Novel aspects of the endocrinology of the menstrual cycle Ioannis E. Messinis, Christina I. Messini, Konstantinos Dafopoulos  Reproductive BioMedicine Online  Volume 28, Issue 6, Pages 714-722 (June 2014) DOI: 10.1016/j.rbmo.2014.02.003 Copyright © 2014 Reproductive Healthcare Ltd. Terms and Conditions

Figure 1 Changes in the strength of the negative feedback mechanism during the normal menstrual cycle. The ovarian mediators are in the early follicular phase oestradiol and inhibin B, in the rest of the follicular phase oestradiol plus progesterone and in the luteal phase oestradiol, progesterone and inhibin A. The LH surge is the result of the positive feedback effect of oestradiol facilitated by progesterone. Reproductive BioMedicine Online 2014 28, 714-722DOI: (10.1016/j.rbmo.2014.02.003) Copyright © 2014 Reproductive Healthcare Ltd. Terms and Conditions

Figure 2 A hypothesis of gonadotrophin surge-attenuating factor (GnSAF) bioactivity during the follicular phase of the normal menstrual cycle: changes in the LH response to gonadotrophin-releasing hormone (GnRH) from the early to late follicular phase. Oestradiol concentration increases as the dominant follicle becomes ovulatory, while that of GnSAF declines. These changes in GnSAF activity facilitate the sensitizing effect of oestradiol on the pituitary response to GnRH leading to the massive discharge of LH during the LH surge. Reproductive BioMedicine Online 2014 28, 714-722DOI: (10.1016/j.rbmo.2014.02.003) Copyright © 2014 Reproductive Healthcare Ltd. Terms and Conditions

Figure 3 The positive feedback mechanism. Factors involved in the control of the onset, amplitude and termination of the endogenous LH surge in the normal menstrual cycle. Oestradiol in high concentration is the main trigger of the onset, facilitated by progesterone on one hand and the withdrawal of the antagonistic action of gonadotrophin surge-attenuating factor (GnSAF) on the other hand (Figure 2). The amplitude of the LH surge is the result of the interaction between the amplifying effect of the increasing concentration of progesterone and the attenuating effect of GnSAF. Finally, the termination of the LH surge is controlled by the ovary via rising progesterone, while the role of oestradiol is unclear. Reproductive BioMedicine Online 2014 28, 714-722DOI: (10.1016/j.rbmo.2014.02.003) Copyright © 2014 Reproductive Healthcare Ltd. Terms and Conditions