Endocrine Abstracts

JOINT805

Background: 3,4-Methylenendioxymethamphetamine (MDMA) has recently been suggested as a novel provocation test to evaluate hypothalamic-posterior pituitary function in suspected cases of oxytocin deficiency. Limited preliminary evidence also suggests that MDMA may stimulate anterior pituitary hormone secretion, potentially contributing to its cardiovascular and neuropsychological effects. However, its effects on the anterior pituitary have not yet been fully investigated. Therefore, this analysis aimed to investigate the effect of MDMA on anterior pituitary hormone axes in healthy adults.

Methods: This secondary analysis utilized data from a double-blind, placebo-controlled crossover randomized clinical trial conducted at the University Hospital Basel, Basel, Switzerland, between Feb 2021 and May 2022. Healthy participants received a single oral dose of MDMA (100 mg) or placebo in randomized order. Plasma hormone levels of the anterior pituitary (adrenocorticotropic hormone [ACTH], thyroid-stimulating hormone [TSH], luteinizing hormone [LH], prolactin, growth hormone [GH] and their peripheral endocrine glands (cortisol, free thyroxin [fT4], testosterone, estradiol) were measured at baseline and 120 minutes after drug-intake. Changes in plasma hormone levels following MDMA vs placebo were compared using paired Wilcoxon test.

Results: A total of 15 healthy participants (median [IQR] age: 35 years [26–48]; 53% female) with a mean (SD) BMI of 23.2 kg/m²(2.1) were included. MDMA strongly stimulated the pituitary-adrenal axis, with plasma ACTH increasing from 12 ng/l [10.5, 14.9] at baseline to 35.5 ng/l [17.6, 58.9] at 120 minutes, resulting in a significant change of ACTH (P = 0.0008). This was accompanied by a cortisol increase from 347 nmol/l [252, 409] to 566 nmol/l [415, 701], resulting in a significant change of cortisol (P = 0.025). Prolactin showed a mild increase from 12 µg/l [7, 16] at baseline to 14 µg/l [10.4, 21.8] at 120 minutes, resulting in a non-significant change of prolactin (P = 0.062). No significant effects of MDMA were observed on GH, the pituitary-gonadotropin axis, or the pituitary-thyroid axis. Under placebo, no relevant hormonal changes occurred.

Conclusion: MDMA partially stimulates the anterior pituitary, strongly activating the pituitary-adrenal axis and mildly increasing prolactin levels. These findings suggest that MDMA may serve as a novel stimulation test for assessing multiple pituitary axes simultaneously. Further validation in larger patient populations is necessary.