Progesterone and Cortisol levels in plasma of patients with Amyotrophic Lateral Sclerosis (ALS): Correlation with Prognostic Factors and Survival

GARGIULO MONACHELLI GISELLA; MEYER M; RODRIGUEZ G; GARAY L; SICA, R.E.P; DE NICOLA A.F; GONZÁLEZ DENISELLE, M.C.

Simposio; First International Syposium of the Journal: Hormone Molecular Biology and Clinical Investigation; 2010

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder in which selective loss of motor neurons in the cerebral cortex, brainstem and spinal cord leads to progressive paralysis. ALS affect spinal or bulbar muscles at onset depending on the group of motoneurons prevalently involved at an earlier stage. An understanding of the factors related to ALS prognosis could help physicians and patients to schedule interventions and researchers to design pharmacologic and non-pharmacologic trials. Worst prognostic factors in ALS are: a) advanced age at onset; b) bulbar onset; c) short time between onset and diagnosis. Progesterone (PROG), a steroid classicaly considered a reproductive hormone, has been recently associated with neuroprotective and promyelinating activities in cases of injury, ischemia and degeneration of the central and peripheral nervous system (CNS and PNS). Its neuroprotective effects make it a particularly promising therapeutic agent for degenerative diseases involving motoneurons. Cortisol, on the other hand, is connected to the response to stress situations and its inappropriate secretion might contribute to neuronal damage. It is known that evening salivary cortisol levels are significantly increased in ALS patients. The goals of the present study were i) to investigate whether PROG serum levels are modified by ALS prognostic factors; ii) to determine whether cortisol follows the same pattern as progesterone in relation to these factors. We determined serum hormonal levels in 27 ALS patients and 21 controls. Both steroid hormones showed significantly increased levels in ALS patients in comparison to controls (mean ± SEM: PROG ALS vs control: 0.54 ± 0.06 vs 0.38 ± 0.04 ng/ml, p<0.05; Cortisol ALS vs control: 17.02 ±1.60 vs 11.83 ± 1.38 mg/dl; p<0.05). Levels of PROG were higher in spinal onset patients than those with bulbar onset (p<0.01), positively correlated with survival time (RRho=0.43, p=0.04) and showed a trend toward significance with time to diagnosis (RRho=0.36, p=0.06). These correlations have not been demonstrated for cortisol.  Conclusion: Elevated serum steroid levels in ALS were probably due to hyperfunction of the HPA axis. However, only PROG correlated with better prognostic factors like spinal onset or survival. Future studies will determine if the different behavior of PROG and cortisol relate to any particular role they may play during the course of this mototoneuron degenerative disease.