Androgen Deprivation Therapy

Androgen refers to male sex hormones that are secreted by gonads (such as testes in males and ovaries in females). The androgens are responsible for vital reproductive and sexual functions in males and females. Among male androgens, testosterone is the most important hormone. The role of male sex hormones after puberty is to develop a boy into a sexually mature adult who is able to reproduce and impregnate a female partner via sexual intercourse. Androgen secretion increases after puberty and peaks in the adult years (20s-30s).

Androgen deprivation therapy is frequently utilized for the management of certain histological varieties of prostate cancer. Previously, known as hormone therapy, ADT is recommended when prostate cancer is progressing or refractory to conventional therapies. Here is all you should know about the Androgen deprivation therapy.

What Is The Mode Of Action Of Androgen Deprivation Therapy?

Before understanding the mode of action of ADT; it is important to learn about the normal functions of androgens:

Testosterone is the key male sex hormone (or androgen) that is required for the development of male sexual characteristics, such as development of penis and testes and growth of facial and body hair. It also helps in the production of sperms due to stimulatory action of the Sertoli cells of testes. Testosterone is not just essential for sexual functions but is also important for overall health and development; such as growth of bones and muscles. Furthermore, testosterone also exert its positive effects on the mood, sexual drive, intellectual thinking and problem solving and mental capacity.

Androgen deprivation therapy acts by either inhibiting the production of testosterone or by peripherally blocking testosterone activity on tissues and cells because the growth of both normal and cancerous cells in the prostate glands depends on the activity of androgens (more specifically, testosterone).

How ADT Helps In Prostate Cancer Management?

ADT reduces the growth of prostate cancer but cannot completely cure the malignancy with solo therapy. It can also help in subsiding the unwanted effects of prostate cancer for some time by reducing the bulk of cancerous mass (especially in patients who are not ideal candidates for surgical intervention). In some men, ADT may not work and cancer cells may start to grow again; in which case doctors suggest other options (as well as other forms of ADT).

When Is ADT Used To Treat Prostate Cancer?

Androgen deprivation therapy is a standard treatment used for aggressive and advanced prostate cancers i.e. cancer which has spread from prostate glands to other organs of body. The key role of ADT is eliminating the source (i.e. male sex hormones/ androgens) that promotes the growth of tumor.

It can also be used for:

• Localized prostate cancer i.e. cancer is only in prostate gland but surgery and radiotherapy are not the best option due to age of the patient (or comorbidities).
• ADT can be used in conjunction with radiotherapy in certain cancers which are more likely to spread quickly.
• Reoccurrence of prostate cancer after surgery or radiotherapy.
• Before radiotherapy so that radiation can work more efficiently.

What Are Other Management Options To Address Prostate Cancer Besides ADT?

Depending upon patient factors and response to ADT, some alternative treatment options include:

• Orchidectomy, the surgical removal of testes: Testosterone production can be completely stopped with this procedure. In the past, Orchidectomy, procedure was the treatment of choice, but due to availability of less invasive treatments, fewer men opt for Orchidectomy today.
• Antiandrogens: Sometimes, along with orchidectomy or gonadotrophin- releasing-hormone (GnRH) agonists another pharmacological agent is prescribed, known as antiandrogens. These pharmacological agents are given to inhibit the action of testosterone on the prostate gland, produced in other parts of body besides testes (e.g. Adrenal glands).
• Abiraterone and enzalutamide are two recently introduced pharmacological agents which are advised when other forms of ADT stops working. Usually these drugs are taken in combination with gonadotrophin- releasing-hormone (GnRH) agonists.

References

1. Karantanos, T., Corn, P. G., & Thompson, T. C. (2013). Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene, 32(49), 5501-5511.

2. Gregory, C. W., He, B., Johnson, R. T., Ford, O. H., Mohler, J. L., French, F. S., & Wilson, E. M. (2001). A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer research, 61(11), 4315-4319.

3. Roach, M., Bae, K., Speight, J., Wolkov, H. B., Rubin, P., Lee, R. J., ... & Pilepich, M. V. (2008). Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. Journal of Clinical Oncology, 26(4), 585-591.