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 HRT. You 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 therapy.

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 This occurs when the hormones, particularly progestin, are withdrawn from your treatment.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.

Breast pain

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

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 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.

Uterine cancer

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 early stage.

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 HRT.

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.

Breast cancer

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 Women’s 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.

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 gallstones.

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.

Surgery

HRT results in vaginal bleeding and, occasionally, in irregular bleeding, which may make you subject to more endometrial samplings (biopsy), diagnostic curettage, and perhaps even hysterectomy.