No surprise that progesterone and the synthetic progestin medroxyprogesterone acetate (MPA) have different effects on the vascular endothelium. MPA inhibits NO production, whereas Progesterone maintains NO production. MPA promoted platelet adhesion whereas Progesterone did not--significant implication in plaque formation.
This was the WHI review of data as it pertains to dementia and cognitive decline in women. The take home here is that the data provides little evidence for premarin with or without medroxyprogesterone acetate in > 65 for prevention of dementia. However, this is in women > 65 and studies show that younger women do indeed receive benefit, especially in those with early ovary removal. Another point here, MPA (medroxyprogesterone acetate) increases cognitive decline. Just don't take MPA, it is a bad drug all the way around!
Estrogen with progestin worsens cognitive decline in women >65. Little can be taken from this study other than, medroxyprogesterone acetate is a bad drug and should not be given to women for any purpose, especially in those >65. One wonders if bioidentical, physiologic hormone replacement would have the same effect? I doubt it. The likely negative impact of hormones on the brain in women >65 is due to the negative effects of MPA, the change in inflammatory cytokines, and the change in receptors.
at both progestogen and glucocorticoid receptors may mediate the effects of high-dose MPA therapy in breast cancer. The possible stimulation of the growth of some cell types by MPA requires further investigation.
Women
who have an oophorectomy before the normal age at menopause show an increased risk for cognitive impairment or dementia later
in life unless they are treated with estrogen until the normal age at menopause
SIRT1 has been implicated in the disruption of mitochondrial bioenergenetics in Alzheimer's
disease and mild cognitive impairment
the increase in dementia observed with CEE/MPA rather than CEE alone suggests potential deleterious effects of
MPA on brain function in older women
Early estrogen therapy in perimenopause and early menopause, with Estradiol, provides more health benefits than later therapy. This article looked at Estrogen's effects on a woman's brain. This likely has its origins in the change in estrogen receptors. The signal is not changing, but the reception of that signal is. How else can one explain a different response to the same hormone dosage?
Approximately 80% of women reported overall satisfaction with the micronized progesterone-containing regimen. A micronized progesterone-containing HRT regimen offers the potential for improved QOL as measured by improvement of menopause-associated symptoms.
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