Endocrine markers of follicle number

Several studies of the pituitary—ovarian axis as a function of increasing age in regularly cycling women have indicated that the most striking observable change is a progressive rise in early follicular and mid cycle FSH levels without significant change in the levels of LH, oestradiol or progesterone (Lee et al 1988). This monotropic rise in FSH is explicable on the basis of changes in the circulating concentrations of inhibin B (Klein et al 1996, Burger et al 2000a). Therefore the authors (Burger et al 2000b) measured the circulating concentrations of oestradiol, FSH and the inhibins in the early follicular phase of 66 regularly cycling women aged 20—50. Serum FSH, inhibin A and oestradiol were all positively correlated with age between years 20 and 50, the increase in FSH being particularly striking in women over the age of 40. Inhibin B levels were not significantly correlated with age, though they showed a tendency to fall slowly, but in women over the age of 40

there was a highly significant inverse correlation between inhibin B and FSH (r = —0.61, P < 0.001). When log FSH was modelled as a function of log inhibin B and log oestradiol, with age fitted as a co-variate, only inhibin B was a significant independent predictor of FSH. Other studies have also shown a decline in circulating serum inhibin B levels as a function of age with no change or even an increase in oestradiol and inhibin A (Danforth et al 1998, Welt et al 1999). Thus it can be postulated that inhibin B is the main form of inhibin regulating FSH during the follicular phase of the menstrual cycle. Inhibin B levels may therefore be a marker of ovarian follicular numbers and/or function.

The importance of inhibin B as a regulator of the pituitary—gonadal axis becomes more evident at the time of onset of menstrual irregularity, marking the beginning of the menopausal transition or perimenopause. Studies from the authors' laboratory have shown that the most clear-cut change in pituitary ovarian function in women who had developed irregular menstrual cycles was a profound fall in inhibin B without significant change in inhibin A and oestradiol, and with a small but statistically non-significant increase in FSH (Burger et al 1998). As progression through the menopause transition occurs, inhibin A and oestradiol levels also fall with further rises in serum FSH. From this prospective study of a community based sample of women experiencing the menopause, it was concluded that at the time of final menses, circulating FSH levels (48.4 Iu/l) were approximately 50% of those which would ultimately be found postmenopausally, whilst circulating oestradiol was also approximately 50% of its early follicular phase levels at about 113pmol/l (Burger et al 1999). Nadir oestradiol levels are reached two to three years postmenopausally as are peak concentrations of FSH. At this time inhibin B is undetectable and inhibin A is also very low or undetectable.

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