Hormones are partial determinants of certain sexually dimorphic behaviors and interact with psychosocial, environmental, and other physiologic factors. The part played by sex hormones in the direct control of overt human behavior is, compared with that found in lower animals, slight and less readily definable. In humans, these hormones, although necessary for maintenance of libido and sexual behavior, seem to control the intensity of such behavior rather than its direction. In most women of reproductive age, the different phases of the menstrual cycle are not associated with major physical or psychologic discomfort. Some women actually report positive changes during the premenstrual period. Only 5-10% of women in this age group have changes in mood, sleep, eating habits, level of energy, and physical symptoms that appear to be linked temporally to the late-luteal phase of the cycle. It is plausible to assume that women with LLPDD are vulnerable to the menstrual cycle as a Zeitgeber. In these women, a cascade of events triggered originally along the HPG axis brings about the shift from an existing vulnerability to the actual manifestations of LLPDD and other forms of female-specific mood disorders. The degree of vulnerability becomes apparent at puberty when girls are exposed to increasing estrogenic influences. Particularly vulnerable times are the periods that mark shifts in the reproductive stages (menarche, the premenstruum, puerperium, and menopause), periods associated with major hormonal turmoil and psychosocial stresses. A conditioning-sensitization model has been described to explain the longitudinal course of affective disorders, and it also has been proposed for PMS. According to this model, even low levels of psychosocial stress are capable of triggering episodes of dysphoria in vulnerable previously sensitized subjects. LLPDD is associated strongly with a lifetime diagnosis of major depression, and the concurrent comorbidity in these women is also high. Future epidemiologic studies on depression should consider the effects of female-specific Zeitgeber on mood disorders in the populations studied.
