is a key component in the control of the erectile mechanism. SMCs can switch their phenotype from a contractile differentiated state to a proliferative and dedifferentiated state in response to a change of local environmental stimuli. Proliferation and contraction are both regulated by the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are degraded by phosphodiesterases (PDEs). The most abundant PDE present in corpora cavernosa is the electrolytic cGMP-specific phosphodiesterase type 5 (PDE5). AIM: We investigated the cellular localization of PDE5 in in vitro cultured corpora cavernosa cells and the effect of mitogenic stimulation on PDE5 expression. METHODS: Biochemical ad molecular techniques on cultured SMCs from human and rat penis. MAIN OUTCOME MEASURES: We studied the ability of the quiescent SMC phenotype vs. the proliferating phenotype in modulation of PDE5 expression. RESULTS: We demonstrated that PDE5 is localized in the cytoplasm, in the perinuclear area, and in discrete cytoplasmic foci. As previously demonstrated in human myometrial cells, the cytoplasmic foci may correspond to centrosomes. In corpora cavernosa, PDE5 protein levels are strongly regulated by the mitotic activity of the SMCs, as they were increased in quiescent cultures. In contrast, treatment with platelet-derived grow factor (PDGF), one of the most powerful mitogenic factors for SMCs, reduces the expression of PDE5 after 24 hours of treatment. CONCLUSION: We found that PDGF treatment downregulates PDE5 expression in proliferating SMCs, suggesting that PDE5 may represent one of the markers of the contractile phenotype of the SMCs of corpora cavernosa.

Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models.

Histone deacetylase inhibitors (HDACi) are promising epigenetic cancer chemotherapeutics rapidly approaching clinical use. In this study, we tested using in vitro and in vivo models the differential biological effects of a novel HDAC inhibitor [belinostat (PXD101)], in a wide panel of androgen-sensitive and androgen-independent tumor cells. Belinostat significantly increased acetylation of histones H3 and H4. Belinostat potently inhibited the growth of prostate cancer cell lines (IC50 range from 0.5 to 2.5 µM) with cytotoxic activity preferentially against tumor cells. This agent induced G2/M arrest and increased significantly the percentage of apoptosis mainly in androgen-sensitive tumor cells confirming its growth-inhibitory effects. The cell death mechanisms were studied in three different prostate cancer cell lines with different androgen dependence and expression of androgen receptor; LAPC-4 and 22rv1 (androgen-dependent and expressing androgen receptor) and PC3 (androgen-independent not expressing androgen receptor). Belinostat induced the expression of p21 and p27, acetylation of p53 and G2/M arrest associated with Bcl2 and Bcl-Xl downmodulation and significant reduction of survivin, IAPs and Akt/pAkt and increased caspase-8 and -9 expression/activity. Belinostat effectiveness was dependent on the androgen receptor (AR), since the stable transfection of AR greatly increased the efficacy of this HDAC inhibitor. These observations were correlated using in vivo models. We demonstrated that belinostat preferentially resulted in antitumor effect in androgen-dependent tumor cells expressing AR. Our findings provide evidence that belinostat may be a promising anticancer drug for prostate cancer expressing AR, supporting its clinical role in prostate cancer.

Ontogenetic profile of the expression of thyroid hormone receptors in rat and human corpora cavernosa of the penis.

INTRODUCTION: In the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones on the penis. AIM: To study the spatiotemporal distribution of mRNA for the thyroid hormone nuclear receptors (TR) alpha1, alpha2 and beta in the penis and smooth muscle cells (SMCs) of the corpora cavernosa of rats and humans during development. METHODS: We used several molecular biology techniques to study the TR expression in whole tissues or primary cultures from human and rodent penile tissues of different ages. MAIN OUTCOME MEASURE: We measured our data by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) amplification, Northern blot and immunohistochemistry. RESULTS: We found that TRalpha1 and TRalpha2 are both expressed in the penis and in SMCs during ontogenesis without development-dependent changes. However, in the rodent model, TRbeta shows an increase from 3 to 6 days post natum (dpn) to 20 dpn, remaining high in adulthood. The same expression profile was observed in humans. While the expression of TRbeta is strictly regulated by development, TRalpha1 is the principal isoform present in corpora cavernosa, suggesting its importance in SMC function. These results have been confirmed by immunohistochemistry localization in SMCs and endothelial cells of the corpora cavernosa. CONCLUSIONS: The presence of TRs in the penis provides the biological basis for the direct action of thyroid hormones on this organ. Given this evidence, physicians would be advised to investigate sexual function in men with thyroid disorders.