“…An additional possibility is that chronic changes in estrogen or progesterone levels due to HC use may have directly altered the endogenous opioid system (Foradori et al, 2002; Foradori et al, 2005; Smith et al, 2006), CRF neuron reactivity (Kirschbaum et al, 1996; Kudielka et al, 1998; Thammacharoen et al, 2009), and luteinizing hormone pulsatility (Elstein et al, 1974; Brenner et al, 1977; Mishell et al, 1977; Snowden et al, 1986), each of which are involved in the regulation of the HPA axis and stress response at the level of the hypothalamus, pituitary, and amygdala (Smith et al, 1998; Drolet et al, 2001; Bilkei-Gorzo et al, 2008). Furthermore, there is evidence that estrogens mediate the diurnal rhythm of the HPA axis (Morin et al, 1977; Burgess and Handa 1992; Norman et al, 1992), which may be due to estradiol’s regulation of CRF gene expression (Vamvakopoulos and Chrousos 1993; Roy et al, 1999; Chen et al, 2008; Lalmansingh and Uht 2008; Zhu and Zhou 2008).…”