Review: An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens, 2019, Paredes et al

Open access, https://www.mdpi.com/1422-0067/20/22/5729/htm

 

It is notable that the narrative review hypothesise that serotonin levels / activation of 5-HT1A receptor is too low, which is not consistent with the various neuroendocrine studies that have suggested normal and occasionally elevated serotonin pathway activity (but the findings of elevated serotonin activity were mostly in men). Likewise various SSRIs have failed to demonstrate efficacy in double blinded trials with CFS patients, for any self reported symptoms including depressive symptoms. This suggests that "low-serotonin" doesn't seem to be a mediator of symptoms, including depression in this group of patients.

The assumption of too little serotonin seems strange since estrogen generally increases serotonin pathway activity. They do mention a single case of a medical condition that was exacerbated by contraceptive hormone therapy, which had a resolution of fatigue after cessation. But the simplest explanation in that case is the fatigue was simply a consequence of the medical condition...

I think that if CFS or ME patients had a noticeable increase in symptoms due to contraceptive medication, we would have been talking about it for a long time.

But they also mention that:

Looking at all the prior evidence, I don't see the relevance of the relationship between estrogen and serotonin to CFS...

 

Jonas Bergquist found Pregnenolone to be significantly lower in people with ME [OMF funded study - https://let-me.be/e107_files/downloads/the_me_global_chronicle_-_30_-_20181222.pdf].

Not sure if this is relevant to this discussion.

 

I think it's not the absolute but relative levels that are important.
The ratios between eg progesterone and estrogen rather than absolute levels seem to be important in pre menopausal women.