The hypothalamicpituitarygonadal axis

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In view of the remarkable gender differences in the prevalence rate of depression, the relatively high rates of postpartum depression, as well as the reduction in libido that is so characteristic of depression, it is plausible to posit a reduction in HPG axis activity in depressed patients. Therefore it is somewhat surprising that so little research has been conducted on HPG axis activity in depression and other psychiatric disorders. Indeed, a comprehensive database on this extraordinarily important area is simply not available, but the field has recently been reviewed. (3D A series of older studies documented no differences in basal gonadotrophin levels in depressed patients when compared to controls. The gonadotrophin-releasing hormone ( GnRH) stimulation test has only been administered to a relatively small number of depressed patients; although the results revealed a blunted or normal response, no firm conclusions can be drawn from this limited data set. Indeed, such studies require control for menopausal status, menstrual-cycle phase, use of oral contraceptives, as well as the measurement of baseline progesterone, oestrogen, and gonadotrophin plasma concentrations. One remarkable finding relevant to these questions is the remarkable effectiveness of the GnRH agonist, leuprolide, in the treatment of the premenstrual syndrome. It is believed to act by producing a chemical ovariectomy through a marked downregulation of adenohypophyseal GnRH receptors and the expected resultant reduction in gonadotrophin and gonadal steroid secretion. Long-term treatment with this compound could theoretically result in bone-density reductions and a risk of cardiovascular disease. Therefore, supplementation with oestrogen and progesterone has been suggested in combination with leuprolide, though there are reports that such a strategy reduces the effectiveness of the treatment.

GnRH was the second of the hypothalamic-hypophysiotrophic hormones to be chemically characterized. It is a decapeptide that is relatively limited in distribution to hypothalamic regions and to the preoptic area and septum. It stimulates the secretion of both luteinizing hormone and follicle-stimulating hormone in both men and women. GnRH is known to act by stimulating GnRH receptors in the anterior pituitary gland, which results in the increased synthesis and release of the pituitary gonadotrophins, in turn causing the release of oestrogen and progesterone in women and testosterone in men. There is some evidence that oestrogens, which have receptors localized extensively throughout the CNS, may possess some antidepressant activity, though the data is far from clear. (32) There are hints from the clinical trial literature that postmenopausal women on oestrogen replacement may respond better to treatment with fluoxetine than women who are not receiving such treatment/33' though the database is small and fraught with many confounds.

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