What medications are used to treat hot flushes in males, particularly those undergoing androgen deprivation therapy (ADT) for prostate cancer?

Medications for Hot Flushes in Males on Androgen Deprivation Therapy

Gabapentin and venlafaxine are the first-line pharmacologic treatments for hot flushes in males undergoing androgen deprivation therapy (ADT) for prostate cancer, with gabapentin showing moderate effectiveness in randomized controlled trials. 1

Pharmacologic Options

First-Line Treatments

1. Nonhormonal Options:

   • Gabapentin: Safe and moderately effective in controlling hot flashes in men with prostate cancer in two randomized controlled trials 1
   • Venlafaxine (SNRI):
     • Shown to improve hot flash symptoms in men with prostate cancer undergoing ADT in case reports and small pilot studies 1
     • In a pilot study, 63% of patients had >50% decrease in hot flash score with 12.5 mg twice daily dosing 2
     • Common side effects include nausea (37%), somnolence (23%), dry mouth (22%), and dizziness (19%) 3

2. Hormonal Options (when not contraindicated):

   • Medroxyprogesterone acetate (MPA): Shown to reduce hot flashes by up to 85% compared to 21% with placebo 4
   • Estrogen: Transdermal estradiol (0.9 mg of 0.1% gel daily) reduced daily hot flush frequency with a mean adjusted difference of -1.6 hot flushes per day 5
   • Cyproterone acetate: Demonstrated efficacy in reducing hot flashes 1, 6

Treatment Algorithm

1. Start with nonhormonal options (safer profile):

   • Gabapentin (starting at low dose and titrating up)
   • Venlafaxine (starting at 12.5 mg twice daily)

2. If inadequate response, consider hormonal options when not contraindicated:

   • Medroxyprogesterone acetate
   • Transdermal estradiol
   • Cyproterone acetate

3. For patients with advanced prostate cancer on ADT:

   • Avoid testosterone/androgens as they are contraindicated 1

Non-Pharmacologic Approaches

Consider these approaches either as first-line or adjunctive therapy:

• Acupuncture: Small studies show effectiveness in controlling hot flashes in men with history of ADT 1, 6
• Cognitive behavioral therapy (CBT): Reduced perceived burden of hot flashes compared to usual care 1
• Lifestyle modifications:
  • Exercise/physical activity
  • Yoga
  • Weight loss if overweight or obese
  • Hypnosis 1

Clinical Considerations

Monitoring and Follow-up

• Assess hot flash frequency and severity using daily diaries
• Evaluate impact on quality of life, as hot flashes can significantly deteriorate physical well-being 7
• Monitor for medication side effects, particularly with venlafaxine (nausea, somnolence, dry mouth) 3

Treatment Pitfalls to Avoid

1. Do not prescribe androgens/testosterone for men with advanced prostate cancer on ADT 1
2. Avoid phytoestrogens, botanicals, and vitamin E supplements:
   • Limited data on effectiveness and safety in men on ADT
   • Concerns that supplemental vitamin E may increase prostate cancer risk 1
3. Consider drug interactions when prescribing venlafaxine:
   • Potential interactions with drugs metabolized by CYP2D6
   • Monitor blood pressure as venlafaxine can cause dose-related increases 3

Alternative ADT Options

If hot flashes are severely disrupting quality of life, discuss with treating oncologist:

• Intermittent ADT
• Antiandrogen monotherapy 1

Special Considerations

For men experiencing both hot flashes and gynecomastia from ADT, tamoxifen may be considered as it can address both issues 1