Hormone Therapy

Dexamethasone and the Paediatric Population

In the past, literature with adult subjects investigating the use of steroids in severe TBI reported conflicting results. The following studies investigated the effects of dexamethasone on children with an ABI.

Table: Effects of Dexamethasone in Severe TBI

Discussion

The paediatric data highlights the fact that dexamethasone suppresses endogenous production of glucocorticoids (Fanconi et al. 1988; Kloti et al. 1987), therefore bringing into doubt any beneficial effect of exogenous glucocorticoids. This evidence, along with findings from Dearden et al. (1986) that dexamethasone failed to show difference in outcome in a mixed adult and paediatric sample, underscores the lack of firm data to support the use of these drugs in individuals with brain injury.

Conclusion

There is Level 2 evidence based on three RCTs that administration of dexamethasone inhibits endogenous production of glucocorticoids and has no proven impact on recovery post brain injury.

 

Administration of dexamethasone inhibits endogenous production of glucocorticoids in children.

Dexamethasone administration has no proven impact on recovery post brain injury in children.

 

Medroxyprogesterone

Sexual dysfunction following TBI has been reported to occur in at least 50% of patients (Emory et al. 1995). Hypersexuality is less common than hyposexuality (decreased libido) but results in a greater negative effect for the individual and results in a great burden of care by limiting independence. Hypersexual behaviour can encompass a range of behaviours, from indiscriminate sexual advances, promiscuity, and exhibitionism, to assault and/or rape (Mania et al. 2006). A recent study revealed inappropriate sexual talk to be the most common inappropriate sexual behaviour in a sample of TBI patients (Simpson et al. 2013).Treatment for sexual offenders without brain injuries has included pharmacological intervention and or counselling and education. Typically, medication is used to reduce the sexual drive, but it is unclear if it has effect on cognitive processing (i.e. preservative thoughts regarding sex).

Table: Effects of Depo-Provera on Sexually Aggressive Behaviour

Discussion

In a retrospective study, Depo-Provera, an anti-androgen drug, was evaluated in terms of its efficacy for controlling sexual aggression in eight males with TBI experiencing onset of sexual aggression three years post injury (Emory et al. 1995). Weekly IM injections of Depo-Provera (400 mg) in conjunction with monthly psychoeducational counseling resulted in a cessation of hypersexual behaviour and reduced testosterone levels. Three subjects re-offended when the drug was stopped, three remained on it and two stopped taking the drug and had maintained cessation of hypersexual behaviour.

Conclusion

There is Level 4 evidence that Depo-Provera and counselling reduces sexually aggressive behaviour.

 

Medroxyprogesterone intramuscularly may reduce sexual aggression.

 

Progesterone

Progesterone has drawn interest as a potential neuroprotective agent. Animal studies suggest that progesterone modulates excitotoxicity, reconstitutes the blood brain barrier, reduces cerebral edema, regulates inflammation, and decreases apoptosis (Stein 2008). In a human population, Groswasser et al. (1998) observed that female patients with TBI seemingly recovered better than males and progesterone was suggested as a possible cause of this disparity. Trials are now being undertaken to accurately assess the effects of progesterone in the ABI population. 

Table: Effects of Progesterone in the Treatment of Acute ABI

Discussion

The findings from an RCT conducted by Xiao et al. (2008) suggest that progesterone may be beneficial from a functional standpoint. The study demonstrated that patients receiving progesterone had significantly better functional outcomes as per Glasgow Outcome Scale and modified Functional Independence Measure than patients treated with placebo at both 3 and 6 month follow-ups. However, findings from other studies suggest that progesterone may not be entirely effective. For instance Wright et al. (2007) found that while progesterone use was associated with improvements in GOS and DRS 30 days post injury, such benefits were limited only to those sustaining moderate (GCS 9-12) injuries. The outcomes for patients with severe (GCS 4-8) injuries were relatively poor, regardless of the treatment. Two recent RCTs have as well demonstrated that progesterone use did not improve functional outcomes at 3 month (Shakeri et al. 2013) and at 6 month (Wright et al. 2014) follow-ups, as indicated by GOS. However, Shakeri et al. (2013) found for the with GCS scores 3-8, those receiving progesterone had favourable outcomes.

With respect to findings of mortality, there is considerable inconsistency as well. While Wright et al. (2007) and Xiao et al. (2008) report that mortality was significantly lower in patients treated with progesterone, Wright et al. (2014) concluded that there was no difference in mortality between progesterone and placebo groups at 6 month follow-up.    

Conclusions

Based on four RCTs, there is conflicting evidence as to the effectiveness of progesterone on functional outcomes post ABI.

There is conflicting evidence whether progesterone improves mortality in patients with ABI. 

 

 There is conflicting evidence regarding the effectiveness of progesterone on functional outcomes.

It remains unclear as to whether progesterone improves mortality in patients with ABI.