leuprolide and Mood-Disorders

Approximately 60-70 percent of women with premenstrual dysphoric disorder (PMDD) show symptomatic improvement in response to the GnRH agonist leuprolide acetate, which suppresses ovarian function. However, it has been very difficult to either predict or understand why some women respond, while others do not. We applied several complementary statistical methods to the dynamics of pre-treatment mood rating data to determine possible predictors of response for women with PMDD. We compared responders (n = 33) to nonresponders (n = 12) in clinical trials of leuprolide (three months in duration) as a treatment for PMDD, on the basis of pre-trial daily self-ratings of sadness, anxiety, and irritability. We analyzed both sequential irregularity (approximate entropy, ApEn) and a quantification of spikiness of these series, as well as a composite measure that equally weighted these two statistics. Both ApEn and Spikiness were significantly smaller for responders than nonresponders (P ≤ 0.005); the composite measure was smaller for responders compared with nonresponders (P ≤ 0.002) and discriminated between the subgroups with high sensitivity and specificity. In contrast, mean symptom levels were indistinct between the subgroups. Relatively regular and non-spiky pre-trial dynamics of mood ratings predict a positive response to leuprolide by women with PMDD with high probability, moreover based on typically less than 3 months of daily records. The statistical measures may have broad and direct applicability to behavioral studies for many psychiatric disorders, facilitating both accurate diagnosis and the prediction of response to treatment.

Topics: Adult; Entropy; Female; Fertility Agents, Female; Hormones; Hot Flashes; Humans; Leuprolide; Mood Disorders; Nonlinear Dynamics; Predictive Value of Tests; Premenstrual Syndrome; Psychiatric Status Rating Scales; Statistics, Nonparametric; Young Adult

The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy.. Three different add-back hormone replacement treatments were evaluated in a randomized, double-blinded, cross-over clinical trial in 27 patients premenstrual dysphoric disorder. The add-back treatments consisted of 1.5 mg estradiol and 400 mg progesterone, 1.5 mg estradiol and placebo, and 0.5 mg estradiol and 400 mg progesterone. The primary outcome measure was daily symptom ratings for mood and physical symptoms.. The highest dose of estradiol in combination with progesterone was associated with the most pronounced symptom recurrence, both in comparison with a lower dose of estradiol together with progesterone and estradiol-only treatment.. Based on the findings of the present study, long-cycle add-back treatment to avoid frequent progestagen use appears to be most beneficial for patients with premenstrual dysphoric disorder.

Topics: Adult; Affect; Anxiety; Cross-Over Studies; Depression; Double-Blind Method; Drug Therapy, Combination; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Irritable Mood; Leuprolide; Middle Aged; Mood Disorders; Placebos; Premenstrual Syndrome; Progesterone; Treatment Outcome

Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression.. The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales.. Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline.. The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.

Topics: Adult; Affect; Cross-Sectional Studies; Depression, Postpartum; Estradiol; Female; Humans; Hypogonadism; Leuprolide; Middle Aged; Mood Disorders; Personality Inventory; Placebos; Progesterone; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome