Getting Answers After HRT Linked to High Cancer Risk

Oct. 28, 2010 — -- An ongoing Women's Health Initiative study released results last week showing postmenopausal women who took a combination of estrogen and progestin therapy had a higher chance of getting aggressive forms of breast cancer and may even be at a higher risk of death because of the disease.

"World News" asked viewers to respond to the Oct. 19 story and they did in the hundreds.

Below are some of the main questions and concerns about hormone replacement therapy and answers from Dr. Marie Savard, an ABC News medical contributor.

What are some of the alternatives to using HRT?

A number of non-hormone treatments have been tried to treat the vasomotor symptoms (such as hot flashes/drenching sweats) of menopause, including soy foods, the herb black cohash, acupuncture and prescription medications such as the antidepressant Effexor and the anti-seizure medication Neurontin.

Although the prescription medications have been tested in clinical studies and found effective for women, the alternative treatments such as soy foods, black cohash and acupuncture have all been inconsistently effective in most small studies. In my practice, I have found that although nothing works as well as estrogen to manage hot flashes, most women are willing and eager to try a number of these non-hormonal treatments and view taking estrogen as a last resort.

The good news is that for most (but not all) women hot flashes will eventually subside.

How dobio-identicals work? Are bio-identical hormones a safer alternative to use? Are bio-identical better, less dangerous than synthetic hormones?

When the Women's Health Initiative study was stopped because the risks of Prempro were thought to outweigh the benefits, a lot of women turned to "bio-identical" hormones, primarily soy-based hormones made primarily by compounding pharmacies. These hormones purportedly customize the hormone dosages to suit any given woman's needs and thus the term "bioidentical."

The problem with bioidentical hormones is that the preparations mixed by the compounding pharmacists have never been tested for safety or efficacy in large studies and there is no reliable way to test a woman's hormone levels to determine exactly what she needs.

Ironically, proponents of the bio-identicals made by compounding pharmacies often claim that these preparations are safer because they are "natural." That's such a reassuring word but they are still hormones and there's no reason to believe they are any safer than pharmaceutical hormones, which have been subject to rigorous testing.

What advice can you give women who did not have hormone theraphy during menopause, but still got breast cancer, and are now being treated for other cancers with hormone therapy?

Women with a diagnosis of breast cancer or who are at very high risk of breast cancer are usually advised not to use estrogen therapy. Indeed, the hormone treatments such as Arimidex and Tamoxifen work by reducing or blocking estrogen effects in the breast and are therefore often referred to as "anti-estrogen" hormones. They often cause hot flashes and drenching sweats similar or even more annoying than symptoms of natural menopause.

Over-the-counter progesterone cream would generally not be recommended for a woman diagnosed with breast cancer and I am not certain from your question why you are on progesterone cream and how it is helping you. Some women use progesterone cream, which does not require a prescription during the peri-menopausal period (the months to years leading up to menopause; a time when estrogen and progesterone levels can be erratic) to treat the symptoms of hot flashes, irregular periods and mood changes.

Is the risk higher for women of natural menopause as opposed to women of surgical menopause? What is the risk for women who are on Premarin and have had a hysterectomy?

The study reported in the segment was describing only women who had not had a hysterectomy and who were therefore on a combination of estrogen and progestin (Prempro). The Women's Health Initiative (the original research reported in the segment) also studied women with hysterectomies who were taking estrogen only in the form of Premarin.

Women with a hysterectomy do not need progestin, which is solely given to prevent the uterine lining build-up that estrogen can cause. These women taking estrogen only after their hysterectomy did not have an increased risk of breast cancer in the very same study. Indeed, their risk of breast cancer was slightly lower than women on the placebo or sugar pill but not considered statistically significant.

This finding gets much less attention but does lead many physicians to suspect that it is primarily the daily use of the synthetic progestin in the Prempro combination that contributed to the breast cancer risk. Most women, after a hysterectomy (women who have not had cancer), are advised to take estrogen at least up until the age of natural menopause, about 52.

On the other hand, some physicians recommend continuing estrogen for longer as it has been found to reduce osteoporosis and fracture risk and to reduce colon cancer risk, as well. Your physician can help you decide when and if you should taper off estrogen based on your personal and family history.

Alzheimer's and Hormone Replacement Therapy

Has there been any research or studies linking Alzheimer's with lack of estrogen or taking the hormone.

The Women's Health Initiative (WHI), the original research study described in the breast cancer segment, tested the women for changes in their memory and did not find that estrogen protected women from cognitive changes. In fact, women treated with estrogen had more decline in cognitive function rather than placebo.

This was surprising because many researchers suspect that estrogen is important to preserve brain function and estrogen has been shown in small studies to potentially be of benefit to women who take it at the time of menopause. The timing of when estrogen is taken may be important and needs to be studied further.

In the WHI, most women had gone through menopause up to 10 years earlier: the average age of woman was 62. It is therefore possible that estrogen given so long after menopause is no longer effective.

What are the effects of women who are put on estrogen and progesterone because of the early menopause, not because of unbearable symptoms?

Women who go through premature menopause -- whether naturally or because of surgery -- are found to have an increased risk of heart disease and osteoporosis, which is minimized by taking hormones. For that reason, doctors routinely recommend that women with such early menopause take hormones up until the time they enter natural menopause, about age 51.

The dose in hormone therapy after menopause is much lower than the amount of hormones your own ovaries would have made before you entered menopause. Doctors have not found an increased risk of breast cancer in younger women taking birth control pills, which is also a combination of estrogen and progestin.

Are general birth controls pills considered a form of hormone replacement therapy that this study covers?

No. Birth control pills are referred to as oral contraceptive therapy (OCPs). Birth control pills, which contain a different combination of estrogen and progestin than studied in the research study reported (WHI), are given to women who are still ovulating and therefore producing their own hormones as well.

OCPs work by suppressing or preventing ovulation. They have been studied extensively in young women and for the most part have not been found to increase the risk of breast cancer. But because the dose of hormones in OCPs is much higher than in hormone therapy after menopause, women are advised to stop OCPs as they approach menopause, or by age 50 or so.

OCPs are not given to older women and, in view of the much higher dose of estrogen, would not be considered a reasonable choice in postmenopausal women.

How can you stop taking hormones cold turkey?

Although there is no medical reason you cannot abruptly stop hormones, most doctors recommend women gradually taper the dose to minimize the chances that hot flashes and other symptoms return. There is no scientific study that has been done, however, that proves tapering is helpful, so many women stop hormones suddenly without any problems.

There is no generally accepted way to taper off hormones, although simply reducing the estrogen dose in half by taking every other day or asking for a lower dose prescription is one alternative. If your symptoms do not return, you can continue to reduce the dose further or simply stop altogether.

If you are also on progestin, however, you will need to ask your doctor what is the best way to taper it. Depending on how you take progestin and how long you were on it, you may bleed or have some vaginal spotting if you stop the progestin abruptly.

Unfortunately a small percentage of women will continue to have hot flashes many years after menopause.

Estroderm Patch: Is It Safe?

Is the estroderm patch considered unsafe? What if you are using estrogen patch and natural progesterone prometrium? Does this also apply to those who use the estrogen patch, which is considered safer that the oral estrogen, and take prometrium?

The WHI only studied the effect of the oral hormones Premarin (conjugated estrogens derived from horse urine) and Provera (synthetic progestin). Oral hormones are first sent directly to the liver and metabolized. This can lead to a number of systemic effects that have some benefits (improvement in healthy cholesterol) and risks (increased blood clotting and inflammation).

Some European studies have found that the transdermal (through the skin) delivery of estrogen has reduced the risk to almost zero of blood clots to the legs and lungs.

Please tell us the dose of estrogen-progestin used in the study. Is there a low-dose considered safe?

The combination estrogen and progestin called Prempro was used in the study. The dose of Premarin (called conjugated estrogens derived from horse urine) was an average dose of 0.625 mg. The dose of Provera (medroxyprogesterone, a synthetic progestin) dose was 2.5 mg. This combination pill was taken daily by the women who did not have a hysterectomy.

Lower doses of estrogen are available in a pill or patch and gel form. Some research suggests that using a transdermal route (skin patch, cream or gel), which bypasses the liver, may be safer than a pill.

Reduced risk of blood clots with the "transdermal" route has been shown in some research studies and there may be other benefits as well. This needs to be studied further, however, and, for now, transdermal is the primary route I would recommend taking estrogen.

IDoes it make a difference how long you took HRT? How long does a women have to be on the drug before she may get cancer?

Most earlier studies suggested the risk of breast cancer increases only after three to five years of taking estrogen. The results of the recent WHI study suggests the increased risk of breast cancer starts early after a woman begins hormones and that the risk quickly is reduced after she stops hormones.

On the other hand, the overall increased risk of breast cancer from hormones is still considered small, though significant. What is often not discussed is that women who took only estrogen (Premarin) did not have an increased risk of breast cancer.

What about Estradiol and Prometrium? Are these medications considered to be unsafe, too? Which HRTs are dangerous?

The combination estrogen and progestin called Prempro was used in the study. The dose of Premarin (called conjugated estrogens derived from horse urine) was an average dose of 0.625 mg. The dose of Provera (medroxyprogesterone, a synthetic progestin) dose was 2.5 mg. This combination pill was taken daily by the women who did not have a hysterectomy.

But other forms of estrogen such as estradiol have been linked to breast cancer, as well. Prometrium is relatively new and a natural microionized form of progesterone, and not a synthetic progestin, as was used in the study. So we don't yet know if there are any long-term adverse effects to Prometrium, although an important earlier study did show that Prometrium did not cause an adverse effect on blood fat levels and may be more beneficial to heart risk.

What about women who decide to take natural supplements and eat foods with phytoestrogen such as Soy Isoflavones, cold mill organic ground Flax Seed and foods with phytoestrogen? Why has no one mentioned synthetic hormones versus the natural hormones derived from plants?

Alternative treatments such as soy foods, black cohash and acupuncture have all been inconsistently effective in most small studies. Doctors are generally afraid to recommend soy foods, which contain estrogenlike compounds in patients who have had breast cancer, for fear they will have harmful effects.

I have found that although nothing works as well as estrogen to manage hot flashes, many women are willing and eager to try a number of these non-hormonal treatments and view taking estrogen as a last resort. It is true that the hormones used in the WHI study included a synthetic progestin and conjugated estrogen derived from horse urine.

Bio-identical hormones are often referred to as natural hormones. These are preparations that are often mixed by compounding pharmacists and have never been tested for safety or efficacy. Ironically, proponents of the bio-identicals made by compounding pharmacies often claim that these preparations are safer because they are "natural."

That may sound reassuring but they are still hormones and there's no reason to believe they are any safer than pharmaceutical grade hormones, which have been subject to rigorous testing.

Transsexual Women on High Level of Hormones

How does estrogen effecttranssexual women? Especially if the levels are far greater then any non-trans woman has to take during the height of their hormone replacement therapy.

I do not have any direct experience treating transsexual women. But I do understand that the hormone estrogen is important for such women to preserve their bone mass and potentially protect their hearts. I am not sure there is any benefit to taking a synthetic progestin if you don't have a uterus. But the risks from synthetic progestin may be important.

Breast cancer arises both from genetic and environmental causes in both men and women and I would assume that a transsexual woman on very high doses of estrogen may have an increased risk of breast cancer. I just don't know of any study to answer this question.

Is the use of an E-STRING considered HRT?

With the loss of estrogen at menopause, vaginal and urethral tissues become thinner dry and more easily irritated. Unlike hot flashes that disappear in most women, vaginal dryness and pain with sex will continue unless a woman takes some form of estrogen.

The good news is that there are many topical cream gels tablets and even an estrogen coated ring (the E-ring) that can be inserted inside the vagina providing great relief. Although a small amount of estrogen may be absorbed and circulate through the body, the risk from topical estrogen is extremely small and no study has ever linked it to breast cancer.

Are there anti-depressants you reccomend as an alternative?

The anti-depressant Effexor is often used for hot flashes and has been successful for some women. The nerve-stabilizing, anti-seizure drug Neurontin is also used. Both of these medications have side effects but are well worth it for some women. I am sure there are a number of other common anti-depressants that may be successful for some women, too.

Are there certain women who are more at risk for taking the Prempro than others who are not?

The WHI studied women who were much older on average, had gone through menopause 10 years earlier and were not currently having hot flashes. Furthermore, many of these women were overweight or obese. We do know that fat tissue after menopause is a major source of estrogen production and therefore overweight or obese women may have an even higher risk of breast cancer if they take estrogen.

In the observational Nurses Health Study, women who had a large amount of abdominal fat as reflected in waist size well beyond 35 inches were much more likely to have postmenopausal breast cancer. Women who have inherited the BRCA 1 or BRCA 2 gene are also generally advised not to take estrogen.