DEFINITION
The disease definition according to a specific consensus conference or to The Diseases Database based on the Unified Medical Language System (NLM)
Also the link to the corresponding Mesh term has to be created
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Alcoholism
EPIDEMIOLOGY
age, sex, seasonality, etc
Epidemiologia e Monitoraggio Alcol Correlato, ISS
SYMPTOMS
DIAGNOSIS
histopathology
radiology
NMR
laboratory tests
PATHOGENESIS
PATIENT RISK FACTORS
Vascular
Genetic
Acquired
Hormonal
Genetic
Acquired
TISSUE SPECIFIC RISK FACTORS
anatomical (due its structure)
vascular (due to the local circulation)
physiopathological (due to tissue function and activity)
COMPLICATIONS
Erectile dysfunction
INTRODUCTION
Erectile dysfunction, testicular atrophy, gynecomastia, and loss of sexual interest are often associated with alcoholism in men.
Use of ethanol might cause gonadal disorders, including structural testicular changes and a decrease in testicular and serum levels of T, which might be involved in the hypogonadism and feminization phenotype.
Ethanol and its metabolite acetaldehyde cause a reduction in LH binding to Leydig cells, an inhibition of the enzymes responsible for the formation of sex hormones.
Van Thiel et al. demonstrated that ethanol acts as a Leydig cell toxin inducing Apoptosis
Moreover, ethanol increases the metabolic clearance rate of T concomitant with an increase in Aromatase expression and increases conversion of androgens into estrogens. Sperm cells might be selectively affected by various substances throughout the process of spermatogenesis to spermiogenesis. Both acute and chronic alcohol intoxication result in dosedependent suppression of plasma T levels in normal men. Alcohol-induced suppression of male T is due to a direct effect on the biosynthetic processes in the testes.
Alcohol seems to exert a dual effect on the hypothalamic– pituitary– gonadal axis by directly inhibiting testicular steroidogenesis and by blocking the release of LH-releasing hormone/LH from the hypothalamic–pituitary axis.
EPIDEMIOLOGY
Sexual disorders have been reported in men who are long-term alcohol users, with the prevalence ranging from 8% to 58% .
PATHOGENESIS:
1-TESTICULAR DAMAGE
1A- LEYDIG CELL APOPTOSIS .
It was demonstrated that TM3 leydig cells treated with ethanol at concentrations of 50 and 100 mM exhibit classical apoptotic feature (characteristic changes in the morphology like cytoplasmic blebbing, nuclear shrinkage, chromatin condensation, irregularity in shape and retraction of processes ). In addition, it was shown that ethanol induces increases in levels of bax and caspase-3 and a decrease in bcl-2 expression. Based on the results, alcohol appears to activate specific intracellular death-related pathways leading to bax-dependant caspase-3 activation and the induction of apoptosis in Leydig cells. Zhang et al. have reported that consumption of ethanol-containing fluid for 9 weeks results in testicular DNA fragmentation and increases in the numbers of apoptotic spermatogonia and spermatocytes. In addition, direct intratesticular injection of a 20% ethanol solution was shown to enhance testicular DNA fragmentation, indicating the induction of apoptosis. El-Sokkary has also shown that alcohol administration at a daily dose of 3 g/kg of for 30 days brings about testicular germ cell degeneration and a significant reduction in the number of Leydig cells.These results suggest that ethanol induces testicular germ cell apoptosis, a possible pathologic mechanism of alcohol-related male urogenital disorder.
1B- ALCOHOL AND HUMAN SEMEN
In human semen, ethanol produces a significant decrease in the percentage of motility, straight-line velocity, and curvilinear velocity of sperm.
Alcohol causes a significant decrease in the number of spermatozoa with normal morphology and an increase in irreversible tail defects.
The sperm of ethanol-consuming animals exhibit alterations in their spermatozoa concentration, abnormal motility and morphology, and a decrease of the fecundation capability .
It has been reported that ethanol abusers might exhibit sperm alterations, such as changes in the count, morphology, and viability of the spermatozoa. Alcohol exerts a dose-related toxic effect on testicular function.
Effect of chronic alcoholism on male fertility hormones and semen quality
2-HORMONAL ALTERATION
2A-Increased Aromatase expression under alcohol stimulation:
In men, testis, testicular germ cells, and epididymal sperm all express aromatase.
Aromatase, a cytochrome P450, catalyzes three consecutive hydroxylation reactions converting C19 androgens to aromatic C18 estrogenic steroids. Upon receiving electrons from NADPH-cytochrome P450 reductase, aromatase converts androstenedione and testosterone to estrone and estradiol, respectively compounds that increase aromatase expression or enhance aromatase activity (or stability) may function as antiandrogens or estrogen-like compounds.
Can alcohol promote aromatization of androgens to estrogens? A review
2B- Hypothalamic-Pituitary-Gonadal axis
In fully sexually mature Men alcohol affects both the testes and the component of the hypothalamic-pituitary-gonadal axis. AAI produced a large increase in ACTH, B endorphin, cortisol and prolactine.
Alcohol increases CRH at the central level, and this elevated CRH may decrease surem LH by a mechanism probably mediated by LHRH so Serum testosterone level decrease in AAI men.
Moreover alcohol decrease testicular T production through modifications in the [NAD+]/[NADH] ratio, modulation of arginino-NO synthase, The opioid system perhaps mediated by B-endorphine , and the neural Adrenergic dependent pathway between the brain and the testes.
REFERENCES:
PUBMED
SCIENCE DIRECT
ALCOHOL JOURNAL
FERTILITY AND STERILITY
AUTHORS:
Joseph Vargas; Marco Mussa
