IGF-1 in gynaecology and obstetrics: update 2002

Recent discoveries on endocrine, paracrine and autocrine involvement of insulin-like growth factor-1 (IGF-1) in the proliferation of many tissues raised the attention of its role in reproduction and in the growth of various cancers as well as of benign proliferations. The intention of this article is to focus on IGF-1 in the field of gynaecology. Perimenopausal women who exhibit high IGF-1 and low IGF binding protein (IGFBP) levels, like IGFBG-3, have an increased risk of developing breast cancer. A higher risk for cervical, ovarian and endometrial cancer is related to high IGF-1 levels in post- and premenopausal women. It has been shown that myomas, by far the most common benign uterine tumor in women, grow in the presence of IGF-1, in vitro as well as in vivo. Studies show that IGF-1 is involved in the differentiation of various reproductive tissues, like endometrium and ovarian tissues. Patients suffering from polycystic ovary syndrome (PCO) frequently show insulin resistance accompanied by an increase of IGF-1 in plasma. Plasma IGF-1 levels are higher in cases of severe endometriosis, however, in endometriosis and in PCO IGF levels locally in the endometrium are reduced, what might explain infertility. Recently, it was shown that IGF facilitates the implantation of the human embryo in the endometrium during IVF. Implantation is a paradox where different immune systems have to collaborate to make implantation and survival of the pregnancy possible. IGF seems to be the starter molecule so that the two epithelia can fuse. A disturbance can result in complications during pregnancy i.e. spontaneous miscarriage, preeclampsia as well as defects of the embryo. Therefore, IGF is a useful marker in successful pregnancy as well. A better mechanistic understanding of IGF-1 action on the cellular level not only provides more elegant mechanistic explanations for the scientist, but the practitioner might find it interesting to utilize its diagnostic potential as a marker for various diseases. The relation between systemic IGF levels and local tissue IGF-1 levels has not yet been determined for all conditions.