Reproductive Hormones and Skeletal Health in Young Women

Abstract

In young women, low estrogen levels complicate a wide variety of diseases, including premature ovarian failure, anorexia nervosa, athletic amenorrhea, prolactinoma, hypopituitarism, and chronic kidney disease. Hypoestrogenemia may also result from therapy with GnRH agonists, glucocorticosteroids, chemotherapy, and especially aromatase inhibitors. All of these situations are associated with bone loss, because estrogen chronically suppresses bone resorption. Several mechanisms are involved: 1) estrogen increases osteoclast apoptosis; 2) by suppressing interleukins and proinflammatory cytokine expression in bone marrow cells, estrogen decreases the number of osteoclasts; 3) by inhibiting the production of receptor activator of nuclear factor-κB ligand, estrogen reduces the number and activity of osteoclasts; and 4) by increasing stromal cell/osteoblast cell expression of TGFβ, estrogen inhibits osteoclast activity. Estrogen also has some positive effects on bone formation by acting as a mitogen to cells early in the osteoblast line, reducing apoptosis of osteoblasts, and increasing expression of TGFβ, bone morphogenetic proteins, and IGF-I (1).