Methylprednisolone
Classification: AATC code: H02AB04
Summary
Large controlled studies on sex differences in the mineral corticoid effect of methylprednisolone are lacking.
A large meta-analysis have shown that high daily doses of oral glucocorticoids increase the risk of bone fractures to a similar degree in men and women, regardless of age and underlying disease. However, another large population-based study found a higher risk of fracture in women than men exposed to oral corticosteroids.
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.
Additional information
Pharmacokinetics and dosing
Pharmacokinetics of methylprednisolone was studied in healthy adults (6 men, 6 women) receiving a dose of 0.6 mg/kg ideal body weight. Clearance was 55% higher in women when corrected for body weight. Women received methylprednisolone during the luteal phase of the menstrual cycle [1]. A study in 13 premenopausal women undergoing renal transplantation observed no sex difference in clearance normalized for body weight when comparing the data to data of their men (18 men) [4].
Effects
Women had lower inhibitory concentration (IC50), meaning women needed less concentration of methylprednisolone than men to produce 50% suppression of cortisol secretion [5].
In patients with septic shock (125 men, 75 women), the effect of hydrocortisone was compared to methylprednisolone. Patients received either hydrocortisone i.v. 50 mg every 6 h or methylprednisolone 20 mg every 12 h, for 7 days. The two treatment groups were similar in terms of survival rates and time to reverse. There were no differences between men or women [6].
Adverse effects
A large meta-analysis of corticosteroid-induced osteoporosis in adults showed that oral corticosteroid treatment with doses above 5 mg/day (of prednisolone or equivalent) reduced bone mineral density and increased the risk of fracture during treatment, irrespective of age, sex, or underlying disease (66 studies with 2891 patients with BMD measures, 71.5% women and 23 studies with 558 with fractures in corticosteroid users, and 244 235 corticosteroid users with fractures in the General Practice Research Database) [1]. However, a study not included in the meta-analysis, retrospectively analyzed the population attributable risk of fracture in a cohort using oral corticosteroids (8192 men, 12034 women). Compared to the general population, corticosteroids users had a higher risk of fracture (RR 1.90), and women had a higher risk than men (RR 2.13) [2]. Another meta-analysis of glucocorticoid therapy in children (in total 287 patients with BMD measure, and 37 819 with fractures) showed corticosteroid use to be associated with reduced spine bone mineral density and no sex difference in the risk for fracture were seen [3].In a study of individuals with chronic low back pain (14 men, 14 women), receiving cumulative methylprednisolone doses of at least 3 g, did not find a relationship between dose and BMD outcome in men or women [7].
Reproductive health issues
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Updated: 2019-02-26
Date of litterature search: 2017-02-02
References
- van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777-87. PubMed
- Donnan PT, Libby G, Boyter AC, Thompson P. The population risk of fractures attributable to oral corticosteroids. Pharmacoepidemiol Drug Saf. 2005;14:177-86. PubMed
- Hansen KE, Kleker B, Safdar N, Bartels CM. A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in children. Semin Arthritis Rheum. 2014;44:47-54. PubMed
- Tornatore KM, Gilliland-Johnson KK, Farooqui M, Reed KA, Venuto RC. Pharmacokinetics and pharmacodynamic response of methylprednisolone in premenopausal renal transplant recipients. J Clin Pharmacol. 2004;44:1003-11. PubMed
- Lew KH, Ludwig EA, Milad MA, Donovan K, Middleton E, Ferry JJ et al. Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 1993;54:402-14. PubMed
- Yu TJ, Liu YC, Yu CC, Tseng JC, Hua CC, Wu HP. Comparing hydrocortisone and methylprednisolone in patients with septic shock. Adv Ther. 2009;26:728-35. PubMed
- Dubois EF, Wagemans MF, Verdouw BC, Zwinderman AH, Van Boxtel CJ, Dekhuijzen PN et al. Lack of relationships between cumulative methylprednisolone dose and bone mineral density in healthy men and postmenopausal women with chronic low back pain. Clin Rheumatol. 2003;22:12-7. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2017-01-26.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson