|Possible increased risk of breast cancer|
|Frequent medical monitoring involving increased costs and potential for surgical
Source: R.L. Young, et. al., Management of
Menopause When Estrogen Cannot Be Used. Drugs, 40(2):220-230,1990
Side Effects of HRT
Most women respond well to HRT taken as prescribed. There are side effects. These range
from minor nuisances to major problems. Most of the nuisances disappear within a few
months after you start therapy, enabling most women to gain the full benefits of
need to pay attention to the serious issues like cancer. For a summary of risks, skip to
the Bottom Line.
Vaginal bleeding after menopause
Whether or not you experience bleeding after starting HRT depends on the hormone
selected for you, the dose you take, the dosing regimen, and your unique response to
After menopause, the normal decrease in estrogen results in the thinning of your
uterine lining. As a result, your periods stop. When estrogen is brought back into your
system through HRT, the lining thickens again. If you are on a cyclic regimen, when you
stop taking the hormone, during the last days of the cycle, the tissue of the lining loses
its nourishment, thins, and is shed as menstrual flow.
Important: If you are not on hormones, any bleeding
from the vagina that occurs six months or longer after menopause is called postmenopausal
bleeding. This is normally a signal that something may be wrong. Do not ignore it. Contact
your doctor immediately. The bleeding may be an early warning of uterine
cancer, or it may represent nothing of significance. Let your physician decide.
On hormone therapy, the bleeding you may experience is called withdrawal bleeding. This
occurs when the hormones, particularly progestin, are withdrawn from your treatment. This
bleeding is normal. However, breakthrough bleeding, which may occur while you are still on
estrogen and progestin, should be reported to your physician.
You may experience swollen or tender breasts. Rarely is the pain so severe that your
medication needs to be changed or stopped. This condition is called mastalgia and
is similar to the breast tenderness that some women of reproductive age feel before the
onset of their menstrual periods. It is caused by the domino-like effect of the added
progestin on the estrogen on the tissue cells in the breast, which may cause a slight
amount of vascular congestion or fluid retention within the breast itself. It is not a
pleasant symptom and it can be difficult to prevent.
To alleviate breast swelling, reduce your intake of salt, coffee, chocolate, and
substances (products) containing caffeine and xanthine. Small doses of vitamin B6 may also
be of help in reducing mastalgia. If the problem is severe, a mild diuretic may be
prescribed. If none of these methods work, the hormone therapy may have to be discontinued
and then started again at a lower dose, especially the progestin.
Other PMS-like symptoms
These appear during the first few months of HRT. Symptoms include:
|Slight swelling of the legs|
|An increase in body weight|
|Minor depression. (Depression is more the result of the progestin than estrogen.)|
Some of these symptoms may be related to mild water retention (edema). Stay with the
treatment. The body will make adjustments. Diuretics are not recommended due to other
Weight gain with HRT often is the result of fluid retention. If you
gain weight, but are not retaining fluid, you are probably eating too much. Hormones can
make you hungrier. Pay strict attention to your diet.
The solutions for reducing these PMS-like symptoms are similar to those described for
breast tenderness. They include:
|Reducing salt intake|
|Avoiding caffeine and xanthine containing products|
|Taking Vitamin B6|
|Increasing physical activities and exercise|
|Reducing the dose of the progestin or trying a different progestin (This is done only if
you do not respond to the treatment above and your situation is serious.)|
The following are the major risks/problems of HRT. You must be fully alert to the
potential risks. These can have serious consequences, so be on the lookout for any warning
signs. Early detection and treatment is important. It may significantly reduce the
likelihood of any of them becoming real risks to you.
The chance of developing uterine cancer after menopause is about one in every thousand
women per year. The risk of uterine cancer to women on estrogen therapy depends on how
high the dose is and for how long it is taken. The worst scenario is that the cancer risk
increases to between four and eight women in every thousand per year. The majority of
these estrogen-induced cases of uterine cancer can be successfully cured if caught at an
Estrogen therapy, without progestin, does carry a risk for a woman who has her uterus
intact. When progestin is added, this increased risk is negated.
The modern way of prescribing estrogen, in low doses and with cycled progestin, makes the
risk of uterine cancer small. However, if you have other risk factors, such as obesity,
abnormal uterine bleeding, a family history of cancer, and, possibly, cigarette smoking,
the individual risk to you is increased and you may want to look at alternatives to
If you are on HRT, tell your physician about problems as they occur. See your doctor
every six months. At these visits, breast and pelvic examinations and cancer screening
tests, if required, should be done. Report any unusual bleeding to your doctor promptly.
Researchers believe that the longer your exposure to naturally occurring estrogen, the
greater your risk of breast cancer.
Investigators at Harvard studied responses to health questionnaires completed by nearly
70,000 postmenopausal women in the Nurses' Health Study, which has tracked their health
for nearly 20 years. Compared with women who had never used postmenopausal hormones, those
who used estrogen alone had a 30 percent increased risk of breast cancer, while the risk
was about 40 percent higher in women using estrogen plus progestin. (The difference
between 30 percent and 40 percent was not statistically significant.) Only women who
currently used hormones and had been taking them for five years or more had an elevated
risk, a risk that increased with a woman's age; those who had taken hormones in the past
but didn't currently use them had no increased risk, even if they had used hormones for
more than five years.
The Harvard study supported earlier evidence that estrogen-replacement therapy plays a
role in increasing the risk of breast cancer. In addition, it shed some light into the
risks at various ages and the effect of adding progestins. Because estrogen therapy alone
raises the risk of uterine cancer, and adding progestins brings the risk back down,
researchers had hoped that the progestins would have a similar effect on breast cancer.
Unfortunately, this study suggested that progestins don't cut breast cancer risk.
A study published in the Journal of the American Medical Association questions the
conclusions made in the Nurse's study. Researchers at the University of Washington
compared hormone use in roughly 500 middle-aged women diagnosed with breast cancer and 500
control women who had not had breast cancer. The percent of women in each group using
estrogen plus progestin hormone therapy was virtually the same (21%), so hormones clearly
didn't increase breast cancer risk.
Recent research indicated that there may be a tradeoff between the higher
density of bones achieved through using HRT and the increased risk of breast cancer.
Higher bone mineral density might go hand-in-hand with a higher risk of breast cancer.
University of Pittsburgh researchers found that, of nearly 7,000 women over age 65
participating in the Study of Osteoporotic Fractures, those who
developed breast cancer had significantly greater bone density than women who didn't
develop the disease. The greater the bone density, the higher the risk: Those with the densest bones had more than double the risk of
those with the lowest bone density. This was published in JAMA.
This finding might seem surprising. But it need not be. Estrogen is known to increase
bone density by inhibiting the function of osteoclasts.
Scientists also know that high levels of estrogen may promote the growth of cancer cells.
The University of Pittsburgh researchers speculate that older women with higher bone
density may have been exposed to greater levels of estrogen throughout their lives and
that this greater lifelong exposure puts them at increased risk of breast cancer.
If this conclusion turns out to be true, postmenopausal women who already have good
bone density may be getting more estrogen than is safe if they go on HRT.
A recent study published in the June 9, 1999, issue of the Journal of the American
Medical Association (JAMA) shows that while the use of hormones is associated with a
slightly increased risk of breast cancer with a favorable outcome, the use of
postmenopausal HRT was not linked to an increased risk of the more commonly diagnosed,
dangerous breast cancers with poorer outcomes.
The study found that women who used HRT for five years have nearly twice the risk of
types of breast cancer usually associated with a favorable outcome, compared with women
who have never used HRT. Moreover, women who have used HRT for more than five years had
2.65 times the risk compared to non-users.
In the JAMA study, use of HRT was not, however, associated with an increased risk of
invasive breast cancers that occur in the milk ducts and lobules of the breast, nor with
an increased risk of a non-invasive cancer of the milk ducts. "Invasive" implies
that the tumor has spread at least locally in breast tissue, and is thus likelier to
spread widely and pose a threat to life. HRT use selectively increases the risk of the
less commonly occurring tumors with a good prognosis.
The new study looked at HRT use and breast cancer risk in 37,105 postmenopausal women
from the Iowa Womens Health Study. During 11 years of follow-up, 1,520 women
developed breast cancer, the study showed. Of these cases, 82 were breast cancers with
usually favorable outcomes.
The study concluded that the benefits of HRT on the bones and heart far outweigh the
minuscule risk of breast cancer.
Your risk of getting breast cancer increases if you:
Studies have been done to determine the effect of estrogens on the clotting substances
in the blood. These showed that the types of estrogens used in treating the postmenopause
do not seem to alter blood coagulation factors significantly. For those who use estrogen
skin patches, studies of blood-clotting factors show that these factors are unchanged.
Recommendation: Women with preexisting risk factors for blood clots should not take
HRT. If there was only a single incidence several years in the past, HRT is OK; use the
skin patch rather than an oral medication.
Liver Problems and Gallstones
Estrogen affects the liver. So, do not take estrogen if you have liver disorders.
Women taking estrogens have a 2.5-time greater chance of developing gallstones
requiring surgical treatment. Obesity is also associated with an increased incidence of
In order to prevent gallbladder problems, reduce cholesterol in your diet. This also
helps to prevent heart disease. Use a form of estrogen replacement that does not involve
the liver. The skin patch appears to have less influence on liver enzymes than oral
estrogen and may reduce the incidence of gallstones.
Increased Blood Pressure, or Hypertension
Estrogen will not normally alter your blood pressure. So you can take HRT even if you
have high blood pressure. Very few patients experience an elevated blood pressure shortly
after starting on the oral estrogens.
Your follow-up examinations with your doctor will include having your blood pressure
checked. If your blood pressure is elevated, switch from the pill to the patch. The patch
will not affect the liver enzymes that elevate blood pressure.
HRT results in vaginal bleeding and, occasionally, in irregular bleeding, which may
make you subject to more endometrial samplings (biopsy), diagnostic curettage, and perhaps