Physiological Dose of Methylprednisolone
The physiological replacement dose of methylprednisolone is 4-6 mg per day, which is equivalent to approximately 20-30 mg of hydrocortisone or 5-7.5 mg of prednisone daily. 1, 2
Understanding Physiological vs. Pharmacological Dosing
Physiological replacement refers to the dose that mimics normal daily cortisol production by healthy adrenal glands, which is approximately 15-25 mg of hydrocortisone per day in adults. 1
Glucocorticoid Equivalency
The conversion between corticosteroids for physiological replacement is critical:
- Hydrocortisone 20 mg = Methylprednisolone 4 mg = Prednisone 5 mg 1
- Methylprednisolone is approximately 5 times more potent than hydrocortisone 1
- Therefore, 4-6 mg of methylprednisolone daily provides physiological replacement 1, 2
Specific Dosing for Adrenal Insufficiency
For patients with primary or secondary adrenal insufficiency requiring true physiological replacement:
- Hydrocortisone 15-25 mg/day remains the preferred agent for physiological replacement, typically given as 10 mg upon awakening and 5 mg at 2 PM 1, 2
- Methylprednisolone 4-6 mg/day can be used as an alternative, though it is less commonly recommended for chronic replacement due to its longer half-life and greater suppression of the HPA axis 1
- Prednisolone 4-5 mg/day is another alternative for select patients 1
Critical Distinction: Replacement vs. Treatment Doses
It is essential to distinguish physiological replacement from pharmacological treatment doses:
- Physiological replacement: Methylprednisolone 4-6 mg/day 1, 2
- Low-dose anti-inflammatory: Methylprednisolone 8-16 mg/day 3
- Moderate pharmacological doses: Methylprednisolone 16-48 mg/day 3
- High-dose treatment (e.g., asthma exacerbations): Methylprednisolone 60-80 mg/day for 3-10 days 1
- Pulse therapy (e.g., multiple sclerosis): Methylprednisolone 200 mg/day (equivalent to 1000 mg prednisone/week) 3
Context-Specific Considerations for Postmenopausal Women
For an adult postmenopausal woman requiring physiological glucocorticoid replacement:
- The standard physiological dose remains 4-6 mg methylprednisolone daily 1, 2
- Body weight does not significantly alter physiological replacement needs in the absence of obesity or extreme cachexia 4
- Postmenopausal status does not change the physiological replacement dose, though it increases the risk of glucocorticoid-induced osteoporosis at any dose 1
Osteoporosis Prevention in Postmenopausal Women
Any dose of prednisone ≥7.5 mg/day (equivalent to methylprednisolone ≥6 mg/day) for ≥3 months warrants osteoporosis prevention measures in postmenopausal women: 1
- Calcium 1000-1200 mg/day and vitamin D 600-800 IU/day 1
- Oral bisphosphonate therapy if T-score ≤-2.5 or FRAX-adjusted 10-year major osteoporotic fracture risk ≥10% 1
- Even physiological replacement doses (methylprednisolone 4-6 mg/day) may require bone protection in high-risk postmenopausal women 1
Common Pitfalls to Avoid
Do not confuse physiological replacement with treatment doses. The Medrol Dose Pack (84 mg over 6 days, starting at 24 mg/day) is a pharmacological treatment regimen, not physiological replacement. 5
Do not use methylprednisolone as first-line for chronic adrenal insufficiency replacement. Hydrocortisone 15-25 mg/day in divided doses is preferred because its shorter half-life better mimics physiological cortisol rhythm and causes less HPA axis suppression. 1, 2
Avoid dexamethasone for physiological replacement as it provides no mineralocorticoid activity and has an excessively long half-life (36-72 hours), making dose titration difficult. 1, 6
Recognize that "physiological" doses can still cause harm. Even 5 mg prednisone daily (equivalent to 4 mg methylprednisolone) for ≥1 month can suppress the HPA axis and increase fracture risk in postmenopausal women. 1
Monitoring Physiological Replacement
Clinical assessment is the primary method for monitoring adequacy of physiological replacement: 1, 2