TRT shows promise as adjunct treatment in rehabilitating ICU patients

Testosterone replacement therapy (TRT) has the potential to be an effective adjunct treatment in the rehabilitation of critically ill patients with intensive care unit (ICU)-associated weakness (AW) and hospital-associated deconditioning (HAD), according to a Singapore study.

"A multidisciplinary approach would ensure that suitable patients benefit from optimal nutrition, optimal rehabilitation, and synergistic testosterone therapy in a clinically sound and resource-efficient fashion,” said the researchers.

In this retrospective analysis, five patients with either ICU-AW or HAD received TRT or oxandrolone for 2 weeks from April to November 2020. These individuals also received standard rehabilitation therapy during the 2-week trial period. The primary outcome measure was grip strength.

The participants showed a mean improvement of 4.2 kg in grip strength in 2 weeks. In addition, they achieved good functional recovery in terms of distance ambulated and required less assistance for ambulation. [Singapore Med J 2024;65:607-613]

In sex hormone analysis performed prior to TRT initiation, four out of five patients were found to be biochemically hypogonadal. None of them dropped out of the study or had any serious adverse events over the 2-week study period. In addition, nearly all participants (n=4) achieved full independence at 3 months after discharge.

“Although there was no control group to benchmark against, we believe that androgen therapy with either oxandrolone or TRT may have contributed a significant proportion of the improvement,” the researchers said.

In a previous case series of oxandrolone use in critically ill patients, grip strength similarly improved in one out of four participants. [Case Rep Crit Care 2018;doi:10.1155/2018/4545623]

“Such gains in strength over a relatively short 2-week period may arguably be due to other factors, rather than just improvement in muscle strength and function,” the researchers said. 

“Nonetheless, the improvements shown by this group of [patients] suggests that clinically evident benefits of the overall therapy may be obtained in a relatively short timeframe. This may translate to reduced total duration of hospitalization and faster return to the community,” they added.

Survival outcomes

Previous studies have reported the negative impact of ICU-AW and HAD on the functional and long-term survival outcomes of patients in the ICU. [Am J Phys Med Rehabil 2009;88:66-77; Curr Opin Crit Care 2020;26:508-515]

Moreover, “[t]he ever-increasing number of ICU survivors has led to increased appreciation of the resultant increased length of hospitalization and poorer long-term outcomes in terms of mortality, physical functioning and quality of life,” the researchers said. [Crit Care 2015;19:196]

“The augmentation of the acute or subacute rehabilitation process through TRT may potentially reverse some of these negative outcomes for this group of patients,” they added.

Notably, if the rate of improvement in strength for patients reaches about 20 percent every 2 weeks, this would translate to shorter hospital stay and better functioning following discharge.

"This conclusion is supported by the generally good 6-month postdischarge outcomes seen in our case series,” according to the researchers.