This article has demonstrated that stress and HPA axis activation affect the reproductive axis. Despite similarities in the HPA axis picture between women with major depression and those with hypothalamic amenorrhea and exercise or nutritional amenorrhea, no abnormalities in LH secretion have been documented in major depression. Lower estradiol in the follicular phase in depressed women and lower testosterone in depressed men however, have been observed [81, 92]. Although PMS would appear to be the best candidate for a mood disorder associated with abnormalities in reproductive hormones, no abnormalities in LH, estradiol or progesterone have been documented in PMS either [62]. Similarly, blockade of progesterone appears to be ineffective as a treatment for PMS [79]. Complete elimination of monthly cycling with leuprolide improves mood, however. No published studies have examined women with major depression to determine whether leuprolide will exacerbate or improve depressive symptoms. Some studies suggest beneficial effects of estrogen on mood in postmenopausal women, but no placebo controlled studies have explored estrogen augmentation in the treatment of major depression in either post- or premenopausal women, although estrogen is beneficial in women with perimenopause-related mood disorders [78].