In the first 10 years after menopause, a woman would have lost 2/3 of her entire bone mass, with the most significant loss occurring the first 1 to 3 years4.
Osteoporosis is defined as when the building of bone is slower than the breaking down of bone5. Bone resorption takes about three weeks and new bone formation take at least 3 months. When an imbalance between these two processes occur favoring bone loss and deterioration, the result is heightened loss, skeletal deformities, and fractures6,7. Osteoporosis can leave the bones so brittle that a fall or even mild structural stresses, such as bending or coughing, may cause a fracture. Common sites of fracture include the spine, hip, forearm and proximal humerus8. Fractures at the hip incur the greatest morbidity and mortality, reducing quality of life and shortening life expectancy. Studies have found that 25% of elderly people with hip fracture die within 6 months of the injury.
For women, one of the greatest risk factors for developing osteoporosis is a decrease in estrogen levels. Estrogen is very involved in bone metabolism. A decrease in estradiol levels sparks a cascade of events, one of which is the increase in bone resorption9.
Estrogen’s three fundamental effects on bone are:
1. It inhibits the activation of bone remodeling and the initiation of new basic multicellular units.
2. It inhibits differentiation and promotes apoptosis of osteoclasts, thereby reducing bone resorption.
3. While estrogen suppresses self-renewal of early mesenchymal progenitors, it promotes the commitment and differentiation and prevents apoptosis of osteoblastic cells, thereby maintaining bone formation at the cellular level10.
Studies show that elderly women with the lowest estrogen levels had the lowest bone density and highest risk of fractures. In one study done by McKane and colleagues, bone resorptions markers of three different groups of women were analyzed: a premenopausal group (age 32 years), an untreated postmenopausal group, and an estrogen-treated post-menopausal group. The researchers found that bone-resorption markers were similar between premenopausal and estrogen-treated groups but were significantly increased in the untreated post-menopausal group. This suggests that estrogen levels play a more significant role than age in bone health. In another study by Martin-Millan, et al, just 6 weeks of estrogen deprivation caused a significant loss of cortical bone, the dense outer surface of bone that forms a protective layer around the internal cavity11,12. This suggests that cortical bone is highly regulated by estrogen levels.
Progesterone also appears to work in bone metabolism, synergistically with Estradiol. Endogenous estradiol slows bone resorption and prevents bone loss while progesterone increases bone formation. In a meta-analysis in postmenopausal women, there was a further 0.4% increase in bone mineral density when women were treated with both progesterone and estrogen together as opposed to estrogen alone13. An article by JC Prior states that for optimal progesterone-related bone formation to occur, the ovulatory cycle needs a luteal phase length of 10-14 days by quantitative basal temperature or 12-16 days by Luteal Hormone peak. In a one-year prospective, observational study of 66 women between the ages of 20-42, those who had one or more short luteal phases or any anovulatory cycles lost bone mineral density at rates of 4-6% per year, whereas those who had normal ovulatory cycles or only one short luteal cycle per year did not lose bone mineral density. In a meta-analysis of randomized controlled trials in menopausal women, a combined therapy of estrogen and progesterone increased spinal bone mineral density by 2/3 of a percentage than estrogen therapy alone. These results support the finding that progesterone plays an important role in bone mineral density and in the prevention of bone loss.
Because osteoporosis is often asymptomatic, it is important to take preventative measures before fractures occur. The strong association between bone metabolism and female hormones imply that bone health can easily be managed with hormone replacement therapy in women nearing menopause or even in peri-menopause when hormones begin their decline. Initiating hormone replacement therapy early in women may help them maintain strong bones, prevent fractures, improve quality of life, and expand life expectancy.
1. Thurston RC, Maki PM, Derby CA, Sejdic E, Aizenstein HJ. Menopausal hot flashes and the default mode network. Fertil Steril. 2015;103(6):1572-1578 e1571.
2. Xu L, Liu B, Li P, et al. Correlations of Serum Hormones and Bone Mineral Density with Fracture and Balance Ability of Postmenopausal Patients and Effects of Calcitriol. Med Sci Monit. 2018;24:7309-7315.
3. Centers for Disease Control and Prevention. FastStats-Osteoporosis. National Center for Health Statistics. https://www.cdc.gov/nchs/fastats/osteoporosis.htm. Updated Aug 17, 2016. Accessed Aug 4, 2019)
4. Zuo H, Sun A, Gao L, et al. Effect of Menopausal Hormone Therapy on Bone Mineral Density in Chinese Women: A 2-Year, Prospective, Open-Label, Randomized-Controlled Trial. Med Sci Monit. 2019;25:819-826.
5. Mayo Clinic. Osteoporosis-Symptoms and Causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/osteoporosis/symptoms-causes/syc-20351968. Updated June 29, 2019. Accessed Aug 4, 2019)
6. Prior JC, Seifert-Klauss VR, Giustini D, Adachi JD, Kalyan S, Goshtasebi A. Estrogen-progestin therapy causes a greater increase in spinal bone mineral density than estrogen therapy - a systematic review and meta-analysis of controlled trials with direct randomization. J Musculoskelet Neuronal Interact. 2017;17(3):146-154.
7. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95(4):1991-1997.
8. WHO SCIENTIFIC GROUP ON THE ASSESSMENT OF OSTEOPOROSIS AT PRIMARY HEALTH CARE LEVEL. Presented at World Health Organization meeting. May, 2004. Brussels, Belgium. https://www.who.int/chp/topics/Osteoporosis.pdf. Accessed Aug 4, 2019)
9. Prior JC. Progesterone for the prevention and treatment of osteoporosis in women. Climacteric. 2018;21(4):366-374.
10. Khosla S, Melton LJ, 3rd, Riggs BL. The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed? J Bone Miner Res. 2011;26(3):441-451.
11. Martin-Millan M, Almeida M, Ambrogini E, et al. The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol. 2010;24(2):323-334.
12. Veritas Health. Cortical Bone Definition. Spine-Health. https://www.spine-health.com/glossary/cortical-bone. 2019. Accessed Aug 4, 2019)
13. Seifert-Klauss V, Schmidmayr M, Hobmaier E, Wimmer T. Progesterone and bone: a closer link than previously realized. Climacteric. 2012;15 Suppl 1:26-31.