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How Long Can You Stay On Lupron For Prostate Cancer

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Drugs That Stop Androgens From Working

Intermittent Hormone Therapy for Prostate Cancer 101 | Ask a Prostate Expert, Mark Scholz, MD

Anti-androgens

For most prostate cancer cells to grow, androgens have to attach to a protein in the prostate cancer cell called an androgen receptor. Anti-androgens are drugs that also connect to these receptors, keeping the androgens from causing tumor growth. Anti-androgens are also sometimes called androgen receptor antagonists.

Drugs of this type include:

They are taken daily as pills.

In the United States, anti-androgens are not often used by themselves:

  • An anti-androgen may be added to treatment if orchiectomy or an LHRH agonist or antagonist is no longer working by itself.
  • An anti-androgen is also sometimes given for a few weeks when an LHRH agonist is first started. This can help prevent a tumor flare.
  • An anti-androgen can also be combined with orchiectomy or an LHRH agonist as first-line hormone therapy. This is called combined androgen blockade . There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH agonist alone. If there is a benefit, it appears to be small.
  • In some men, if an anti-androgen is no longer working, simply stopping the anti-androgen can cause the cancer to stop growing for a short time. This is called the anti-androgen withdrawal effect, although it is not clear why it happens.

Newer anti-androgens

Enzalutamide , apalutamide and darolutamide are newer types of anti-androgens. They can sometimes be helpful even when older anti-androgens are not.

These drugs are taken as pills each day.

Figure : How Hormone Therapy Affects The Androgen Cascade

The male sex hormones are known as androgens. Probably the best known hormone in this family is testosterone. Most androgens are produced in the testicles.

Androgens fuel the growth of prostate cells, including prostate cancer cells. Hormone therapy also known as androgen-deprivation therapy seeks to cut off the fuel supply. But different therapies work in different ways.

A. The hypothalamus releases pulses of LHRH, which signals the pituitary gland to release the hormones FSH and LH.

B. LH travels through the bloodstream. When it reaches the testicles, it binds to specialized cells that secrete testosterone into the bloodstream.

C. In the prostate, the enzyme 5-alpha-reductase converts testosterone and other types of androgens into dihydrotestosterone , which stimulates the growth of prostate cells and fuels the growth of cancer, if it is present.

Centrally acting agents

LHRH agonists flood the pituitary gland with messages to crank out LH. This causes a temporary surge of testosterone until receptors in the pituitary are overloaded. Then testosterone levels drop sharply.

The GnRH antagonist jams receptors in the pituitary gland so that it cannot respond to the pulses of LHRH sent by the hypothalamus. This prevents the LH signal from being sent and no testosterone is made in the testicles.

DES inhibits secretion of LHRH from the hypothalamus.

Peripherally acting therapies

Orchiectomy removes the testicles, preventing testosterone production.

Treatment To Lower Testicular Androgen Levels

Androgen deprivation therapy, also called ADT, uses surgery or medicines to lower the levels of androgens made by the testicles.

Orchiectomy

Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles, where most of the androgens are made. This causes most prostate cancers to stop growing or shrink for a time.

This is done as an outpatient procedure. It is probably the least expensive and simplest form of hormone therapy. But unlike some of the other treatments, it is permanent, and many men have trouble accepting the removal of their testicles. Because of this, they may choose treatment with drugs that lower hormone levels instead.

Some men having this surgery are concerned about how it will look afterward. If wanted, artificial testicles that look much like normal ones can be inserted into the scrotum.

LHRH agonists

Luteinizing hormone-releasing hormone agonists are drugs that lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called medical castration because they lower androgen levels just as well as orchiectomy.

With these drugs, the testicles stay in place, but they will shrink over time, and they may even become too small to feel.

  • Leuprolide mesylate

LHRH antagonists

Possible side effects

Many side effects of hormone therapy can be prevented or treated. For example:

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Why Is This Medication Prescribed

Leuprolide injection is used to treat the symptoms associated with advanced prostate cancer. Leuprolide injection is used in children 2 years of age or older to treat central precocious puberty . Leuprolide injection is used alone or with another medication to treat endometriosis . Leuprolide injection is also used with other medication to treat anemia caused by uterine fibroids . Leuprolide injection is in a class of medications called gonadotropin-releasing hormone agonists. It works by decreasing the amount of certain hormones in the body.

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Impact On Everyday Care

Fatima Karzai, M.D., of the Genitourinary Malignancies Branch in NCIs Center for Cancer Research, called relugolix an exciting option for men with advanced prostate cancer. Its most obvious role will be in men with advanced prostate cancer who also have cardiovascular disease, Dr. Karzai said.

Although trial participants who received relugolix had a more than 50% lower risk of serious cardiac events, she said its unclear exactly why it poses less of a threat to the heart. Some studies have suggested, she noted, that the difference in how the two drugs work may also influence how they affect plaque deposits in the cardiovascular system.

Relugolix is not the first GnRH antagonist to be approved by FDA to treat men with advanced prostate cancer. Degarelix was approved more than a decade ago. However, degarelix is given as a monthly injection, and the injections can cause intense pain at the injection site, greatly limiting its use.

Dr. Karzai noted that there are still questions about using relugolix in patient care. For example, there might be problems with mens ability to take a pill every day, as opposed to only having to get an injection of leuprolide or related drugs every few months.

Dr. Morgans agreed that this could be a concern but noted that men with more advanced forms of prostate cancer also receive other drugs that are taken as pills and have been generally good about using them as prescribed.

Controversies In Hormone Therapy

The use of hormone therapy requires as much art as science. Physicians do not always agree about when it is best to start treatment, whether it needs to be continuous or can be stopped and started up again periodically, and whether monotherapy or combination therapy is best. Here are the salient issues, what the studies say and what I believe and follow in my own practice.

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Possible Side Effects Of Leuprolide Acetate

There are a number of things you can do to manage the side effects of leuprolide acetate. Talk to your care team nurse about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Tumor Flare

When starting an LHRH agonist, the body initially has a temporary increase in testosterone levels. This “flare” can lead to a temporary increase in the tumor size, causing symptoms related to the cancer to worsen. Your healthcare team can tell you what to look for in your particular case and the treatment necessary. The symptoms typically diminish 3 to 4 weeks after your first injection was given.

Hot Flashes

There are a few things you can do to help with hot flashes. Several medications have been shown to help with symptoms, including clonidine , low doses of certain antidepressants , and gabapentin. Talk to your healthcare team about these prescription products to determine if they are right for you.

Non-medical recommendations include:

  • Keep well-hydrated with eight glasses of water daily.
  • Drink ice water or apply an ice pack at the onset of a hot flash.
  • Wear cotton or lightweight, breathable fabrics and dress in layers so you can adjust as needed.
  • Exercise on a regular basis.
  • Try practicing meditation or relaxation exercises to manage stress, which can be a trigger.
  • Avoid triggers such as warm rooms, spicy foods, caffeinated beverages, and alcohol.

Muscle, Back, or Joint Pain/Aches

Depression

Fatigue

Intermittent Or Continuous Therapy

Reducing Side Effects of Hormone Therapy for Prostate Cancer | Prostate Cancer Staging Guide

Once prescribed, hormone therapy used to continue for life, but scientists are now reevaluating that strategy and investigating whether hormone therapy can be taken intermittently, with so-called holidays from treatment. The thinking is that this may not only help restore quality of life as, for example, returning libido and sexual health but also delay the hormone resistance that eventually develops in men taking hormone therapy.

Clinical trials evaluating whether intermittent therapy is as effective or more effective than continuous therapy are now under way, so it is too early to say for sure.

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Does Leuprolide Cause Weight Gain

Weight changes may occur with Lupron Depot use. One of the most common side effects of women taking Lupron Depot is weight gain. However, some women may experience weight loss instead.

How long is leuprolide good for?

Storing Leuprolide Two Week Kit Dosage Refrigerate after first use at a temperature of 36 degrees to 46 degrees Fahrenheit for up to 30 days, after opening. Protect prescription from light. At Mandells, we recommend storing in the refrigerator after the first use.

How often do you get a leuprolide injection?

Leuprolide injection also comes as a long-acting suspension that is injected subcutaneously by a doctor or nurse in a medical office or clinic and is usually given every 1, 3, 4, or 6 months.

What happens to your hormones after a leuprolide injection?

Leuprolide may cause an increase in certain hormones in the first few weeks after injection. Your doctor will monitor you carefully for any new or worsening symptoms during this time. Ask your pharmacist or doctor for a copy of the manufacturers information for the patient.

Secondary Treatment Following Relapse

Hormone therapy may also be used as a secondary or salvage treatment when PSA levels rise following initial prostate cancer treatment, indicating the cancer has returned. This situation is known as biochemical recurrence. The salient points to keep in mind are that hormone therapy is most often used as a salvage treatment when PSA doubling time is less than six months, indicating that the cancer is aggressive or may have already metastasized.

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What Are Male Sex Hormones

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 are a class of hormones that control the development and maintenance of male characteristics. The most abundant androgens in men are testosterone and dihydrotestosterone .

Androgens are required for normal growth and function of the prostate, a gland in the male reproductive system that helps make . Androgens are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells . Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow .

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 cancer cells acquire the ability to do so .

Hormone Therapy For Prostate Cancer

  • By , Editor in Chief, HarvardProstateKnowledge.org
*Disclosure Dr. Garnick is currently serving as a consultant to SpecialtyEuropeanPharma, which is developing abarelix in Europe.

Androgens, the family of male sex hormones that includes testosterone, function as a fuel for growth a quality that explains their central role in both normal development and prostate cancer. In adolescent boys, androgens not only trigger sexual development, but also contribute to a deeper voice, a beard, and increased muscle strength and bone mass. When prostate cancer develops, however, this androgen fuel contributes to tumor growth and progression.

About 90% to 95% of androgens are produced in the testicles, while another 5% to 10% are produced by the adrenal glands. Androgen-deprivation therapy, more commonly known as hormone therapy, is one of the most powerful weapons in the fight against prostate cancer because it significantly reduces the fuel supply that is feeding malignant growth. Hormone therapies now available target testosterone production by the testicles or androgens activity in the body.

Once reserved solely as a treatment for metastatic prostate cancer, hormone therapy is now also used in a variety of other ways. And medication options in terms of both the number of drugs available and choices about the timing and duration of therapy have also evolved and improved.

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What Is Intermittent Adt

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 mans quality of life.

Randomized clinical trials have shown similar overall survival with continuous ADT or intermittent ADT among men with metastatic or recurrent prostate cancer, with a reduction in some side effects for intermittent ADT .

When Is Hormone Therapy Used

Hormone therapy may be used:

  • If the cancer has spread too far to be cured by surgery or radiation, or if you cant have these treatments for some other reason
  • If the cancer remains or comes back after treatment with surgery or radiation therapy
  • Along with radiation therapy as the initial treatment, if you are at higher risk of the cancer coming back after treatment
  • Before radiation to try to shrink the cancer to make treatment more effective

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How Effective Is It For Treating Prostate Cancer

Although Lupron for prostate cancer is not a novel idea, studies on this subject are scarce. Current evidence confirms administration of leuprolide acetate can, indeed, suppress the production of testosterone, i.e., it is effective for androgen deprivation.

Not only is leuprolide effective in suppressing testosterone, but it is also well-tolerated.

Not every patient with prostate cancer will need to take Lupron. Doctors recommend and prescribe leuprolide acetate to men with late-stage prostate cancer.

Its highly unlikely for most doctors to start treating early-stage prostate cancer with hormonal therapies, including Lupron.

Doctors may prescribe Lupron for cases when cancer comes back after surgery or radiation therapy.

Hormone therapy such as Lupron may be recommended to patients whose cancers spread too much for radiation therapy and surgery to cure it.

Patients who cant have surgery or radiation therapy could benefit from Lupron and other hormone therapy approaches to treat prostate cancer.

Doctors may also recommend Lupron to shrink cancer before employing radiation therapy.

Prostate cancer patients undergoing radiation therapy and having a high risk of cancer returning may also get a prescription for Lupron therapy.

Now youre probably wondering why doctors cant start with hormonal therapy such as Lupron at early prostate cancer stages? Whats stopping them?

However, cancer may become resistant to the medication and stop responding to the treatment.

What Are The Long Term Effects Of Lupron

Which is Better – Surgery vs. Radiation for Prostate Cancer?

Long-term side effects included migraines, hot flashes/sweating, joint pain, and decreased libido .

How long does Lupron stay in your system?

The effects of Leuprolide acetate will decrease after you stop taking the medicine. If youve been getting Lupron® every 3 months, your period will usually return within 4 to 8 months after your last shot. If youve been getting Lupron Depot® every month, your period will likely return 68 weeks after your last shot.

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Improved Testosterone Suppression Lower Cardiac Risks

More than 900 men with advanced prostate cancer whose tumors still relied on testosterone were enrolled in the HERO trial, which was funded by Myovant Sciences, the manufacturer of relugolix.

Participants were assigned at random to take relugolix daily for 48 weeks or to receive leuprolide injections every 3 months for the same length of time.

Approximately 97% of men treated with relugolix reached and maintained very low testosterone levels through 48 weeks, compared with 89% of men who received leuprolide. In addition, men in the relugolix group also did substantially better on several other measures, including being able to return to normal testosterone levels within a few months of stopping therapy.

The latter finding is very important, Dr. Shore said. Suppressing testosterone for long periods can lead to significant side effects, he explained, including fatigue, hot flashes, and bone problems. And in clinical practice, ADT might only be used for short periods, such as when its being given along with radiation therapy.

So if your testosterone level returns to normal values faster after stopping ADT, that to me is a real positive, he said.

When the HERO trial investigators looked specifically at men who had a history of heart problems, the difference in the frequency of these cardiac side effects was even more stark: 17.8% in the leuprolide group versus 3.6% in the relugolix group.

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