-
Molecules (Basel, Switzerland) Dec 2011The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone... (Review)
Review
The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes.
Topics: Animals; Biotransformation; Endocrine Disruptors; Enzyme Inhibitors; Enzymes; Humans; Metabolic Networks and Pathways; Testosterone
PubMed: 22138857
DOI: 10.3390/molecules16129983 -
Tidsskrift For Den Norske Laegeforening... Mar 2023
Topics: Female; Humans; Testosterone; Testosterone Congeners
PubMed: 36919306
DOI: 10.4045/tidsskr.22.0799 -
Best Practice & Research. Clinical... Sep 2022Anabolic-androgenic steroid (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to... (Review)
Review
Anabolic-androgenic steroid (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to stop AAS are prone to distressing withdrawal symptoms which may trigger relapse in use. It is important to develop therapies to support AAS withdrawal. The illicit nature of AAS use has impeded the robust characterisation of its clinical withdrawal syndrome within any single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use, and AAS withdrawal. Reported clinical features of AAS withdrawal include headache, fatigue, myalgia, restlessness, insomnia, low mood and libido, anorexia, suicidal ideation, body image dissatisfaction, and steroid cravings; novel therapies for AAS withdrawal would need evaluation against these symptoms.
Topics: Anabolic Agents; Androgens; Humans; Male; Performance-Enhancing Substances; Steroids; Testosterone Congeners
PubMed: 35999138
DOI: 10.1016/j.beem.2022.101691 -
Andrology Jan 2016Despite numerous contraceptive options available to women, approximately half of all pregnancies in the United States and worldwide are unplanned. Women and men support... (Review)
Review
Despite numerous contraceptive options available to women, approximately half of all pregnancies in the United States and worldwide are unplanned. Women and men support the development of reversible male contraception strategies, but none have been brought to market. Herein we review the physiologic basis for male hormonal contraception, the history of male hormonal contraception development, currents agents in development as well as the potential risks and benefits of male hormonal contraception for men.
Topics: Contraception; Contraceptive Agents, Male; Humans; Male; Norprogesterones; Testosterone; Testosterone Congeners
PubMed: 26453296
DOI: 10.1111/andr.12110 -
Substance Abuse Treatment, Prevention,... Nov 2023Anabolic-androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general...
BACKGROUND
Anabolic-androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms.
METHODS
An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support.
RESULTS
The majority of respondents were white, aged 18-30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community.
CONCLUSIONS
Our survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and suicidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use.
Topics: Male; Humans; Adolescent; Young Adult; Adult; Anabolic Androgenic Steroids; Anabolic Agents; Testosterone Congeners; Testosterone; Hypogonadism; Substance Withdrawal Syndrome; Surveys and Questionnaires
PubMed: 37951896
DOI: 10.1186/s13011-023-00573-8 -
Redox Biology Apr 2020The molecular and pharmacological manipulation of the endogenous redox system is a promising therapy to limit myocardial damage after a heart attack; however,... (Review)
Review
The molecular and pharmacological manipulation of the endogenous redox system is a promising therapy to limit myocardial damage after a heart attack; however, antioxidant therapies have failed to fully establish their cardioprotective effects, suggesting that additional factors, including antioxidant system interactions with other molecular pathways, may alter the pharmacological effects of antioxidants. Since gender differences in cardiovascular disease (CVD) are prevalent, and sex is an essential determinant of the response to oxidative stress, it is of particular interest to understand the effects of sex hormone signaling on the activity and expression of cellular antioxidants and the pharmacological actions of antioxidant therapies. In the present review, we briefly summarize the current understanding of testosterone effects on the modulation of the endogenous antioxidant systems in the CV system, cardiomyocytes, and the heart. We also review the latest research on redox balance and sexual dimorphism, with particular emphasis on the role of the natural antioxidant system glutathione (GSH) in the context of myocardial infarction, and the pro- and antioxidant effects of testosterone signaling via the androgen receptor (AR) on the heart. Finally, we discuss future perspectives regarding the potential of using combing antioxidant and testosterone replacement therapies to protect the aging myocardium.
Topics: Antioxidants; Female; Glutathione; Humans; Male; Oxidation-Reduction; Oxidative Stress; Testosterone
PubMed: 32169396
DOI: 10.1016/j.redox.2020.101490 -
Molecules (Basel, Switzerland) Jul 2019As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has... (Review)
Review
As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has become apparent that those compounds that naturally occur in animals can also be found as natural constituents of plants and vice versa, i.e., they have essentially the same fate in the majority of living organisms. This review summarizes the current state of knowledge on the occurrence of animal steroid hormones in the plant kingdom, particularly focusing on progesterone, testosterone, androstadienedione (boldione), androstenedione, and estrogens.
Topics: Androstadienes; Androstenedione; Animals; Biosynthetic Pathways; Estrogens; Phytosterols; Plants; Progesterone; Steroids; Testosterone
PubMed: 31315257
DOI: 10.3390/molecules24142585 -
British Journal of Clinical Pharmacology Jul 2012The large variation in disposition known for most drugs is also true for anabolic androgenic steroids. Genetic factors are probably the single most important cause of... (Review)
Review
The large variation in disposition known for most drugs is also true for anabolic androgenic steroids. Genetic factors are probably the single most important cause of this variation. Further, there are reasons to believe that there is a corresponding variation in efficacy of doping agents. Doped individuals employ a large variety of doping strategies in respect of choice of substance, dose, dose interval, duration of treatment and use of other drugs for enforcement of effects or correction of side effects. Metabolic steps up-stream and down-stream of testosterone are genetically variable and contribute substantially to the variation in disposition of testosterone, the most common doping agent in sports and in society. Large inter- and intra-ethnic variation in testosterone glucuronidation and excretion is described as well as the pit-falls in evaluation of testosterone doping test results. The hydrolysis and bioactivation of testosterone enanthate is also genetically variable yielding a 2-3 fold variation in excretion rate and serum concentration, thereby implicating a substantial variation in 'efficacy' of testosterone. Given this situation it is logical to adopt the new findings in the doping control programme. The population based cut-off level for the testosterone : epitestosterone ratio should be replaced by a Bayesian interpretation of consecutive tests in the same individual. When combined with the above genetic information the sensitivity of the test is considerably improved. The combination of the three approaches should reduce the rate of falsely negative or positive results and the number of expensive follow-up tests, stipulated by the World Anti-Doping Agency.
Topics: Androgens; Doping in Sports; Epitestosterone; Genetic Variation; Humans; Substance Abuse Detection; Testosterone
PubMed: 22506612
DOI: 10.1111/j.1365-2125.2012.04294.x -
Andrology Feb 2022To improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal... (Review)
Review
BACKGROUND
To improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations.
OBJECTIVE
To compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age.
MATERIALS AND METHODS
A literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed.
DISCUSSION AND CONCLUSION
Endogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.
Topics: Age Factors; Aging; Circadian Rhythm; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Testosterone; Testosterone Congeners
PubMed: 34510812
DOI: 10.1111/andr.13108 -
Depression and Anxiety Dec 2022The purpose of this study was to investigate the psychiatric morbidity among men with abuse of anabolic steroids.
OBJECTIVE
The purpose of this study was to investigate the psychiatric morbidity among men with abuse of anabolic steroids.
METHODS
The design is a retrospectively matched cohort study. Five hundred and fourty-five males, who tested positive for anabolic steroids in Danish fitness centers during the period January 3, 2006 to March 1, 2018, were matched with 5450 randomly chosen male controls. Data was cross-referenced with seven national registers pertaining to information about education, employment status, and psychiatric comorbidity. Main outcomes and measures were prescription of psychopharmacological treatment.
RESULTS
The incidence of treatment with anxiolytics (HR: 2.34, 95% CI: 1.62-3.38) and antipsychotics (HR: 2.69, 95% CI: 1.99-3.63) displayed a remarkable increase in the years following doping sanction, compared to the control group. The prevalence of antidepressant use was already markedly elevated several years before doping sanction, but also displayed a higher incidence in the years following sanction (HR: 1.65, 95% CI: 1.28-2.13). The associations remained highly significant after controlling for socioeconomic factors.
CONCLUSION
Anabolic steroids use is strongly associated with psychiatric morbidity.
Topics: Male; Humans; Anabolic Agents; Cohort Studies; Retrospective Studies; Testosterone Congeners; Incidence
PubMed: 36281632
DOI: 10.1002/da.23287