Progesterone and Osteoporosis
Osteoporosis Treatment During or Shortly After Menopause
Progesterone Helps Build Bone
by John R. Lee, M.D.
As I have reported in my articles and books, and as found by many others, progesterone is important in the treatment of osteoporosis in postmenopausal women. In my practice experience treating women of mean age 65 years without clinical signs of estrogen deficiency, I observed, after three years of transdermal progesterone treatment, a 15% improvement in bone mineral density (BMD) and good protection against fracture without using estrogen supplementation. This does not mean that estrogen (estradiol) has no role in osteoporosis. Both hormones are important. Estradiol inhibits osteoclast-mediated bone resorption while progesterone stimulates osteoblast-mediated new bone formation. Thus, my clinical results mean that the majority of women at this age continue to produce estradiol sufficient for its bone benefit for many years after menopause.
The case of bone loss during the 3-4 years around actual menopause is a different story. Prior to menopause, estrogen levels remain at levels essentially the same as during premenopause. Osteoporosis, however, begins at about age 35 when progesterone levels begin to decline despite continued good estrogen levels. This is an indication that progesterone deficiency is the major cause of the early appearance of the osteoporosis process. At menopause, estrogen levels decline markedly: estrone declines about 40% and estradiol about 60%. This abrupt decline in estradiol results in an acceleration of osteoclast-mediated bone resorption. Also, the decrease in estradiol levels results in a decrease of progesterone receptors, thus decreasing new bone formation. During the 3-4 years around menopause, it is not unusual to observe in industrialized countries a decrease of BMD in the range of 3-4 % per year, compared to 1-1.5% per year later in postmenopausal life.
It is interesting to note that Dr. Peter Ellison, in his WHO-sponsored transcultural studies of hormone levels (using saliva hormone assay), that the premenopausal estrogen levels of women of industrialized countries were considerably higher than that of women in non-industrialized countries. Thus, the magnitude of the decline of estrogen at menopause was greater among women of industrialized countries. This may explain the fact that bone loss at menopause is greater among women of industrialized countries.
However, after this 3-4 years of accelerated bone loss, the typical rate of bone loss reverts to only 1.5% per year, indicating an adaptive tolerance to the lower estradiol levels. This hypothesis is strongly supported by a recent study in the New England Journal of Medicine of 10 September 1998 in which endogenous hormone production in women aged 65-80 was compared with their fracture incidence. The study found that a serum estradiol concentration of 5 pg/ml provided optimal estrogen benefit to bone and this level of estradiol was present in two thirds (67%) of the women without using ERT or HRT supplements.
This study also found that sex hormone binding globulin (SHBG) concentrations were even more strongly inversely correlated with bone benefit than estradiol concentration is. That is, the greater the concentration of SHBG, the less bone benefit from estradiol. This is readily understandable since SHBG-bound estradiol is significantly less bioavailable than estradiol itself. Both the authors of the study and the accompanying editorial lamented the lack of a good test for non-protein-bound estradiol. The writers did not know that this is one of the benefits of saliva hormone assay: it is our most accurate means of testing for non-protein-bound steroids.
Dr. Helene Leonetti has now completed one year of a FDA-approved osteoporosis study among women who are within five years of menopause using transdermal progesterone without estrogen supplementation. While she found significant benefit in sense of wellbeing and relief of hot flushes among progesterone users, she found essentially no difference in BMD among women using progesterone compared to placebo users. This indicates, in my opinion, the importance of the rapid decline of estradiol in both groups causing acceleration of osteoclast-mediated bone resorption and a decline of progesterone receptors during these menopausal years. However, if the study is continued for another year or two, it is likely that an adaptive tolerance of lower concentrations of estradiol will occur and the improved new bone formation among progesterone users will be revealed by rising BMD results among the progesterone users. Bone turnover (modeling) is a slow process and studies of longer duration will be necessary to truly test the benefit of progesterone in this age group.
It was my experience that small dose supplements of estrogen are needed in women with clinical signs of estrogen deficiency, particularly vaginal dryness and/or vaginal mucosal atrophy. If the decline in estrogen at menopause is converted from a rapid loss to a slow decline by using low dose estrogen supplementation during these menopausal years, the loss of BMD due to osteoclast-mediated bone resorption can be prevented. Further, the progesterone bone benefit of improved new bone formation can eventually restore the bone loss that occurs during the years around menopause. It is my hope that the study will be funded for at least another two years.
For much more information about osteoporosis, please read the updated and revised edition of What Your Doctor May Not Tell You About Menopause, which has an excellent and detailed chapter on the subject.
Note to Reader from Virginia Hopkins
Dr. John Lee was my great friend, mentor, co-author and business partner. This website is dedicated to continuing the work that Dr. Lee and I did together to educate and inform women and men about natural hormones, hormone balance and achieving optimal health. Dr. John Lee was a courageous pioneer who changed the face of medicine by introducing the concepts of natural progesterone, estrogen dominance and hormone balance to a large audience of women and men seeking answers to their hormone questions. Dr. Lee has left us a wonderful collection of writings from his newsletters that are, in large part, freely shared on this website. Enjoy!