Showing papers by "David R. Rubinow published in 2005"

Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression

Abstract: Context Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants. The adrenal androgen and neurosteroid dehydroepiandrosterone (DHEA) is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects. Objective To evaluate the efficacy of DHEA as a monotherapy treatment for midlife-onset depression. Design A double-blind, randomized, placebo-controlled, crossover treatment study was performed from January 4, 1996, through August 31, 2002. Settings The National Institute of Mental Health Midlife Outpatient Clinic in the National Institutes of Health Clinical Center, Bethesda, Md. Patients Men (n = 23) and women (n = 23) aged 45 to 65 years with midlife-onset major or minor depression participated in this study. None of the subjects received concurrent antidepressant medications. Intervention Six weeks of DHEA therapy, 90 mg/d for 3 weeks and 450 mg/d for 3 weeks, and 6 weeks of placebo. Main outcome measures The 17-Item Hamilton Depression Rating Scale and Center for Epidemiologic Studies Depression Scale. Additional measures included the Derogatis Interview for Sexual Functioning. Results were analyzed by means of repeated-measures analysis of variance and post hoc Bonferroni t tests. Results Six weeks of DHEA administration was associated with a significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P Conclusion We find DHEA to be an effective treatment for midlife-onset major and minor depression.

Cortisol Response to Ovine Corticotropin-Releasing Hormone in a Model of Pregnancy and Parturition in Euthymic Women with and without a History of Postpartum Depression

Abstract: Hypothalamic-pituitary-adrenal axis abnormalities have been reported in depressed women and those with postpartum blues, compared with nondepressed women. We investigated the effect of gonadal steroids on the hormonal response to ovine CRH in women with (n = 5) and without (n = 7) a past history of postpartum depression (PPD) by creating an endocrine model of pregnancy and the postpartum. Ovine CRH (1 microg/kg) stimulation tests were performed in the baseline follicular phase, during hormone add-back (leuprolide acetate plus supraphysiologic doses of estradiol and progesterone-mimicking pregnancy), and after precipitous withdrawal of hormone replacement (mimicking the puerperium). Significant phase by time (P < 0.005) and phase by diagnosis (P < 0.05) interactions were observed, reflecting increased stimulated cortisol during the supraphysiologic phase, particularly in subjects with a history of PPD. Cortisol area under the curve also showed a significant phase by diagnosis effect (P < 0.05). Significant increases during the supraphysiologic phase were also seen for urinary free cortisol (P < 0.05), cortisol area under the curve (P < 0.001), and plasma corticosteroid-binding globulin (P < 0.05). Our data show that in humans, as in animals, supraphysiologic gonadal steroid levels enhance pituitary-adrenal axis activity, and, further, that women with a history of PPD have an enhanced sensitivity of the pituitary-adrenal axis to gonadal steroids.

Sex-Related Differences in Stimulated Hypothalamic- Pituitary-Adrenal Axis during Induced Gonadal Suppression

Abstract: Context: Sex-related differences in the stress response are well described in the animal literature but in humans are inconsistent and appear to reflect both the method used to stimulate the hypothalamic-pituitary-adrenal (HPA) axis and the age of the subjects. Sex-related differences in reproductive steroid levels further confound efforts to define the specific role of the sex of the individual in stress axis responsivity. Objective: The aim of this study was to address this role independent of differences in reproductive steroid levels. We compared HPA axis response to pharmacological (CRH) and physiological (exercise) stressors in two groups of young to middle-aged (18–45 yr) men (n = 10 and 8) and women (n = 12 and 13) undergoing gonadal suppression with leuprolide acetate (monthly im injection of 7.5 mg in men and 3.75 mg in women). Design: Exercise and CRH stimulation tests were performed during induced hypogonadal conditions. Setting: The study was conducted at a National Institutes of Health Clini...

Reproductive steroids in context.

Abstract: The effects of reproductive steroids on the brain are highly context-dependent, a concept necessary to understand disorders of mood related to the reproductive endocrine system.