gms | German Medical Science

Introduction: We tested the hypothesis that decreased pregnenolone levels are common in patients with rheumatoid arthritis (RA) and fibromyalgia (FMS).

Pregnenolone (PR) synthesis is the first and rate-limiting step in steroidogenesis, in which cholesterol is converted in mitochondria to pregnenolone, the precursor of all steroid hormones. Pregnenolone was used successfully in the 1940’s with effects on fatigue and cognition in the1940’s (Pincus, 1945 [1]) and later at higher doses in RA (Dordick, 1951 [2]). PR lost its focus when the more effective synthetic cortisone was implemented.

Methods: Serum pregnenolone sulphate (PR-S) levels were analysed to assess PR deficiency. Levels range from 27 to 80 ug/l depending on age.

We studied 90 patients (78 females/12 males) with a mean age of 58.1 years.

40 patients with RA: 20 with seropositive RA (RF and/or CCP positive) and 20 with a clinical diagnosis of seronegative RA.

50 patients with a clinical diagnosis of FMS.

All PR-S values were compared with a control group of 50 patients with MS/migraine, low back pain.

Results: The mean PR-S level in seropositive RA patients was 21.9 μg/l, and 24.5 in FMS patients compared to 34.8 in seronegative RA patients and 42.1 μg/l in the control group (mean age of 53.8 years, 42 f/8 m).

Conclusion: These results suggest a high probability of low PR-S levels/PR deficiency in seropositive RA and FMS patients with very low levels in seropositive RA and FMS.

As a limiting hormone for all biological steroid hormones, PR is a likely biomarker for mitochondrial dysfunction. This and the “forgotten” effects of PR as an active neurosteroid (Vallee, 2016 [3]) may lead to possible future therapeutic approaches as we now have the ability to measure PR levels instead of relying solely on clinical symptoms.

Further studies are needed to prove the hypothesis that low PR-S levels cause a “supply chain problem” and thus explain the diversity of symptoms in RA and FMS. Pregnenolone or new synthetic analogues may be an interesting therapeutic target especially for patients with a co-morbidity of fatigue or as an add-on drug for patients with requiring cortisone on basic immunotherapy with a high risk of osteoporosis or RA with low humoral activity.