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Hampered by hormones: treating prostate cancer

Patricia Smith
RGN MSc Psychodynamic Counselling Advanced Dip Cancer/Palliative Care
Support and Information Nurse Specialist
The Prostate Cancer Charity

An estimated 215,000 men are alive in the UK having received a diagnosis of prostate cancer.1 Despite the incidence and impact of this condition, men with prostate cancer have consistently reported worse experiences of NHS care than patients with other cancers.2

Advanced prostate cancer cannot be cured; however, hormone therapy can control progression of the disease and, for some men, be effective for several years.

Hormone therapy is also used for prolonged periods in men with locally advanced disease, often as an adjuvant treatment to radiotherapy but also as a monotherapy. These two groups of men account for nearly 40% of all those newly diagnosed with prostate cancer.3

Treatment is initiated in hospital and then typically continues in primary care for those men receiving luteinising hormone-releasing hormone (LHRH) agonists, which are administered in the form of an injection, either monthly or every three months. Such regular contact provides practice nurses with an ideal opportunity to play a key role in the management of resultant side-effects.

Survey
Earlier this year, 332 men receiving hormone therapy and 100 partners responded to a survey carried out by The Prostate Cancer Charity.

Over half of men who responded felt that they did not receive enough information before starting hormone therapy and nearly two thirds reported that they had not received appropriate support from healthcare professionals to help them cope with the impact of the side-effects on their lives.

Importantly, many respondents were not asked about their side-effects by healthcare professionals after starting treatment.

Following on from this, in June 2009, The Prostate Cancer Charity launched its "Hampered by Hormones" campaign to highlight the needs of men on hormone therapy.

Recommendations from this included:

  • Ensuring access to appropriate information.
  • Regular assessment of side-effects and associated support needs.
  • The provision of interventions and support to men (and their partners) to help them cope with and manage the side-effects of hormone therapy.

Pharmacology
In the 1940s, Huggins and Hodges demonstrated that testosterone is essential for the growth of prostate cancer.4 They found that, in the absence of testosterone, tumour cells undergo apoptosis. For a long time orchidectomy (surgical castration) was the gold standard treatment for advanced prostate cancer. However, since the mid-1980s, pharmacological advances have meant that reversible non-surgical forms of hormone therapy, which aim to deprive prostate cancer cells of testosterone, have largely replaced orchidectomy as treatment for locally advanced and advanced
prostate cancer.

Hormone therapy targets prostate cancer cells wherever they are in the body, reducing tumour size and delaying disease progression. Hormone therapy can work in two ways:
LHRH agonists and gonadotrophin-releasing hormone (GnRH) receptor blockers stop the production of testosterone from the testes. The same effect can be achieved through orchidectomy (surgical removal of testicles), although this is now much less commonly performed. Anti-androgens block the testosterone receptors on the prostate cancer cells.

A few patients may benefit from a combination of these two types of hormone therapy and this is termed maximal androgen blockade (MAB). However, this combination treatment is more likely to increase side-effects. Oestrogen therapy can also be used when the prostate cancer is no longer responding to first line hormone therapy as outlined above. This stage is known as hormone refractory prostate cancer or castration resistant prostate cancer.   

Side-effects of treatment
Box 1 shows the side-effects of hormone therapy, which can be divided into three broad categories:  

  • Physical side-effects.
  • Effects on sexuality.
  • Effects on mental wellbeing.

[[Box 1 horm]]
 
Hot flushes
Although the pathophysiology of hot flushes is poorly understood, it is thought that neurotransmitters, including oestrogen and testosterone, have an effect on the thermoregulatory centre in the hypothalamus.5 Studies have shown that between 50-80% of men taking hormone therapy will get hot flushes.6 Hot flushes can vary in intensity and frequency and can be described as mild, moderate or severe. A simple definition of this might enable men to communicate the severity of their symptoms (see Box 2).

Health professionals can offer practical advice regarding simple measures that can be taken to help reduce the severity of hot flushes. These include smoking cessation and reducing intake of spicy food, alcohol, and drinks that contain caffeine, such as tea and coffee. Using a fan, cotton bedsheets and wearing cotton clothes may also help.

Most treatments used for hot flushes in men on hormone therapy are similar to those used for post-menopausal women in whom this has been studied more extensively. Some men report that complementary therapies, including sage and evening primrose oil, have been of some help; however, scientific evidence is needed to substantiate this. Men considering taking any herbal or complementary treatment should discuss this with their specialist in the first instance as some may interact with existing hormone therapy treatment.  Currently, evidence that acupuncture is effective in controlling hot flushes in men with prostate cancer is inconclusive and further research is needed.7

After consultation with their specialist, men experiencing severe hot flushes may be considered suitable for treatment with one of the following:

  • Megestrol acetate (a form of progesterone).
  • Oestrogen in the form of diethylstilbestrol (DES).
  • Oestrogen patches.
  • The anti-androgen drug, cyproterone acetate.

Suitability for these treatments may depend on the individual's existing hormone therapy treatment regimen and, of course, carry a risk of additional side-effects.

A small number of trials have shown that a low dose selective serotonin reuptake inhibitor (SSRI)-type antidepressant may reduce hot flushes in men on hormone therapy.8 Gabapentin, a GABA analogue, has also been reported in some studies of men taking hormone therapy for prostate cancer to moderately reduce hot flushes.9

Gynaecomastia
Gynaecomastia (breast pain and swelling) can be a source of embarrassment and pain in men on hormone therapy, compounded by other body image issues caused by weight gain, decreased muscle mass and sexual function, impacting on a man's sense of masculinity.

Gynaecomastia is caused by an increase in oestrogen and most often occurs within the first year of hormone therapy; after this time it is not reversible. Gynaecomastia is more common in men taking oestrogen therapy and anti-androgens. Prophylactic single dose radiotherapy to the breast tissue can be considered at the start of treatment with anti-androgens.

Tamoxifen is sometimes used and can be initiated to both prevent and treat gynaecomastia in men with prostate cancer, although this may be contraindicated if on oestrogen therapy.
Surgery to remove excess breast tissue may be an option for men who have not responded to other treatments; however, it does carry the risk of nipple damage and loss of feeling.10

Depression
It is not clear whether hormone therapy causes depression, but it would be reasonable to expect that confounding factors, including the impact of diagnosis or recurrent disease would contribute to levels of depression.11 There is some evidence to suggest that men with a past history of depression may be at particular risk for recurrence of their depression while undergoing hormone therapy.12 Some men may require ongoing emotional support and may consider counselling. The Prostate Cancer Charity survey did reveal that the effects of hormone therapy on mental wellbeing tended to have a greater impact on men than the impact of physical and sexual effects.

Cognitive function
Studies researching the impact of hormone therapy on cognitive function have been small, with sometimes conflicting results. However, some studies have shown a decline in one cognitive area in between 47% and 69% of participants.13

Fatigue
Fatigue is an important but under-recognised side-effect of hormone therapy and differs from tiredness in that it presents as extreme physical and mental weakness. More is known about cancer-related fatigue and further research is needed into the relationship between fatigue and hormone therapy for prostate cancer. The health professional can support men on hormone therapy by encouraging exercise such as swimming or walking.

Sexual dysfunction
The role of testosterone is thought to be complex and is not fully understood, although it appears to have an effect on both erectile function and libido. Studies have shown variable degrees of erectile dysfunction in men receiving hormone therapy for prostate cancer. The use of phosphodiesterase type 5 (PDE5) inhibitor drugs, intrapenile injections of vasoactive drugs and vacuum-assisted devices may be effective for men on hormone therapy. It is very common for men taking LHRH agonists to have little or no libido; therefore, use of PDE5 inhibitor drugs in this group of men is very limited.

The Prostate Cancer Charity survey revealed that many men accept a decline in their sexual function and libido as a part of the ageing process, while others feel this is a price that they must pay to prevent progression of their cancer. This can have a considerable impact on intimacy and relationships. Talking through some of these issues may help a man (and his partner) come to terms with these changes and should have access to erectile dysfunction services and counselling.

Osteoporosis
The relationship between hormones and the mechanism of bone metabolism is complex and under current research. However, there is evidence that hormone therapy-associated bone loss adversely affects bone health and quality of life in men with prostate cancer.14

Increased awareness and lifestyle modification, including smoking cessation, moderation of alcohol and caffeine intake and weight-bearing exercise, may all promote bone health. Adequate exposure to sunlight to enable production of vitamin D in the body is also necessary for bone health.15

It is important for men on hormone therapy to get enough vitamin D and calcium in their diet to help prevent osteoporosis. Men on hormone therapy should aim to get between 1,000-1,500 mg of calcium per day, ideally from their diet. Caution should be taken that calcium intake does exceed more than 2,000 mg per day due to evidence that high levels of calcium from dairy products increases prostate cancer risk. 

Cardiovascular disease
Men with prostate cancer on long-term hormone therapy are at greater risk of developing abnormal lipids, insulin resistance, hyperglycaemia and metabolic syndrome, which might predispose them to a greater risk of cardiovascular disease.16 It is not unusual for men to develop an increased fat mass and waist circumference, which may predispose them to cardiovascular disease. Health professionals can offer support and advice to men on hormone therapy to maintain a healthy weight, diet and active lifestyle.

Loss of muscle mass
Loss of muscle mass and strength can lead to a loss of independence, falls, and gait difficulties which may be combated by diet and exercise as recommended for bone health.

Summary of interventions and support needs
Men receiving hormone therapy should receive information regarding medical interventions and support:

  • Treatment and strategies for reducing hot flushes.
  • Advice on the benefits of resistance exercise to help with bone fatigue, weight control and prevention of cardiovascular disease.
  • Lifestyle and dietary advice to help reduce hot flushes, weight gain and osteoporosis.
  • Where appropriate, treatment for gynaecomastia, including preventative measures.
  • Access to erectile dysfunction services.
  • Access to counselling services including relationship and psychosexual counselling.
  • Access to support organisations (see Resources). 

Implications for practice
Men on hormone therapy should be supported by health professionals with written and verbal information at the start of treatment. Men should be assessed both in primary and secondary care throughout their ongoing treatment so that appropriate interventions can be implemented and support needs met. Respondents to The Prostate Cancer Charity survey revealed that nearly a third of men did not have access to a clinical nurse specialist. This further highlights the importance of the practice nurse's role in supporting men outside of secondary care.

References
1. Cancer Research UK. UK Prostate Cancer incidence statistics. Available from: http://info.cancerresearchuk.org/cancerstats/types/prostate/incidence/
2. House of Commons Committee of Public Accounts. Department of Health: Tackling Cancer: Improving the patient journey. London: The Stationery Office; 2005.
3. BAUS Cancer Registry. Analyses of minimum data set for urological cancers, 31 January - 31 December 2007. London: BAUS; 2008: 41.
4. Huggins C, Hodges CV. Studies on prostate cancer. I. The effects of castration of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293-7.
5. Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. Pathophysiology and treatment of hot flashes. Mayo Clin Proc 2002;77:1207-18.
6. Higano CS. Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. Urology 2003;61(2 Suppl 1):32-8.
7. Lee MS, Kim KH, Shin BC, Choi SM, Ernst E. Acupuncture for treating hot flushes in men with prostate cancer: a systematic review. Support Care Cancer 17(7):763-70.
8. Quella SK, Loprinzi CL, Sloan J et al. Pilot evaluation of venlafaxine for the treatment of hot flashes in men undergoing androgen ablation therapy for prostate cancer. J Urol 1999;162:98-102.
9. Loprinzi CL, Dueck AC, Khoyratty BS et al. A phase III randomized, double-blind, placebo-controlled trial of gabapentin in the management of hot flashes in men (N00CB). Ann Oncol 2009;20:542-9.
10. Di Lorenzo G, Autorino R, Perdona S, De Placido S. Management of gynaecomastia in patients with prostate cancer: a systematic review. Lancet Oncol 2005;6:972-9.
11. Pirl WF, Greer JA, Goode M, Smith MR. Prospective study of depression and fatigue in men with advanced prostate cancer receiving hormone therapy. Psychooncology 2008;17:148-153.
12. Pirl WF, Siegel GI, Goode MJ, Smith MR. Depression in men receiving androgen deprivation therapy for prostate cancer: a pilot study. Psychooncology 2002;11(6):518-23.
13. Nelson CJ, Lee JS, Gamboa MC, Roth AJ. Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer 2008;113(5):1097-106.
14. Eastham JA. Bone health in men receiving androgen deprivation therapy for prostate cancer. J Urol 2007;177:17-24
15. National Osteoporosis Society. The Sunlight Campaign. Available from: http://www.nos.org.uk/NetCommunity/Page.aspx?pid=535&srcid=261
16. Hakimian P, Blute M Jr, Kashanian J, Chan S, Silver D, Shabsigh R. Metabolic and cardiovascular effects of androgen deprivation therapy. BJU Int 2008;102(11):1509-14.