Animal studies have suggested that neuroactive steroids, in particular progesterone and its metabolites, have stress-dampening effects. However, few studies have explored these effects in humans. In a study published in a recent issue of Experimental and Clinical Psychopharmacology, researchers investigated the effects of acute progesterone administration on responses to the Trier Social Stress Test (TSST) to induce stress under laboratory conditions . Healthy men participated in the TSST 3.5 hrs after intramuscular injection of 0, 50, or 100 mg progesterone (sample sizes of 16, 14, and 14 respectively). Cardiovascular heart rate, blood pressure , hormonal plasma adrenocorticotrophic hormone, cortisol, and noradrenaline , and subjective e.g., anxiety, arousal responses to stress in the three groups were also measured. Before the TSST, progesterone injections increased plasma levels without altering physiological or subjective states. Stress produced its expected physiological and subjective effects among placebo-treated individuals. Progesterone 50 mg attenuated peak increases in plasma cortisol and reduced changes in negative mood and ALERTness after stress, yet it increased plasma noradrenaline and systolic blood pressure. Progesterone 100 mg also attenuated stress-induced increases in ALERTness and arousal, yet it potentiated stress-induced increases in diastolic pressure. Thus, progesterone dampened some of the psychological effects of stress but produced inconsistent effects on physiological stress responses. The researchers discuss the results in terms of the paradoxical nature of progesterone and related substances. Whether progesterone can restore homeostasis after a stressful event is something that requires further research with larger samples.