What medications can cause cold intolerance?

Medications That Cause Cold Intolerance

Beta-blockers are the primary medication class causing cold intolerance, with up to 50% of treated hypertensive patients developing cold hands and feet, compared to only 18% on diuretics alone. 1, 2

Beta-Adrenergic Blockers

Beta-blockers cause cold sensitivity through peripheral vasoconstriction and reduced peripheral blood flow:

• Propranolol causes the highest frequency of cold extremity symptoms among beta-blockers, with significantly more complaints than atenolol or oxprenolol 1
• Non-selective beta-blockers (propranolol) produce more severe cold sensitivity than selective agents 3, 1
• Approximately 40% of patients on beta-blockers develop new-onset cold extremity complaints after starting therapy 2
• Cold sensitivity worsens under mild cold stress (20°C ambient temperature), affecting more than half of beta-blocked patients 3
• Switching from propranolol to oxprenolol can improve symptoms in affected patients 1
• Combined alpha- and beta-blockade (labetalol) provides some protection against cold sensitivity compared to beta-blockade alone, though one-third of patients still experience symptoms under cold stress 3

Clinical Manifestations

• Raynaud's phenomenon develops as a side effect in beta-blocked hypertensive patients 1
• Measurable skin temperature decreases occur after propranolol administration 1
• Patients without palpable foot pulses are more likely to experience cold hands 1

Thiazide Diuretics

Diuretics cause cold intolerance less frequently than beta-blockers but still affect nearly one-fifth of patients:

• 18% of patients on diuretics alone develop new cold extremity symptoms 2
• The mechanism differs from beta-blockers and likely relates to volume depletion effects 2

Thyroid Hormone Replacement

Hypothyroidism itself causes cold intolerance, and inadequate thyroid hormone replacement perpetuates this symptom:

• Cold intolerance is a recognized symptom of hypothyroidism requiring evaluation 4
• Patients with unexplained cold intolerance should undergo thyroid function testing (TSH, free T4) 4
• Lifelong thyroid hormone replacement is needed for checkpoint inhibitor-induced hypothyroidism 4

Important Caveat

When both adrenal insufficiency and hypothyroidism are present, steroids must always be started before thyroid hormone to avoid precipitating adrenal crisis 4

Medications Causing Heat Intolerance (Opposite Effect)

For context, certain medications impair heat tolerance rather than cold tolerance:

• Antidepressants (fluoxetine, lithium carbonate) can cause heat intolerance and predispose to heat stroke under hot conditions 5
• Hyperthyroidism from any cause produces heat intolerance, palpitations, and hypermetabolic symptoms 4

Clinical Approach

When evaluating cold intolerance in patients on antihypertensive therapy:

• Review all beta-blocker use first, as this is the most common culprit 1, 2
• Consider switching from non-selective to selective beta-blockers or to combined alpha-beta blockade 3, 1
• Evaluate for peripheral vascular disease (check foot pulses), as absent pulses correlate with worse symptoms 1
• Screen thyroid function if cold intolerance is disproportionate to medication effects 4
• Do not assume age, sex, smoking, or atherosclerosis history predict who will develop symptoms - these factors show no significant association 2