Effects of Dehydroepiandrosterone Therapy on Pubic Hair Growth and Psychological Well-Being in Adolescent Girls and Young Women with Central Adrenal Insufficiency: A Double-Blind, Randomised, Placebo-Controlled Phase III Trial

• Published in: Endocrinology (Philadelphia) Vol. 150; no. 2; p. 1070
• Main Authors: Binder, G, Weber, S, Ehrismann, M, Zaiser, N, Meisner, C, Ranke, M. B, Maier, L, Wudy, S. A, Hartmann, M. F, Heinrich, U, Bettendorf, M, Doerr, H. G, Pfaeffle, R. W, Keller, E
• Format: Journal Article
• Language: English
• Published: Washington Endocrine Society 01-02-2009; Oxford University Press
• Subjects: Adolescents; Adrenocorticotropic hormone; Androgens; Androstenedione; Anxiety; Clinical trials; Confidence intervals; Criteria; Dehydroepiandrosterone; Diabetes mellitus; Epidemiology; Females; Girls; Hair; Hypothalamus; Liquid chromatography; Mental depression; Mental disorders; Metabolites; Patients; Pituitary; Placebos; Psychological factors; Psychological stress; Remission; Serum levels; Tumors; Well being
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.150.2.9996

Context and Objective: The efficacy of oral dehydroepiandrosterone (DHEA) in the treatment of atrichia pubis and psychological distress in young females with central adrenal insufficiency is unknown. Our study aimed to evaluate this therapy.
Design and Patients: 23 young females (mean age 18 yrs, range 13–25) were enrolled in a double-blind randomised placebo-controlled trial. Inclusion criteria: ACTH deficiency plus ≥2 additional pituitary deficiencies, serum DHEA <400 ng/ml and pubertal stage >B2. Exclusion criteria: cerebral radiation, tumor remission <1 yr, amaurosis, hypothalamic obesity, psychiatric disorders and instable hormone medication.
Intervention: Patients were randomised to placebo (n = 12) or 25 mg HPLC-purified DHEA/d (n = 11) p.o. for 12 months after stratification into a non-tumor (n = 7) and a tumor group (n = 16).
Main Outcome Measures: Clinical scoring of pubic hair stage was performed at 0, 6, 12 months (primary endpoint) and psychometrical evaluation (symptom checklist-90-R and the Center for Epidemiological Studies-Depression scale) at 0, 12 months (secondary endpoint). Androgen levels and safety parameters were measured at 0, 6, 12 months; 24h-androgen urinary excretion rates at 0, 12 months.
Results: In the placebo-group, 4 patients dropped out because of recurrence of craniopharyngeoma, manifestation of type I diabetes and change of residence (n = 2); in the DHEA-group, one patient because of recurrent anxiety attacks. DHEA substitution resulted in normalization of DHEAS and androstanediol glucuronide morning serum levels 2 hours after drug intake (P < 0.006) and of its 24 hour urinary metabolite levels (P < 0.0001), placebo had no effect. Morning serum levels of androstenedione increased in the DHEA group (P < 0.02), but did not normalize. The DHEA group exhibited a significant progress in pubic hair growth from Tanner stage 1–3 to 2–5 (mean: +1.5 stages) while the placebo group did not (relative risk: 0.138, 95%-confidence interval: 0.021–0.914, P = 0.0046). Importantly, eight of the ten SCL-90-R scores including those for depression, anxiety, interpersonal sensitivity and the global severity index improved in the DHEA group in comparison to the placebo group (P < 0.048). DHEA was well tolerated.
Conclusions: In adolescent girls with central adrenal insufficiency daily replacement with 25 mg DHEA p.o. is beneficial: atrichia pubis vanishes and psychological well-being improves significantly.