O-79:Polycystic Ovary Syndrome:Disease Or Adaptation?

The etiology of polycystic ovary syndrome (PCOS) remains uncertain. The three most commonly accepted causes are: a metabolic alteration that results in insulin resistance; an enzymatic defect in the steroidogenic pathway that increases androgen production; and a primary defect of the hypothalamic GnRH pulse generator that increases LH and decreases FSH. Some have argued that PCOS is invariably linked to insulin resistance, but this explanation does not fully account for the gonadotropin aberrations and resulting anovulation that are so characteristic of this syndrome. Part of the uncertainty regarding the etiology of PCOS relates to its variable presentation. For instance, thin women with PCOS are less likely to display insulin resistance and more likely to have excessive androgen levels. If ultrasound criteria are used to make the diagnosis of PCOS, even thin, eumenorrheic women who are ovulatory may be diagnosed as having PCOS. Our research objective has been to determine the etiology of the anovulation characteristic of PCOS so as to refine therapeutic approaches. In an effort to find a parsimonious explanation, we are seeking to determine the role of insulin resistance and hyperandrogenism in the genesis of the gonadotropin aberrations characteristic of PCOS. Indeed, available data suggest that both androgens and insulin increase GnRH drive and that increased GnRH drive secondarily reduces FSH to levels insufficient to fully support folliculogenesis to the point of ovulation. These data argue for more than one cause of PCOS. These insights form the basis for individualizing treatment approaches. For those not seeking immediate fertility, common treatments include anti-androgens, insulin action modifiers, metformin, and oral contraceptives alone or in combination. For those seeking fertility, the use of metformin alone or in combination has been advocated. A recent randomized trial suggested that clomiphene was superior to metformin for the treatment of infertility due to PCOS (Legro RS et al. New Abstract of the 8th Royan International Twin Congress, Tehran, Iran, 5-7 September 2007 Yakhteh Medical Journal, Vol 9, Sup 1, Summer 2007 47 Engl J Med 2007; 356: 551). Treatment efficacy varies widely and likely reflects etiologic nonhomogeneity. Recent advances in our understanding of the link between metabolism and aging suggest that PCOS may represent an adaptation to low fuel environments. If so, then it will be especially important to focus on nutritional counseling as a means of ameliorating symptom progression.