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

Photo of a woman outdoors (PantherMedia / andersonrise)

Hormone therapy can offer temporary relief for severe menopause symptoms. But long-term use of hormones 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 doesn't necessarily cause problems in all women. Some women, though, find that symptoms like hot flashes, sweats or mood swings are such a big problem that they'd 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 taking 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. On the contrary: Large studies have shown that long-term hormone therapy increases rather than lowers the risk of some serious diseases, including strokes, heart attacks and blood clots in the legs or lungs (thromboembolism).

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 22 studies involving more than 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.

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 progestogen. The other group took a dummy drug (a placebo).

The advantages and disadvantages of hormone therapy

The analysis of the studies produced by 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.

The following tables show how common certain medical conditions were in women who had taken hormones after menopause. For comparison, the tables also show how common those medical conditions were in women who took a placebo instead of hormones. Because the numbers 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 numbers are mainly based on the results of the Women`s Health Initiative Study. They are only averages. This means that a woman’s individual risk will depend on her own individual circumstances, and could be higher or lower.

Hormone therapy with estrogen-progestin drugs

Table: Advantages - After five and a half years of hormone therapy:

Medical condition

Frequency when taking an estrogen-progestin drug

Frequency without hormone therapy (placebo)

Bone fractures

87 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 - During treatment

Medical condition

Frequency when taking an estrogen-progestin drug

Frequency without hormone therapy (placebo)

Heart attack

After one year

After two years

After four years

 

4 out of 1,000 women

9 out of 1,000 women

11 out of 1,000 women

 

2 out of 1,000 women

6 out of 1,000 women

8 out of 1,000 women

Thromboembolism

After one year

After two years

After five years

 

7 out of 1,000 women

9 out of 1,000 women

20 out of 1,000 women

 

2 out of 1,000 women

3 out of 1,000 women

10 out of 1,000 women

 Table: Disadvantages - During treatment

Medical condition

Frequency when taking an estrogen-progestin drug

Frequency without hormone therapy (placebo)

Stroke

After three years

After eight years

 

8 out of 1,000 women

19 out of 1,000 women

 

6 out of 1,000 women

14 out of 1,000 women

Breast cancer

After five years

After eight years

 

24 out of 1,000 women

33 out of 1,000 women

 

19 out of 1,000 women

26 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. Also, one analysis showed that women who have long-term hormone therapy are more likely to develop dementia.

Hormone therapy with estrogen alone

 Table: Advantages - After seven years of hormone therapy:

Medical condition

Frequency when taking estrogen

Frequency without hormone therapy (placebo)

Bone fractures

103 out of 1,000 women

141 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

24 out of 1,000 women

Thromboembolism

After two years

After seven years

 

5 out of 1,000 women

21 out of 1,000 women
 

2 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.

Long-term treatment does more harm than good

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 five and a half years, and hormone therapy with estrogen alone was stopped after almost seven years. The researchers stayed in touch with the participants 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 had stopped taking it.

Research so far does not support the preventive use of hormones. It’s a good idea to talk to your doctor and carefully weigh the pros and cons if you have severe menopause symptoms. If you decide to use hormones, the treatment should be as short as possible and at a low dose.