Hormone Therapy For Prostate Cancer
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Hormone therapy is also called androgen suppression therapy. The goal is to reduce levels of male hormones, called androgens, in the body, or to stop them from fueling prostate cancer cells.
Androgens stimulate prostate cancer cells to grow. The main androgens in the body are testosterone and dihydrotestosterone . Most androgens are made by the testicles, but the adrenal glands as well as the prostate cancer itself, can also make a fair amount.
Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancers shrink or grow more slowly for a time. But hormone therapy alone does not cure prostate cancer.
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 .
How Hot Flushes May Feel
Hot flushes can vary from one person to another. They can start as a feeling of warmth in your neck or face. This often spreads to other parts of your body. You might have:
- reddening of the skin
- feelings of your heart beating in your chest
- feelings of panic or irritability
Hot flushes can last between 2 to 30 minutes. You may have a few a month or more often. The flushes usually last for a few months but for some people they carry on for longer.
They can be disruptive and might make sleeping difficult.
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Will Side Effects Limit What I Can Do
What you are able to do will depend on which side effects you have and how bad they are. Many men are able to work, cook meals, and enjoy their usual daily activities when they have hormone therapy for their prostate cancer. Other men find that they need more rest than before they started hormone therapy so they cant do as much. You should try to keep doing the things you enjoy as long as you don’t get too tired.
Are There Medications That Help Reduce Hot Flashes
If youre having a hard time managing your hot flashes at home, you may want to ask your doctor about medications. If your hot flashes are a result of your body being put into medical menopause, your care team may treat you with some form of hormone therapy, because estrogen is the main hormone given to manage symptoms of menopause. However, not everyone can take estrogen replacements. Some cancers, like receptor-positive breast cancer, are sensitive to estrogen, so the replacement drugs may not be helpful.
If you dont want to, or cant, take hormones, other medications may be effective. The antidepressant paroxetine is approved by the U.S. Food and Drug Administration to treat hot flashes. Patients typically receive a lower dose for hot flashes than for treating depression. Some blood pressure medications and Gabapentin®, which is used to control seizures and nerve pain, have been shown to help, too.
Expert cancer care
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How To Manage Hormone Therapy
Although hot flashes are most commonly associated with menopause, this uncomfortable feeling can also be a side effect that occurs in patients with cancer who are being treated with hormone therapy.
Although hot flashes are most commonly associated with menopause, this uncomfortable feeling can also be a side effect that occurs in patients with cancer who are being treated with hormone therapy.
Because certain malignancies are dependent on sex hormones for growth, like subtypes with breast and prostate cancers, patients are treated with hormone therapies that deprive cancers of these sex hormones.
As a result, hot flashes similar to that of menopause can occur. Arjun Gupta, M.D., an oncologist at UT Southwesterns Simmons Cancer Center, defined these hot flashes as, uncomfortable episodes of a sudden sensation of heat originating in the upper part of the body and spreading throughout.
Although hot flashes may only last a few minutes, they are typically accompanied with and followed by sweating and anxiety. These episodes can occur anywhere, anytime sporadically or even several times a day and worst yet, can even happen during sleep.
They can be very troubling, and can disturb sleep and daily activities, Gupta said in an interview with CURE. Recognizing and reporting them to your oncologist is the first step towards treating them.
Another big difference between the two: Hormone therapy-related hot flashes can also occur in men.
Related Content:
Testing The Effects Of Oxybutynin For The Treatment Of Hot Flashes In Men Receiving Hormone Therapy For Prostate Cancer
| The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| First Posted : October 23, 2020Last Update Posted : July 18, 2022 |
- Study Details
| Drug: Oxybutynin ChlorideDrug: Placebo AdministrationOther: Quality-of-Life AssessmentOther: Questionnaire Administration | Phase 2 |
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To assess the effects of two doses of oxybutynin chloride on hot flash scores relative to placebo.
SECONDARY OBJECTIVES:
I. To assess study accrual rates and compliance with the therapy. II. To characterize the safety and adverse event profile of two doses of oxybutynin in the study population.
III. To evaluate the consistency of the results across the various methods used to evaluate the efficacy of oxybutynin .
IV. To compare patient-reported quality of life and hot flash interference, as measured by the Hot Flash Related Daily Interference Scale , across arms.
V. To compare other changes in patient symptoms, as measured by the Symptom Experience Questionnaire, across arms.
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How Are Hormone Therapy Medicines Used
Hormone therapy medicines may be used alone, with another type of hormone therapy, or with another type of prostate cancer treatment.
Monotherapy
Monotherapy is when only one type of hormone therapy medicine is used to lower the amount of testosterone in your body. Monotherapy can be effective in shrinking a prostate cancer tumor, slowing the spread of your prostate cancer, and relieving pain caused by your prostate cancer. Monotherapy may be used with neoadjuvant therapy or adjuvant therapy. Please read When is Hormone Therapy Used for Prostate Cancer? to learn more about neoadjuvant and adjuvant therapy.
Combination therapy
Can Hormone Therapy Cure My Prostate Cancer
No, hormone therapy cannot cure your prostate cancer. The goal of hormone therapy is to stop or slow the growth of the prostate cancer cells in your body. Hormone therapy can shrink prostate cancer tumors and may stop or limit the spread of your prostate cancer. Hormone therapy is used to control your prostate cancer.
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Other Drugs May Be Useful In Some Patients
Studies of non-estrogen drugs to treat hot flashes in women with a history of breast cancer have reported that many of them do not work as well as estrogen replacement or haveside effects. Megestrol and medroxyprogesterone , certain antidepressants, anticonvulsants, and clonidine are non-estrogen drugs used to control hot flashes.
Why Does Hormone Therapy Cause Side Effects
If testosterone is taken away or blocked by hormone therapy, prostate cancer cells will usually shrink, wherever they are in the body. But reducing or blocking testosterone can cause other things to change in your body too.
Testosterone controls the development and growth of the sexual organs, including the prostate, and affects the way you think and feel. It also controls other male characteristics, such as erections and muscle strength. So when testosterone is reduced, or taken away by hormone therapy, all of these things can change.
The diagram below shows how testosterone affects a man’s body. Knowing this can help you understand what side effects you might get when you’re having hormone therapy.
The side effects of hormone therapy are caused by lowered testosterone levels. Side effects will usually last for as long as you are on hormone therapy. If you stop your hormone therapy, your testosterone levels will gradually rise again and some side effects will reduce. Your side effects wont stop as soon as you finish hormone therapy it may take several months.
Surgery to remove the testicles cant be reversed, so the side effects are permanent. But there are treatments that can help reduce or manage some of the side effects.
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Hot Flashes Related To Cancer Treatment
Women receiving treatment for hormone-dependent breast cancer can experience an abrupt depletion of estrogen from chemotherapy-induced premature menopause, discontinuation of menopausal hormone therapy, or prolonged use of estrogen suppression therapies , Kaplan et al. reported. The hormones are involved in thermoregulation, and replacement therapies typically used for menopausal women in the general population are contraindicated in women with hormone-dependent breast cancer. Use of androgen deprivation therapy to manage prostate cancer results in a similar depletion of testosterone, leading men to experience hot flashes, Kaplan et al. explained.
The ONS Guidelines share evidence-based pharmacologic and nonpharmacologic alternatives to manage hot flashes in either population of patients with cancer.
How Might Hormone Therapy Make Me Feel
Hormone therapy itself can affect your mood. You may find that you feel more emotional than usual or just different to how you felt before. Some men find that they cry a lot. You may also get mood swings, such as getting tearful and then angry. Just knowing that these feelings are caused by hormone therapy can help.
Everyones different some men are surprised by the side effects and how upsetting they find them. Others have fewer symptoms or are not as worried by them.
Some of the other side effects of hormone therapy are hard to come to terms with. Physical changes, such as putting on weight, or changes to your sex life, might make you feel very different about yourself. Some men say they feel less masculine because of their diagnosis and treatment.
If youre starting hormone therapy very soon after being diagnosed with prostate cancer, you might still feel upset, shocked, frightened or angry about having cancer. These feelings are normal, and it’s okay to feel this way.
Things in your day-to-day life can change because of the hormone therapy. Your relationships with your partner, family and friends might change. Or you might be too tired to do some of the things you used to do.
Some men experience low moods, anxiety or depression. This could be directly caused by the hormone therapy itself, or because you’ve been diagnosed with prostate cancer. It could also be due to the impact that treatment is having on you and your family.
What can help?
Talking about it
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Effect Of Estradiol On Vasomotor Symptoms
VMS, predominantly hot flushes and night sweats, are experienced by 7080% of women during the perimenopause and a similar proportion of men undergoing ADT . Rapid estrogen withdrawal appears to mediate flushes in women via an increase in release of neurokinin B, and possibly other mediators, from the hypothalamus . Neurokinin B acts on neurokinin 3 receptors in the hypothalamic median preoptic nucleus, to stimulate heat dissipation effectors such as cutaneous vasodilatation, diaphoresis and cold-seeking behaviour . In perimenopausal and postmenopausal women, estrogen replacement is the most effective pharmaceutical strategy for mitigating hot flushes , although an oral neurokinin 3 receptor antagonist recently appears promising . Topical E2 is effective at applied doses as low as 12.525µg daily . However, in hypogonadal men, including those undergoing ADT, the relative roles of androgen and estrogen deficiency to the pathophysiology of hot flushes have only been recently explored.
In the treatment of VMS, small uncontrolled studies of low-dose oral DES and transdermal E2 patches suggest estrogens might be effective in treating hot flashes in men receiving other, non-estrogen-based forms of ADT. In a double-blind placebo-controlled crossover trial, 1mg DES was effective in reducing hot flush severity in 14 men after orchiectomy .
Estradiol Reference Ranges And Thresholds For Effect
There is some data from population-based cohorts to establish an approximate reference range for E2 in healthy elderly men. In the Health in Men Study cohort from Australia, 3690 community dwelling elderly men aged 77.0±3.6 years had morning sex steroids measured by mass spectrometry . This cohort excluded men with a history of androgen or antiandrogen therapy, orchiectomy or PCa. BMI was 26.5±3.6kg/m2 and 47.1% self-assessed their own health to be very good or excellent. The mean E2 concentration was 73.4pmol/L with a reference range of 25.0139.9pmol/L. These ranges are consistent with E2 levels in 1830 elderly Swedish men taking part in the MrOS study . However, more studies are needed to more definitively establish age-adjusted reference ranges for E2, in particular among older men in whom hypogonadism has been rigorously excluded.
Both E2 and testosterone appear to be important for sexual function. In Finkelsteins study, when testosterone levels were in the mild-moderately hypogonadal range , greater decrements in sexual desire were seen when E2 levels were < 10pg/mL compared to when E2 levels were > 10pg/mL . The effects of E2 above and below 37pmol/L in the context of castrate testosterone levels are unknown.
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Venous Thromboembolism And Cardiovascular Risk
Cardiovascular toxicity from oral DES comprised fluid retention, hypertension, and arterial and venous thromboembolism, manifesting as stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism . Orally administered estrogens induce liver synthesis of coagulation factors, renin substrate, and many carrier proteins including SHBG . There are also alterations in lipoprotein metabolism with increases in triglycerides and HDL cholesterol with reduced hepatic cholesterol uptake from HDL . The adverse cardiovascular impact of early DES regimens for PCa is likely to have been predominantly due to the prothrombotic milieu created. Orally administered estrogens for PCa increase procoagulant factors such as Factor VII, and decrease antithrombin III, on a background of an existing hypercoagulable state . This effect is amplified for synthetic orally administered estrogens because unlike E2, they are not converted to the less-potent estrone by gut-wall 17-beta hydroxysteroid dehydrogenase .
Transdermal administration of E2 avoids hepatic first pass metabolism so that up to 20-fold lower doses can be administered to achieve similar serum levels . This means that hepatocytes are exposed to lower doses and alterations in protein synthesis and accumulation of estrone sulphate are greatly reduced . Even high doses of parenteral E2 used for ADT in men with PCa largely avoid disturbance in hepatic protein metabolism .
Complementary Therapies For Hot Flushes
There is limited scientific evidence that complementary therapies can help hot flushes in men with prostate cancer.
Acupuncture
Small studies suggest people experience less extreme hot flushes whilst having acupuncture.
Cognitive behavioural therapy
This treatment suggests there is a link between your thoughts and actions. It focuses on calming your body and mind and keeping a positive outlook. This may help with hormonal symptoms such as hot flushes.
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Effect Of Estradiol On Bone
The reduction in bone density associated with male hypogonadism appears to be mediated by deficiency of both testosterone and E2, although E2 deficiency appears to be most important. testosterone effects may be partly indirect, through anabolic effects on muscle mass, which increases bone mass by increasing mechanical load. Untreated men and women with congenital aromatase deficiency develop eunuchoid skeletal proportions, continued linear growth and high-turnover osteoporosis . A similar skeletal phenotype was described in a man with a homozygous ER mutation . In the cases of aromatase deficiency, but not in the case of ER deficiency, estrogen treatment reduced bone turnover, fused epiphyses and improved bone density. In a cross-sectional study, women with complete androgen insensitivity syndrome had moderate deficits in lumbar spine BMD that was more marked in those with poor adherence to estrogen therapy . There was no deficit in areal BMD in women with partial androgen insensitivity suggesting some beneficial effects on BMD of residual androgen responsiveness in bone or muscle. While instructive, the phenotype of patients with deficiency of sex steroid action during fetal, childhood and pubertal growth and development may not accurately represent the pathophysiology of bone disease that occurs during adult onset hypogonadism .
How Will I Know That My Hormone Therapy Is Working
Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual mans prostate cancer. 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 mans cancer 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 mans prostate cancer has become resistant to the hormone therapy that is currently being used.
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What Will I Learn By Reading This
You and your doctor may be talking about using hormone therapy to control your prostate cancer. It is important for you to learn about hormone therapy so that you will know what to expect and how best to take care of yourself before, during, and after treatment. You will learn:
It is important to think about how you will work these things into your everyday life if you and your doctor decide that hormone therapy is the best way for you to control your prostate cancer..