What to prescribe for a patient experiencing hot flashes while taking Depo-Provera (medroxyprogesterone acetate) injections?

Management of Hot Flashes in Patients on Depo-Provera

Primary Recommendation

Start with venlafaxine 37.5 mg daily, increasing to 75 mg daily after one week if needed, as this is the most effective non-hormonal option for hot flashes. 1, 2

Clinical Context

Depo-Provera (medroxyprogesterone acetate) itself can paradoxically be used to treat hot flashes, yet some patients still experience vasomotor symptoms while on it. 3, 4 This creates a unique clinical scenario where additional progestin therapy is unlikely to help, making non-hormonal approaches your primary strategy.

First-Line Pharmacological Treatment: SNRIs

Venlafaxine (Preferred)

• Start at 37.5 mg daily for one week, then increase to 75 mg daily 1, 2
• Reduces hot flashes by approximately 60% compared to placebo 5
• The 75 mg dose provides optimal benefit with limited additional improvement at higher doses 1, 2
• Common side effects include dry mouth, decreased appetite, nausea, and constipation, which are dose-related and typically improve after 1-2 weeks 1, 2
• Monitor blood pressure as venlafaxine can occasionally cause increases 2
• Taper gradually when discontinuing to avoid withdrawal symptoms 2

Second-Line Pharmacological Options

Gabapentin

• Use 900 mg daily (divided doses) for maximum efficacy 1
• The 300 mg daily dose is less effective (33% reduction) compared to 900 mg daily (49% reduction in hot flash severity) 1
• Side effects include somnolence and fatigue in a small percentage of patients 1
• Works through central temperature regulatory centers 1

SSRIs (Use with Caution)

• Paroxetine 10-12.5 mg daily reduces hot flashes by 40-62% 1
• Critical caveat: If the patient is also taking tamoxifen, avoid paroxetine and fluoxetine as they inhibit CYP2D6 and reduce tamoxifen's active metabolite (endoxifen) 1
• Citalopram has minimal effects on tamoxifen metabolism and is safer if an SSRI is needed 1

Non-Pharmacological Interventions (Adjunctive)

Lifestyle Modifications

• Dress in layers and keep rooms cool 1, 2
• Avoid triggers: spicy foods, caffeine, and alcohol 1, 2
• Regular exercise may provide modest benefit 1

Alternative Therapies

• Acupuncture has shown benefit in meta-analyses of breast cancer survivors 1
• Cognitive behavioral therapy (CBT) can reduce the perceived burden of hot flashes 1
• Hypnosis demonstrated a 59% decrease in hot flashes in pilot studies 1

What NOT to Recommend

• Avoid estrogen therapy entirely, as adding estrogen to progestin-only contraception is not recommended outside clinical trials 1
• Vitamin E provides only modest benefit (similar to placebo) and should not be a primary treatment 1
• Clonidine has modest efficacy with significant side effects (dry mouth, constipation, drowsiness) and should be discouraged 1, 5
• Black cohosh and herbal supplements lack evidence and may contain estrogenic compounds of unknown safety 1

Clinical Algorithm

1. Assess severity: If hot flashes significantly impact sleep or daily function, proceed with pharmacological treatment 5
2. Start venlafaxine 37.5 mg daily, increase to 75 mg after one week 1, 2
3. If inadequate response after 4 weeks, switch to gabapentin 900 mg daily 1
4. If still inadequate, consider paroxetine 10-12.5 mg daily (ensuring no tamoxifen interaction) 1
5. Add lifestyle modifications and environmental changes at any stage 1, 2

Important Pitfall

Do not assume the patient needs more progestin. While depot medroxyprogesterone can treat hot flashes when given at higher doses (400-500 mg) 3, 6, the patient is already on Depo-Provera for contraception. The standard contraceptive dose (150 mg every 3 months) may not be sufficient for vasomotor symptom control, but increasing progestin exposure carries other risks and is not the standard approach. 4