Reproductive Abnormalities in Depression

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In depression, response to GnRH has been assessed by several groups. Some studies have reported a normal LH and FSH response to GnRH in pre- and postmenopausal women (Unden et al. 1988; Winokur et al. 1982). However, given the major differences in LH pulse amplitude and mean LH levels between follicular and luteal phases, it would be extremely difficult to observe a difference in basal LH secretion between major depression and control women without strict control of menstrual cycle phase. However, Brambilla et al. (1990) noted a decreased LH response to GnRH in both premenopausal and postmenopausal women, with lower baseline LH concentrations in postmenopausal depressed women. It may be that the increased secretion of LH following removal of the negative feedback of gonadal steroids in postmenopausal women unmasks a decrease in LH secretion that is not as easily observed in women with intact estrogen and progesterone feedback. Other studies examining depressed patients of both sexes, which were not analyzed separately, observed no change in baseline or GnRH-stimulated LH and FSH secretion (Unden et al. 1988).

Only recently have studies begun to focus on the pulsatile rhythm of LH secretion in women with major depression. Thus far, there have been only four published studies examining pulsatile LH secretion in depressed women: two by Meller et al. (1997, 2001), a third by us (Young et al. 2000b), and a fourth looking at the data from both Meller and Young with spectral analysis (Grambsch et al. 2004). The data from the Meller studies showed slower LH frequency in the follicular phase. Our data revealed significantly lower estradiol in the follicular phase in a small sample of depressed women. Since our publication in December 2000, a large-scale epidemiological study by Harlow et al. (2003) has found that earlier menopause is accompanied by lower estradiol in perimenopausal depressed women. Thus, three recent carefully done studies using modern techniques with sophisticated analyses have found evidence of reproductive axis abnormalities in depressed women. One study of the reproductive axis in men with major depression (Schweiger et al. 1999) also revealed decreased testosterone and a trend for slower LH pulses, suggesting that abnormalities in the reproductive axis are also found in men. Consequently, further studies on the reproductive axis in depression are indicated.

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Defeat Depression

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