-
Physiological Research 2011Hyperandrogenic states in pregnancy are almost always the result of a condition that arises during pregnancy. The onset of virilization symptoms is often very fast. The... (Review)
Review
Hyperandrogenic states in pregnancy are almost always the result of a condition that arises during pregnancy. The onset of virilization symptoms is often very fast. The mother is protected against hyperandrogenism by a high level of SHBG, by placental aromatase and a high level of progesterone. The fetus is protected from the mother's hyperandrogenism partly by the placental aromatase, that transforms the androgens into estrogens, and partly by SHGB. Nevertheless there is a significant risk of virilization of the female fetus if the mother's hyperandrogenic state is serious. The most frequent cause of hyperandrogenic states during pregnancy are pregnancy luteoma and hyperreactio luteinalis. Hormonal production is evident in a third of all luteomas, which corresponds to virilization in 25-35 % of mothers with luteoma. The female fetus is afflicted with virilization with two thirds of virilized mothers. Hyperreactio luteinalis is created in connection with a high level of hCG, e.g. during multi-fetus pregnancies. This condition most frequently arises in the third trimester, virilization of the mother occurs in a third of cases. Virilization of the fetus has not yet been described. The most serious cause of hyperandrogenism is represented by ovarian tumors, which are fortunately rare.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenocortical Adenoma; Adrenocortical Carcinoma; Adult; Androgens; Aromatase; Female; Fetus; Humans; Hyperandrogenism; Luteoma; Ovarian Neoplasms; Ovary; Placenta; Pregnancy; Pregnancy Complications; Ultrasonography, Prenatal; Virilism
PubMed: 21114372
DOI: 10.33549/physiolres.932078 -
Archives of Toxicology Jul 2022Dietary supplements sold for anabolic benefits or performance enhancement often contain substances, which are non-approved and might lack quality controls. With regard...
Dietary supplements sold for anabolic benefits or performance enhancement often contain substances, which are non-approved and might lack quality controls. With regard to athletes, the inclusion of substances or methods in the prohibited list of the World Anti-Doping Agency is based on medical or scientific evidence. 5α-hydroxy-laxogenin is a synthetic spirostane-type steroid, which is contained in dietary supplements and advertised as anabolic agent. To date, evidence is missing on anabolic or androgenic activity of 5α-hydroxy-laxogenin. We investigated its androgenic potential in two in vitro bioassays. While no activity was observed in the yeast androgen screen, 5α-hydroxy-laxogenin was able to trans-activate the androgen receptor in human prostate cells in a dose-dependent manner. Interestingly, a biphasic response was observed with antagonistic properties at lower concentrations and agonistic effects at higher concentrations tested. The demonstrated androgenic properties of the higher concentrations demonstrate that further investigations should focus on the safety as well as on potential anabolic effects of 5α-hydroxy-laxogenin. This is of interest with regard to abuse for doping purposes.
Topics: Anabolic Agents; Androgens; Dietary Supplements; Doping in Sports; Humans; Male; Spirostans; Steroids; Testosterone Congeners
PubMed: 35344071
DOI: 10.1007/s00204-022-03283-5 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2020Androgen plays an important role in singing of songbirds. Recent studies have shown that androgen levels in vivo not only affect the external morphology of songbirds,... (Review)
Review
Androgen plays an important role in singing of songbirds. Recent studies have shown that androgen levels in vivo not only affect the external morphology of songbirds, but also affect their singing behavior. Androgens (including derivatives) affect singing behavior and singing system in many ways. Based mainly on the results from our research group in the zebra finch, this review summarizes the effects of androgen on singing behavior, excitability and synaptic transmission of projection neurons of singing system, and the interaction of androgen with other neurotransmitter receptors in the brain of songbirds.
Topics: Androgens; Animals; Brain; Songbirds; Vocalization, Animal
PubMed: 32328618
DOI: No ID Found -
American Journal of Obstetrics and... Mar 1999Ovarian hormones-estrogens, androgens, and progesterone-produce a myriad of effects in the nervous system. The effects of androgens in the brain are mediated through... (Review)
Review
Ovarian hormones-estrogens, androgens, and progesterone-produce a myriad of effects in the nervous system. The effects of androgens in the brain are mediated through androgen-specific receptors and by the aromatization of testosterone to estradiol. Alterations in the circulating levels of androgens play an important role in psychologic and sexual changes that occur after menopause. The effects of short-term estrogen therapy in improving psychologic symptoms, maintaining vaginal lubrication, decreasing vaginal atrophy, and increasing pelvic blood flow in postmenopausal women are well documented. However, some patients require more than estrogen alone to improve psychologic dysfunction, decreased sexual desire, or other sexual problems associated with menopause. Results from clinical studies show that hormone replacement therapy with estrogen plus androgens provides greater improvement in psychologic (eg, lack of concentration, depression, and fatigue) and sexual (eg, decreased libido and inability to have an orgasm) symptoms than does estrogen alone in naturally and surgically menopausal women.
Topics: Affect; Androgens; Female; Hormone Replacement Therapy; Humans; Libido; Postmenopause; Quality of Life
PubMed: 10076172
DOI: 10.1016/s0002-9378(99)70727-1 -
Clinical & Translational Oncology :... Feb 2023Androgen receptor (AR) plays a vital role in prostate cancer (PCa), including castration-resistant PCa, by retaining AR signalling. Androgen deprivation treatment (ADT)... (Review)
Review
The androgen receptor-targeted proteolysis targeting chimera and other alternative therapeutic choices in overcoming the resistance to androgen deprivation treatment in prostate cancer.
Androgen receptor (AR) plays a vital role in prostate cancer (PCa), including castration-resistant PCa, by retaining AR signalling. Androgen deprivation treatment (ADT) has been the standard treatment in the past decades. A great number of AR antagonists initially had been found effective in tumour remission; however, most PCa relapsed that caused by pre-translational resistance such as AR mutations to turn antagonist into agonist, and AR variants to bypass the androgen binding. Recently, several alternative therapeutic choices have been proposed. Among them, proteolysis targeting chimera (PROTAC) acts different from traditional drugs that usually function as inhibitors or antagonists, and it degrades oncogenic protein and does not disrupt the transcription of an oncogene. This review first discussed some essential mechanisms of ADT resistance, and then introduced the application of AR-targeted PROTAC in PCa cells, as well as other AR-targeted therapeutic choices.
Topics: Male; Humans; Receptors, Androgen; Androgens; Prostatic Neoplasms; Androgen Antagonists; Prostatic Neoplasms, Castration-Resistant; Proteolysis Targeting Chimera; Drug Resistance, Neoplasm
PubMed: 36203075
DOI: 10.1007/s12094-022-02957-x -
Hormones and Behavior May 2008Adolescence is associated with increases in pleasure-seeking behaviors, which, in turn, are shaped by the pubertal activation of the hypothalamo-pituitary-gonadal axis.... (Review)
Review
Adolescence is associated with increases in pleasure-seeking behaviors, which, in turn, are shaped by the pubertal activation of the hypothalamo-pituitary-gonadal axis. In animal models of naturally rewarding behaviors, such as sex, testicular androgens contribute to the development and expression of the behavior in males. To effect behavioral maturation, the brain undergoes significant remodeling during adolescence, and many of the changes are likewise sensitive to androgens, presumably acting through androgen receptors (AR). Given the delicate interaction of gonadal hormones and brain development, it is no surprise that disruption of hormone levels during this sensitive period significantly alters adolescent and adult behaviors. In male hamsters, exposure to testosterone during adolescence is required for normal expression of adult sexual behavior. Males deprived of androgens during puberty display sustained deficits in mating. Conversely, androgens alone are not sufficient to induce mating in prepubertal males, even though brain AR are present before puberty. In this context, wide-spread use of anabolic-androgenic steroids (AAS) during adolescence is a significant concern. AAS abuse has the potential to alter both the timing and the levels of androgens in adolescent males. In hamsters, adolescent AAS exposure increases aggression, and causes lasting changes in neurotransmitter systems. In addition, AAS are themselves reinforcing, as demonstrated by self-administration of testosterone and other AAS. However, recent evidence suggests that the reinforcing effects of androgens may not require classical AR. Therefore, further examination of interactions between androgens and rewarding behaviors in the adolescent brain is required for a better understanding of AAS abuse.
Topics: Adolescent; Adolescent Behavior; Androgens; Animals; Female; Humans; Male; Rats; Receptors, Androgen; Reinforcement, Psychology; Reward; Sexual Behavior; Sexual Behavior, Animal; Steroids
PubMed: 18343381
DOI: 10.1016/j.yhbeh.2008.01.010 -
Vascular Health and Risk Management 2008Cardiovascular disease (CVD) remains the leading cause of death in Western society today. There is a striking gender difference in CVD with men predisposed to earlier... (Review)
Review
Cardiovascular disease (CVD) remains the leading cause of death in Western society today. There is a striking gender difference in CVD with men predisposed to earlier onset and more severe disease. Following the recent reevaluation and ongoing debate regarding the estrogen protection hypothesis, and given that androgen use and abuse is increasing in our society, the alternate view that androgens may promote CVD in men is assuming increasing importance. Whether androgens adversely affect CVD in either men or women remains a contentious issue within both the cardiovascular and endocrinological fraternities. This review draws from basic science, animal and clinical studies to outline our current understanding regarding androgen effects on atherosclerosis, the major CVD, and asks where future directions of atherosclerosis-related androgen research may lie.
Topics: Androgens; Animals; Arteriosclerosis; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Risk Factors
PubMed: 18629352
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2006Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.
OBJECTIVES
To assess the beneficial and harmful effects of anabolic-androgenic steroids for patients with alcoholic liver disease based on the results of randomised clinical trials.
SEARCH STRATEGY
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register in The Cochrane Library, MEDLINE, EMBASE, LILACS, and Science Citation Index Expanded until June 2006. Electronic searches were combined with full text searches. Manufacturers and researchers in the field were also contacted.
SELECTION CRITERIA
Randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis, and/or alcoholic cirrhosis were included. Interventions encompassed anabolic-androgenic steroids at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published, and no language limitations were applied.
DATA COLLECTION AND ANALYSIS
Outcomes are assessed at maximal follow-up. All analyses were performed according to the intention-to-treat method. The statistical package RevMan Analyses was used. The methodological quality of the randomised clinical trials was assessed.
MAIN RESULTS
Combining the results of five randomised clinical trials randomising 499 patients with alcoholic hepatitis and/or cirrhosis demonstrated no significant effects of anabolic-androgenic steroids on mortality (relative risk (RR) 1.01, 95% confidence interval (CI) 0.79 to 1.29), liver-related mortality (RR 0.83, 95% CI 0.60 to 1.15), complications of liver disease (RR 1.25, 95% CI 0.74 to 2.10), and liver histology. Anabolic-androgenic steroids did not significantly affect a number of other outcome measures, including sexual function and liver biochemistry. Anabolic-androgenic steroids were not associated with a significantly increased risk of non-serious adverse events (RR 1.14, 95% CI 0.50 to 2.59) or with serious adverse events (RR 4.54, 95% CI 0.57 to 36.30).
AUTHORS' CONCLUSIONS
This systematic review could not demonstrate any significant beneficial effects of anabolic-androgenic steroids on any clinically important outcomes (mortality, liver-related mortality, liver complications, and histology) of patients with alcoholic liver disease.
Topics: Anabolic Agents; Androgens; Humans; Liver Diseases, Alcoholic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17054157
DOI: 10.1002/14651858.CD003045.pub2 -
British Medical Journal May 1971
Topics: 17-Ketosteroids; Cushing Syndrome; Female; Hirsutism; Humans; Hyperplasia; Ovarian Cysts; Ovarian Neoplasms; Ovary; Ovulation; Testosterone; Virilism
PubMed: 5572389
DOI: 10.1136/bmj.2.5756.264 -
Chemical Research in Toxicology Apr 2017Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using...
Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference. The in vitro HTS assays probed perturbations of the AR pathway at multiple points (receptor binding, coregulator recruitment, gene transcription, and protein production) and multiple cell types. Confirmatory in vitro antagonist assay data and cytotoxicity information were used as additional flags for potential nonspecific activity. Validating such alternative testing strategies requires high-quality reference data. We compiled 158 putative androgen-active and -inactive chemicals from a combination of international test method validation efforts and semiautomated systematic literature reviews. Detailed in vitro assay information and results were compiled into a single database using a standardized ontology. Reference chemical concentrations that activated or inhibited AR pathway activity were identified to establish a range of potencies with reproducible reference chemical results. Comparison with existing Tier 1 AR binding data from the U.S. EPA Endocrine Disruptor Screening Program revealed that the model identified binders at relevant test concentrations (<100 μM) and was more sensitive to antagonist activity. The AR pathway model based on the ToxCast/Tox21 assays had balanced accuracies of 95.2% for agonist (n = 29) and 97.5% for antagonist (n = 28) reference chemicals. Out of 1855 chemicals screened in the AR pathway model, 220 chemicals demonstrated AR agonist or antagonist activity and an additional 174 chemicals were predicted to have potential weak AR pathway activity.
Topics: Androgen Receptor Antagonists; Androgens; Area Under Curve; High-Throughput Screening Assays; Humans; Models, Theoretical; Protein Binding; ROC Curve; Receptors, Androgen; Transcriptional Activation
PubMed: 27933809
DOI: 10.1021/acs.chemrestox.6b00347