Hyperinsulinism, Insulin Resistance and Fertility

© 2005 Elsevier España, S.A. Insulin resistance (IR) and related hyperinsulinism have been associated with different types of hyperandrogenism. Among them polycystic ovarian syndrome (PCOS) stands out both for its frequency and for its short and long-term consequences. This endocrine disturbance coincides in 25 to 60% of the cases depending on genetic, environmental, and weight-related factors. The ovary is able to respond to the stimulation of insulin and related growth factors synergically with LH on theca cells. This tissue is abundant in PCO and secretes specifically androgens. When both IR and PCOS are present, androgen secretion and cutaneous related changes (Hirsutism, acne and seborrhea) are amplified and coincide with those specifically induced by hyperinsulinism (acanthosis nigricans). Androgens, and estrogens produced by peripheral aromatization, chronically modify the feed-back mechanisms regulating the gonadal axis, block ovulation, alter the menstrual pattern and induce subfertility. Which is the primary endocrine disturbance and thus triggers the clinical situation remains a matter of debate. However, hyperinsulinism remains the most plausible cause of hyperandrogenism in spite of the ability of high androgen levels to induce, in turn, hyperinsulinism. The role of obesity as an inducer or consequence of these metabolic changes remains unsettled. The adequate management of hyperandrogenic states requires the ability to discriminate those where insulin resistance is also present. There are no simple, clinician-friendly methods to identify insulin resistance. The tendency is to the implementation of easy approaches based on the values of basal glucose and insulin, like insulin /glucose ratio or the indexes derived like HOMAor QUICKI. However the application of these methods should be regulated. This discrimination is specially suitable when dealing with the use of insulin sensitizing substances like metformin. In a geographical setting like Europe, where the incidence barely reaches 30%, there is the risk of overindication of such substances if we follow the standard in USA, where the frequency of insulin resistance is much higher. Insulin sensitizers can change the future of these patients both in their metabolic control or in the management of relevant clinical manifestations like obesity, hirsutism or ovulation induction.