The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest.
This review exposes the follicular abnormalities responsible for anovulation in polycystic ovary syndrome (PCOS). The putative pathophysiological explanations involve the principal intra- and extra-ovarian regulators which intervene during normal folliculogenesis to control the initial recruitment and growth and then the cyclic recruitment. We propose the hypothesis that the follicular problem in PCOS is 2-fold, but with the two abnormalities being linked. First, the intra-ovarian hyperandrogenism may promote early follicular growth, leading to a 2-5 mm follicle excess. Second, the ensuing excessive number of selectable follicles would inhibit the selection process, presumably through follicle-follicle interaction involving granulosa cell (GC) products such as the anti-Müllerian hormone (AMH). These factors would induce a reversible refractoriness to the FSH-induced differentiation of GC. This explanation challenges but does not exclude other hypotheses about the follicular arrest, such as the premature LH action on the GC of selectable follicles. Hyperinsulinism or insulin resistance would act as a second hit, worsening the follicular arrest either through amplification of the intra-ovarian hyperandrogenism or through dysregulation of the GC. The loss of cyclic rhythm would prevent the inter-cycle elevation of FSH, thus perpetuating the impairment of the ovulation process.
Jonard
Sophie
S
Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre, Avenue Eugène Avinée, CHRU, 59037 Lille, France.
Dewailly
Didier
D
D000728:Androgens / Q000378:metabolism; D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006801:Humans; D017588:Hyperandrogenism / Q000378:metabolism / Q000473:pathology*; D007333:Insulin Resistance; D007986:Luteinizing Hormone / Q000378:metabolism; D006080:Ovarian Follicle / Q000473:pathology; D010053:Ovary / Q000473:pathology*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism / Q000473:pathology*; D012016:Reference Values
D000728:Androgens; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone