STEROIDS

The recent discovery of three closely related cell surface receptors that bind to progesterone and mediate its actions on various cytoplasmic signalling cascades has been heralded as a major break-through. The reason for this is all too obvious. Progesterone is an essential regulator of all major reproductive events and progestins and antiprogestins are widely used in the treatment of many different gynaecological and obstetrical disorders. The novel membrane progestin receptors (mPRalpha, beta, gamma) reportedly resemble and function as G-protein-coupled receptors and therefore are promising pharmaceutical targets. However, our studies failed to corroborate that mPRs are expressed on the cell surface, that they mediate rapid progesterone signalling events, and even that they are bona fide progestin binding moieties. While the reason for these startling opposing results remains unclear, a critical review of existing data may help to shed some light onto the controversial mPRs. Time has come to talk.

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. ...

Steroid hormone measurement, first developed with radioimmunoassay, is now becoming easier with the use of automated platforms of immunoassay. However, some hormones remain uneasily detectable because of their low blood concentration, their structural homology or the presence of interferences. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be considered as an alternative to immunoassays. This approach allows the simultaneous determination of several parameters thanks to its selectivity led by the detector mass spectrometer and the separate dimension of chromatography liquid. In addition, recourse to UHPLC (ultra high performance liquid chromatography) allows improving selectivity and sensitivity while limiting the samples volumes. The "ready-to-use" kits are now available and added to the "homemade" techniques developed by laboratories, thus giving opportunity for measurement of a wide steroid panel with only one sample. Finally, mass spectrometry ...

In T47D breast cancer cell line, progestin (R5020) induces de novo synthesis of an alkaline phosphatase enzyme. Based on inhibitor profiles and antigenic specificity, it is apparent that this enzyme belongs to the class of membrane-associated tissue-unspecific alkaline phosphatases. Enzyme induction was uniquely specific to progestins and not altered by other steroid hormones or synthetic analogues. The progestin induction of the tissue-unspecific alkaline phosphatase was time and dose dependent. The protein synthesis inhibitor cycloheximide blocks the enzyme synthesis and tunicamycin blocks the enzyme activity, showing that the induction was new synthesis of protein in its complete glycosylated form and not activation of a preexisting enzyme. To our knowledge this is the first report of progesterone-induced expression of a tissue-unspecific alkaline phosphatase gene of such magnitude (about 30- to 100-fold) in a progesterone-responsive tissue.

Introduction. In a society that perpetuates the strive for a perfect appearance, a fit body has become synonymous with success, but simultaneously hard to achieve. This represents a fertile ground for the development of Exercise Addiction (EA) alongside other disorders, such as Body Dysmorphic Disorder (BDD). This study aims to explore the diffusion of EA in fitness settings in the United Kingdom, Italy, Netherlands, Hungary and the previously unexplored association with appearance anxiety, BDD, self-esteem and the use of fitness supplements. Methods. A large cross-sectional sample (N = 1711) was surveyed in fitness settings using the Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI) and Rosenberg’s Self Esteem Scale (RSE) in addition to questions surrounding the use of fitness supplements. Results. Compulsive exercise, appearance anxiety and low self-esteem were present in this sample according to the psychometric measures used (EAI, AAI, RSE). 11.7% scored over the cut off for EA, with alarming peaks in the Netherlands (20.9%) and the United Kingdom (16.1%). 38.5% were found at risk of BDD, mainly female (47.2%). 39.8% used fitness enhancing supplements without medical consultation (95.5%). This cohort of supplement users scored higher in both EAI and AAI. The logistic regression model revealed a strong association  between the consumption of sport products and the level of EA across the sample with an odds ratio (OR) of 3.03. Other co-variable factors among female were appearance anxiety (AAI; OR 1.59) and to a lesser extent self-esteem (RSE) (OR 1.08). Conclusions. This study identified a high risk of EA, appearance anxiety and BDD amongst a cohort of gym users internationally. The previously-unexplored association between these disorders and the unsupervised use of a variety of fitness products, including illicit drugs, highlights the need for informed and integrated responses targeting such vulnerable individuals.

A protocol for percutaneous absorption studies has been validated, based on the use of reconstructed human epidermis (RHE) and aqueous solutions of test substances. However, it is often the case that it is more-complex formulations of drugs or chemicals which will make contact with the skin surface. To investigate whether RHE and the reconstructed full-thickness skin model (FT-model) can be used to predict uptake from formulations, we compared the permeation of hydrocortisone and testosterone when applied in emulsion form and as a solution containing the penetration enhancer, ethanol. Human and pig skin and a non-cornified alveolar model served as references. The results were compared with steroid release from the formulations. The permeation rates of the steroids were ranked as: alveolar model > RHE > FT-model, pig skin > human skin. In accordance with the rapid hydrocortisone release from the formulations, the permeation rates of this steroid exceeded those of testosteron...

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4-RD can occur in various organs, including the pancreas, lacrimal gland, salivary gland, thyroid, lung, bile duct, liver, gastrointestinal tract, kidney, prostate, retroperitoneum, arteries, lymph nodes, skin, and breast. Steroid therapy is often effective. In the field of neurology, pachymeningitis (IgG4-related pachymeningitis) and hypophysitis (IgG4-related hypophysitis) are known to be related to IgG4-RD. Recently, a few papers have described the involvement of peripheral nerves in IgG4-RD. Here, we describe the concept of IgG4-RD and highlight the involvement of the central and peripheral nervous systems in IgG4-RD.

The stability of the contraceptive steroid, Nestorone (16-methylene-17 alpha-acetoxy-19-nor-pregn-4-ene-3,20-dione) in the solid state and in aqueous solutions, was investigated using reverse-phase high-performance liquid chromatography. In the solid state, whether as a powder or when it is incorporated into Silastic implants, the steroid does not undergo detectable degradation even under severe experimental conditions. In solution, the drug undergoes slow degradation that is dependent on temperature and pH of the medium. The decomposition is defined by first-order mechanism. As expected, the reaction rate increases with increasing storage temperature. The linearity of the Arrhenius plot indicates that there is no change in the reaction mechanism within the temperature range studied. In alkaline media, the drug degrades at a faster rate through hydrolytic rather than an oxidative mechanism. The major hydrolytic degradation product, 16-methylene-17 alpha-hydroxy-19-nor-pregn-4-ene-3,...

Anabolic-androgenic steroids (AAS) are synthetic forms of the hormone testosterone and their non-medical use is related to increased muscle size, muscle mass, and strength. A primary concern regarding exogenous AAS use is its potential to suppress endogenous (natural) testosterone production. In response, some users seek out substances to use post-cycle to mitigate problems associated with the resumption of endogenous testosterone production. This study sought to understand issues related to post-cycle therapy (PCT) among a sample of performance and image enhancing drugs (PIED) users in Australia. Semi-structured interviews were conducted with 26 participants (n = 24 male) who reported the use of a range of performance and image enhancing drugs (PIEDs), including AAS, human chorionic gonadotropin, growth hormone, clenbuterol, tamoxifen, insulin, and peptides. Interviews were conducted in person or by telephone, recorded, and transcribed. Data were analysed following a process of thematic analysis. Three themes emerged: (1) access to PCT; (2) maintenance of gains, maintenance of health; and (3) PCT and links to mental health. Steroids were seen as easier to access than PCT; as such, participants tended to continue to use steroids rather than taper down their use, leading to health concerns. Participants wanted access to PCT for several reasons, including minimising any loss of muscle or strength gained through their PIED cycle; because they were concerned that they were no longer naturally producing hormones; or because they were concerned about their mental health, particularly when coming 'off cycle', and the need for PCT to help adjust. This study contributes to the existing literature suggesting that PCT may act as a harm reduction measure, allowing PIED users to safely reduce or cease steroid use or to address any negative effects from use, particularly those related to mental health.

A variety of progestins are available for therapeutic use. It is convenient to classify them into those related in chemical structure to progesterone or testosterone. Progestins related to progesterone can be subdivided into pregnanes and 19-norpregnanes, whereas those related to testosterone can be subdivided into those with and without a 17-ethinyl group. 17-Ethinylated progestins consist of the families of norethindrone

Social media has been associated with body dissatisfaction and eating disorder symptoms among young women and adolescent girls. However, despite notable evidence of susceptibility to body image pressures, it remains unknown whether these associations generalize to sexual minority men. A nationwide sample of 2,733 sexual minority men completed an online survey advertised to Australian and New Zealand users of a popular dating app. Participants answered questions about how frequently they used 11 different social media platforms in addition to questions about their dating app use, body image, eating disorder symptoms, and anabolic steroids. Facebook, Youtube, Instagram, and Snapchat were the most frequently used social media platforms. A pattern of small-sized and positive associations emerged between social media use and body dissatisfaction, eating disorder symptoms, and thoughts about using anabolic steroids. Facebook, Instagram, and Snapchat evidenced the strongest associations. The associations of social media use with both muscularity dissatisfaction and eating disorder symptoms were stronger for image-centric social media platforms (e.g., Instagram) than nonimage-centric platforms (e.g., Wordpress); no differences were observed for body fat dissatisfaction, height dissatisfaction , or thoughts about using anabolic steroids. Previously documented associations of social media use with body dissatisfaction and related variables among women and girls appear to generalize to sexual minority men. Social media platforms that more centrally involve imagery may be of greater concern than nonimage-centric platforms. Additional research with sexual minority men is needed to elucidate the distinctions between adaptive and maladaptive social media use in the context of body dissatisfaction, eating disorders, and anabolic steroid use.