Pregnancy has a positive effect on MS patients, especially during the 3rd trimester. Rebound of MS increases in the postpartum period. Estriol is the dominant pregnancy estrogen. Progesterone is also produced at high levels. The withdrawal of these hormones in the postpartum period are likely to lead to this rebound in MS.
It is now well recognized
that the disease manifestation is reduced in pregnant women with
relapsing-remitting MS
This occurs particularly during the
third trimester when levels of estrogens (estradiol and estriol) and
progesterone (see Table 2) are elevated
up to about 20 times
This seems
well correlated with a decrease in active white matter lesions detected by MRI
This clinical improvement is
however followed by temporary rebound exacerbations at post-partum, when the
hormone levels decline
a shift from Th1 to Th2 immune response, expansion of
suppressive regulatory T lymphocytes and decrease in the number of circulating
CD16+ natural killer (NK)-cells
Th2 cytokines are
associated with down-regulation of Th1 cytokines and this Th2 shift is believed
to provide protection from allograft rejection during pregnancy as well as from
Th1-mediated autoimmune disease
it is
worth noting that the levels of other hormones with anti-inflammatory activity
(1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase
by 2 to 4 times during late pregnancy
1,25-dihydroxy vitamin D3
induces regulatory T-cell function important for development of self-tolerance
breast-feeding does not alter the
relapse rate in women with MS
Leptin is a pleiotropic
hormone produced primarily by adipocytes but also by T lymphocytes and neurons
Several lines of evidence indicate that leptin
contributes to EAE/MS pathogenesis, influencing its onset and clinical severity,
by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg)
anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma)
and reduced Th2 (IL-4) cytokine production
circulating leptin levels are increased in relapsing-remitting MS
patients (men and women analyzed together) while the
CD4+CD25+Treg population decreases
As the leptin plasma concentrations are
proportional to the amount of fat tissue, obese/overweight individuals produce
higher levels of leptin
Nielsen et al found that estradiol and progesterone exert
neuroprotection against glutamate neurotoxicity, while MPA antagonizes the
neuroprotective effect of estradiol and exacerbated neuron death induced by
glutamate excitotoxicity
Older study that found that E3 provides estrogenic signaling per macro molecular proliferation. This was a cell MCF-7 study. This study did not differentiate between ERalpha and ERbeta.
Fantastic article on the review of the clinical use of saliva testing. Of note, is the extensive documentation of the validation studies of hormone saliva testing. Clearly, if a physician is against saliva testing, it is because of a lack of knowledge on the subject.