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European Urology May 2016The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has... (Review)
Review
CONTEXT
The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer.
OBJECTIVE
To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer.
EVIDENCE ACQUISITION
We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer.
EVIDENCE SYNTHESIS
The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events.
CONCLUSIONS
An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life-and the ability of testosterone therapy to mitigate these effects-has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency.
PATIENT SUMMARY
In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.
Topics: Androgens; Contraindications, Drug; Hormone Replacement Therapy; Humans; Male; Prostatic Neoplasms; Testosterone
PubMed: 26719015
DOI: 10.1016/j.eururo.2015.12.005 -
Hormones (Athens, Greece) Mar 2023
Topics: Humans; Hydrocortisone; COVID-19; Dehydroepiandrosterone Sulfate; Dehydroepiandrosterone
PubMed: 36374475
DOI: 10.1007/s42000-022-00417-3 -
International Journal of Molecular... Dec 2022Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the... (Review)
Review
Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency.
Topics: Humans; Male; Female; Mice; Animals; Testosterone; Androgens; Virilism; Mutation; Dihydrotestosterone; 17-Hydroxysteroid Dehydrogenases
PubMed: 36555196
DOI: 10.3390/ijms232415555 -
Environmental Research Dec 2022Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels.
OBJECTIVE
We conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women.
METHODS
We included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors.
RESULTS
In premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results.
CONCLUSION
Our findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.
Topics: Androgens; Androstenedione; Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Estrone; Female; Gonadal Steroid Hormones; Humans; Sex Hormone-Binding Globulin; Testosterone
PubMed: 36088991
DOI: 10.1016/j.envres.2022.114285 -
The Canadian Journal of Urology Aug 2021
Topics: Androgen Antagonists; Humans; Male; Prostatic Neoplasms; Testosterone
PubMed: 34378508
DOI: No ID Found -
Minerva Urologica E Nefrologica = the... Jun 2019Adult-onset hypogonadism is used to define androgen deficiency and its associated symptoms commonly occurring in middle-aged and elderly men, who are unable to mount an... (Review)
Review
Adult-onset hypogonadism is used to define androgen deficiency and its associated symptoms commonly occurring in middle-aged and elderly men, who are unable to mount an adequate compensatory gonadotropin response but may also have an element of testicular failure. It often occurs in relation with chronic metabolic conditions such as diabetes and the metabolic syndrome. There is a growing demand from elderly men for testosterone therapy. The physician should therefore be well-informed so as the patient can make an informed decision. Indeed, testosterone therapy in older men has been a matter of debate, especially with regard to its impact on cardiovascular events and mortality. Not all studies have reported consistent results regarding its effect on diabetes, obesity and the metabolic syndrome. In contrast, it appears to improve sexual, physical function and bone density and it does not appear to increase the risk of prostate cancer; however, it increases hematocrit and hemoglobin levels. Therefore, testosterone therapy might provide significant beneficial effects in older symptomatic hypogonadal men; treatment should be individualized, and comorbidities addressed. Further research is required into its long-term effects.
Topics: Aged; Aged, 80 and over; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Middle Aged; Testosterone
PubMed: 30700083
DOI: 10.23736/S0393-2249.19.03301-0 -
Respirology (Carlton, Vic.) Mar 2022
Topics: Androstadienes; Asthma; Fluticasone; Humans
PubMed: 35104914
DOI: 10.1111/resp.14213 -
Biomolecules Nov 2022Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone,... (Review)
Review
Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). These steroids modulate the development and function of immune response cells. Androgens are generally attributed to immunosuppressive effects; however, this is not always the case. Variations in the concentrations of these hormones induce differences in the innate, humoral, and cell-mediated immune response, which is concentration dependent. The androgens at the highest concentration in the organism that bind to the androgen receptor (AR) are DHEA and testosterone. Therefore, in this work, we review the effects of DHEA and testosterone on the immune response. The main findings of this review are that DHEA and testosterone induce similar but also opposite effects on the immune response. Both steroids promote the activation of regulatory T cells, which suppresses the Th17-type response. However, while testosterone suppresses the inflammatory response, DHEA promotes it, and this modulation is important for understanding the involvement of androgens in infectious (bacterial, viral and parasitic) and autoimmune diseases, as well as in the sexual dimorphism that occurs in these diseases.
Topics: Testosterone; Dehydroepiandrosterone; Androgens; Dihydrotestosterone; Adaptive Immunity
PubMed: 36551196
DOI: 10.3390/biom12121768 -
Mayo Clinic Proceedings Apr 2023To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of...
OBJECTIVE
To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17β-estradiol.
PATIENTS AND METHODS
Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17β-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant.
RESULTS
Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17β-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17β-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17β-estradiol levels did not differ between male patients with COVID-19 and male HVs.
CONCLUSION
Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.
Topics: Humans; Male; Female; Middle Aged; Adult; Estradiol; Dihydrotestosterone; COVID-19; Testosterone
PubMed: 36872195
DOI: 10.1016/j.mayocp.2022.12.018 -
The Journal of Steroid Biochemistry and... Jun 2019The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other...
The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other primates. The human adrenal also secretes 11-oxygenated androgens (11-oxyandrogens), including 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), of which 11OHT and 11KT are bioactive androgens. The 11-oxyandrogens, particularly 11KT, have been recognized as biologically important testicular androgens in teleost fishes for decades, but their physiological contribution in humans has only recently been established. Beyond fish and humans, however, the presence of 11-oxyandrogens in other species has not been investigated. This study provides a comprehensive analysis of a set of C steroids, including the traditional androgens and 11-oxyandrogens, across 18 animal species. As previously shown, serum DHEA and DHEAS were much higher in primates than all other species. Circulating 11-oxyandrogens, especially 11KT, were observed in notable amounts in male, but not in female trout, consistent with gonadal origin in fish. The circulating concentrations of 11-oxyandrogens ranged from 0.1 to 10 nM in pigs, guinea pigs and in all the primates studied (rhesus macaque, baboon, chimpanzee and human) but not in rats or mice, and 11OHA4 was consistently the most abundant. In contrast to fish, serum 11KT concentrations were similar in male and female primates for each species, despite significantly higher circulating testosterone in males, suggesting that 11KT production in these species is not testis-dependent and primarily originates from adrenal-derived 11-oxyandrogen precursors.
Topics: Androgens; Animals; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Male; Species Specificity; Testosterone
PubMed: 30959151
DOI: 10.1016/j.jsbmb.2019.04.005