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Local (and systemic) estradiol can stimulate lesion production of PGE2, which can activate pain fibers, enhance neuronal invasion of lesions by stimulating production of NGF and other neurotrophins, and promote sprouting of nociceptors that contribute persistent inflammatory pain and inhibit neuronal apoptosis

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The Endocrine Society Clinical Practice Guideline recommends beginning at 100 to 200 mg weekly of testosterone cypionate or enanthate, yet some clinics push men to 250 mg or higher on day one