The ageing female reproductive axis I

Henry G. Burger*, Emma Dudleyf, Pam Mamers{, David Robertson*, Nigel Groome} and Lorraine Dennersteinf

*Prince Henry's Institute of Medical Research, Moonash Medical Centre, 246 Clayton Rojad, Clayton, Australia, {Office for Gender & Health, The University of Melbourne, 6th Floor, Charles Connibere Building, Royal Melbourne Hospital, Vic 3050, Australia, {Department of Obstetrics & Gynaecology, Moonash Medical Centre, Clayton, Australia and }School of Biological & Molecular Sciences, Oxford Brookes University, Gipsy Lane Campus, Headingtoon, Oxford, UK

Abstract. 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.

2002 Endocrine facets of ageing. Wiley, Chichester (Novartis Foundation Symposium 242) p 161-171

In women as opposed to men, there is a striking and readily observable marker of reproductive ageing, the spontaneous cessation of menstrual bleeding or menopause. In this paper, the characteristics of the hypothalamo—pituitary— gonadal axis are summarized with respect to contemporary research on the inhibins in particular. The overall perspective put forward is that the endocrine changes which characterize female reproductive ageing are the consequence of the progressive decline in ovarian follicle number, with the ultimate loss of granulosa cell function. The precise mechanisms underlying follicular loss remain to be characterized fully. While much research has concentrated on changes in oestradiol levels and their consequences, this review also summarizes data on the inhibins and on androgens, particularly testosterone.

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