Stress, serotonergic function, and mood in users of oral contraceptives.

ABSTRACT

PIP: Serotonin, a neurotransmitter, may be involved in premenstrual mood and appetite changes such that the reduced central activity of serotonin is frequently associated with depressed mood and increased food intake. The plasma ratio of tryptophan, the precursor of serotonin, to the sum of the other large neutral amino acids (LNAAs) is important for the uptake of tryptophan in the brain and the subsequent central synthesis of serotonin; an increase in the plasma tryptophan to other LNAAs ratio produces an increase in brain tryptophan and serotonin. Higher insulin levels induced by carbohydrate uptake cause an increase in tryptophan to other LNAAs ratio, while progesterone and progestagens induce insulin resistance as well as a direct increase of insulin-release by the pancreatic islets in response to glucose. Using a sample of 102 female, oral contraceptive-using Utrecht University students, the authors investigated the relationship between stress and changes in insulin levels, plasma ratio of tryptophan to other LNAAs, mood, and food intake. All participants were current users of monophasic oral contraceptives containing progestagens. The study found the subjects who experienced high levels of stress to display significant decreases of insulin and tryptophan to other LNAAs ratios, before and after the consumption of a standard meal during a pill-free period as compared with the period of pill use. The decline of the tryptophan to other LNAAs ratio was accompanied by worsening of mood. In a control group of subjects experiencing low levels of stress, there was no relationship between insulin and tryptophan to other LNAAs ratio, nor between tryptophan to other LNAAs ratio and mood. These results suggest that the combination of stress and alterations in sex hormones may be responsible for mood changes during the pill-free period in women taking oral contraceptives.