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The
practice of taking hormone replacement therapy or HRT (restoration of
approximately 50% portion of the ovarian steroid output) after the ovarian
function has “retired” has now been done for many decades.
Originally it was used for the purpose of easing the transition to
menopause, particularly for the women who had a difficult time with hot flashes.
Estrogen was also found to improve vaginal dryness and urinary loss
problems. Decades ago, it was observed that estrogen used alone (ERT) increased
the risk of endometrial (uterine) cancer, and that the addition of progesterone
neutralized this risk.
Along
the way estrogen was observed to have a profound protective effect against
osteoporosis. This is a major cause of disability, affecting about 15% of
postmenopausal women in the U.S. One out of two Caucasian women will experience
an osteoporotic fracture at some point in her lifetime! The average age of hip fracture, for example, is 74.
Further
along the way, HRT was observed to greatly decrease the risk of cardiovascular
disease (atherosclerosis, hardening of the arteries). This is the process that
leads to heart attack and stroke, which together cause 45% of deaths in U.S.
women. The evidence was so strong for up to a 50 % reduction in risk
that there was a big movement to initiate HRT for this reason alone.
A large study was undertaken (HERS) to see whether or not HRT could help
protect women who already had cardiovascular disease. Results published in 1998
showed that starting HRT in these women (average age 67) actually increased
their chance of a problem initially. With
time the risk decreased and there was no overall benefit shown.
So it appeared HRT alone could not help when blood vessels were already
affected by arteriosclerosis.
Controversy
has existed for many years about whether HRT increased the chance of breast
cancer. The effect is so small it’s difficult to detect, but it has been
generally acknowledged that with somewhere between five and fifteen years of use
there as a slightly increase chance of detecting breast cancer.
The risk may be slightly greater with higher doses of estrogen or with
the combination of estrogen and progesterone.
Breast cancer accounts
for approximately 3.5% of deaths in U.S. women.
Cancer as a whole accounts for 23%.
Interestingly, the prognosis in women who develop breast cancer is better
if they had been on HRT than if they had not. The rate of women being diagnosed
with breast cancer peaked in 1987. This
was thought to be due to a statistical “surge” from early detection.
It has been decreasing since.
This summer, preliminary results and
recommendations were dramatically released from a large trial, the Women’s
Health Initiative (WHI) that suggested some seemingly surprising things.
One arm (Premarin with Provera) of this large, prospective trial was
halted, citing that the 1992 predetermined threshold for the development of
invasive breast cancer had been exceeded. The risk was 0.3% per year if not on
HRT and 0.37% if on it. Interestingly,
a family history of breast cancer was not found to be a factor as to whether or
not a woman had a greater chance of breast cancer being detected if HRT was
used. In addition, 5.2 years into
the planned 8.5 year trial, the risks overall were exceeding the benefits the
trial was set up to study for this group of patients. The average age of women
was 63.3 years at the start, and they were at least one year postmenopausal. The
outcomes measured were coronary heart disease, invasive breast cancer, stroke,
pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and
death due to other causes. Interestingly, there was no difference in death rates
between the groups over that span of time. The investigators, however, felt that
over time, the risks of HRT would even more outweigh the benefits they were
measuring.
Critics
of the WHI point out that the diagnosis of breast cancer in HRT users was not
statistically significant, so in theory may have been due to chance alone. There
is also the intriguing notion that HRT may not initiate new tumors, it may just
accelerate the growth of existing ones. The
consistent observation of a better breast cancer prognosis on HRT may be
explained if these tumors are thus able to be detected at an earlier, more
treatable stage. Also, 7.7% of
participants had known preexisting cardiovascular disease, and would be expected
to have problems with starting HRT as the HERS trial showed. If these women had
been excluded from the trial, it seems that any difference in cardiovascular
disease outcomes would not be statistically significant, either.
Another
point is that if this study is to shed light on primary prevention of
cardiovascular disease, why not start HRT at or soon after menopause (average
age of menopause is 52), when blood vessels are less likely to already be
diseased? Yet another problem is that not all of the data has been published, so
thorough independent review and critique is not yet possible. Plus it’s hard
to say that a 5-year study can speak to long term net effects of HRT.
So where does that leave us? The American Heart
Association recommends HRT not be started for the secondary prevention of
cardiovascular disease. They do not
have recommendations regarding initiating HRT for primary prevention, citing
insufficient data. Modification of lifestyle and ”statin” drugs, when
indicated, are the current recommended first line approaches.
In either case, they say HRT may be continued based on assessment of
other benefits, risks, and patient preference.
The
use of HRT in women who have gone through an early menopause (generally prior to
50) naturally or surgically is a different situation and has not been addressed
by the WHI study. As HRT during the
years from early menopause until 50 would represent exposure to less hormone
potency than if the ovaries had been functional, it would seem that those women
would experience fewer problems than women who go through menopause at the more
usual time.
The
American College of OBGYN actually recommends patients who are on HRT solely for
cardioprotection to stop it. They recommend alternatives to HRT for osteoporosis
prevention be explored. HRT is acknowledged to be the most effective treatment
for hot flashes and related problems, the shortest duration and lowest effective
dose is suggested. Annual reviews of your HRT status with your physician are
recommended, and discontinuance after 5 years is sought. To date, taking
estrogen alone seems OK. Formulations
of HRT other than Premarin and Provera are assumed to pose the same concerns.
Dr. McLauchlan, Rickie Guida NP, Barbara Ferris, NP:
We
feel HRT in standard or low doses is safe to start in early menopause and offers
many health benefits. At this point we do not feel that it is necessary to stop
HRT if one has been on it for several years and is enjoying quality of life
benefits such as improved sexual health, incontinence control, hot flash or mood
improvement or osteoporosis protection. If
one has cardiovascular disease or risk factors and had been on HRT for several
years, we do not see a need to stop HRT, particularly if there are other
realized benefits. These patients should be evaluated for other risk reducing
interventions.
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