Background: Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core... Show moreBackground: Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms. Methods: In 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years. Results: None of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5 alpha-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms. Conclusions: These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5 alpha-DHT may be associated with some individual MDD symptoms. Show less
Background: The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women... Show moreBackground: The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women, a contribution of sex hormones has been proposed.Objectives: We undertook this systematic literature review to investigate: (1) the role played by male and female sex hormones in the pathogenesis of SSc; (2) how sex hormone levels change in SSc patients and how hormonal variations modify the progression of SSc; (3) the effect of therapies targeting sex hormones on the disease course.Methods: A literature search was performed in Pubmed, Embase, Web of Science, and Cochrane library databases. Given the heterogeneity in study design, different quality assessment tools were applied where appropriate.Results: We retrieved 300 articles and 30 were included in the review. The available evidence points to a fibrogenic, but also a vasodilatory, role of estrogens in SSc. With the limitation of small sample sizes, women with SSc tend to have lower levels of androgens and non-significantly higher levels of estradiol compared to healthy controls, while in men we found increased levels of estradiol and discordant results for androgens. After menopause the skin score seems to decrease and prevalence of pulmonary artery hypertension seems to rise, which might be prevented by the use of hormone replacement therapy. No recent high-quality trial evaluated the efficacy of hormone-targeting therapies in SSc.Conclusions: Few translational studies of varying quality evaluated the role of sex hormones in SSc showing possible profibrotic and vasodilatatory effects of estrogens, but more research is needed to elucidate the extent of this contribution. Insights on the influence of sex hormones, along with the availability of new compounds acting on estrogen pathways, might provide ideas for additional studies on the application of sex hormone-targeting therapies in SSc. (C) 2019 Elsevier Inc. All rights reserved. Show less
Marra, G.; Dell'Oglio, P.; Baghdadi, M.; Cathelineau, X.; Sanchez-Salas, R.; EvaluatioN HIFU Hemiablation Short 2019
Focal therapy (FT) for localized prostate cancer (PCa) is emerging to reduce adverse effects of radical treatments, while maintaining comparable oncological outcomes. However, an area for... Show moreFocal therapy (FT) for localized prostate cancer (PCa) is emerging to reduce adverse effects of radical treatments, while maintaining comparable oncological outcomes. However, an area for improvement still exists and a gap in cancer control needs to be filled by complementing FT with additional forms of treatment to minimize failures. Part of the recurrences/persistences after FT may be related to PCa microenvironment favouring tumorigenesis of benign tissue or indolent PCa left untreated. FT-induced inflammation may alter microenvironment in a pro-tumorigenic fashion. On the contrary, androgen deprivation therapy (ADT) modifies PCa microenvironment and suppresses PCa tumorigenesis. So far, ADT has proven effective in combination with radiotherapy, has been evaluated in the context of AS and to reduce prostate volume in the context of whole-gland high-intensity focused ultrasound (HIFU). However, no prospective data exist evaluating FT/ADT combination in terms of cancer control for the treatment of localized PCa. We will perform the ENHANCE pilot study (EvaluatioN of HIFU Hemiablation and short-term AndrogeN deprivation therapy Combination to Enhance prostate cancer control). Twenty men with localized unilateral csPCa will receive HIFU hemi-ablation and concomitant short-term ADT. Oncologic efficacy will be assessed 1-year post-treatment considering the persistence/recurrence of csPCa. Complications and functional outcomes will be evaluated using internationally validated questionnaires. If the hypothesis of an oncological benefit together with no relevant additional toxicity is confirmed, the ENHANCE study will allow an evidence-based starting point for a large randomized controlled trial against the standard of care and/or HIFU hemiablation alone. Show less
Giltay, E.J.; Enter, D.; Zitman, F.G.; Penninx, B.W.J.H.; Pelt, J. van; Spinhoven, P.; Roelofs, K. 2012
