Appropriate
Hormone Replacement Therapy known as HRT, remains a viable and important
health care option for postmenopausal women.
The most significant
effects of HRT are increased longevity, a better quality of life and
prevention of the accelerated aging associated with hormone deficiency.
This remains true despite a media conflagration generated by the publication
of the findings of two studies: 1) The Heart and Estrogen/progestin
Replacement Study Follow Up (HERS II) and 2) The Women’s Health
Initiative (WHI) study. Both studies were published in the Journal of
the American Medical Association (JAMA) in July 2002. The articles seem
to question the wisdom of hormone replacement.
The media response
was explosive. While some of the coverage was accurate and representative,
much of it pandered to fears of women and health providers alike. Although
there was no difference in all-cause mortality in either study between
hormone users and non-users, many postmenopausal women felt that the
underlying message was that hormone replacement represented a health
risk and discontinued their therapy. This impression was reinforced
as scores of physicians informed their menopausal patients -based on
the results of the studies, which most had not read - that it was time
to discontinue hormone replacement therapy.
Are these legitimate
responses that reflect the findings of the published studies? It doesn’t
seem so. Five key points follow:
1) It was not clear to most women that both studies
did not address hormone replacement in general, but was limited to users
of Prempro, which is a sub-optimal hormone replacement preparation distributed
by Wyeth-Ayerst. Prempro is a combination of conjugated equine estrogen
(CEE) and medroxyprogesterone acetate (MPA) and is taken daily as continuous
combined therapy. It is indicated for use in women who have not had
a hysterectomy and require protection of the uterine lining with a form
of progesterone, in this case MPA.
2)
Hormone replacement with Prempro appears to have a less favorable risk/benefit
profile than other replacement preparations, particularly those that
are non-oral and those in which a progestin component is not used continuously.
Studies completed following the commencement of the HERS II and WHI
trials suggested that the specific combination in Prempro demonstrated
both: 1) a less favorable effect on coronary arteries than other regimens
and 2) a small, but significant excess of a relatively uncommon form
of breast cancer, which has not been associated with use of other forms
of hormone replacement. Had this information been available it is unlikely
that HERS II or WHI studies would have been initiated.
3)
The weight of previous research utilizing other regimens of hormone
replacement had suggested a more positive outcome. The commentary in
both studies did state that it was “possible” that the unexpected
negative findings were due to the combination in Prempro. Surprisingly,
unencumbered by the limitations of the data, the researchers included
all forms of hormone replacement in their conclusions and recommendations.
Dr. Wulf H. Utian, MD, PhD, Executive Director and Honorary Founding
President of The North American Menopause Society and a pioneer in menopause
research, stated that the financial relationship existing between authors
of both studies and Wyeth-Ayerst (the manufacturer of Prempro), raised
issues of ethics and potential bias.
4)
Physicians are encouraging women to stop using HRT, without a legitimate
rationale. This is an irresponsible and potentially life-altering recommendation.
The Director of the WHI study Dr. Jacque E. Rossouw, of the National
Institutes of Health, stated that it was his impression that few physicians
had actually read the studies or had an in-depth knowledge of the details,
or conclusions. Dr. Rossouw went on to say that in his opinion appropriate
hormone replacement does not cause breast cancer, or coronary artery
disease and that he was “comfortable” with this type of
hormone use “for as long as it is necessary.”
5)
The big losers are menopausal women who have been deterred from using
hormone replacement as a valuable health care and quality of life enhancing
strategy.
Dr. Trudy L. Bush,
who was one of the nation's preeminent researchers and teachers of issues
related to women's health - particularly the effects of hormones and
replacement therapy on the cardiovascular and reproductive systems -
published a hallmark study in the Journal of the American Medical Association
in February of 1983. This examined all-cause mortality in estrogen users
compared with non-users. During the 5.6 years of the study, the risk
of death among non-users was twice as high as users of estrogen if they
had no gynecological surgery. It was three times higher if they had
a hysterectomy and eight times higher if both ovaries had been removed.
Since that time, Dr. Bush and a number of other respected authors, have
published numerous articles confirming the association of estrogen use
with lower all-cause mortality.
Accordingly, it
is reasonable to postulate that the difference in the HERS II and WHI
studies was likely due to the specific hormone preparation. Therefore,
it is not possible to extrapolate any conclusions, or recommendations
to other forms and types of hormone replacement. This was confirmed
recently by both the North American Menopause Society Advisory Panel
on Postmenopausal Hormone Therapy and the Executive Committee of the
International Menopause Society.
PERSONAL
CHOICE
When it comes to the question of whether to use hormone replacement
therapy the answer is always one of personal choice.
What
is OPTIMUM HORMONE REPLACEMENT?
In
this section, Dr N discusses optimal hormone replacement regimens.