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Bone loss, leading to reduced bone mineral density (BMD) and eventually osteoporosis, is the result when osteoclast-mediated bone resorption and osteoblast-mediated bone formation become unbalanced. In the normal state, the bone is in a state of homeostasis in which bone is formed at the same rate as it is resorbed (i.e., broken down to release calcium into the bloodstream, which is a mechanism for maintaining blood calcium levels) and this is referred to as “bone turnover”.
Hormones play a significant role in these processes. Progesterone has bone-forming activity by binding to receptors on the osteoblasts. This explains the decreases in spinal bone density seen in premenopausal women with low progesterone levels. In the Michigan Bone Health Study, those premenopausal women with the lowest bone mass had the highest rates of progesterone deficiency.
The effects of progesterone and estrogen on bone are synergistic and complementary to each other, and some clinical trials have found greater increases in spinal BMD when the progestin medroxyprogesterone acetate (MPA) is added to estrogens than with estrogens alone. However, fracture risk data for conjugated equine estrogens (CEE) and CEE/MPA were not analyzed separately in the Women’s Health Initiative study, which reported a reduction in fractures with hormone therapy.
The wide variation in synthetic progestins and progesterone formulations has hindered the statistical power of meta-analyses to detect the effects on BMD of the progesterone/progestin component of hormone therapy, but tibolone (a synthetic progestin widely used in Europe but not approved in the US) was shown to have similar effects on BMD to any estrogen compound in one meta-analysis (see Dören 2003).
At the time of the menopausal transition, the rate of bone turnover is still high and so progesterone’s bone-forming effects are harder to see. However, longer term studies of progesterone treatment, currently in progress, may further confirm the benefit of this hormone for maintenance of bone density after the first few years following the onset of menopause.