Hormone Therapy

"Hormone replacement therapy - Is it for me? If so, should I use pills, patches, or creams? What about natural hormones?" As a pharmacist specializing in women's hormones for the last 30 years, these are some of the questions I have been asked. This basic website attempts to answer the many questions that women have about hormone replacement therapy (HRT). It will enable you to work with your health clinician to decide what is your best choice. - Joe Gartner R.Ph.

Hormone Replacement Therapy (HRT) Is It For You?

If there is one symptom that many menopausal women share, it is the initial confusion of trying to make sense of all of the conflicting information about hormones. Hardly a month seems to go by without a new report in the media about either the benefits or the risks of hormone replacement therapy (HRT).

The use of the term "replacement" in HRT has been questioned. The amount of hormones used in post menopause are much lower than those produced by younger women and are technically not a replacement. Some specialists feel that hormone therapy is a more accurate term, but as of now, HRT is the most widely recognized term so I will continue to use it.

A woman who is considering HRT is no doubt faced with many different opinions concerning the most appropriate form of hormone therapy. Some women even question whether HRT should be used at all.

I would like my Web site to give you an overall view of HRT and a look at what the current studies are showing. The results of the large Women's Health Initiative (July 2002) have raised questions as to whether the benefits of the most commonly prescribed HRT, Prempro, exceed the risks in long-term use.

Every woman’s situation is slightly different. HRT is not a case of "one size fits all". I hope my Web site will provide you with the information you need to make informed decisions about your hormone replacement therapy.

Ask yourself: Are you looking for short-term treatment (hot flashes and mood swings), long- term prevention (heart and bones), or a combination of both?

Keep in mind, if you have serious concerns about long-term therapy, you can always opt for taking HRT for just a short time.

Let’s look at the benefits and risks…

BENEFITS OF HRT…

Relieving Hot Flashes
Helping the Bones
Helping the Heart
Helping Vaginal/Urinary Health
Helping Moods/Cognitive Function

RISKS OF HRT…
Endometrial Disease
Breast Cancer
Circulatory Problems
Gallbladder Disease

Relieving Hot Flashes

What HRT can do for you…

Estrogen is very effective in reducing the frequency and severity of hot flashes. There seems to be a direct correlation--increasing the dosage decreases the severity.

Sleep Deprivation

Don’t underestimate the effect of night sweats and the resulting loss of sleep on your overall health and well-being. Sleep deprivation is a contributing factor for some of the mental confusion, mood swings, and anxiety that often accompany menopause.

Phytoestrogens

Sleep deprivation and night sweats are two areas where many of the phytoestrogens (estrogenic substances in plants like soy) may be beneficial. Soy foods and herbal products have all proved useful in relieving hot flashes for some women. Their relative safety makes them a good first choice of treatment. You won’t need a major study to tell you if phytoestrogens are working – you’ll know. However, for many women phytoestrogens are not strong enough to control the symptoms, and prescription estrogens may be a better choice.
Breast Cancer Risk

Prescription estrogen does not seem to increase the risk of breast cancer when used for the short-term (under 5 years) treatment of hot flashes. The preliminary results of the large Women's Health Initiative study did not show any increase in the breast cancer rate until a threshold of 4-5 years was reached. After that, a slight increase in the breast cancer rate was observed in those taking Premarin (equine estrogens) and Provera (synthetic progestin). No increase has been seen yet in those taking only Premarin. Unfortunately for women who have had breast cancer, there is conflicting evidence about the safety of HRT. For this reason, many physicians are hesitant to use either prescription or plant estrogen for these women. Alternative treatments for hot flashes for women with breast cancer include the prescription drugs clonidine, Megace, Effexor, Prozac, and over-the-counter (OTC) bioflavanoids (Peridin-C). Most recently a small study has suggested that the prescription drug Neurontin might prove useful.

Progesterone Creams

A few studies have shown that topical progesterone cream is effective in reducing hot flashes. Over-the-counter progesterone creams have a great variation in the amount of progesterone they contain. Progesterone creams containing mexican yam are ineffective because the human body has no enzyme to convert mexican yam to progesterone.

The most potent and economical progesterone cream is the prescription strength cream/gel available from a compounding pharmacy. When comparing equivalent amounts of progesterone, the prescription product is usually significantly less expensive than its OTC counterparts.

What are your needs?

Ask yourself:

Can you live with your hot flashes?
How severe are your hot flashes?
...an occasional "power surge"?
...frequent discomfort?
...severe sleep disruption?

Additions/alternatives to HRT

When looked at in medical studies, treatments for hot flash symptoms have a placebo response of up to 65%; it is noteworthy that most other medical treatments have a 30% placebo response rate. Because two-thirds of women report relief from hot flashes with any type of treatment including a sugar pill, many companies feel free to claim that their products help with hot flashes. Therefore, it is important to look carefully at controlled studies to find the most evidence of effectiveness.

The most effective alternative treatments for hot flashes:

Lifestyle changes: The most obvious is to dress to stay cool, to exercise, and to eat more soy protein.

Herbs: Although many herbs are recommended for hot flashes, the most effective one seems to be black cohosh.

Supplements: Isoflavones (the active substances in soy protein) seem to have the most benefit.

You are probably thinking that there are some items missing from this list. What about dong quai, vitamin E, evening primrose oil to name a few? The list reflects the treatments that have been shown to be the most effective in placebo-controlled studies. Most supplements have a low side effect profile, so there is little harm (other than to your pocketbook) in trying different treatments to see what works for you.

Benefit to Risk

Based on current statistics, when HRT is used for hot flashes:

The benefits are probably greater than the risks: If you are suffering from hot flashes and have no history of breast cancer.

The risks are probably greater than the benefits: If you have a history of breast cancer.

If you want to treat these symptoms as simply as possible, just start with the alternative treatments to see if they help you.

Helping The Bones

Osteoporosis is the fourth leading cause of death in women – after heart disease, cancer, and stroke. The weakened bones of osteoporosis cause 80-90% of all fractures in postmenopausal women.

Estrogen has been clearly shown to slow bone loss; its use results in a significant reduction in the amount of fractures in the elderly. In addition, it has an effect on the body’s ability to utilize calcium and vitamin D, which results in increased bone mineral density.

Although oral micronized progesterone may have some beneficial effects on the bones, the benefits are not as significant as some books may lead you to believe. Most osteoporosis experts believe progesterone has much less of an effect on bone density than estrogen.

There is little evidence to support the claims that over-the-counter progesterone creams have a significant beneficial effect on bone density. There is one very good ongoing study regarding the use of high-dose oral micronized progesterone and bone density that unfortunately won’t be completed until 2003.

Testosterone supplementation can be beneficial to the bone. However, the dose must be adjusted on an individual basis to prevent the side effects associated with higher doses.

What are your needs?

Ask yourself:

Do you have a family history of osteoporosis?
Are you thin with a small frame?
Have you ever used steroids (like prednisone or cortisone) long term?
Do you have a sedentary lifestyle?
Do you have a diet low in calcium or high in caffeine or alcohol?
Do you smoke?

If you answered "yes" to any these, a bone density test might be useful. Discuss this with your primary care provider. The test can help to determine what course of action you should take. If you have low to moderate bone loss, you may be able to protect yourself with lifestyle changes such as diet and weight-bearing exercise. More severe bone loss would indicate the need for additional medication.

Additions/alternatives to HRT

Simple steps for prevention-

Calcium
Most people don’t get enough of it. Dairy products are the most concentrated natural form of calcium, but an increasing amount of fortified foods, like orange juice, are now available. Supplements are very useful, and the most cost effective is calcium carbonate. Calcium citrate is a good choice for those people on acid-reducing medications like Prilosec and Zantac. You should take the calcium with added vitamin D, preferably at mealtime.

Weight Bearing Exercise
Something as simple as walking provides benefits. There is an increasing amount of evidence that training with weights is important for women of all ages. It is also very useful in controlling weight.

Dietary changes
Excessive use of alcohol and caffeine can contribute to bone loss. Although the data is not conclusive, soy protein may be beneficial for bone health.

Other medications
Evista (a SERM - see the estrogen section), Miacalcin, Fosamax and Actonel are all approved medications that help with bone loss when used alone or in combination with HRT. The most profound effect on the bones is seen with the drugs like Fosamax and Actonel. Both of these drugs are available in a once a week dosage. Actonel seems to cause less stomach upset.

Benefit to Risk

The initial results of the Women's Health Initiative study (July 2002) have questioned the benefit to risk ratio of Prempro (equine estrogen and synthetic progestin) for bone health. Until further studies are available, many feel that drugs like Fosamax or Actonel would be more appropriate than Prempro for those at high risk of osteoporosis. Other studies indicate that for the postmenopausal treatment of osteoporosis the benefit of HRT (other than Prempro) may be greater than the risk for women who have no increased risk of breast cancer and fall into one of the following four categories:

Age Bone Mineral Density Score Additional Risk History of Fractures

Under 65 at or below - 2.0 None
Under 65 at or below - 1.5 One
Over 65 at or below - 2.5 None
Over 65 Yes

Helping The Heart

Cardiovascular disease (heart attack and stroke) is the leading cause of death in women. In fact, it kills nine times more women than breast cancer. Estrogen’s effect in preventing cardiovascular disease is the subject of intense debate. Conflicting studies in the last few years have shown that the use of hormone replacement therapy (HRT) seems to result in either a 20 –30% reduction in heart disease or no reduction at all. However, the most recent studies are showing that estrogen’s effect in reducing cardiovascular disease is not as significant as had been previously believed.

Why the difference in studies?

Observational Studies

Until recently most of our information on the benefits and risks of hormone replacement therapy (HRT) came from observational studies consisting of a group of people who are observed for a long time. Researchers do not assign either a drug or a placebo; they simply monitor selected health patterns of the participants and analyze the results. The "granddaddy" (or in this case "grandmommy") of them all is the ongoing Harvard Nurses’ Health Study, which has been following 120,000 nurses since 1976. The participants, my mother is one of them, fill out questionnaires every two years about their lifestyle and health.

The use of such a large number of people in the Nurses' Health Study gives weight to its conclusions. However, these studies have limitations because the researchers can’t randomly assign a control group (a group getting no treatment). This particular study has been criticized for its "healthy women bias"--nurses tend to be more educated, wealthier, and have healthy life-styles, all of which have been associated with a lower incidence of cardiovascular disease. The most current results (August 2000) of the Nurses' Health Study showed that HRT caused a 9% reduction in cardiovascular disease; however, greater results were obtained with lifestyle choices--a 16% reduction with diet improvements and a 13% reduction with decreased smoking.

Controlled Studies

These studies are expensive to conduct and are usually much smaller and shorter, but they are considered the "gold standard" of studies. In the best of these studies, people are chosen at random and neither the patients nor the researchers know who has been assigned the drug or placebo.

Two of these controlled studies have cast doubt on the degree of estrogen’s beneficial effect in reducing cardiovascular disease. In 1998, the HERS study looked at 2000 women who already had cardiovascular disease and concluded that HRT did nothing to reduce the incidence of deaths in those who already had the disease. Many researchers thought that the addition of progestin (medroxyprogesterone/Provera) in this study may have prevented any benefit. In August 2000, the results of a three-year study of 300 women (some of whom did not take a progestin) showed that even estrogen alone did not slow the progression of cardiovascular disease. The most recent study, the Women's Health Initiative (July 2002), has also questioned HRT's benefit to the heart. It now appears that your decision to take HRT should not be based on heart benefits.

The conflicting results between the observational and controlled studies might be explained by the fact that estrogen has mixed effects on the cardiovascular system:

Estrogen’s Heart Benefits

Oral estrogen has been shown to have a very positive effect on cholesterol--increasing HDL ("good" cholesterol) and decreasing LDL ("bad" cholesterol). It is uncertain whether estrogen patches and creams will provide the same amount of cholesterol benefit because they are metabolized by the body differently.

Estrogen’s Heart Risks

Estrogen may promote clotting, which is a factor in both heart attacks and stroke. It will also raise the levels of a substance called C-reactive protein, which is associated with increased inflammation in the arteries and may be a major risk for heart disease. Ask your primary care provider to perform this inexpensive blood test on your next visit.

So what should you do?

From what we know now, for those women who already have a an established case of heart disease, HRT offers no benefit; for those women at risk of developing heart disease, HRT should not be the primary preventative measure. Diet, smoking cessation, and exercise have been shown to be more effective as primary measures. Medication may be added to control high blood pressure and cholesterol when lifestyle changes are ineffective.

Progesterone Benefits

HRT should not be considered as a primary treatment for high cholesterol. There has been recent interest in the use of micronized progesterone (often referred to as natural progesterone) as the progesterone compound of choice for those women with high cholesterol who are taking HRT. A major study has shown natural progesterone to be superior to the synthetic medroxyprogesterone ( Provera) because it does not reduce estrogen’s cholesterol benefit. (Note: Progesterone compounds are needed to offset estrogen’s negative effect on the uterus.)

What are you needs?

Ask yourself:

Do you have a family history of cardiovascular disease?
Do you have high cholesterol?
Do you have high blood pressure?
Do you smoke?
Do you have diabetes?
Are you obese?

Additions/Alternative to HRT-

Lifestyle Changes

Diet, exercise, and smoking cessation should be the cornerstone of any therapy to prevent cardiovascular disease. These lifestyle changes have a more significant effect on cardiovascular health than HRT--with little risk of side effects. Lifestyle changes also have a profound effect on almost every other disease state that HRT helps.

Supplements

Antioxidants are the most studied supplements in preventing cardiovascular disease. Although currently subject to debate, vitamin E and coenzyme-Q10 seem to be the most beneficial. However, instead of the "supplement du jour" for heart health, it is usually best to try to eat a wide variety of fruits and vegetables (5-7 servings a day) before adding supplements.

Prescription drugs

Estrogen has a beneficial effect on cholesterol levels but prescription cholesterol-lowering agents are much more effective. Estrogen is not effective in controlling high blood pressure, so prescription medication may be needed. Again, lifestyle changes may prevent the need for both of these types of medications.

Benefit to Risk

The benefit to risk ratio of HRT and cardiovascular disease is a subject of much debate. Yet, there is little debate about the benefits of lifestyle changes, so these and other risk factors such as high blood pressure, high cholesterol and diabetes should be addressed first.

The current statistical consensus on the use HRT for cardiovascular disease for those women with no increased risk of breast cancer:

The risks probably outweigh the benefits:

~for those women who do not already have cardiovascular disease but are at an increased risk. For now, risk of cardiovascular disease should probably not be the primary reason for taking HRT. If you are taking estrogen for some other purpose such as osteoporosis, the long term use of HRT may possibly be beneficial for your heart.

No evidence of benefit:

~for those women who already have cardiovascular disease. However, if you already have cardiovascular disease and have been on HRT for more than a year, it may better to continue until newer studies clarify the benefit of long term use.

Helping Vaginal And Urinary Health

Approximately one-third of women over fifty years old experience some vaginal or urinary tract problems as a result of menopause.

Estrogen deficiency can result in vaginal dryness and painful intercourse. It can also affect the bladder causing urination to become more painful, frequent, and urgent. One of the more common symptoms is stress incontinence--urinary leakage under simple physical stress such as sneezing, laughing, coughing or sudden movement. Recurrent urinary tract infections may also be a problem.

Estrogen has been shown to be very effective in relieving many of these symptoms. However, it does not relieve all types of incontinence because some may be due to mechanical or neurological problems.

If vaginal or urinary tract problems are the only symptoms of menopause that need treatment, low-dose topical therapy can be instituted that does not require the addition of progesterone to balance the stimulatory effect of estrogen on the uterus.

Premarin and Estrace vaginal cream have been used for years, but there is an increasing trend towards newer products. Estring is a vaginal ring that is inserted (much like a diaphragm) and releases low-dose estradiol over a period of 90 days. Estriol vaginal cream is formulated only by compounding pharmacies and is one of the most widely sold products in Europe under the name Ovestin. Estriol offers women one of the lowest doses of estrogen to control uro-genital symptoms.

If you are already on oral or transdermal (patch or cream) estrogen, you may not need to use the vaginal preparations.

What are your needs?

Ask yourself:

Am I experiencing vaginal dryness or painful intercourse?
Am I having "bladder problems" such as painful and frequent urination or stress incontinence?

Additions/Alternatives to HRT

Vaginal moisturizers
A variety of vaginal moisturizers are on the market in both gels and suppositories. It is important to choose one that is water-based because products with excessive oils may disrupt the natural balance of the vagina.

Soy products
There is conflicting evidence as to whether oral soy supplementation may be helpful in controlling vaginal dryness. It may have other benefits, so there is little harm in trying it.

Vitamin E
Although there are no studies to confirm its effectiveness, many women have reported success using oral vitamin E 400 IU daily for vaginal dryness. Other women have reported success using it vaginally, by first puncturing the end of the capsule before insertion. Like soy, it may help in the prevention of other diseases, so there is little harm in trying it.

Kegel Exercises
These exercises should be the first choice of treatment for stress incontinence. They tone the bladder and the vaginal area and have proved very helpful for many women.

Benefit to Risk

The dose used in topical vaginal treatment is usually very low, so the benefits clearly are greater than the risks. With most of the creams, their use can be reduced to just several times a week after the first few months. This reduces the body’s exposure to estrogen even further.

Helping Moods And Cognitive Function

There is considerable evidence that estrogen has a positive effect on mood and cognitive function (memory and thinking processes). Although, there is a debate as to the degree of help that estrogen provides.

Mood

In general, estrogen’s greatest effect on mood is seen in perio-menopause (those few years just before menopause) when hormone levels are very irregular. Because perio-menopausal women are still menstruating, there is often no need for the addition of progesterone to balance the stimulatory effect of estrogen on the uterus.

Clinical depression and panic attacks do not seem to be related to menopause, so estrogen would not be the drug of choice for their treatment in post-menopausal women.

Memory

When it comes to short term memory, the benefits of estrogen are not conclusive. The same is true of cognitive function. Some studies show an improvement in verbal domains but not in numerical or spatial domains. Other studies show no improvement at all.

Alzheimer's Disease

The most evidence of estrogen having an effect on cognitive function is in preventing Alzheimer’s disease. The benefits seem to be proportional to the length of time on estrogen. However, a recent study revealed that there appears to be no benefit in estrogen treatment for someone who already has Alzheimer’s.

HRT Therapy

Any benefit of estrogen on mood may be offset by the progesterone compound that most women need to take along with the estrogen. When this progesterone compound is the synthetic progestin Provera (medroxyprogesterone), it tends to eliminate much of the benefits on mood. Micronized or natural progesterone does not seem to have the amount of mood problems as that of synthetic progestins.

We will learn much more about estrogen and cognitive function in five years when the second phase of the Women’s Health Initiative Study is published.

What are your needs?

Ask yourself:

Are you having mood swings during perio-menopause?

Do you have a family history of Alzheimer’s?

Additions/alternatives to HRT

Alternatives treatments for mood swings could be a Web site in itself. Stress reduction techniques, cognitive therapy, and yoga are but a few of the many useful activities to help with mood swings. When dealing with short-term memory loss, it is important to realize that we all experience this to some degree as we age. Try to focus on the many things you remember instead of the few you forget.

Supplements may be of some help for cognitive function. St. John’s wort has been shown to be effective in mild depression, although prolonged depression should always be treated by a professional. Kava has some benefit as an anti-anxiety agent. Valerian can help with sleep. Although gingko has been shown to help with memory loss, its benefits seem to be greater in older people who have lost some blood flow to the brain.

Benefit to Risk

Based on current statistics, when HRT is used for mood or memory:

The benefits are probably greater than the risks:

If you are in perio-menopause and experiencing mood swings.

If you are post-menopausal and having cognitive problems and are using HRT for less than 5 years.

The benefits are possibly greater than the risks:

If you are post-menopausal and have an immediate family history of Alzheimer’s disease.

The risks are probably greater than the benefits:

If you are postmenopausal and using HRT to treat memory and cognitive functions for longer than 5 years..

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Endometrial Disease

Although estrogen doesn’t cause cancer directly, it does set up the body for a pre-cancerous condition, and it does stimulate cancer that is already present. This effect was first seen decades ago when estrogen was given without an opposed progesterone compound; the unopposed estrogen caused an 8-fold increase in cancer of the endometrium (the lining of the uterus).

The addition of progesterone is generally thought to eliminate the risk of endometrial cancer. However, a few studies have indicated that long cycle HRT regimens, where progesterone is only used every 3 months, may not offer complete protection.

Progesterone is added (or opposed) to estrogen to eliminate the risk of endometrial disease. Women who have had a hysterectomy do not need opposed estrogen for this purpose. There is some debate whether a small amount of micronized natural progesterone might be useful in these women to increase bone density.

Other risk factors for endometrial disease include:

Obesity

20 - 50 pounds overweight increases the risk 3-fold.
Over 50 pounds overweight increases the risk 19-fold.

High blood pressure and diabetes

These both increase the risk 3-fold, although some of this may be due to the fact that obesity often accompanies these diseases.

Breast Cancer

Numerous studies confirm that a woman’s greatest fear of hormone replacement therapy (HRT) is breast cancer. Contrary to what many women believe, breast cancer as a cause of death ranks below other cancers, heart disease, stroke, and osteoporosis.

Statistical Risk

Many women are aware that the lifetime incidence of breast cancer is 1 in 8. However, this statistic reflects a life-time risk. When the risk is adjusted by age, it is quite different--1 in 77 in your forties, 1 in 42 in your fifties, and 1 in 45 in your eighties.

Until women reach their mid-fifties, death from breast cancer is greater than from heart disease. After these years, heart disease deaths rise dramatically and breast cancer deaths decrease. The leading cause of cancer death in post-menopausal women is actually lung cancer.

Women may be justifiably fearful of breast cancer because everyone seems to know a woman who in the prime of her life has had breast cancer. This fear must somehow be balanced with the facts of its relative risk. But to put that fear in perspective, men die at a much earlier age than women but undoubtedly would give the same pause to a therapy that could be beneficial in increasing their life-span but that involved a slight increase in the relative risk of testicular cancer.

HRT and Breast Cancer

There are conflicting studies regarding the related risks of HRT to breast cancer. The news media tends to report any study regardless of its size or significance. Several years ago in the same week, two studies about HRT were covered in the news that had opposite conclusions, confusing the issue even further.

When all of the major studies are looked at together in a meta-analysis, it appears that there is an approximate 20-30% increase in the relative risk of breast cancer for each 10 years of HRT use. This means that a woman in her 60’s on HRT for 10 years would have a 1 in 29 risk instead of a 1 in 36 risk of developing breast cancer.

Recently, one study suggested that an estrogen/progesterone compound combination increased the risk even further. It must be noted that this study used the estrogen Premarin in higher dosages than may now be recommended. Also, the progesterone compound used was the synthetic medroxyprogesterone (Provera). No study has examined whether micronized natural progesterone would prove to be any safer.

The results of the large scale Women's Health Initiative study (July 2002) confirmed some of the earlier studies showing a 24 per cent increase in the breast cancer rate for those taking the combination of Premarin (equine estrogen) and Provera (synthetic progestin) for longer than 5 years. For those women who had a hysterectomy and were only taking Premarin, there was no increase in the breast cancer rate. This most recent study has lead many to use micronized natural progesterone instead of Provera in those women who have a uterus.

HRT users who do develop breast cancer tend to get a less invasive and more treatable cancer, and some studies even show a lower death rate in HRT users. It is not clear if this is due to the estrogen itself or due to the "healthy woman bias" producing an earlier detection--women taking HRT generally choose healthier lifestyles, dieting, exercising, not smoking, and having regular medical check-ups.

Other risk factors for breast cancer include:

Lifetime Exposure to Estrogen

Early menstruation, late menopause, and never having been pregnant have been shown to increase your risk for breast cancer.

Family History

A mother or sister with breast cancer doubles your risk. If you have had an estrogen dependent breast cancer or family history of one, you are not a good candidate for HRT. If you have had a non-estrogen dependent breast cancer or family history of one, some primary care providers are now considering short-term symptomatic treatment when alternative treatments have failed.

Alcohol Consumption

There is a strong correlation between heavy alcohol use and increased breast cancer risk. You will be hearing a lot about this in the coming years. A recent study has shown that having 1 drink per day results in a 9% increase in breast cancer and that 2-5 drinks per day results in a 41% increase. This is a greater increase than associated with HRT use. The degree to which excessive drinking while on HRT further increases the risk of breast cancer is not known. (One drink = 1 oz of alcohol, 4 oz of wine or 12 oz of beer).

Lower Body Weight

A large study has shown that women with lower body weight on HRT tend to have higher rates of breast cancer, although it is not precisely known why. Paradoxically, this is the same group that may be at a higher risk for osteoporosis.

Regardless of your decision concerning HRT, it is a good idea to do regular breast self-exams, to have mammograms (the starting age and frequency are still a matter of debate), and to limit alcohol intake to reduce your chances of breast cancer.

Circulatory Problems

Blood Clots

Although hormone replacement therapy (HRT) has been shown to have a positive effect on blood vessel elasticity, several studies in 1996 showed that HRT caused an increase in blood clots. Specifically, there was a 2 to 4-fold increase in phlebitis (inflammation and clots) in the veins of the legs and a 2-fold increase in pulmonary embolism (a potentially fatal situation when a blood clot travels to the lungs).

Blood clots are relatively uncommon and are not a problem for most women using HRT. However, special consideration is given for those who have had a history of such problems. There is a debate about what kind of clotting history precludes the use of HRT.

Factors that are taken into consideration include: frequency of episodes of clotting problems, degree of symptomatic treatment required, whether the woman smokes, and risk factors of other diseases.

Most of estrogen’s clotting effects occur after liver transformation. Because transdermal (patch or cream) estrogen bypasses this transformation, this form probably would be a better choice for women at risk of circulatory problems. The addition of progesterone seems to have little effect on clotting.

Birth control pills have a dose-related increased risk of clotting problems. The new low-dose pills have significantly reduced this risk. It is probable that low-dose estrogen in HRT would do the same. It is important to note that smoking greatly increases the risk of clotting problems with any type of oral estrogen therapy.

High Blood Pressure

It was once believed that women with high blood pressure were not good candidates for HRT. That belief changed after a large study showed that the majority of women had no problems with high blood pressure while on HRT.

Still, a small percentage of women (about 1 in 20) will experience a rise in blood pressure once oral HRT is initiated. Oral estrogen may cause the kidneys to release substances that increase blood pressure, so women whose blood pressure is elevated by HRT would likely benefit most from transdermal estrogen.

Gallbladder Disease

Estrogen has a direct effect on bile metabolism. Even women who do not take estrogen have more gallbladder attacks then men.

Gallbladder disease is not life threatening or relatively common. However, women with a history of gallbladder attacks may not be good candidates for oral estrogen, which doubles the normal risk of attacks.

Transdermal estrogen bypasses the liver, which is responsible for bile production, so estrogen in patch or cream form may offer an alternative for those women at risk.

Other factors that increase gallbladder disease risk include:

Family history
Obesity
High-fat diet