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Betamethasone – systemic use

Classification: B

Drug products: BENTELAN 0,5 mg, Betametason AB Unimedic, Betametason Alternova, Betametason Evolan, Betamethasone, Betamethasone American Regent, Betapred, Betnesol, CELESTAMINE N0,5 Tabletten, Celeston® bifas®

ATC code: H02AB01

Summary

Published controlled studies on sex differences in effect of betamethasone are lacking, except in prevention of respiratory distress syndrome in premature infants and the results from these studies are contradictory.
 
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.
 
The present evidence concerning differences between men and women is very limited and do not motivate differentiation in dosing or treatment.

Additional information

Pharmacokinetics and dosing

Healthy adults (2 men, 6 women) receiving betamethasone 8 mg i.v. and betamethasone phosphate 10.6 mg i.v. showed no apparent sex difference in any pharmacokinetic parameter. Body weight did not affect AUC or half-life [3].

Effects

No studies with a clinically relevant sex analysis regarding the effect of betamethasone have been found, except for use during pregnancy. In pregnancy, corticosteroid can be used to encourage fetal lung maturation where premature delivery is expected [4] as immature lung development can lead to respiratory distress syndrome (RDS) [5]. A systematic review and meta-analysis, including four studies using betamethasone and four studies using dexamethasone (in total 1109 boys, 968 girls), found no difference in the reduction of RDS between girls and boys (relative risk 0.57 vs. 0.50). However, all four trials with betamethasone showed a benefit only for boys, while all four trials with dexamethasone showed benefit only in girls [6]. In contrast to this, other studies [7, 8] have shown a beneficial response to betamethasone only in girls. One possible explanation to these contradictory findings may be heterogeneous groups with different average gestational ages and birth weights in the studies [6-8].

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].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

There has been concern that prenatal use of corticosteroids to increase lung maturation in premature infants is associated with long term effects, such as cognitive deficits [4]. A cross-sectional study evaluated children (117 boys, 105 girls) born to women at risk of preterm delivery   treated with synthetic betamethasone or dexamethasone as a single course during pregnancy. Cognitive testing was performed when the children were at age 8-11 years old along with a structured interview with the mothers. Boys born to women with a pathologic pregnancy with or without receiving glucocorticoid scored lower IQ than controls. No differences in IQ scores between groups were seen in girls [9]. A study of individuals aged 20-22 years (43 men, 38 women) who had antenatally been exposed to one course betamethasone for prevention of neonatal respiratory distress syndrome showed no effect on cognitive functioning [10]. Another observational study of long-term effects of antenatal corticosteroid use (betamethasone or dexamethasone) showed that boys had a higher risk of epilepsy than girls (OR 1.74 vs. 0.50). Children were followed up until their ninth birthday [11].

The effect of betamethasone on fetal heart rate and behavior in preterm twin pregnancy was analyzed in 18 pregnant women receiving 12 mg of betamethasone i.m. Betamethasone decreased basal fetal heart rate and body and breathing movements. The response in one fetus was highly associated with that in the co-twin, and independent of sex [7].

Updated: 2020-08-28

Date of litterature search: 2016-09-15

References

  1. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777-87. PubMed
  2. 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
  3. 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
  4. Petersen MC, Nation RL, McBride WG, Ashley JJ, Moore RG. Pharmacokinetics of betamethasone in healthy adults after intravenous administration. Eur J Clin Pharmacol 1983;25(5):643-50 PubMed
  5. The United Kingdom Teratology Information Service (UKTIS) - Exposure in pregnancy. Corticosteroids in pregnancy. Newcastle upon Tyne: Public Health England. 2012 [cited 2016-09-15.] länk
  6. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2015;7:CD003935. PubMed
  7. Roberge S, Lacasse Y, Tapp S, Tremblay Y, Kari A, Liu J et al. Role of fetal sex in the outcome of antenatal glucocorticoid treatment to prevent respiratory distress syndrome: systematic review and meta-analysis. J Obstet Gynaecol Can. 2011;33:216-26. PubMed
  8. Ballard PL, Ballard RA, Granberg JP, Sniderman S, Gluckman PD, Kaplan SL et al. Fetal sex and prenatal betamethasone therapy. J Pediatr. 1980;97:451-4. PubMed
  9. Papageorgiou AN, Colle E, Farri-Kostopoulos E, Gelfand MM. Incidence of respiratory distress syndrome following antenatal betamethasone: role of sex, type of delivery, and prolonged rupture of membranes. Pediatrics. 1981;67:614-7. PubMed
  10. Alexander N, Rosenlöcher F, Dettenborn L, Stalder T, Linke J, Distler W et al. Impact of Antenatal Glucocorticoid Therapy and Risk of Preterm Delivery on Intelligence in Term-Born Children. J Clin Endocrinol Metab. 2016;101:581-9. PubMed
  11. Dessens AB, Haas HS, Koppe JG. Twenty-year follow-up of antenatal corticosteroid treatment. Pediatrics. 2000;105:E77. PubMed
  12. Eriksson L, Haglund B, Ewald U, Odlind V, Kieler H. Short and long-term effects of antenatal corticosteroids assessed in a cohort of 7,827 children born preterm. Acta Obstet Gynecol Scand. 2009;88:933-8. PubMed
  13. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-09-15.] Socialstyrelsens statistikdatabas
  14. Conicse. Stockholm: eHälsomyndigheten. 2015 [cited 2016-03-23.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson