During this phase there is a significant increase in the risk for major depression, especially in those women who have a past history of depressive episodes.96 As with any other stage of life, treatment of depressive disorder in the peri- and postmenopausal period usually involves antidepressant treatment. However, given that this phase of life is associated with progressive ovarian failure and hypoestrogenism, the role of estrogen replacement therapy in the treatment of depression has been a focus of research.97-101 In some but not all open-label and placebo-controlled

studies,97-101 Inhibitors,research,lifescience,medical estrogen has been shown to reduce both physical and depressive symptoms. In particular, two of three recent controlled trials99-101 documented the efficacy of estrogen replacement therapy in reducing depression in postmenopausal women. Estrogen replacement therapy may also enhance antidepressant response in such women. Inhibitors,research,lifescience,medical The potential clinical efficacy of estrogen in postpartum and postmenopausal depression, or in any other psychiatric indications associated Inhibitors,research,lifescience,medical with altered gonadal function, has to take side effects into consideration.83-101 Common side effects include gastrointestinal

dysfunction, headaches, and exacerbation of migraine as well as breast tenderness, vaginal bleeding, and infection. Hypertension and venous thrombosis are also concerns, although this risk is potentially reduced by use of transdermal rather than oral estrogen preparations.83-101 The relationship between estrogen therapy and risk of breast and uterine cancer is beyond the scope of this review, but remains

an issue to consider in instituting estrogen treatment for these various depressive syndromes. Pineal gland Inhibitors,research,lifescience,medical Melatonin is the major secretory hormone of the pineal gland. One of the main physiological effects of melatonin is the regulation of circadian rhythms.102 Given the prominence of sleep disturbance and the demonstrated alteration of various circadian parameters in major depression,103 Inhibitors,research,lifescience,medical several studies have attempted to determine whether a specific abnormality of melatonin all secretion could be demonstrated in major depression and, further, whether it could be of potential etiological significance.104 Findings from these studies have been inconsistent with many showing decreased amplitude of the nocturnal surge of melatonin while others showed increased or no change in nocturnal melatonin secretion.104 The-well described XAV 939 sedative effect of this hormone and its effect on circadian function has led to its widespread use in insomnia, jet lag, and difficulties associated with shift work.105 The use of melatonin as an antidepressant has been examined in both seasonal and nonseasonal depression. In seasonal depression, although a normalizing phase advance has been consistently demonstrated, the antidepressant action of melatonin has been inconsistent.