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!

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