Mark Seigel, MD, FACOG

As women transition into menopause there is a gradual but steady decrease in ovarian hormones. This can cause a wide range of symptoms that can negatively affect daily activities and hurt the quality of life. Many women who are near menopause would have few dangers from receiving hormone replacement therapy (HRT), and for many the benefits outweigh the risks of taking them. Yet there are questions about the safety of taking hormones. Who should take them and who not?

There have been significant developments since the Women’s Health Initiative (WHI) report came out in 2002 and changed our beliefs in the value of hormone replacement therapy. The WHI was focused on heart disease, and some 70% of the women in the study were older than age 60. Women who were having menopausal symptoms were not allowed to be in the study, which may have biased the results. The results were mainly negative, and showed that HRT did not give a benefit in reducing heart disease. This caused skepticism about whether hormone therapy could ever be used safely. Now, years later, we can say that there was a mistake in interpretation by trying to extrapolate and apply the results to all women. Further information that has come out since the WHI report was published has shown that women in their 50’s who start HRT near the time of menopause have fewer cardiovascular problems and fewer deaths in general, compared with those who start HRT years later. This can be thought of as a window during which time therapy, if started, is safer. Even better, it has recently been confirmed that women who took only estrogen had a lower risk of getting heart disease, a lower chance of getting breast cancer, and a lower risk of colon cancer.

Here’s what recent research says about which women should be taking hormone replacement therapy:

Hot Flashes and related symptoms. About 70% of women who are going through menopause suffer from hot flashes, night sweats, dryness, difficulty in sleeping and other problems. In 20% of women the problems are serious enough to disrupt productivity and harm the quality of life. Estrogen is the best treatment for these symptoms. Studies have shown it can increase the production of neurotransmitters that improve mood, memory, attention, sleep and response to pain. If women can’t or don’t want to take hormones there are alternatives. There can also be relief from lifestyle changes such as avoiding too much caffeine or alcohol; increasing the amount of time spent exercising is very helpful.  Other medications to prevent bone loss are available, and for vaginal dryness a lubricant can be beneficial. But for women who are taking multiple medicines, it doesn’t make sense to take an antidepressant, a sleep aid and an anti-anxiety pill to do what estrogen alone can do better at less cost and with fewer side effects.

Breast Cancer. This is the biggest fear and the greatest reason that women avoid hormone therapy. The numbers tell a different story. The increase in risk is actually very small. In the group of women who take an estrogen with a progestin, the risk of breast cancer death is 2.6 per 10,000 women per year, compared with 1.6 women per 10,000 per year in the group taking no medication. Women in the group taking only estrogen had a 63% lower risk than the group on no medication, leading to consideration that the main risk is not estrogen, but may be the progestin ingredient of HRT, medroxyprogesterone. In hormone replacement therapy, the need for a progestin is based on whether or not the uterus is present, as taking progesterone protects against uterine cancer. One conclusion here is that if a woman has had a hysterectomy and thereby does not need progesterone as part of treatment, taking estrogen significantly reduces her risk of breast cancer.

Heart Disease. Observational studies have long shown that women who used estrogen had a lower risk of heart disease, but most were younger than 55 when they started taking the medication. Studies show that estrogen staves off hardening of the arteries but cannot undo the damage once it has occurred. The timing for starting HRT is crucial here. Starting it closer to the menopause increases the cardiovascular benefit.

Stroke. The WHI study showed that both estrogen alone and estrogen with progestin raised the risk of stroke and blood clots. The risks appear to be the same regardless of when the medication is started. Most experts advise avoiding HRT if you are at increased risk of having a stroke or blood clots. If you take it, a lower dose is safer.

Osteoporosis. Considering that 50% of women over 65 eventually develop osteoporosis, some say that this benefit of HRT in preventing osteoporosis has been improperly ignored. Having a fractured hip, getting fractures, or losing height are detrimental and dangerous. There are other medications for preventing osteoporosis, but they all have side effects of their own.

Diabetes. Taking hormones appears to reduce the risk of Type 2 diabetes, by 21% in the estrogen progestin group and by 12% in the estrogen alone group. More research is needed to evaluate this potential new benefit of HRT.

Whether HRT can be safely used is an important question. However, there is no simple correct answer. Many factors determine the correct choice for each person. When considering this question, there are 3 factors that profoundly affect the risk benefit profile for each person: age at initiation of therapy, hormone dose, and route of administration.

Age at HRT Initiation. The beneficial action of estrogen is its ability to prevent harmful deterioration over years that can irreversibly result in bone loss, vaginal and bladder atrophy and reduced skin elasticity. The timing of initiation of HRT is critical. Studies show there is a therapeutic window for starting therapy. If therapy is started before age 60 there is definitely a greater benefit in preserving the normal functioning of many types of tissue including bone, skin, and the urogenital, cardiovascular and nervous systems.

HRT Dosage. A second important influence on the risk benefit profile of HRT is the amount that is given. Substantial evidence exists that a low dose HRT dosage is effective in preventing bone loss and in treating menopausal symptoms with less bleeding and other side effects compared with higher doses. This is especially seen in the risk of stroke, which increases as higher doses of estrogen are used.

Route of HRT Administration. The use of HRT through patches, known as transdermal hormone therapy, has been shown to have a lower risk of venous thromboembolism compared with oral administration. People who are at greater risk of stroke such as those who have cardiovascular disease, multiple cardiovascular risk factors, history of venous thromboembolism, or known increased risk of stroke through genetic causes need to be aware of the lowered risk through transdermal use. Recent studies show that the use of transdermal estrogen does not result in an increased risk of blood clots and stroke, even when used in high-risk patients.

Individualizing HRT Choices. A decision about whether to start HRT should be based on an assessment of the risks and benefits as it pertains to you. Starting HRT in early menopause or peri-menopause is associated with many benefits and low risk. Multiple studies support the protective effect of estrogen therapy on cardiovascular disease, dementia and overall mortality.

Women with an intact uterus are usually given estrogen with progesterone to help protect the uterus from overstimulation. An advantage of using a low dose estrogen is that it can be balanced with a low dose progestin to minimize bleeding and undesirable side effects. In many cases using a transdermal delivery system will minimize the effect of estrogen on the liver, which decreases the production of blood clotting proteins and lowers the risk of blood clots or a stroke. We need to consider contraindications such as a previous history of breast cancer, blood clots or undiagnosed vaginal bleeding. If you meet the proper criteria, your risk-benefit analysis can show that hormone therapy will give many advantages resulting in an improved quality of life. It’s something important to think about and discuss with your health care professional to make the right decision for you.