Gonadal steroids and affective symptoms during in vitro fertilization: implication for reproductive mood disorders

Gonadal steroids (GSs) have been associated with the onset of a number of reproductive-related mood disorders in women, in which fluctuating or unstable hormonal levels are postulated to act as the trigger for the destabilization of mood. There is, however, rather limited direct clinical evidence that can link rapidly changing GS levels with the induction of mood symptoms. We aimed to study the effect of controlled and rapid GS fluctuations on mood in an in vivo model. Women undergoing in vitro fertilization (n=108) were assessed for depression and anxiety levels on 3 time points: during a low estradiol and progesterone baseline, during a gonadotropin stimulated estradiol-dominant phase, and after embryo transfer, during a progesterone-dominant low estrogen phase. Plasma levels for estrogen and progesterone were drawn on these time points. Symptoms of depression and anxiety significantly increased from baseline to the high estradiol levels but were not correlated with estrogen. The sharp drop from high estradiol levels at the estradiol-dominant phase to low levels at the progesterone-dominant phase was significantly correlated with rising depression scores. The rise in progesterone levels from low levels at the estradiol-dominant phase to high levels at the progesterone-dominant phase was significantly and inversely correlated with depression scores. This study suggests that the mechanism underlying the role of estrogen in reproductive-related mood disorders involves an abrupt and precipitous drop in its plasma level that can precipitate negative mood states. This finding has implications on the treatment of GS-related mood disorders.