Is there a role for reproductive steroids in the etiology and treatment of affective disorders?

Abstract

A variety of hormones have been shown to play a role in affective disorders. Reproductive steroids are particularly informative in our efforts to understand the pathophysiology of affective dysregulation for several reasons: i) Reproductive endocrine-related mood disorders (premenstrual dysphoric disorder, perinatal depression, perimenopausal depression) are wonderful clinical models for investigating the mechanisms by which affective state changes occur; ii) Reproductive steroids regulate virtually every system that has been implicated as disturbed in the ontogeny of affective disorders; iii) Despite the absence of a reproductive endocrinopathy a triggering role in the affective disturbance of reproductive mood disorders has been shown clearly for changes in reproductive steroids. The existing data, therefore, support a differential sensitivity to reproductive steroids in reproductive mood disorders such that an abnormal affective state is precipitated by normal changes in reproductive steroids. The therapeutic implications of these findings for affective illness are discussed.

Keywords: PMDD; affect; depression; hormone; reproductive steroid.

Figure 1.. Recurrence of sadness in women with premenstrual syndrome during estradiol or progesterone add-back in the context of GnRH agonist-induced ovarian suppression. Ten women with premenstrual syndrome and 15 control women had minimal mood symptoms while receiving leuprolide acetate (a GnRH agonist). In contrast, the women with premenstrual syndrome but not the controls had a significant increase in sadness during the administration of either estradiol or progesterone. Values are the means (SE) of the seven daily scores on the sadness scale of the Daily Rating Form for each of the 8 weeks preceding hormone replacement (leuprolide alone) and during the 4 weeks of estradiol (plus leuprolide) and progesterone (plus leuprolide) replacement. A score of 1 indicates that the symptom was not present, and a score of 6 indicates that it was present in the extreme. P=0.003 for interaction of treatment condition, diagnostic group, and week. From ref 36: Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome N Engl J Med. 338(4):209-216. Copyright © 1998, Massachusetts Medical Society. Reprinted with permission.

Figure 2.. Upper Panel: Plasma estradiol (A) and progesterone (B) were significantly increased in the three months of estradiol/progesterone addback compared with the last month of leuprolide and the month of single-blind placebo. There were no significant differences in plasma levels between the first month of estradiol/progesterone addback compared with the second and third months of estradiol/progesterone addback. Lower Panel: The pattern of between month differences in symptom severity reflects the presence of significantly increased Premenstrual Tension-self (C) and -rater (D) scores during the first month of estradiol/progesterone addback (Month 5) compared with all other months (ie, last month of leuprolide alone, placebo, and the second and third months of estradiol/progesterone addback). In contrast, there were no significant differences in symptom severity scores in either Premenstrual Tension-self or -rater scores between the last month of leuprolide alone (Month 3) and scores during placebo, second and third month of estradiol/progesterone addback. Finally, Premenstrual Tension scores in the second and third months of estradiol/progesterone addback also were not significantly different. Reproduced with permission from ref 36: Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome N Engl J Med. 338(4):209-216. Copyright © 1998, Massachusetts Medical Society. Reprinted with permission.