Hormones are substances that are made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs.
Androgens (male sex hormones) are a class of hormones that control the development and maintenance of male characteristics. The most abundant androgens in men are testosterone and dihydrotestosterone (DHT).
Androgens are required for normal growth and function of the prostate, a gland in the male reproductive system that helps make semen. Androgens are also necessary for prostate s to grow. Androgens promote the growth of both normal and ous prostate cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells (1). Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow (2).
Metastatic Hormone Sensitive Prostate Cancer (mhspc): Advances And Treatment Strategies In The First Line Setting
Almost all testosterone is produced in the testicles; a small amount is produced by the adrenal glands. Although prostate cells do not normally make testosterone, some prostate cells acquire the ability to do so (3).
Early in their development, prostate s need androgens to grow. Hormone therapies, which are treatments that decrease androgen levels or block androgen action, can inhibit the growth of such prostate s, which are therefore called castration sensitive, androgen dependent, or androgen sensitive.
Most prostate s eventually stop responding to hormone therapy and become castration (or castrate) resistant. That is, they continue to grow even when androgen levels in the body are extremely low or undetectable. In the past, these tumors were also called hormone resistant, androgen independent, or hormone refractory; however, these terms are rarely used now because the tumors are not truly independent of androgens for their growth. In fact, some newer hormone therapies have become available that can be used to treat tumors that have become castration resistant.
Ai May Predict Benefit With Hormone Therapy Plus Radiotherapy In Prostate Cancer
Androgen production in men. Drawing shows that testosterone production is regulated by luteinizing hormone (LH) and luteinizing hormone-releasing hormone (LHRH). The hypothalamus releases LHRH, which stimulates the release of LH from the pituitary gland. LH acts on specific cells in the testes to produce the majority of testosterone in the body. Most of the remaining androgens are produced by the adrenal glands. Androgens are taken up by prostate cells, where they either bind to the androgen receptor directly or are converted to dihydrotestosterone (DHT), which has a greater binding affinity for the androgen receptor than testosterone.
Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate and the first type of hormone therapy that most men with prostate receive. This form of hormone therapy (also called androgen deprivation therapy, or ADT) includes:
Treatments that block the action of androgens in the body (also called antiandrogen therapies) are typically used when ADT stops working. Such treatments include:
Sequencing Of Systemic Therapies In The Management Of Advanced Prostate Cancer In India: A Delphi Based Consensus
Early-stage prostate with an intermediate or high risk of recurrence. Men with early-stage prostate that has an intermediate or high risk of recurrence often receive hormone therapy before, during, and/or after radiation therapy, or after prostatectomy (surgery to remove the prostate gland) (7). Factors that are used to determine the risk of prostate recurrence include the grade of the tumor (as measured by the Gleason score), the extent to which the tumor has spread into surrounding tissue, and whether tumor cells are found in nearby lymph nodes during surgery.
The use of hormone therapy (alone or in combination with chemotherapy) before prostatectomy has not been shown to be of benefit and is not a standard treatment. More intensive androgen blockade prior to prostatectomy is being studied in clinical trials.
Relapsed/recurrent prostate . Hormone therapy used alone is the standard treatment for men who have a prostate recurrence as documented by CT, MRI, or bone scan after treatment with radiation therapy or prostatectomy.
Management Of Prostate Cancer
Hormone therapy is sometimes recommended for men who have a biochemical recurrence—a rise in prostate-specific antigen (PSA) level following primary local treatment with surgery or radiation—especially if the PSA level doubles in fewer than 3 months.
Advanced or metastatic prostate . ADT used alone was for many years the standard treatment for men who are found to have metastatic disease (i.e., disease that has spread to other parts of the body) when their prostate is first diagnosed (8). More recently, clinical trials have shown that such men survive longer when treated with ADT plus another type of hormone therapy (abiraterone/prednisone, enzalutamide, or apalutamide) than when treated with ADT alone (9–17).
In addition, an NCI-sponsored trial showed that men with hormone-sensitive metastatic prostate lived longer when treated with the chemotherapy drug docetaxel (Taxotere) at the start of ADT than men treated with ADT alone (18). Men with the most extensive metastatic disease appeared to benefit the most from the early addition of docetaxel.
Hormone Therapy In Prostate Cancer 1
Although hormone therapy can delay progression of disease and may be able to prolong survival, it can also have substantial side effects. Men should discuss the risks and potential benefits of hormone therapy with their doctor in light of their own medical concerns.
Palliation of symptoms. Hormone therapy is sometimes used alone for palliation or prevention of local symptoms in men with localized prostate who are not candidates for surgery or radiation therapy (19). Such men include those with a limited life expectancy, those with locally advanced tumors, and/or those with other serious health conditions.
Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual man’s prostate . Therefore, men who take hormone therapy for more than a few months are regularly tested to determine the level of PSA in their blood. An increase in PSA level may indicate that a man’s has started growing again. A PSA level that continues to increase while hormone therapy is successfully keeping androgen levels extremely low is an indicator that a man’s prostate has become resistant to the hormone therapy that is currently being used.
Neoadjuvant Hormonal Therapy Before Radical Prostatectomy In High Risk Prostate Cancer
Men with castration-resistant prostate who receive these treatments will continue to receive ADT (e.g., an LHRH agonist) to keep testosterone levels low, because an increase in testosterone could lead to tumor progression in some men (20).
Randomized clinical trials in men with metastatic castration-resistant prostate have shown improved survival among men receiving abiraterone or enzalutamide in addition to ADT compared with those receiving ADT alone, whether or not they have previously received chemotherapy (11, 12, 15–17).
Similarly, in randomized clinical trials, men with nonmetastatic castration-resistant prostate who received apalutamide, enzalutamide, or darolutamide in addition to ADT lived longer than those who received ADT alone (21–23).
The Current State Of Hormonal Therapy For Prostate Cancer
Researchers have investigated whether a technique called intermittent androgen deprivation can delay the development of hormone resistance. With intermittent androgen deprivation, hormone therapy is given in cycles with breaks between drug administrations, rather than continuously. An additional potential benefit of this approach is that the temporary break from the side effects of hormone therapy may improve a man’s quality of life.
Randomized clinical trials have shown similar overall survival with continuous ADT or intermittent ADT among men with metastatic or recurrent prostate , with a reduction in some side effects for intermittent ADT (24–26).
Antiandrogens can cause diarrhea, breast tenderness, nausea, hot flashes, loss of libido, and erectile dysfunction. The antiandrogen flutamide may damage the liver, and enzalutamide and apalutamide may cause fractures. Darolutamide may avoid some central nervous system–related side effects seen with enzalutamide and apalutamide, such as seizures and falls.
Treatment Options After Your First Hormone Therapy
Estrogens avoid the bone loss seen with other kinds of hormone therapy, but they increase the risk of cardiovascular side effects, including heart attacks and strokes. Because of these side effects, estrogens are rarely used today as hormone therapy for prostate .
Although the addition of ADT to radiation therapy has been shown to increase survival for men with high-risk prostate , it worsens some adverse effects of radiotherapy, particularly sexual side effects and vitality (28). Many of the side effects of ongoing hormone therapy also become stronger the longer a man takes hormone therapy (27).
Men who lose bone mass during long-term hormone therapy may be prescribed drugs to slow or reverse this loss. The drugs zoledronic acid (Zometa) and alendronate (Fosamax) (both of which belong to a class of drugs called bisphosphonates) can be used to increase bone mineral density in men who are undergoing hormone therapy (29, 30), as can a newer drug, denosumab (Prolia), which increases bone mass through a different mechanism (31). However, drugs to treat bone loss are associated with a rare but serious side effect called osteonecrosis of the jaw (20).
Combined Hormone And Radiotherapy Treatment In Local Treatment And Biochemical Recurrence Of Prostate Cancer
Exercise may help reduce some of the side effects of hormone therapy, including bone loss, muscle loss, weight gain, fatigue, and insulin resistance (20, 32). Several clinical trials are examining whether exercise can reverse or prevent side effects of hormone therapy for prostate .
The sexual side effects of hormone therapy for prostate can be some of the most difficult to deal with. Erectile dysfunction drugs such as sildenafil (Viagra) do not usually work for men undergoing hormone therapy because these drugs do not address the loss of libido (sexual desire) that is associated with a lack of androgens.
More information about the sexual side effects of treatment can be found on
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