PCOS Forum

Research in Polycystic Ovary Syndrome Today and Tomorrow

Renato Pasquali; Elisabet Stener-Victorin; Bulent O. Yildiz; Antoni J. Duleba; Kathleen Hoeger; Helen Mason; Roy Homburg; Theresa Hickey; Steve Franks; Juha S. Tapanainen; Adam Balen; David H. Abbott; Evanthia Diamanti-Kandarakis; Richard S. Legro

Disclosures

Clin Endocrinol. 2011;74(4):424-433. 

In This Article

Determinants of Ovarian Morphology – Influence of Gonadotrophins

Initiation of growth and early differentiation of follicles are thought to be regulated independently of gonadotrophin stimulation. The later stages of growth and differentiation, selection of the cohort and cyclic recruitment are largely dependent on FSH activity. In the PCO, there is loss of the selection process from an increased pool to a dominant follicle. Enhanced steroidogenesis, excess androgens, hyperinsulinaemia and lack of growth differentiation factor (GDF9) have all been implicated but FSH refractoriness may be key. FSH concentrations in PCOS are generally in the lower normal range. Adding FSH (with clomiphene or exogenous FSH) restores normal follicular growth, suggesting an endogenous inhibition of FSH action in PCOS. The source of this inhibition is probably ovarian as loss of ovarian tissue (wedge resection or laparoscopic ovarian diathermy, or age >40 years old)[37] is capable of restoring normal follicular development and ovulation. Following laparoscopic ovarian drilling, there is a rapid steep rise in FSH in those who respond. Thus, it seems that the size of the 2- to 5-mm follicle pool is an independent, important contributor to the follicular arrest. Candidates for the source of FSH refractoriness include transforming growth factor-alpha, epidermal growth factor, follistatin and particularly the high concentrations of AMH in PCOS.[38] LH receptor overexpression in PCO granulosa cells leads to terminal differentiation and premature arrest of follicle growth.[39] Finally, the lack of circulating progesterone encourages high LH levels, exacerbating androgen excess, multiple small follicles and the consequences. These data highlight the role of appropriate gonadotrophin action within the ovary in restoring follicular development and ovulation in women and PCOS and provide evidence for the ovary as the primary determinant of inappropriate gonadotrophin secretion in PCOS, although this remains an area of debate among researchers.

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