Relationships of serum estradiol levels, menopausal duration, and mood during hormonal replacement therapy

A study was undertaken in 38 menopausal women on cyclic HRT (estropipate and estropipate + norethindrone). Serum estradiol levels during treatment were related to mood changes and platelet MAO activity. The relationship between serum estradiol levels and mood changes was found to be a function of the duration of menopause. Women with a short duration of menopause (12.9 months ± 6.1) were compared to women with a long duration of menopause (76.6 months ± 52.3). Women with a short duration of menopause had significantly lower mean serum estradiol levels during HRT compared to women with a long duration of menopause (216.9 ± 62.3 vs. 291.13 ± 118.12, respectively, p < .02). It had previously been reported that estrogen treatment in menopausal women had a positive effect on mood, whereas the combination of estrogen plus a progestin had a negative effect on mood. We found that the women with a long duration of menopause and higher treatment serum estradiol levels had significantly more dysphoria when receiving a combination of estrogen plus progestin than did the women with a short duration of menopause and lower serum estradiol levels. However, both short and long duration menopausal groups showed improvement in mood when estrogen was administered alone. Platelet MAO levels, a marker of adrenergic and serotonergic function thought to relate to mood, were negatively correlated with serum estradiol levels during HRT. We suggest that these paradoxical findings may be secondary to a prolonged estrogen deficiency state in women with a long duration of menopause.