How Is Hormone Therapy Used To Treat Hormone
Hormone therapy may be used in several ways to treat hormone-sensitive prostate cancer, including:
Early-stage prostate cancer with an intermediate or high risk of recurrence. Men with early-stage prostate cancer that has an intermediate or high risk of recurrence often receive hormone therapy before, during, and/or after radiation therapy, or after prostatectomy . Factors that are used to determine the risk of prostate cancer recurrence include the grade of the tumor , 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 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 cancer. Hormone therapy used alone is the standard treatment for men who have a prostate cancer recurrence as documented byCT, MRI, or bone scan after treatment with radiation therapy or prostatectomy.
Hormone therapy is sometimes recommended for men who have a “biochemical” recurrencea rise in prostate-specific antigen level following primary local treatment with surgery or radiationespecially if the PSA level doubles in fewer than 3 months.
Cap And Normal Or High Serum Testosterone Levels
Studies examining the relationship between normal and high pretreatment serum testosterone levels and CaP have yielded often conflicting results . A number of studies have reported an increased risk of CaP with high pretreatment serum testosterone levels. In 1996, Gann et al. reported a positive association between men in the highest quartile of testosterone levels and an increased risk of CaP . Similarly, a meta-analysis published in 2000 found that when stratified by pretreatment testosterone levels, men in the highest quartile were 2.34 times more likely to develop CaP . While this meta-analysis adjusted for BMI, age and serum hormone levels, it only incorporated data from two studies . A 2007 study enrolling 420 men found that while there was no significant relationship between pretreatment testosterone levels and prostate biopsy results, men with PSA < 10 ng/mL eventually diagnosed with CaP had higher serum testosterone levels than men diagnosed with benign prostatic disease .
Table 2
The relationship between Gleason score and high serum testosterone levels has also been examined. In 2014, Porcaro et al. found a relationship between men with higher normal pretreatment testosterone levels and Gleason sum 8 disease when compared to men with lower testosterone . In 2016, Porcaro et al. found that high testosterone levels predicted an increased risk of Gleason score upgrading .
Treatment To Lower Androgen Levels From Other Parts Of The Body
LHRH agonists and antagonists can stop the testicles from making androgens, but cells in other parts of the body, such as the adrenal glands, and prostate cancer cells themselves, can still make male hormones, which can fuel cancer growth. Some drugs can block the formation of androgens made by these cells.
Abiraterone blocks an enzyme called CYP17, which helps stop these cells from making androgens.
Abiraterone can be used in men with advanced prostate cancer that is either:
- Castration-resistant
This drug is taken as pills every day. It doesnt stop the testicles from making testosterone, so men who havent had an orchiectomy need to continue treatment with an LHRH agonist or antagonist. Because abiraterone also lowers the level of some other hormones in the body, prednisone needs to be taken during treatment as well to avoid certain side effects.
Ketoconazole , first used for treating fungal infections, also blocks production of androgens made in the adrenal glands, much like abiraterone. It’s most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working.
Ketoconazole also can block the production of cortisol, an important steroid hormone in the body, so men treated with this drug often need to take a corticosteroid .
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Do Gnrh Agonists Have Unique Properties
Heyns and colleagues compared T suppression in 140 and 137 men receiving monthly leuprolide acetate versus triptorelin pamoate, respectively. The primary endpoint of the trial was the percentage of men whose serum T declined and remained at or below castration level during the 9-month treatment duration. The probability of maintenance of castration T levels is shown at monthly intervals throughout the 9-month study . A Kaplan-Meier survival analysis for the maintenance of castration levels measured 3.75 mg triptorelin pamoate or 7.5 mg leuprolide. The cumulative maintenance of castration levels were 96% and 91% for triptorelin pamoate and leuprolide, respectively . In this study, a greater proportion of men maintained medical castration with triptorelin pamoate at 29 days.
The maintenance of castration in men treated with triptorelin pamoate, 3.75 mg , or leuprolide acetate, 7.5 mg , for 9 months . Reproduced with permission from Heyns CF et al.
Mean serum testosterone levels were analyzed every 28 days in 277 men receiving androgen deprivation with either leuprolide acetate or triptorelin pamoate. These levels fell below the predefined levels for medical castration at 29 days and 57 days for 91% and 98% of subjects in the triptorelin pamoate group and 99% and 97% of the subjects in the leuprolide group. Although the mean difference was significant between the groups at 29 days, it was not significant at 57 days. Reproduced with permission from Heyns CF et al.
Prostate Cancer In Men Receiving Exogenous Testosterone
To date no study or review has documented any direct evidence that testosterone therapy increases incident prostate cancer risk. However, it is still difficult to argue that androgen replacement is safe since no long-term studies have been completed in large populations receiving exogenous androgens over many years. The question of whether androgen replacement increases prostate cancer incidence in an aging population has yet to be answered. The Institute of Medicine, recognizing the need for additional clinical trials to clarify the risks and benefits of testosterone replacement therapy , formed a committee to evaluate the present status of TRT in 2003. This was the most recent statement on the issue of TRT from the Institute of Medicine.
Even studies of TRT in men with high risk for incident prostate cancer because of preexisting prostatic intraepithelial neoplasia did not show an increased risk of prostate cancer. There has been one small study examining the risk of TRT in men with high-grade PIN. These men should presumably be at higher risk for prostate cancer development. After a year of TRT, only one patient with previous high-grade PIN had a detected prostate cancer. The study included 70 men overall 20 with high-grade PIN and 50 controls. This study suggests that TRT does not significantly increase the risk of incident cancer even in an already high-risk population.
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Prostate Cancer Information: Prostate Cancer Hormone Therapy
Prostate cancer hormone therapy is the systemic ablation of the bodys testosterone which, for a period of time, will slow or stop the growth and spread of prostate cancer. Hormone therapy may also be called androgen deprivation or androgen ablation.
The Role of Hormones in Prostate Cancer The male sex hormone, testosterone, causes the growth of the prostate gland and other sex organs in the developing male. Even as men pass through the age of puberty, testosterone continues to contribute to the growth of the organ. Testosterone will fuel the growth of any prostatic cell: the chemical cannot discriminate between the receptors of healthy tissue and cancerous tissue. Prostate cancer hormone therapy removes the chemical that feeds cells and can stop or slow the growth and spread of the tumor.
Where does Testosterone Come From? A chemical sequence in the brain signals the testicles, which make 90% of the bodys hormones, to begin production. A structure in the brain called the hypothalamus continually monitors the blood stream for adequate levels of testosterone. If these levels drop, the hypothalamus releases a chemical called GnRH or LHRH . GnRH acts as a messenger and travels to the pituitary gland where it plugs into designated receptors.
How is Hormone Therapy Administered? There are four basic methods androgen deprivation: castration, estrogen, anti androgens, and combine androgen blockade.
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High Dose Testosterone Causes Dna Damage And Suppresses Prostate Cancer Growth
Posted July 28, 2020 Michael Schweizer, M.D., University of Washington
Since the discovery that blocking hormones can slow the growth of cancer cells in the 1960s, androgen deprivation therapy has been the standard treatment for prostate cancer. This mode of therapy seeks to either stop the production or the activity of androgens, such as testosterone, in the body to treat the disease – a process termed castration. This depletion of testosterone is associated with many debilitating side effects for men that lessen the quality of life, such as lower energy and diminished libido. Eventually, prostate cancer cells often mutate to increase sensitivity towards low concentrations of testosterone to trigger tumor growth leading to castration resistance. This increasing arms race is difficult to control and often progresses to metastatic disease and death.
Based on their investigation, they have launched a Phase II clinical trial testing the combination of high dose testosterone with Olaparib, a drug that inhibits DNA damage repair and has recently received FDA approval for the treatment of prostate cancer. Importantly, the increase of testosterone associated with this treatment helps patients feel more active during treatment, improving their quality of life. They hope that combining these therapies will be synergistically effective for treating castration-resistant prostate cancer.
Publications:
Link:
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About The Southwest Prostate Cancer Symposium
The Southwest Prostate Cancer Symposium is a multi-day conference that seeks to educate urologists, radiation oncologists, medical oncologists, and other healthcare professionals involved in the treatment of prostate cancer. The topics focus on current technical aspects of diagnosis and treatment of localized and advanced disease, particularly regarding imaging, technology, and training in the related devices. Dr. Morgentaler presented this lecture during the 24th SPCS in 2019. In 2020, the 25th SPCS will also offer training sessions involving imaging, scanning, and prostate cancer treatment related devices on site. Please visit this page in order to register for future SPCS meetings.
New Testosterone Derivatives As Semi
Volume 11, Issue 6, 2015
Page: Pages: 9
Abstract
Title:New Testosterone Derivatives as Semi-Synthetic Anticancer Agents Against Prostate Cancer: Synthesis and Preliminary Biological Evaluation
Volume: 11Issue: 6
Nathalie Morin, Julie Bruneau, Sebastien Fortin, Kevin Brasseur, Valerie Leblanc, Eric Asselin and Gervais Berube
Affiliation:
Keywords:Testosterone-7 -linked amides, prostate cancer, anticancer agents.
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How Will I Know If My Treatment Is Working
You will have regular appointments to check how well your treatment is working and monitor any side effects. These will involve regular prostate specific antigen blood tests to measure the amount of PSA in your blood.
PSA is a protein produced by cells in your prostate and also by prostate cancer cells, even if they have spread to other parts of your body. The PSA test is a good way to check how well your treatment is working.
How your treatment is monitored will depend on whether youre having hormone therapy as part of treatment that aims to cure your prostate cancer, or having life-long hormone therapy to keep advanced prostate cancer under control.
You can contact your nurse at the hospital, or our Specialist Nurses, between appointments if you have any side effects or symptoms that youd like to talk about.
Side Effects Of Hormone Therapy
Most side effects experienced by patients receiving HT are caused by low testosterone. The three most reported side effects are fatigue, hot flashes and sexual changes, including decreased libido and reduced erectile function.
Many of these side effects develop over time. Patients treated for eight months or less time are less likely to experience many of them, although some, such as hot flashes and sexual side effects, usually manifest within the first four to six weeks. Most of these side effects are reversible, diminishing or disappearing when the therapy is stopped and testosterone levels recover.
Not all patients experience all side effects, and there is much variability in their severity.
Here are the side effects patients most often report, along with suggestions for minimizing them:
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When Hormone Therapy Is Indicated
HT can be administered before, during or after a localized treatment, such as radical prostatectomy, radiation, high-intensity focused ultrasound or cryotherapy. When given before a localized treatment, it is called neoadjuvant therapy. When given after localized treatment without evidence of prostate cancer recurrence, it is called adjuvant therapy. When HT is prescribed after localized treatment for a prostate cancer recurrence, it is called salvage therapy. If a patient’s PSA starts rising after a radical prostatectomy, HT is typically given in combination with radiation therapy. Treatment recommendations are based on each patient’s specific circumstances.
Sometimes we give neoadjuvant HT while the patient is deciding on his primary treatment or to reduce the tumor’s size before starting primary treatment. Neoadjuvant HT will usually slow or stop cancer growth for a period of time.
Many radiation oncologists use HT along with radiation treatment in the belief that HT weakens cancer cells so that they’re more susceptible to destruction by the radiation. Clinical studies have suggested a synergy between radiation therapy and hormone therapy meaning they work better together. Clinical trials have shown improved outcomes for patients who receive combined therapy.
Who Can Have Hormone Therapy
Hormone therapy is an option for many people with prostate cancer, but its used in different ways depending on whether your cancer has spread.
Localised prostate cancer
If your cancer hasnt spread outside the prostate , you might have hormone therapy alongside your main treatment. Hormone therapy can shrink the prostate and any cancer inside it, which makes the cancer easier to treat. It can also make your main treatment more effective. You might have hormone therapy:
- for six months before, during or after external beam radiotherapy
- for up to three years after external beam radiotherapy, if there is a risk of your cancer spreading outside the prostate
- for a few months before starting permanent seed brachytherapy, and before and after high dose-rate brachytherapy both are types of internal radiotherapy
- before having high-intensity focused ultrasound .
Hormone therapy is not usually given to men having surgery to remove their prostate .
Read more about localised prostate cancer.
Locally advanced prostate cancer
If your cancer has spread to the area just outside the prostate , you may have hormone therapy before, during and after radiotherapy. Hormone therapy can help shrink the prostate and any cancer that has spread, and make the treatment more effective.
You may be offered hormone therapy for up to six months before radiotherapy. And you may continue to have hormone therapy during and after your radiotherapy, for up to three years.
Advanced prostate cancer
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Questions To Ask Your Doctor Or Nurse
- What is the aim of treatment?
- What type of hormone therapy are you recommending for me and why?
- How often will I have my injections or implants?
- How will my treatment be monitored?
- How long will it be before we know if the hormone therapy is working?
- What are the possible side effects, and how long will they last?
- What will happen if I decide to stop my treatment?
- Are there any clinical trials that I could take part in?
Adverse Effects Of Adt
T suppression is associated with bone loss, which may also be influenced by other factors such as obesity, age, and sedentary lifestyle. Moreover, ADT and attendant bone demineralization is associated with an increased risk of skeletal fracture. Skeletal fractures are of particular concern, given their documented correlation with decreased overall survival in men with prostate cancer.
The morbidities of ADT should be considered in the context of the existing comorbidities of the patient when choosing palliative ADT. As per the AUA guidelines, ADT may be used for the palliation of symptomatic patients with more extensive or poorly differentiated tumors, whose life expectancy is too short to benefit from treatment with curative intent. When making treatment decisions about ADT, physicians and patients should discuss and review existing guidelines for lifestyle modifications, and the increased risk of adverse effects such as osteoporosis, fracture risks, obesity, alteration in lipids, diabetes and cardiovascular disease., Patients should be monitored with periodic follow-up evaluations including assessment of blood pressure, lipid profile, and glucose level. Patients with cardiac disease should receive appropriate secondary preventive measures as recommended by existing guidelines.,
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Patients On As At Risk For Developing Cap Or Who Have High Risk Cap
Few studies to date have studied TTh in men with active CaP and have reported predominantly positive outcomes in men with CaP, with a common theme of caution. A 2016 review concluded that although the data on using TTh in men on AS are limited, preliminary studies show no, or minimal, increased risk compared to the quality of life improvements seen with treatment of hypogonadism . Conversely, a 2011 study following 25 men with CaP reported highly variable outcomes after starting TTh. The authors urged caution in treating these patients and concluded that an international registry to collect more data would be the only way to address whether TTh was safe in men with CaP . While the preliminary studies of TTh in the setting of AS appear to demonstrate the relatively safety of treating hypogonadism with TTh in this setting, it is important to note that none of these studies were randomized or controlled and that more work must be done before unequivocally determining the safety of such treatment.