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Protective actions of sex steroid hormones in Alzheimer's disease
Frontiers in Neuroendocrinology, 06/24/09

Pike CJ et al. – A review of the protective actions of sex steroid hormones in Alzheimer’s disease (AD) reports that the successful use of hormone therapies in aging men and women to delay, prevent, and or treat AD is pending research to optimize key parameters of hormone therapy and development of selective estrogen- and androgen-receptor modulators.

• Review of the protective actions of sex steroid hormones in AD

• Etrogens and progestogens depletion hypothesized to increase susceptibility to AD pathogenesis -- supported by epidemiologic evidence but refuted by some clinical findings
• Experimental evidence for neuroprotective actions of estrogen for AD prevention: promotion of neuron viability and reduction of beta-amyloid accumulation
• Diminished neural responsiveness to estrogen with age and reduced neuroprotective actions of estrogen limit use of hormone therapies in aged women
• Modulation of estrogen neuroprotective actions by progestogens
• Continuous progestogen exposure associated with inhibition of estrogen actions vs cyclic delivery of progestogens that enhances estrogen neural benefits
• Normal age-related testosterone loss in men associated with increased risk for AD
• Testosterone as an endogenous neuroprotective factor increases neuronal resilience and reduces beta-amyloid accumulation
• Androgen neuroprotective effects mediated both directly by androgen pathway activation and indirectly by aromatization to estradiol and initiation of protective estrogen signaling mechanisms

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