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Current Opinion in Endocrinology,... Jun 2012To summarize recent advances in studies of illicit use of androgens and other hormones. (Review)
Review
PURPOSE OF REVIEW
To summarize recent advances in studies of illicit use of androgens and other hormones.
RECENT FINDINGS
Androgens and other appearance-enhancing and performance-enhancing substances are widely abused worldwide. Three notable clusters of findings have emerged in this field in recent years. First, studies almost unanimously find that androgen users engage in polypharmacy, often ingesting other hormones (e.g., human growth hormone, thyroid hormones, and insulin), ergo/thermogenic drugs (e.g., caffeine, ephedrine, and clenbuterol), and classical drugs of abuse (e.g., cannabis, opiates, and cocaine). Second, reports of long-term psychiatric and medical adverse effects of androgens continue to accumulate. In cardiovascular research particularly, controlled studies have begun to supersede anecdotal evidence, strengthening the case that androgens (possibly acting synergistically with other abused drugs) may cause significant morbidity and even mortality. Third, it is increasingly recognized that androgen use may lead to a dependence syndrome with both psychological and physiological origins. Androgen dependence likely affects some millions of individuals worldwide, and arguably represents the least studied major class of illicit drug dependence.
SUMMARY
Given mounting evidence of the adverse effects of androgens and associated polypharmacy, this topic will likely represent an expanding area of research and an issue of growing public health concern.
Topics: Adolescent; Adult; Androgens; Behavioral Symptoms; Cardiovascular Diseases; Dietary Supplements; Female; Fitness Centers; Humans; Hypogonadism; Male; Performance-Enhancing Substances; Public Health; Substance-Related Disorders; Young Adult
PubMed: 22450858
DOI: 10.1097/MED.0b013e3283524008 -
The Journal of Pathology. Clinical... Jul 2023The androgen receptor (AR) plays a crucial role in the development and homeostasis of the prostate and is a key therapeutic target in prostate cancer (PCa). The gold...
Cell-by-cell quantification of the androgen receptor in benign and malignant prostate leads to a better understanding of changes linked to cancer initiation and progression.
The androgen receptor (AR) plays a crucial role in the development and homeostasis of the prostate and is a key therapeutic target in prostate cancer (PCa). The gold standard therapy for advanced PCa is androgen deprivation therapy (ADT), which targets androgen production and AR signaling. However, resistance to ADT develops via AR-dependent and AR-independent mechanisms. As reports on AR expression patterns in PCa have been conflicting, we performed cell-by-cell AR quantification by immunohistochemistry in the benign and malignant prostate to monitor changes with disease development, progression, and hormonal treatment. Prostates from radical prostatectomy (RP) cases, both hormone-naïve and hormone-treated, prostate tissues from patients on palliative ADT, and bone metastases were included. In the normal prostate, AR is expressed in >99% of luminal cells, 51% of basal cells, and 61% of fibroblasts. An increase in the percentage of AR negative (%AR-) cancer cells along with a gradual loss of fibroblastic AR were observed with increasing Gleason grade and hormonal treatment. This was accompanied by a parallel increase in staining intensity of AR positive (AR+) cells under ADT. Staining AR with N- and C-terminal antibodies yielded similar results. The combination of %AR- cancer cells, %AR- fibroblasts, and AR intensity score led to the definition of an AR index, which was predictive of biochemical recurrence in the RP cohort and further stratified patients of intermediate risk. Lastly, androgen receptor variant 7 (ARV7)+ cells and AR- cells expressing neuroendocrine and stem markers were interspersed among a majority of AR+ cells in ADT cases. Altogether, the comprehensive quantification of AR expression in the prostate reveals concomitant changes in tumor cell subtypes and fibroblasts, emphasizing the significance of AR- cells with disease progression and palliative ADT.
Topics: Male; Humans; Receptors, Androgen; Prostate; Prostatic Neoplasms; Androgens; Androgen Antagonists
PubMed: 37073437
DOI: 10.1002/cjp2.319 -
Endocrinology Nov 2021Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and... (Review)
Review
Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17β-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.
Topics: Aging; Androgens; Animals; Estrogens; Female; Gonadal Steroid Hormones; Humans; Male; Neurodegenerative Diseases; Oxidative Stress; Sex Characteristics
PubMed: 34467976
DOI: 10.1210/endocr/bqab185 -
Neuroscience and Biobehavioral Reviews Mar 2022An abundance of data indicates there are sex differences in endogenous opioid peptides and opioid receptors, leading to functional differences in sensitivity to opioid... (Review)
Review
An abundance of data indicates there are sex differences in endogenous opioid peptides and opioid receptors, leading to functional differences in sensitivity to opioid receptor mediated behaviors between males and females. Many of these sex differences are mediated by the effects of gonadal hormones on the endogenous opioid system. Whereas much research has examined the role of ovarian hormones on opioid receptor mediated endpoints, comparatively less research has examined the role of androgens. This review describes what is currently known regarding the influence of androgens on opioid receptor mediated endpoints and how androgens may contribute to sex differences in these effects. The review also addresses the clinical implications of androgenic modulation of opioid receptor mediated behaviors and suggests future lines of research for preclinical and clinical investigators. We conclude that further investigation into androgenic modulation of opioid receptor mediated effects may lead to new options for addressing conditions such as chronic pain and substance use disorders.
Topics: Androgens; Female; Humans; Male; Opioid Peptides; Receptors, Opioid; Sex Characteristics
PubMed: 34995646
DOI: 10.1016/j.neubiorev.2022.104522 -
PloS One 2015Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to...
Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR). Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs) to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE) in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders.
Topics: Androgens; Animals; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Profiling; Gene Expression Regulation; Histone Demethylases; Humans; Placenta; Pregnancy; Protein Binding; Proteome; Receptors, Androgen; Sheep; Testosterone Propionate; Transcriptome; Vascular Endothelial Growth Factor A
PubMed: 25675430
DOI: 10.1371/journal.pone.0117472 -
Cleveland Clinic Journal of Medicine 1990The most common signs of androgen excess in women are acne, alopecia, and hirsutism. Less common manifestations include android obesity, virilization, and acanthosis... (Review)
Review
The most common signs of androgen excess in women are acne, alopecia, and hirsutism. Less common manifestations include android obesity, virilization, and acanthosis nigricans. These changes appear to be the result of excessive androgen production or increased target organ sensitivity. To evaluate excessive androgen production, an androgen screening protocol is recommended that includes measurement of dehydroepiandrosterone sulfate, testosterone, androstenedione, prolactin, follicular stimulating hormone, and luteinizing hormone. When androgen excess is confirmed, dexamethasone suppression is recommended to determine the source of the androgen(s). Once excessive androgen production is confirmed, more specific therapies can be administered.
Topics: Acne Vulgaris; Alopecia; Androgens; Clinical Protocols; Endocrine System Diseases; Female; Hirsutism; Humans
PubMed: 2142637
DOI: 10.3949/ccjm.57.5.423 -
BMC Endocrine Disorders Feb 2023Considering the high prevalence of polycystic ovary syndrome (PCOS) in women of reproductive age and the metabolic disorders associated with it, this study was conducted... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Considering the high prevalence of polycystic ovary syndrome (PCOS) in women of reproductive age and the metabolic disorders associated with it, this study was conducted to determine the effects of curcumin on metabolic indices and androgen level (primary outcomes), and menstruation characteristics, and hirsutism (secondary outcomes) in women with PCOS.
METHODS
This triple-blind randomized controlled trial was conducted on women with PCOS who visited the health centers at Eslamshahr County (Tehran Province-Iran) from 2020 to 2022. The participants were allocated into two groups (curcumin and placebo) using block randomization method. The treatment group received two 500 mg edible curcumin tablets together at the same time per day for twelve weeks while the control group received placebo tablets similar to curcumin. Biochemical parameters such as Fasting Blood Insulin (FBI), Fasting Blood Sugar (FBS), triglyceride, total cholesterol, Low Density Lipoprotein- cholesterol (LDL-C), High Density Lipoprotein- cholesterol (HDL-C) were measured before intervention and then 3 months after the intervention. Sex Hormone Binding Globulin (SHBG) and testosterone serum levels were measured 3 months after the intervention. Questionnaires regarding the menstrual cycle characteristics and the Ferriman-Gallwey score were also filled for evaluating hirsutism before the intervention as well as 3 months after the intervention. The independent t-test, Mann-Whitney U test, and ANCOVA were used to analyze the data.
RESULTS
There was no statistically significant difference between the two groups in terms of socio-demographic and the baseline levels of measured outcomes. After 12 weeks of intervention, the mean serum FBS levels in the curcumin group were significantly lower than in the placebo group (mean difference: 6.24; 95%confidence interval: -11.73 to -0.76; P = 0.027) but there was no significant difference between the two groups in terms of triglyceride (P = 0.351), cholesterol (P = 0.528), LDL (P = 0.064), HDL (P = 0.306), FBI (p = 0.929), SHBG (p = 0.682), and testosterone (p = 0.133) serum levels. After the intervention, amenorrhea and oligomenorrhea frequency in the curcumin group was significantly lower than in the placebo group (13% vs. 22%, P = 0.038). There was no significant difference in terms of duration of menstruation (P = 0.286) and hirsutism (P = 0.630) between the two groups.
CONCLUSION
Curcumin decreased FBS levels and improved menstruation characteristics (amenorrhea, oligomenorrhea, and menstrual irregularities) in women with PCOS but did not affect other metabolic, hormonal, and hirsutism indices. More studies using a larger sample size are required for a definitive conclusion.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N51 Date of registration: 30/11/2019. URL: https://en.irct.ir/user/trial/40597/view ; Date of first registration: 30/11/2020.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Androgens; Curcumin; Amenorrhea; Oligomenorrhea; Iran; Testosterone; Triglycerides; Cholesterol; Cholesterol, LDL
PubMed: 36788534
DOI: 10.1186/s12902-023-01295-5 -
British Medical Journal Feb 1980
Review
Topics: Androgens; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hair Removal; Hirsutism; Humans; Polycystic Ovary Syndrome; Prednisolone; Virilism
PubMed: 6988040
DOI: 10.1136/bmj.280.6211.369 -
Experimental and Clinical Endocrinology... Jan 2024Hyperandrogenism is among the most common endocrine disorders in women. Clinically, it manifests as hirsutism, acne, and alopecia. A healthy lifestyle, including...
BACKGROUND
Hyperandrogenism is among the most common endocrine disorders in women. Clinically, it manifests as hirsutism, acne, and alopecia. A healthy lifestyle, including nutritious dietary patterns and physical activity, may influence the clinical manifestation of the disease. This study determined the effect of a low-glycemic index anti-inflammatory diet on testosterone levels and sex hormone-binding globulin (SHBG) and clinical symptoms in hyperandrogenic women at their reproductive age.
METHODS
The study included 44 overweight and obese women diagnosed with hyperandrogenism. The anthropometrics (weight, height, body mass index, waist circumference, hip circumference), physical activity, and dietary habits were assessed using valid questionnaires, scales, stadiometer, and tape meter. The significant p-value was <0.001. Serum testosterone and SHBG levels were measured using automated immunoassay instruments.
RESULTS
The intervention based on a low-glycemic index diet with anti-inflammatory elements and slight energy deficit decreased total testosterone levels (p<0.003), increased SHBG levels (p<0.001), and decreased the free androgen index (FAI; p<0.001). Post-intervention, overall well-being was much higher than in the pre-intervention period (p<0.001), and stress was diminished (p<0.001). Western nutritional patterns positively correlate with clinical hyperandrogenism progression, whereas several factors of the low-glycemic index diet with anti-inflammatory elements and slight energy deficit positively associate with reduced clinical hyperandrogenism symptoms.
CONCLUSIONS
In overweight and obese women, proper selection of diet, introduction of moderate physical activity, and reduction in weight, stress factors, and alcohol consumption translate into several positive effects, including reduced FAI and symptoms such as acne, hirsutism, menstrual disorders, and infertility.
Topics: Female; Humans; Hyperandrogenism; Hirsutism; Androgens; Polycystic Ovary Syndrome; Testosterone; Overweight; Obesity; Acne Vulgaris; Diet; Hypoglycemia; Anti-Inflammatory Agents; Sex Hormone-Binding Globulin; Body Mass Index
PubMed: 38237611
DOI: 10.1055/a-2201-8618 -
Substance Abuse Treatment, Prevention,... Mar 2015As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS)... (Review)
Review
BACKGROUND
As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS) users has been published.
METHOD
We systematically reviewed and synthesized qualitative/descriptive literature gathered from searches in electronic databases and by inspecting reference lists of relevant literature to investigate AAS users' polypharmacy. We adhered to the recommendations of the UK Economic and Social Research Council's qualitative research synthesis manual and the PRISMA guidelines.
RESULTS
A total of 50 studies published between 1985 and 2014 were included in the analysis. Studies originated from 10 countries although most originated from United States (n=22), followed by Sweden (n=7), England only (n=5), and the United Kingdom (n=4). It was evident that prior to their debut, AAS users often used other licit and illicit substances. The main ancillary/supplementary substances used were alcohol, and cannabis/cannabinoids followed by cocaine, growth hormone, and human chorionic gonadotropin (hCG), amphetamine/meth, clenbuterol, ephedra/ephedrine, insulin, and thyroxine. Other popular substance classes were analgesics/opioids, dietary/nutritional supplements, and diuretics. Our classification of the various substances used by AAS users resulted in 13 main groups. These non-AAS substances were used mainly to enhance the effects of AAS, combat the side effects of AAS, and for recreational or relaxation purposes, as well as sexual enhancement.
CONCLUSIONS
Our findings corroborate previous suggestions of associations between AAS use and the use of other licit and illicit substances. Efforts must be intensified to combat the debilitating effects of AAS-associated polypharmacy.
Topics: Anabolic Agents; Androgens; Drug Users; Humans; Polypharmacy; Self Medication
PubMed: 25888931
DOI: 10.1186/s13011-015-0006-5