This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this book Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burger, H. G. Articles by Dennerstein, L. Search for Related Content PubMed PubMed Citation Articles by Burger, H. G. Articles by Dennerstein, L.

Hormonal Changes in the Menopause Transition

Henry G. Burger^*, Emma C. Dudley, David M. Robertson^* and Lorraine Dennerstein

^* Prince Henry’s Institute of Medical Research at Monash Medical Centre, Clayton, Victoria, Australia
Office for Gender and Health, Royal Melbourne Hospital, Parkville, Victoria, Australia

The menopause is the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. It is heralded by the menopausal transition, a period when the endocrine, biological, and clinical features of approaching menopause begin. A common initial marker is the onset of menstrual irregularity. The biology underlying the transition to menopause includes central neuroendocrine changes as well as changes within the ovary, the most striking of which is a profound decline in follicle numbers. Follicle-stimulating hormone (FSH) is an established indirect marker of follicular activity. In studies of groups of women, its concentration, particularly in the early follicular phase of the menstrual cycle, begins to increase some years before there are any clinical indications of approaching menopause. The rise in FSH is the result of declining levels of inhibin B (INH-B), a dimeric protein that reflects the fall in ovarian follicle numbers, with or without any change in the ability of the lining granulosa cells to secrete INH-B. Estradiol levels remain relatively unchanged or tend to rise with age until the onset of the transition and are usually well preserved until the late perimenopause, presumably in response to the elevated FSH levels. During the transition, hormone levels frequently vary markedly - hence, measures of FSH and estradiol are unreliable guides to menopausal status. Concentrations of testosterone have been reported to fall by about 50% during reproductive life, between the ages of 20 and 40. They change little during the transition and, after menopause, may even rise. Dehydroepiandrosterone (DHEA) and DHEAS, its sulphate, on the other hand, decline with age, without any specific influence of the menopause. Symptoms of the menopause can be interpreted as resulting primarily from the profound fall in estradiol, occurring over a 3- to 4-year period around final menses, a fall that presumably contributes importantly to the beginning, in the late perimenopause, of loss of bone mineral density.

This article has been cited by other articles:

				P. Abidi, H. Zhang, S. M Zaidi, W.-J. Shen, S. Leers-Sucheta, Y. Cortez, J. Han, and S. Azhar Oxidative stress-induced inhibition of adrenal steroidogenesis requires participation of p38 mitogen-activated protein kinase signaling pathway J. Endocrinol., July 1, 2008; 198(1): 193 - 207. [Abstract] [Full Text] [PDF]

				N. Santoro, S. L. Crawford, W. L. Lasley, J. L. Luborsky, K. A. Matthews, D. McConnell, J. F. Randolph Jr., E. B. Gold, G. A. Greendale, S. G. Korenman, et al. Factors Related to Declining Luteal Function in Women during the Menopausal Transition J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1711 - 1721. [Abstract] [Full Text] [PDF]

				H.G. Burger, G.E. Hale, D.M. Robertson, and L. Dennerstein A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project Hum. Reprod. Update, November 1, 2007; 13(6): 559 - 565. [Abstract] [Full Text] [PDF]

				R. Wang, J. Xu, N. Mabjeesh, G. Zhu, J. Zhou, M. Amin, D. He, F. F. Marshall, H. E. Zhau, and L. W.K. Chung PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression Clin. Cancer Res., October 15, 2007; 13(20): 6040 - 6048. [Abstract] [Full Text] [PDF]

				P. Collins, G. Rosano, C. Casey, C. Daly, M. Gambacciani, P. Hadji, R. Kaaja, T. Mikkola, S. Palacios, R. Preston, et al. Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists Eur. Heart J., August 2, 2007; 28(16): 2028 - 2040. [Abstract] [Full Text] [PDF]

				G. E. Hale, X. Zhao, C. L. Hughes, H. G. Burger, D. M. Robertson, and I. S. Fraser Endocrine Features of Menstrual Cycles in Middle and Late Reproductive Age and the Menopausal Transition Classified According to the Staging of Reproductive Aging Workshop (STRAW) Staging System J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3060 - 3067. [Abstract] [Full Text] [PDF]

				M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]

				W. Zheng, M. Jimenez-Linan, B. S. Rubin, and L. M. Halvorson Anterior Pituitary Gene Expression with Reproductive Aging in the Female Rat Biol Reprod, June 1, 2007; 76(6): 1091 - 1102. [Abstract] [Full Text] [PDF]

				P. M. Meyer, S. L. Zeger, S. D. Harlow, M. Sowers, S. Crawford, J. L. Luborsky, I. Janssen, D. S. McConnell, J. F. Randolph, and G. Weiss Characterizing Daily Urinary Hormone Profiles for Women at Midlife Using Functional Data Analysis Am. J. Epidemiol., April 15, 2007; 165(8): 936 - 945. [Abstract] [Full Text] [PDF]

				D. S. Perrien, N. S. Akel, P. K. Edwards, A. A. Carver, M. S. Bendre, F. L. Swain, R. A. Skinner, W. R. Hogue, K. M. Nicks, T. M. Pierson, et al. Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength Endocrinology, April 1, 2007; 148(4): 1654 - 1665. [Abstract] [Full Text] [PDF]

				M. E. Wierman, R. Basson, S. R. Davis, S. Khosla, K. K. Miller, W. Rosner, and N. Santoro Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3697 - 3710. [Abstract] [Full Text] [PDF]

				J. L. Downs and H. F. Urbanski Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta) Biol Reprod, October 1, 2006; 75(4): 539 - 546. [Abstract] [Full Text] [PDF]

				V. Jazbutyte, K. Hu, P. Kruchten, E. Bey, S. K.G. Maier, K.-H. Fritzemeier, K. Prelle, C. Hegele-Hartung, R. W. Hartmann, L. Neyses, et al. Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats Hypertension, October 1, 2006; 48(4): 579 - 586. [Abstract] [Full Text] [PDF]

				I. E. Messinis Ovarian feedback, mechanism of action and possible clinical implications Hum. Reprod. Update, September 1, 2006; 12(5): 557 - 571. [Abstract] [Full Text] [PDF]

				J. C. Beehner, D. A. Onderdonk, S. C. Alberts, and J. Altmann The ecology of conception and pregnancy failure in wild baboons Behav. Ecol., September 1, 2006; 17(5): 741 - 750. [Abstract] [Full Text] [PDF]

				H. S. Kok, K. M. van Asselt, Y. T. van der Schouw, I. van der Tweel, P. H.M. Peeters, P. W.F. Wilson, P. L. Pearson, and D. E. Grobbee Heart Disease Risk Determines Menopausal Age Rather Than the Reverse J. Am. Coll. Cardiol., May 16, 2006; 47(10): 1976 - 1983. [Abstract] [Full Text] [PDF]

				M. Manikkam, T. L. Steckler, K. B. Welch, E. K. Inskeep, and V. Padmanabhan Fetal Programming: Prenatal Testosterone Treatment Leads to Follicular Persistence/Luteal Defects; Partial Restoration of Ovarian Function by Cyclic Progesterone Treatment Endocrinology, April 1, 2006; 147(4): 1997 - 2007. [Abstract] [Full Text] [PDF]

				K Larsson, D Mellstrom, C Nordborg, A Oden, and E Nordborg Early menopause, low body mass index, and smoking are independent risk factors for developing giant cell arteritis Ann Rheum Dis, April 1, 2006; 65(4): 529 - 532. [Abstract] [Full Text] [PDF]

				W. Yin and A. C Gore Neuroendocrine control of reproductive aging: roles of GnRH neurons. Reproduction, March 1, 2006; 131(3): 403 - 414. [Abstract] [Full Text] [PDF]

				L. P. Mayer, C. A. Dyer, R. L. Eastgard, P. B. Hoyer, and C. L. Banka Atherosclerotic Lesion Development in a Novel Ovary-Intact Mouse Model of Perimenopause Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1910 - 1916. [Abstract] [Full Text] [PDF]

				P. S. Malhi, G. P. Adams, and J. Singh Bovine Model for the Study of Reproductive Aging in Women: Follicular, Luteal, and Endocrine Characteristics Biol Reprod, July 1, 2005; 73(1): 45 - 53. [Abstract] [Full Text] [PDF]

				K.-H. Tung, L. R. Wilkens, A. H. Wu, K. McDuffie, A. M. Y. Nomura, L. N. Kolonel, K. Y. Terada, and M. T. Goodman Effect of Anovulation Factors on Pre- and Postmenopausal Ovarian Cancer Risk: Revisiting the Incessant Ovulation Hypothesis Am. J. Epidemiol., February 15, 2005; 161(4): 321 - 329. [Abstract] [Full Text] [PDF]

				A.K. Sullivan, M. Marcus, M.P. Epstein, E.G. Allen, A.E. Anido, J.J. Paquin, M. Yadav-Shah, and S.L. Sherman Association of FMR1 repeat size with ovarian dysfunction Hum. Reprod., February 1, 2005; 20(2): 402 - 412. [Abstract] [Full Text] [PDF]

				A. C. Gore, B. M. Windsor-Engnell, and E. Terasawa Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta) Endocrinology, October 1, 2004; 145(10): 4653 - 4659. [Abstract] [Full Text] [PDF]

				F. Miro, S. W. Parker, L. J. Aspinall, J. Coley, P. W. Perry, and J. E. Ellis Relationship between Follicle-Stimulating Hormone Levels at the Beginning of the Human Menstrual Cycle, Length of the Follicular Phase and Excreted Estrogens: The FREEDOM Study J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3270 - 3275. [Abstract] [Full Text] [PDF]

				B.-M. Landgren, A. Collins, G. Csemiczky, H. G. Burger, L. Baksheev, and D. M. Robertson Menopause Transition: Annual Changes in Serum Hormonal Patterns over the Menstrual Cycle in Women during a Nine-Year Period Prior to Menopause J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2763 - 2769. [Abstract] [Full Text] [PDF]

				T. Piltonen, R. Koivunen, A. Ruokonen, and J. S. Tapanainen Ovarian Age-Related Responsiveness to Human Chorionic Gonadotropin J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3327 - 3332. [Abstract] [Full Text] [PDF]

				M. C. Carr The Emergence of the Metabolic Syndrome with Menopause J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2404 - 2411. [Abstract] [Full Text] [PDF]

				L. A. Fortepiani, H. Zhang, L. Racusen, L. J. Roberts II, and J. F. Reckelhoff Characterization of an Animal Model of Postmenopausal Hypertension in Spontaneously Hypertensive Rats Hypertension, March 1, 2003; 41(3): 640 - 645. [Abstract] [Full Text] [PDF]