by Etsuko Ueda
It isn't just estrogen and progesterone that go through changes. FSH and LH rise and so does the stress hormone cortisol, while most hormones, including human growth hormone, DHEA, insulin-like growth factors, inhibins, thyroid, etc. start to decline as early as mid 30's.
Amongst, the hormone well known for its destructive power on bone is a stress hormone cortisol, and it is well established that cortisol increases with age.
- Aging and the adrenal cortex. S S Yen, G A Laughlin 1998,
- Effects of aging on adrenal function in the human: responsiveness and sensitivity of adrenal androgens and cortisol to adrenocorticotropin in premenopausal and postmenopausal women. Parker CR Jr, Slayden SM, Azziz R, Crabbe SL, Hines GA, Boots LR, Bae S. 2000 (maximally stimulated levels of DHEA after ACTH bolus were significantly lower in the older women than in younger women; those of androstenedione were similar in both age groups, and the maximally achieved levels of Cortisol were higher in the older women than in the younger women.)
- Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. Jonathan Q Purnell, David D Brandon, Lorne M Isabelle, D Lynn Loriaux, Mary H Samuels. 2004 (24-h plasma free cortisol levels were increased with age in association with increased cortisol production rate)
- Changes with aging of steroidal levels in the cerebrospinal fluid of women. K Murakami, T Nakagawa, M Shozu, K Uchide, K Koike, M Inoue 1999
Catabolic effect of Cortisol
Cortisol, also known as glucocorticoid, is well known for it's catabolic (breakdown) effects on bones, muscles, and protein in general. This is one of catabolic hormones along with epinephrine and glucagon.
- Acute response of human muscle protein to catabolic hormones. D C Gore, F Jahoor, R R Wolfe, D N Herndon, 1993
- Bone mineral density, prevalence of vertebral fractures and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian Multicenter Study. Iacopo Chiodini, et. al., 2009
- Cortisol secretion, bone health and bone loss: a cross-sectional and prospective study in normal non-osteoporotic women in the early postmenopausal period. Giangiacomo Osella, Massimo Ventura, Arianna Ardito, Barbara Allasino, Angela Termine, Laura Saba, Rosetta Vitetta, Massimo Terzolo, Alberto Angeli, 2012
Cortisol increases especially during the late perimenopause and early post menopause years when menstrual irregularities are greatest, and menopausal symptoms are most severe.
- Increased urinary cortisol levels during the menopause transition., Nancy F Woods, Molly C Carr, Eunice Y Tao, Heather J Taylor, Ellen S Mitchell, 2006
- Cortisol levels during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study. Nancy Woods, Ellen Mitchell, Kathleen Smith-Dijulio, 2009).
Cortisol is an important stress hormone that allows us to be alert and energetic to face life's challenges with less pain. But it comes with a price, and our body is not built to stay in that state days and weeks on end, much less months and years. Except for a lucky few (less than 10%), women go through a stressful menopausal symptoms during the late perimenopause and early post menopause years (Bresilda Sierra, et.al. 2005), which is accompanied by elevated cortisol, epinephrine, and norepinephrine levels (Pituitary hormones during the menopausal hot flash. D R Meldrum, J D Defazio, Y Erlik, J K Lu, A F Wolfsen, H E Carlson, J M Hershman, H L Judd, 1984. Biophysical and endocrine-metabolic changes during menopausal hot flashes: increase in plasma free fatty acid and norepinephrine levels. M Cignarelli, E Cicinelli, M Corso, M R Cospite, G Garruti, E Tafaro, R Giorgino, S Schonauer. 1989). That is, unless something is done about it (Here lies a dilemma of research on menopause. You have to find women who agree to do nothing about it, which may not be easy or ethical, and potential for biased sampling).
"Glucocorticoids (GCs) are used frequently in a variety of diseases because of their strong anti-inflammatory and immunosuppressive effects. However, corticosteroids have many metabolic side effects, such as insulin resistance, hypertension, glaucoma, and osteoporosis. GC-induced osteoporosis (GIOP) is one of the most devastating side effects because bone loss during long-term GC treatment is generally irreversible and because of its clinical manifestations (eg, vertebral and nonvertebral fractures)." (Advances in glucocorticoid-induced osteoporosis. Debby den Uyl, Irene E M Bultink, Willem F Lems, 2011).
The mechanism has been identified at molecular level: Glucocorticoid preserves osteoclasts (cells involved in bone resorption) while reducing and impairing osteoblasts and osteocytes (cells involed in bone formation and mineralization). In addition, it impairs bone metabolism via inhibition of calcium resorption in the gastrointestinal tract and inhibition of the kidney's ability to reabsorb calcium (Glucocorticoid-induced osteoporosis: pathophysiology and therapy. E. Canalis & G. Mazziotti & A. Giustina & J. P. Bilezikian, 2010).
- Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Charles A OBrien, Dan Jia, Lilian I Plotkin, Teresita Bellido, Cara C Powers, Scott A Stewart, Stavros C Manolagas, Robert S Weinstein, 2004
- Glucocorticoids suppress bone formation via the osteoclast. Hyun-Ju Kim, Haibo Zhao, Hideki Kitaura, Sandip Bhattacharyya, Judson A Brewer, Louis J Muglia, F Patrick Ross, Steven L Teitelbaum 2006
suppress bone formation by attenuating osteoblast
differentiation via the monomeric glucocorticoid
receptor. Alexander Rauch,
Sebastian Seitz, Ulrike Baschant, Arndt F Schilling, Anett Illing, Brenda Stride, Milen Kirilov, Vice Mandic, Andrea Takacz, Ruth Schmidt-Ullrich, Susanne Ostermay, Thorsten Schinke, Rainer Spanbroek, Mario M Zaiss, Peter E Angel, Ulf H Lerner, Jean-Pierre David, Holger M Reichardt, Michael Amling, Gunther Schutz, Jan P Tuckermann, 2010
Bone series articles:
- Menopause and What Really Happens to your Bones
- False Promise of Fosamax
- Estrogen Paradox
- Role of Progesterone in Bone Health
- Stress Hormones Destroy Bones <<You are here
- Menopause and How estrogen helps bone health?
- Sad State of Progesterone Research
- Menopause and Bone Quality
- How to Maintain Bone Health