Androgen loss therapy ( ADT ), also called androgen suppression therapy , is an antihormone therapy whose primary use is in treating prostate cancer. Prostate cancer cells usually require androgen hormones, such as testosterone, to grow. ADT reduces androgen hormone levels, with drugs or surgery, to prevent prostate cancer cells from developing. Pharmacy approaches include antiandrogen and chemical castration.
Several studies have concluded that ADT has shown benefits in patients with metastatic disease, and in addition to radiation therapy in patients with advanced local disease, as well as those with locally at-risk high risk or unfavorable high risk. However, in patients with low-risk prostate cancer, ADT has shown no survival advantage, and significant harm, such as impotence, diabetes and bone loss.
Therapy can also eliminate cancer cells by inducing aging deposition of orrogen deprivation. Lowering androgen levels or stopping them into prostate cancer cells often make prostate cancer shrink or grow slower for a while. However, this treatment needs to be combined with radiation therapy (RT) because ADT itself does not eradicate cancer; it only reduces its aggressiveness.
Video Androgen deprivation therapy
Type
Operational based methods
- Orchiectomy (surgical castration)
- This consists of removing the testicles, organs in which androgens are synthesized, from cancer patients. This is the most radical treatment to end androgen production. In addition this is the easiest and cheapest. The main disadvantage is that surgical castration is a permanent method.
Drug-based methods
The synthesis of testosterone is mediated by a process chain that begins in our brain. When our body detects low testosterone levels, the hypothalamus begins to produce LHRH, a hormone that, once received by the pituitary gland, activates LH synthesis (Luteinizing hormone). LH runs into the testicles where it induces the formation of testosterone. There are two methods of androgen deprivation therapy based on drugs. One works prevents the pituitary gland from releasing LH and the other blocks the body's ability to use androgens.
- Chemical castration
- There are two different drugs, LHRH agonists and antagonists, which decrease the amount of testosterone made by the testes. They work to inhibit the formation of LH in the pituitary gland. LHRH agonists result in a sudden increase in testosterone levels followed by a large decrease, a process called flare , whereas LHRH antagonists directly decrease the amount of testosterone. Some of the most common LHRH agonists and antagonists are leuprolide, goserelin, triptorelin, histrelin and degarelix.
- These drugs are injected under the skin that achieve the same results as surgical castration. Although much more expensive, men tend to prefer this option because they are usually reluctant to cut their testicles.
- Antiandrogen therapy
- The adrenal glands are found as centers of androgen production even after castration. Therefore a complementary treatment was developed that uses antiandrogens to block the body's ability to use any androgen. The prostate cells contain Androgen Receptor (AR), which when stimulated by androgens such as testosterone, promotes growth and maintains prostate differentiation. However, this pro-growth signal can be a problem when it occurs in cancer cells. Antiandrogens can enter the cells and prevent the binding of testosterone to the receptor protein, due to its higher affinity for Androgen Receptors.
- The main antagonists are cyproterone acetate, flutamide, nilutamide, bicalutamide, and enzalutamide all of which are administered in the form of oral pills. New antidrogens targeting the synthesis of testosterone (abiraterone acetate and seviteronel) or nuclear translocation of AR (enzalutamide, apalutamide, and darolutamide), and combined therapy (galeterone) have been developed recently and can function to better target androgen-responsive cells in combination with ADT. But it may also have an adverse negative role in CRPC development.
Maps Androgen deprivation therapy
Effects on male sexuality
Normal male sexuality seems to rely on very specific and complex hormonal patterns that are not fully understood. One study showed that ADT may alter the hormonal balance necessary for male sexual activity. As we age, testosterone levels fall by about 1% a year after age 30; However, it is important to determine whether low testosterone is caused by normal aging, or illness, such as hypogonadism. Testosterone plays an important role in sexual function; therefore, declining testosterone levels can naturally lead to a decrease in normal sexual function. A further decrease in testosterone serum may adversely affect normal sexual function, leading to a decrease in the quality of life.
Erectile dysfunction is not uncommon after radical prostatectomy and men undergoing ADT in addition to this tend to show a further decrease in their ability to perform penetration relationships, as well as their desire to do so. A study that looked at differences in the use of GnRH-A (and androgen suppressant) or orchiectomy reports differences in sexual interest, erectile experience, and prevalence participate in sexual activity. Men who reported no increased sexual interest increased from 27.6% to 63.6% after orchiectomy, and from 31.7% to 58.0% after GnRH-A; men who did not experience an erection increased from 35.0% to 78.6%; and men who did not report engaging in sexual activity increased from 47.9% to 82.8% after orchiektomi and 45.0% to 80.2%. This study shows that GnRH-A and orchiectomy have similar effects on sexual function. A vicious circle that lowers testosterone levels leads to a decrease in sexual activity, which in turn causes free and total free testosterone levels to fall further. This shows the importance of androgens to maintain sexual structure and function.
Adverse effects
Although the androgen axis targeting has clear therapeutic benefits, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. Androgen removal has been shown to activate the epithelial-mesencalal (EMT) transition, transdiferensial neuroendocrine (NEtD) and gene programs such as cancer stem cells.
- EMT has established a role in promoting the biological phenotype associated with tumor development (migration/invasion, tumor cell survival, cancer stem cell trait, radiation resistance and chemotherapy) in several types of human cancers.
- NETD in prostate cancer is associated with resistance to therapy, visceral metastasis, and aggressive disease.
- The phenotype of Stem Cell Cancer is associated with recurrence of disease, metastasis, and cell survival in circulation as circulating tumor cells.
Thus, activation of these programs through inhibition of the androgen axis provides the mechanism by which tumor cells can adapt to promote recurrence and disease progression.
Orchiektomi, LHRH analogue and LHRH antagonist can cause the same side effect, due to changes in sex hormone (testosterone) level.
A program has been developed for patients and their partners to recognize and manage the more aggravating side effects of androgen deprivation therapy. One of the programs built around the 2014 book "Androgen Deprivation Therapy: An Important Guide to Prostate Cancer Patients and the Pure", supported by the Canadian Urological Association.
One recent study suggests ADT may increase the risk of Alzheimer's disease, and increased risk may be related to ADT duration.
See also
- Estrogen deprivation therapy
- Maximum androgen blockade
References
Source of the article : Wikipedia
0 Comments