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==AR signaling== | ==AR signaling== | ||
AR has two mechanisms of action: the DNA binding-dependent (genomic AR signaling) and the DNA binding independent (non-genomic AR signaling). | AR has two mechanisms of action: the DNA binding-dependent (genomic AR signaling) and the DNA binding independent (non-genomic AR signaling). | ||
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===DNA-Binding dependent actions of the AR=== | ===DNA-Binding dependent actions of the AR=== | ||
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One of the problems associated with the use of T as a therapeutic agent in TRT are the delivery method, tending to have low efficacy orally administered <ref name="NR" /><ref name="SARMs therapy" /> and having some inconvenients with intramuscular injections or implants <ref name="NR" />. Also, the use of this hormone as a treatment could triggered a lot of AR widespread around the body and a long-term exposure to a high dose could lead to related side effects like erythrocytosis <ref name="NR" /><ref name="SARMs therapy" />, dyslipidemia, hepatotoxicity <ref name="SARMs therapy" /> and in some clinical trials it has been described an increase in cardiovascular risk <ref name="Testosterone" /><ref name="hypogonadism" />. | One of the problems associated with the use of T as a therapeutic agent in TRT are the delivery method, tending to have low efficacy orally administered <ref name="NR" /><ref name="SARMs therapy" /> and having some inconvenients with intramuscular injections or implants <ref name="NR" />. Also, the use of this hormone as a treatment could triggered a lot of AR widespread around the body and a long-term exposure to a high dose could lead to related side effects like erythrocytosis <ref name="NR" /><ref name="SARMs therapy" />, dyslipidemia, hepatotoxicity <ref name="SARMs therapy" /> and in some clinical trials it has been described an increase in cardiovascular risk <ref name="Testosterone" /><ref name="hypogonadism" />. | ||
Due to all these problems, some institutions like the FDA warn about the safety issues related with this therapy assessing the reduction of its use <ref name="Testosterone" /><ref name="hypogonadism" />. However, other agencies like the EMA supported by the European Academy of Andrology establish the practical use of this therapy in men’s hypogonadism <ref name="Testosterone" /><ref name="hypogonadism" />. So, there is still some controversy about its use, and it’s still currently studied in clinical trials <ref name="Testosterone" />. | Due to all these problems, some institutions like the FDA warn about the safety issues related with this therapy assessing the reduction of its use <ref name="Testosterone" /><ref name="hypogonadism" />. However, other agencies like the EMA supported by the European Academy of Andrology establish the practical use of this therapy in men’s hypogonadism <ref name="Testosterone" /><ref name="hypogonadism" />. So, there is still some controversy about its use, and it’s still currently studied in clinical trials <ref name="Testosterone" />. | ||
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===Antagonist: Steroid ARA=== | |||
The development of these drugs were one of the first approaches to treat prostate cancer, targeting AR activity by having a structure with an steroidal skeleton <ref name="ARA prostate" />. | The development of these drugs were one of the first approaches to treat prostate cancer, targeting AR activity by having a structure with an steroidal skeleton <ref name="ARA prostate" />. | ||
This kind of antiandrogens have another steroid receptor affinity (glucocorticoids receptor, progesterone receptor…) having low efficiency and some side effects like hepatotoxicity and increased cardiovascular risks <ref name="ARA prostate" />. Some examples are cyproterone acetate (CPA) <ref name="ARA prostate" /><ref name="bicalutamide">PMID: 15833816</ref><ref name="nonsteroidal">PMID: 16841196</ref> or megestrol acetate <ref name="ARA prostate" />. | This kind of antiandrogens have another steroid receptor affinity (glucocorticoids receptor, progesterone receptor…) having low efficiency and some side effects like hepatotoxicity and increased cardiovascular risks <ref name="ARA prostate" />. Some examples are cyproterone acetate (CPA) <ref name="ARA prostate" /><ref name="bicalutamide">PMID: 15833816</ref><ref name="nonsteroidal">PMID: 16841196</ref> or megestrol acetate <ref name="ARA prostate" />. | ||
===Agonist: Anabolic Androgen Steroids (AAs)=== | ===Agonist: Anabolic Androgen Steroids (AAs)=== | ||
These drugs have been produced since the middle of the 20th century <ref name="Steroids">PMID: 33148520</ref>. They have anabolic activity which improves muscular mass and physical function. However, their uncontrolled use and abuse lead to several side effects like: testicular atrophy, alopecia, gynecomastia in the case of males, and clitoral hypertrophy, menstrual irregularities in the case of women. Men and women can experience mood disorders and the chronic abuse could result in high risk of suffering cardiovascular disease and prostate cancer <ref name="Steroids" />. | These drugs have been produced since the middle of the 20th century <ref name="Steroids">PMID: 33148520</ref>. They have anabolic activity which improves muscular mass and physical function. However, their uncontrolled use and abuse lead to several side effects like: testicular atrophy, alopecia, gynecomastia in the case of males, and clitoral hypertrophy, menstrual irregularities in the case of women. Men and women can experience mood disorders and the chronic abuse could result in high risk of suffering cardiovascular disease and prostate cancer <ref name="Steroids" />. | ||