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Menopause: What are the benefits and risks of long-term hormone therapy?

Created: ; Last Update: August 24, 2016; Next update: 2019.

Even if hormone therapy may offer relief from severe menopause symptoms in the short term, long-term treatment has many serious side effects. This is particularly true for combinations of estrogen and progestin. Although these hormones lower the risk of bone fractures, they increase the risk of other diseases, including cardiovascular disease and breast cancer.

Women’s hormone levels change during menopause. This does not always cause any symptoms, but some women find that things like hot flashes and sweats are such a big problem that they would like to have treatment. One treatment option is hormone therapy with estrogen, or with a combination of estrogen and progestin. Hormones can relieve menopause symptoms.

In the past it was thought that it was a good idea for women to carry on using hormones for years after menopause, to protect them from serious diseases like coronary artery disease, osteoporosis or dementia. But this assumption turned out to be wrong. In fact, large studies have shown that long-term hormone therapy actually increases the risk of some serious diseases rather than decreasing it.

Research on long-term hormone therapy

Researchers from the Cochrane Collaboration wanted to summarize what is known about long-term hormone therapy. To do that, they looked for and analyzed all of the studies in which women had taken hormones or a dummy drug (placebo) every day for at least a year. They found a total of 23 studies involving almost 43,000 women. In most of the studies the women were about 60 years old on average. So most of the women were post-menopausal. This means they had already gone through the menopause when they took part in the studies.

The majority of the women (about 27,000 women) had participated in a big, two-part U.S. study called the “Women’s Health Initiative Study” (WHI). In that study, one group of women took either estrogen alone or a combination of estrogen and progestin. The other group took a dummy drug (a placebo).

The advantages and disadvantages of hormone therapy

After analyzing and summarizing the results of the studies, the Cochrane Collaboration found that hormone therapy both with estrogen and estrogen-progestin combinations led to a number of disadvantages over time. Because estrogens stimulate the growth of the membranes lining the womb when taken alone, taking estrogens alone is only an option for women who have had their womb removed (a hysterectomy).

The following tables show how common certain medical conditions were in women who had taken hormones after menopause. For comparison, they also show how common those medical conditions were in women who took a placebo instead of hormones. Because the figures are different for hormone therapy with estrogen alone and hormone therapy with an estrogen-progestin combination, the results for each form of hormone therapy are shown in separate tables. The figures are mainly based on the results of the Women's Health Initiative Study. They are averages – the risk for individual women could be somewhat higher or lower.

Estrogen and progestin combination products

Table: Advantages - After about five years of hormone therapy:

Medical condition Frequency when taking an estrogen-progestin drug Frequency without hormone therapy (placebo)
Bone   fractures 86 out of 1,000 women 111 out of 1,000 women

Some analyses of the studies also suggest that hormone therapy could lower the risk of bowel cancer somewhat.

Table: Disadvantages - After one year of hormone therapy: 

Medical condition Frequency when taking an estrogen-progestin drug Frequency without hormone therapy (placebo)
Heart attack 4 out of 1,000 women 2 out of 1,000 women
Blood clots in the legs and/or in the lungs (thromboembolism) 7 out of 1,000 women 2 out of 1,000 women

 Table: Disadvantages - After about five years of hormone therapy:

Medical condition Frequency when taking an estrogen-progestin drug Frequency without hormone therapy (placebo)
Stroke 19 out of 1,000 women 14 out of 1,000 women
Breast cancer 23 out of 1,000 women 19 out of 1,000 women
Gallbladder problems that require surgery 27 out of 1,000 women 16 out of 1,000 women
Blood clots in the legs and/or in the lungs (thromboembolism) 20 out of 1,000 women 10 out of 1,000 women

If women take a combination of estrogen and progestin for longer than five years, their risk of breast cancer will probably stay higher even after they stop hormone therapy. One analysis showed that women who have long-term hormone therapy are somewhat more likely to die of lung cancer. Hormone therapy also increased the risk of developing dementia in women over the age of 65.

Estrogen products

 Table: Advantages - After seven years of hormone therapy:

Medical condition Frequency when taking estrogen Frequency without hormone therapy (placebo)
Bone fractures 102 out of 1,000 women 140 out of 1,000 women

Table: Disadvantages - After two years of hormone therapy: 

Medical condition Frequency when taking estrogen Frequency without hormone therapy (placebo)
Blood clots in the legs and/or in the lungs (thromboembolism) 5 out of 1,000 women 2 out of 1,000 women

 Table: Disadvantages - After seven years of hormone therapy:

Medical condition Frequency when taking estrogen Frequency without hormone therapy (placebo)
Stroke 32 out of 1,000 women 23 out of 1,000 women
Gallbladder problems that require surgery 48 out of 1,000 women 27 out of 1,000 women
Blood clots in the legs and/or in the lungs (thromboembolism) 21 out of 1,000 women 16 out of 1,000 women

The risk of breast cancer and heart attacks was not higher in women who only took estrogen.

Over the long term the harms outweigh the benefits

The large WHI Study was stopped early, when it became clear that the treatment was doing more harm than good. Hormone therapy with estrogen-progestin drugs was stopped after about five years, and hormone therapy with estrogen alone was stopped after almost seven years. The researchers stayed in touch with the women for several years after they stopped taking hormones. They wanted to find out whether women who had taken hormones for several years were still affected by the medication after they stopped taking it.

The research thus far suggests that hormones should not be taken for a long period of time. Hormone therapy should be used to treat menopause symptoms such as hot flashes for as short as possible and at the lowest possible dose, if at all.

Sources

  • Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2012; (7): CD004143. [PubMed: 23208255]
  • IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

    Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. We do not offer individual consultations.

    Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

© IQWiG (Institute for Quality and Efficiency in Health Care)
Bookshelf ID: NBK279308

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