The biological basis of the menopause.

Age-related changes occur throughout the reproductive lifespan of normal healthy women. From the age of 20, the menstrual interval gradually shortens and becomes increasingly regular until the perimenopause. This is related to a shortening of the follicular rather than the luteal phase of the cycle. Serum FSH concentration is elevated during the follicular phase in older women who are still menstruating regularly, while serum inhibin levels are decreased in both the follicular and luteal phases. The relationship between FSH secretion, ageing and feedback inhibition by oestradiol, inhibin, or other presently unmeasured factors in women with regular menses, remains to be elucidated. The primary factor influencing the transition from regular menses to the perimenopause and subsequent menopause appears to be the size of the residual primordial follicle pool. Fecundability begins to decline by the age of 29 years. There is considerable evidence from the experience gained in assisted fertilization procedures that this is related to the effect of age on the quality of the oocyte rather than on the endometrium. At the time of the last menses, few follicles remain. There are no endocrine markers to signal the last cycle. Hence, menopause can only be identified retrospectively when there is no further menses. The probability of being menopausal increases with the duration of amenorrhea and age. Considerable evidence suggests that both serum FSH and serum inhibin are biomarkers of the number and/or quality of follicles remaining in the ovary. There is also evidence that the age of menopause, itself, is a potent biomarker of the general ageing state of the individual.