Elevated Neuroactive Progesterone Metabolites
in Women with Chronic Fatigue Syndrome

Beverley E. Pearson Murphy, MD, PhD, a.-Missagh Ghadirian, MD, MSc, Cyndie M. Allison, MSc, and Craig Watts, MD
J Steroid Biochem Molec Biol 74:137-142, 2000


Background:  Although some ring A-reduced progesterone metabolites are known to be powerful anaesthetics at high doses, and to have anxiolytic or soporific effects at lower doses, their physiological relevance remains unknown.

Methods:  We measure five of these steroids, along with progesterone and its precursor pregnenolone, in 20 women with chronic fatigue syndrome (CFS) and in 13 age-matched control women.

Findings:  Mean values for all five of the metabolites, but not for progesterone or pregnenolone, were significantly increased (p=0.029 to 0.0003) in the CFS group (n=20) compared with controls (n=13).  When mildly depressed patients (n=10) were compared to moderately to severely depressed patients (n=10), the mean values in the mildly depressed patients tended to be higher than those in the moderately to severely depressed patients, reaching significance for progesterone (p=0.018).   However, when the moderately to severely depressed group was compared with controls, only the level of 3b,5a-THP was elevated (p=0.024).  On the other hand, levels in the mildly depressed group were higher for 5a-DHP (p=0.037), 3b,5a-THP (p=0.004) and progesterone (p=0.032) and of borderline significance (p 0.1) for 5b-DHP, 3b,5b-THP and 3a,5a-THP.

Interpretation:  These results suggest that increases in neuroactive progesterone metabolites, particularly 3b,5a-THP, are associated with chronic fatigue syndrome and that this syndrome is not attributable merely to depression.




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