Female hormones affect disease activity; 82% of women report worse symptoms before menses (Smith and Studd 1992). The progesterone/17-beta-estradiol ratio increases during the luteal phase of the menstrual cycle, and this corresponds to higher MRI activity (Pozzilli et al 1999). MRI activity increases during ovulation when estradiol is high and progesterone is low (Bansil et al 1999). Symptoms improve with aspirin, without affecting body temperature.
http://www.ncbi.nlm.nih.gov/pubmed/10071166Patients with high estradiol and low progesterone levels had a significantly greater number of Gd enhancing lesions than those with low levels of both these hormones. Patients with a high estrogen to progesterone ratio had a significantly greater number of active MRI lesions than those with a low ratio.
We found that progesterone and the synthetic 19-norprogesterone derivative 16-methylene-17α-acetoxy-19-norpregn-4-ene-3,20-dione (Nestorone) promote the remyelination of axons by oligodendrocytes after lysolecithin-induced demyelination in organotypic cultures of cerebellar slices taken from postnatal rats or mice.
Progesterone can promote the remyelination, but whether it exerts beneficial effect on treatment of MS still remains unclear. . . . The results indicate that the progesterone is beneficial to attenuating neurological behavioral deficits, for it can promote more successful remyelination of EAE with aid of the nucleus-sublocalized Olig1 protein.
Progesterone treated animals showed reduced peak disease scores and cumulative disease indices, and decreased inflammatory cytokine secretion (IL-2 and IL-17).
In conclusion, progesterone enhanced axonal density, decreased axonal damage and prevented GAP43 hyperexpression in the spinal cord of EAE mice.
Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection.
In peripheral neuropathies, progesterone and reduced derivatives promote remyelination, axonal regeneration and the recovery of function. In traumatic brain injury (TBI), progesterone has the ability to reduce edema and inflammatory cytokines, prevent neuronal loss and improve functional outcomes. Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury. In experimental spinal cord injury (SCI), molecular markers of functional motoneurons become impaired, including brain-derived neurotrophic factor (BDNF) mRNA, Na,K-ATPase mRNA, microtubule-associated protein 2 and choline acetyltransferase (ChAT). . . . SCI also causes oligodendrocyte loss and demyelination. In this case, a short progesterone treatment enhances proliferation and differentiation of oligodendrocyte progenitors into mature myelin-producing cells, whereas prolonged treatment increases a transcription factor (Olig1) needed to repair injury-induced demyelination.
A concept is emerging that progesterone may exert different actions and use different signaling mechanisms in normal and injured neural tissue. . . . Progesterone and its metabolites promote the viability of neurons in the brain and spinal cord. Their neuroprotective effects have been documented in different lesion models, including traumatic brain injury (TBI), experimentally induced ischemia, spinal cord lesions and a genetic model of motoneuron disease. Progesterone plays an important role in developmental myelination and in myelin repair, and the aging nervous system appears to remain sensitive to some of progesterone's beneficial effects. Thus, the hormone may promote neuroregeneration by several different actions by reducing inflammation, swelling and apoptosis, thereby increasing the survival of neurons, and by promoting the formation of new myelin sheaths.
The main hormonal abnormalities consisted of decreased progesterone level, increased oestradiol level or both. The sex hormone pattern was abnormal in 56% of patients. Hypotha-lamic lesions were found on MRI in 53% of cases. The abnormal hormonal pattern correlated with intensity of MR changes (p < 0.05, Fisher's exact test), but neither with presence of hypothalamic changes nor with disease parameters (Expanded Disability Status Scale, relapse rate, disease duration).
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