In the present study we evaluated the hypothesis that decreased pregnenolon levels are frequent in patients with fibromyalgia (FMS). 

Synthesis of Pregnenolon(PR) is the first and rate-limiting step in steroidogenesis, converting cholesterol to pregnenolone in mitochondria  (Illustration)  as  a precursor to all biological steroid hormones. PR is a potential  biomarker for  mitochondrial function.SFN can explain neuropathic pain symptoms in FMS,  estimated in a metaanalysis (Oaklander,2019) in 49% of FMS  patients as  a frequent condition.

Pregnenolon-sulfate (PR-S) serum levels can be easily tested to evaluate PR- deficiency. Normal levels range from 27 - 80 ug /l. We studied 44 patients with the clinical diagnosis of FMS, (40 f/4 m) ,average age of 53,8 years. Twenty-two (22) had the  skin biopsy confirmed diagnosis of SFN, the other 22 had negative SFN biopsy results.

All PR-S serum levels were compared to a control group. 

The average PR-S level in the entire study group of 44 FMS patients were 21.4 ug/l (median 20). No difference was found in PR-S levels of SFN positive patients versus patients with normal small fiber density.

The average PR-S range in FMS patients was significantly lower compared to a control group of 35 patients, average age 51,2 (29f/6m) with various neurological disorders (migraine/ MS/ low back pain) with a PR-S range of 41,2ug/l, (median 41).

Our findings suggest a high probability of an association of low PR-S levels and PR deficiency in FMS patients.

Acting as a limiting hormone for steroid synthesis ,PR is not only a probable biomarker for mitochondrial dysfunction but in addition could  act as an effective neurosteroid to fatigue. This could lead to possible therapeutic approaches. Further studies are necessary in order to prove the hypothesis that low PR-S levels cause a “supply chain problem”, thus explaining symptoms in FMS, especially fatigue and post exertion malaise.