Males still dominate animal studies.

Currently available treatments for multiple sclerosis (MS) reduce inflammatory lesions on MRI and decrease clinical relapses but have limited effects on disability. Novel treatment options that target both the inflammatory as well as the neurodegenerative component of the disease are therefore needed. A growing body of evidence from basic science and clinical studies supports the therapeutic potential of estrogens in MS. Mechanisms of action include both immunomodulatory and directly neuroprotective pathways. A first pilot trial of oral estriol treatment showed encouraging results. There are now several phase II trials underway to further determine the efficacy of estrogen treatment in MS.

Despite abundant evidence of sex differences in the effects of drugs on nonsexual behaviour in rats and mice, most researchers continue to investigate male animals exclusively. This was evident from a survey of all relevant research reports published during the period February 2005-September 2006 (inclusive) in recent issues of five representative behavioural pharmacological journals. Reasons for excluding female animals from most studies are discussed along with attempts to justify the use of either male or female animals only, and the value of including both sexes (especially when a drug effect is poorly understood). Although there are other factors that can influence the effects of drugs, such as strain, age and social density, the sex of experimental animals is the easiest to control and thus is well suited to inclusion in pharmacological investigations. It is accordingly suggested that, as has been recommended many times in the past, animals' sex should play a more important part in future research than is still currently the case.

Estrogens are essential for normal brain function throughout life. The source of estrogens is not only from the periphery, but local production has also been demonstrated in the CNS. Actions of estrogens involve a variety of effects, which include modulation of gene expression, regulation of neurotransmitter release, or direct inter-actions with neurotransmitter receptors. By these effects, estrogens affect neuronal excitability and thus may play an important role in seizure disorders. Although the original clinical as well as animal studies suggest that estrogens have exclusively proconvulsant properties, it has now become clear that estrogens also produce anticonvulsant effects. These opposite effects of estrogens on seizures may depend on treatment duration, latency prior to seizure testing, mode of administration, estrogen dose and hormonal status, estrogenic species, the region/neurotransmitter system involved, seizure type/model used, and sex. Animal data also suggest that estrogens, specifically beta-estradiol, have neuroprotective effects on seizure-induced hippocampal damage. Further studies are necessary to understand the role of estrogens in seizure disorders. Such under-standing is important, especially for women with epilepsy, to make qualified decisions regarding administration of contraceptives and hormonal replacement therapy as well as for the design of new therapeutic strategies for better seizure control and prevention of seizure-induced neuronal damage.