The synthesis of reproductive hormones is under the influence of the hypothalamic-pituitary-gonadal axis. The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which stimulates pituitary synthesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH promote the synthesis of reproductive hormones in the testes or ovaries. Progesterone and androstenedione are synthesized in the zona reticularis of the adrenal cortex.
Progesterone exerts an anti-proliferative effect on the endometrium, promotes endometrial secretion, and is essential to maintain pregnancy. In the testes, androstenedione is first converted to testosterone and then into dihydrotestosterone, which is the major masculinizing androgen. In the ovaries, androgen precursors are aromatized to estradiol and estrone, which share common feminizing properties. The most potent naturally occurring estrogen is 17β-estradiol.
Estradiol and estrone are further metabolized in adipose tissue to estriol, a weak estrogen. Estriol is the main source of estrogen in man and it is the major source of circulating estrogen in postmenopausal women. Pharmacotherapeutic agents in the top 200 include: hormone receptor agonists and antagonists, and hormone formulations for contraception (Table 17).17 The risk of a MME is predicated on adverse drug events and/or other, concurrent variables.37,38