17 - Physiology and Pathology of the Female Reproductive Axis

Abstract

Ovulation and the preparation of the uterus for pregnancy are extremely delicate and parallel physiologic processes that are tightly regulated by a number of hormones released primarily by the hypothalamus, pituitary, and ovary. The hypothalamus and pituitary secrete gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) to induce oocyte maturation together with the secretion of the ovarian hormones, estradiol and progesterone, for the preparation of the endometrium for embryo implantation. Ovarian estradiol, progesterone, and inhibin provide critical feedback signals to the brain for the regulation of GnRH, FSH, and LH secretion. Additionally, the adrenal gland and ovary secrete androgen and estrogen precursors that are converted to biologically active steroids—estradiol, testosterone, and dihydrotestosterone—in the peripheral tissues. A premenopausal woman often seeks medical help because of disorders that disrupt or complicate ovulation, normal menses, or fertility; the most common disorders include hypothalamic anovulation, hyperprolactinemia, polycystic ovary syndrome, ovarian insufficiency, endometriosis, and uterine fibroids. Combination oral contraceptives are commonly prescribed to suppress ovarian activity for the management of various benign causes of anovulatory uterine bleeding or androgen excess, such as polycystic ovary syndrome, and for the management of cyclic or chronic pelvic pain associated with endometriosis. Menopause is the depletion of all oocytes and their surrounding follicular cells in the ovary; it effectively stops secretion of estradiol and progesterone. The management of postmenopausal ovarian deficiency, characterized by vasomotor symptoms, bone loss, and vulvovaginal atrophy, is challenging and still highly debated in regard to the effectiveness and the side effects of existing treatment regimens.