hot flushes (flashes) secondary to hormone therapy in prostate cancer

Last edited 05/2020

Hot flushes secondary to hormone therapy in prostate cancer (1)

• medroxyprogesterone (20 mg per day) should be offered, initially for 10 weeks, to manage troublesome hot flushes caused by long-term androgen suppression
  • evaluate the effect at the end of the treatment period
    
    
• cyproterone acetate (50 mg twice a day for 4 weeks) should be considered to treat troublesome hot flushes if medroxyprogesterone is not effective or not tolerated
  
  
• there is no good-quality evidence for the use of complementary therapies to treat troublesome hot flushes

A review has stated (2):

• there are a number of treatments which have been studied for the treatment of hot flushes in men undergoing Androgen deprivation therapy (ADT), all other than cyproterone are currently unlicensed for this indication
  
  
• NICE recommends that medroxyprogesterone be used first line to treat troublesome hot flushes caused by long-term androgen suppression (unlicensed) and that cyproterone be considered if medroxyprogesterone is not effective or tolerated


• Other possible treatments used for treatment of hot flushes in this scenario include (2):

• Clonidine

  Initial: 50micrograms twice a day

  Increase to 75micrograms twice a day after 2 weeks if no response. May take 2-4 weeks for full effect. Max reported dose: 150micrograms twice a day over 2 years.

• SSRIs and related

  Paroxetine Initial: 10mg a day Max cited: 37.5mg a day Sertraline: 75 – 100mg a day Venlafaxine Initial: 37.5mg a day Maintenance 75mg a day

  Consider doubling doses at 1-2 weeks if no symptom improvement (do not exceed max licensed doses).

• Gabapentin

  300mg three times a day

  Max reported dose: 1500mg a day

• Oxybutynin

  5mg twice a day

• there are no well-designed, large-scale randomised studies. Most published data comes from small-scale open-label or pilot studies, or case reports. Many of these are from the 1990s or early 2000. Most randomised studies lacked a placebo arm

optimum doses of the individual drugs may be difficult to determine, and it may be a case of starting with a low dose and titrating upwards until hot flushes are controlled, or until adverse events lead to discontinuation. Bear in mind that patient variability means that one specific treatment may not be suitable for every patient.

Notes:

• ADT involves the use of a luteinising hormone-releasing hormone (LHRH) agonist, or bilateral orchidectomy, which removes the supply of endogenous hormone
• ADT may be continued for up to 3 years in patients with high-risk localised prostate cancer
• ADT carries a risk of side-effects, particularly urinary and sexual dysfunction, loss of fertility, radiation-induced enteropathy, and hot flushes
• although there is limited evidence, intermittent therapy may be considered for patients who are having long-term ADT, to reduce drug toxicity
• the exact mechanism of hot flushes is not fully understood
• the thermoregulatory centre in the hypothalamus maintains the core body temperature within a normal thermoregulatory zone
• it is hypothesised that the withdrawal or reduction of the sex hormones not only causes disruption of the thermoregulatory centre in the hypothalamus but also causes noradrenaline fluctuations that induce hot flushes (also called vasomotor symptoms or hot flashes)

Reference:

• NICE (May 2019). Prostate cancer: diagnosis and management
• NHS Specialist Pharmacy Service. How can hot flushes in men being treated for prostate cancer be managed? (April 28th 2020)