The ageing female reproductive axis I.

The female reproductive axis includes the hypothalamo-pituitary unit, the ovaries and the uterus. While changes in the brain may contribute to reproductive ageing, the major focus of current research is on the ovary, where the progressive loss of follicles ultimately leads to absent follicular function and consequent permanent cessation of menstruation, the menopause. The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, stimulate ovarian secretion of oestradiol and the inhibins from follicular granulosa cells, and androgens from interstitial cells, including the theca. A primary event in the ageing of the reproductive axis appears to be a decline in the secretion of inhibin B as follicle numbers fall. This leads to a slow rise in FSH in women who continue to cycle regularly, particularly in the last decade of reproductive life. As the menopause approaches, decreasing concentrations of both oestradiol and inhibin B lead to more marked increases in the gonadotropins, which reach their postmenopausal peak 2-3 years after final menses. In contrast, total testosterone concentrations are maintained across the menopausal transition, with a fall in sex hormone binding globulin (SHBG) and hence a rise in free testosterone.