Hot flushes (flashes) in the perimenopause (menopause)

• hot flushes (hot flashes)
  • one of the common symptoms of the climacteric
  • occur in a great majority of menopausal women
  • primarily affect women who are in the transition to menopause or have become menopausal
  • incidence of hot flashes is highest in the peri-menopausal years
    • incidence ranges from 58 to 93% after menopause
    • incidence ranges from 28 to 65% in pre-menopausal women
  • magnitude, duration and intensity of hot flushes can vary among individuals
    • in some cases women flush and/or sweat profusely, whilst others do not
    • hot flushes can occur once a month or as frequently as every 10 min
    • frequency and severity of hot flashes tend to reduce with time
    • proportion of women experiencing symptoms increases sharply in the 2 years before final menstrual period, and peaks 1 year after final menstrual period (1)
      • a study revealed that nearly 50% of all women reported vasomotor symptoms 4 years after final menstrual period, and 10% of all women reported symptoms as far as 12 years after final menstrual period (1)
        
        
  • management of hot flushes:
    
    • hormonal therapies:
      • oestrogen therapy is the most effective modality in reducing hot flush frequency and severity
        • results in rapid resolution of symptoms
          • however long-term hormonal therapy is associated with various adverse effects including breast cancer, stroke, and thromboembolism
      • progestogens (both oral and intramuscular formulations) have shown efficacy in management of hot flushes
        • note though that the possible role of progesterone in the pathogenesis of breast malignancy withholds its use as an alternative to oestrogens in symptomatic women with hot flushes who are concerned about possible development of breast cancer
          
          
    • two anti-hypertensive agents, clonidine and methyldopa, have shown modest efficacy in the management of hot flushes. However their use has been associated with a relatively high rate of adverse effects (2):
      - only licensed option (8)
      • methyldopa 250-500 mg twice daily has been shown to halve the frequency of hot flushes in comparison to placebo (3)
      • clonidine
• there is evidence that clonidine improves the symptoms of menopausal hot flushes in approximately 40% of women (4)
  
  
  
  
  • note however that clonidine is often used as a first-line treatment in a dose of two or three 25μg tablets twice daily (4)
    
    
  • a maximum of 75 micrograms bd or 50mcg tds should be used (8)
    
    
  • however side effect with clonidine treatment are common and include dizziness, irritability, nausea and dry mouth
  • interaction with anti-hypertensive drugs and not suitable for patients with baseline low blood pressure
  • must be reduced gradually otherwise causes rebound hypertension (8)
    
    
  • dose related side-effects include sleep disturbance in at least 50% of patients, dry mouth nausea and fatigue (8)
    
    
    • other pharmacological agents:
      • SSRI anti-depressants (paroxetine and fluoxetine), venlafaxine and the anti-convulsant gabapentin have yielded encouraging results based on small well-conducted studies
      • gabapentin
        • this agent has been evaluated in the treatment of hot flashes in patients with breast cancer (5)
          • gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day
          • the authors concluded that this drug should be considered for treatment of hot flashes in women with breast cancer
            
            
    • other agents:
      • review of the evidence suggests that only modest and delayed improvement of symptoms could be expected by agents such as Black Cohosh and vitamin E (2)
      • a more recent trial concluded that Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms (6)

The respective summary of drug characteristics should be consulted before prescribing any drug detailed.

Notes:

• low dose oestrogen
  • there is evidence of the effectiveness of the use of low dose oestrogen patches over a 12-week period (6):
    • micro-dose 17-ß-oestradiol (0.014 mg/d) was clinically and statistically significantly more effective than placebo in reducing the number of moderate and severe hot flushes

Reference:

• (1) Politi MC et al. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis.J Gen Intern Med. 2008 Sep;23(9):1507-13.
• (2) Haimov-Kochman R et al. Hot flashes revisited: pharmacological and herbal options for host flashes management. What does the evidence tell us? Acta Obset Gynecol Scan 2005;84:972-9.
• (3) Nesheim BI, Saetre T. Reduction of menopausal hot flushes by methyldopa. A double blind crossover trial. Eur J Clin Pharmacol 1981; 20: 413-6.
• (4) Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med. 2006;355(22):2338-47.
• (5) Pandya KJ et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blined placebo-controlled trial. Lancet 2005; 366:818-24.
• (6) Newton KM et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006 Dec 19;145(12):869-79.
• (7) Bachmann GA et al. Lowest effective transdermal 17beta-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial.Obstet Gynecol. 2007 Oct;110(4):771-9.
• (8) British Menopause Society. Prescribable alternatives to HRT (Accessed 12/2/2020).