A number of steroid hormones and their metabolites fluctuate in the circulation across the human menstrual cycle. In addition to their classic actions on the hypothalamo-pituitary-gonadal axis, many of these hormones act as 'neuroactive steroids' to alter the function of neurotransmitters, such as GABA, within central nervous system circuits. Clinically, these steroids are important because they have not only acute but also long-term effects, and 'withdrawal' properties. This review discusses the effects of steroids such as 3α-OH-5α-pregnan-20-one (3α,5α-THP or allopregnanolone) which alter GABA function in distinct ways dependent upon the time course of exposure, to either enhance or decrease inhibition in the brain. These effects are discussed in light of recent clinical findings which seek to further character-ize the steroid milieu which underlies pre-menstrual dysphoria.
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