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Neurology of sex steroids and oral contraceptives

Neurology of sex steroids and oral contraceptives

Neurologic Clinics 4(4): 721-751

This review of the effects of sex steroids and oral contraceptives (OCs) on neurologic function in health and disease covers the following: sex steroids and their interaction with neural tissues; the human menstrual cycle and OCs; and sex hormones and OCs in human neurologic disease, i.e., stroke (thromboembolic cerebral infarction, subarachnoid hemorrhage, vascular malformations, and cerebral venous thrombosis), migraine, movement disorders, nervous system neoplasm, and the peripheral nerve. The various sex hormones may exert their effects on the nervous system directly or undergo conversion to more active metabolites. Interactions of sex hormones with neural substrates subserve numerous activities essential to both the well-being and perpetuation of the individual and the species. These interactions are key to the sexual differentiation of the brain, control of the brain-pituitary-gonad axis, and to the establishment of normal patterns of sexual and aggressive behavior in both sexes. Additionally, they play a role in temperature regulation (progesterone), caloric homeostasis (estrogen), and possibly sensory discrimination. The potent influences exerted by sex steroids on catecholamine and indoleamine turnover and the colocalization of labeled E2 within catecholamine and luteinizing hormone-releasing hormone (LHRH) positive perikarya suggest that many of the physiologic effects of sex steroids are mediated by modulation of specific monoaminergic and peptidergic pathways. Estrogens and aromatizable androgens also induce irreversible structural alterations in the rodent hypothalamus during the neonatal and peripubertal periods that are predominantly synaptogenic. In adult mammals, estrogens induce pathologic changes in the hypophysiotropic hypothalamus that may contribute to reproductive senescence in some species. Data from a series of retrospective and prospective studies have implicated OC use as an independent risk factor for the development of hemorrhagic and nonhemorrhagic stroke. Hormonal changes accompanying the pregnant state and the estrogen (and possibly progestogen) content of OCs may be predisposing factors in thromboembolic cerebral infarction, subarachnoid hemorrhage, cerebral venous thrombosis, and bleeding from intracranial and spinal vascular malformations. There are well-documented temporal associations of migrainous headache with specific phases of the menstrual cycle and the modifying influences of pregnancy, the menopause, and OC use. Also well established are relationships between endogenous and exogenous sex hormones and chorea. Fluctuating sex steroids also influence neuropsychiatric states, such depression and neuroendocrine disorders.

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Accession: 040789865

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PMID: 3025581

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