Communication between brain neurohormone and endocrine hormone production is central to neuroendocrine integration. Neuroendocrine hormones influence multiple metabolic functions as well as mood, sleep, memory, neurogenesis, and neuronal myelination. Demyelination is one of the hallmarks of multiple sclerosis (MS), and remyelination is a major treatment target. Several hormones have been investigated as potential therapies for people living with MS.
The thyroid produces two hormones, T3 and T4. Thyroid hormones promote neuronal growth and synaptogenesis. They are also critical for the maturation of oligodendrocytes, the cells responsible for myelination.1,2 In particular T3, the active form of thyroid hormone, has been shown to increase remyelination and improve neurological symptoms in animal models of MS.3,4 A preliminary study of people with MS demonstrated that treatment with a T3 synthetic analog was safe and tolerated, and researchers recommended that larger clinical studies be done to determine its effectiveness.5
T3 also supports nerve growth, proliferation, function, and myelination by promoting nerve growth factor.6
The estrogens are a family of hormones that includes estrone, estradiol, and estriol. Neurons express estrogen receptors, and estrogen supports nerve growth and the repair of damaged brain cells.7 Estriol is thought to be the most beneficial estrogen with regard to MS. In a study of pregnant women with MS, participants had a 70% decrease in relapse rates in their third trimester of pregnancy, when estriol levels are at their highest.8 In a 2-year study, women with relapsing-remitting MS were given standard of care medication plus oral estriol or placebo. The women on oral estriol had significant reductions in relapse rates compared to the placebo group.9 In a similar study, oral estriol decreased the inflammatory immune response and caused the regression of brain lesions.10 The type of estrogen treatment is crucial. Natural or bioidentical hormones appear to have a greater beneficial effect; oral contraceptives with synthetic estrogens were shown not to have a beneficial impact on symptoms or relapse rates for MS.11
Testosterone supports cognition and nerve differentiation. Low levels of testosterone in men with MS are associated with disability.12 A one-year pilot study of testosterone gel in men with MS found it improved cognitive performance and slowed brain atrophy.13 Another small study demonstrated that testosterone was anti-inflammatory and neuroprotective.14 Testosterone therapy may be most clinically useful in men who have low levels of this hormone.
Acute MS symptom flares can be treated with intravenous (IV) methylprednisolone, which decreases the concentration of T cells and proinflammatory cytokines like IFN-γ and TNF-α.15 Flares are managed with 1000mg methylprednisolone daily for 3-5 days, with results lasting up to 30 days. However, because of its impact on the HPA axis, side effects can include insomnia, poor memory, and mood changes.16 Adrenocorticotropic hormone (ACTH), which stimulates endogenous cortisol release in the body, was shown to decrease relapse rates more than methylprednisolone.17 People with MS tend to have low levels of cortisol, and so clinicians might consider supplementing their MS patients with 5 mg-10 mg/day of bioidentical hydrocortisone. At this physiological dosage range, there is no suppression of the HPA axis. On the contrary, it helps the body maintain optimal cortisol levels, which in turn relieve symptoms of fatigue, and promote healthy immune function.
Melatonin is a neurohormone released by the pineal gland in accordance with the circadian rhythm. It has been studied extensively in sleep disorders and is generally regarded as safe.18 Recent evidence indicates that melatonin secretion is dysregulated in people with MS.19 In addition, night-shift workers often have disrupted melatonin secretion, which may be associated with an increased risk for developing MS.20 Melatonin has been shown to improve MS symptoms in animal models.21 Findings from a study of people with MS suggest that supplementation with melatonin at 5mg per day for 90 days improved oxidative stress parameters and quality of sleep.21