New nonsteroidal molecules as blockers of the steroidogenic pathway

Background: Testosterone circulating levels decrease in aging. This fact affects the emotional response to captivating pictures. Therefore, naturally increasing androgens within neurons could be a way to improve the mood of agedpeople. Objective: This study aimed to determine the biological activity of new nonsteroidal derivatives of 2-aminonaphthalene-1,4-dione (2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione) as inhibitors of the aldo-keto reductase 1 enzymes (AKR1C1, AKR1C2). Method: The 2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione were synthesized, and their effect in vivo and in vitro was determined. The human prostate cell membrane was used as a source of steroidogenic enzymes. The 2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione bindings to the androgen receptors were also assayed using cytosol from the rat prostate. In vivo experiments, we determined the effects of 2-amino-3-iodonaphthalene-1,4-dione, 2-(iodoamino)-3-methylnaphthalene-1,4-dione on the weight of androgen-dependent glands of castrated hamsters treated with testosterone and finasteride or 2-amino-3-iodonaphthalene-1,4-dione or 2-(iodoamino)-3-methylnaphthalene-1,4-dione was determined. Results: 2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione inhibited AKR1C1 enzyme activity with an IC50 value of 420 nM (2-amino-3-iodonaphthalene-1,4-dione) and 1.95 µM (2-(iodoamino)-3-methylnaphthalene-1,4-dione), respectively. They also blocked AKR1C2 with an IC50 value of 300 nM (2-amino-3-iodonaphthalene-1,4-dione) and 1.52 µM (2-(iodoamino)-3-methylnaphthalene-1,4-dione). Thus 2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione prevent the formation of 3α and 3β-androstanediols. Moreover, these compounds did not bind to AR and did not reduce prostate and seminal vesicle weight. The latter is because of the accumulation of dihydrotestosterone, which is an anabolic androgen. Conclusion: 2-amino-3-iodonaphthalene-1,4-dione and 2-(iodoamino)-3-methylnaphthalene-1,4-dione inhibited AKR1C1 and AKR1C2 enzyme activity; consequently, dihydrotestosterone was accumulated in androgen-dependent glands. These derivatives could potentially use therapeutics via direct nasal administration in aged patients, increasing DHT in neurons.

Prevalence, mental health and substance use of anabolic steroid users: a population-based study on young individuals

Aims: The use of anabolic androgen steroids to enhance performance is not a modern phenomenon. However, the majority of today’s anabolic androgen steroid users are not competitive athletes, but individuals who want to look leaner and muscular. This study aimed to examine the prevalence of anabolic androgen steroid use among young individuals and assess whether their mental health, lifestyle and substance use differ from non-anabolic androgen steroid users. Methods: A population-based study conducted in secondary schools, mean age was 17.3 years. A total of 10,259 participants (50% young women, 1% reported gender as ‘other’, 49% young men) answered questions on mental health, anabolic androgen steroid use, substance use and sports participation. Statistical analysis included descriptive statistics, t-test, χ2 and logistic regression. Results: The prevalence of anabolic androgen steroid use was 1.6%, and 78% of users were young men. Anabolic androgen steroid users had more anger issues, anxiety, depression, and their self-esteem was lower than among non-anabolic androgen steroid users ( P<0.05). A larger proportion of anabolic androgen steroid users, 30%, had attempted suicide compared to 10% of non-users (χ2 (1, 9580) = 57.5, P<0.001). Proportionally, anabolic androgen steroid users were more likely to take medicine for mental health problems and misuse substances than non-users. Participation in non-organised sports, increased anger and body image were associated with increased odds of using anabolic androgen steroids. Conclusions: Anabolic androgen steroid use is a public health threat. It had an alarming effect on the life of individuals who report having used anabolic androgen steroids. Authorities, healthcare workers, parents and others working with young people need to be informed of the signs and risks of anabolic androgen steroid use to reduce future negative implications.

Esterified Anabolic Androgen-Induced Liver Injury in a Hepatitis C Virus-Positive Patient: A CaseReport

Background: Cases of drug induced liver injury still perplex gastroenterologists due to its wide range of presentations that mimic acute and chronic liver conditions. Moreover, matters get complicated when clinicians face the possibility of drug-induced injury in the presence of pre-existing chronic liver disease. Case: A 69 year-old male who was recently discovered to have a hepatitis C viral infection presented with acute manifestations (mixed cholangio-hepatocellular injury) not fully explained by the underlying chronic disease, we suspected an idiosyncratic reaction from an esterified anabolic androgen. His manifestations have appeared acutely after the drug intake and include acute onset of jaundice, abdominal pain, pruritus and choluria. He was improving on drug discontinuity and conservative measures during his brief hospital stay. Conclusion: The underlying chronic disease constitutes a dilemma in diagnosis of superimposed drug-induced liver injury, as the proof of causality is a daunting task. In such cases, it is tempting to link such new emerging manifestations to be a flare-up of the underlying chronic disease rather than to the drug. However, certain clues helped to point this clinical presentation towards a drug-induced liver injury