General introduction 15 Figure 1.1. Image of the effect of endogenous sex hormones and exogenous sex hormones on the Hypothalamic-Pituitary-Gonadal axis. GnRH=Gonadatropin-Releasing Hormone, FSH= Follicle-Stimulating Hormone and LH=Luteinizing Hormone, AR=Androgen Receptor, ER= Estrogen Receptor, PR=Progesterone Receptor. Created using Biorender.com. Exogenous sex hormones The molecule structures of oestrogen, progesterone and testosterone were discovered in the late 1920s and early 1930s (Tata, 2005). These discoveries gave rise to research into the production of synthetic versions of these hormones, and in the 1940s, researchers developed methods to synthesize exogenous sex hormones to be used as therapies (Sturgis & Albright, 1940). In the decades following these experiments, scientists discovered ways to modify or optimize the molecule structures of exogenous sex hormones in order to optimize absorption (Strecker et al., 1979), adapt effects on the menstrual cycle (Pincus et al., 1958) and to reduce the risk of adverse effects, such as risk for thrombosis (Inman et al., 1970). These discoveries led to the release of the first forms of hormone therapy for menopause
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