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Life Stages

Everything we know about menopause and hormone replacement therapy (HRT)

The history of HRT is controversial. Here is the latest research.

by Nicole Telfer, Science Content Producer Reviewed by Maegan Boutot, Science Writer for Clue
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Top things to know:

  • Hormone replacement therapy (HRT) is used to treat some symptoms of perimenopause and menopause, like hot flashes and night sweats, and usually involves some sort of synthetic estrogen and progestin

  • Initial results from a major study found substantial increased risk of developing cardiovascular disease and breast cancer from oral HRT —but later analyses found the relationship wasn’t so clear cut

  • Data from new studies suggests that these risks vary by age and when you use HRT

  • Many healthy women who have recently entered perimenopause can safely use hormone replacement therapy to treat hot flashes and night sweats

Editor’s note: Hormone replacement therapy (HRT) is controversial, so we wanted to be extra clear. Clue did accept sponsorship funding to pay the writers, editors, and fact checkers who produced this article. But the sponsor has no say in any part of this content—the idea was ours, the research was ours, and the finished product is all ours. Our goal is to give you unbiased, evidence-based information that can benefit your life. We do not endorse using HRT or one therapy over another—that choice is up to you and your healthcare provider. 

What is Hormone Replacement Therapy (HRT), and which hormones does it include?

Hormone replacement therapy (HRT) is used to help treat and relieve some symptoms of perimenopause (the menopausal transition) and menopause (when your periods have stopped), like hot flashes and night sweats (1). 

HRT involves “adding back” hormones like estrogen (and often a progestin too) to relieve the symptoms of menopause. 

HRT is often available in many forms, depending on the treatment goal. These forms include: pills, patches, gels, sprays, or creams (1,2). We’ll focus exclusively on the use of oral hormone therapy pills, which have been the most controversial. 

The hormones in oral HRT depend on whether or not a person has had a hysterectomy. For people with a uterus, HRT usually contains both a synthetic estrogen and a progestin. Estrogens stimulate the endometrium (the lining of the uterus) to grow into a thick layer (3). Since this layer is usually shed during one’s period, the endometrium of those who do not experience periods can potentially be stimulated to grow continuously under the influence of estrogen therapy, which is a risk factor for endometrial cancer (4). Adding progestins into a formula prevents the endometrium from building up too much. 

If a person has already had a hysterectomy—meaning that they no longer have a uterus—then they can take estrogen therapy without progestins (1). 

But HRT is no longer popular. Here’s why. 

HRT has been prescribed to treat symptoms of perimenopause and menopause since the 1940s. In the 80’s and 90’s, observational research on HRT suggested that HRT might also be beneficial for heart health (5,6). 

These results seemed to indicate that women could use HRT to lower their risk of coronary heart disease, to lengthen their lives, and to improve their health overall. In order to test this theory, researchers in the United States conducted a large ranging study of the effects of HRT called the Women’s Health Initiative (WHI) (6). 

But early results from the study demonstrated an association between the use of HRT and an increased risk of heart disease—contrary to what researchers hypothesized. They also found a higher risk for breast cancer and stroke among oral HRT users (6-8). The trials were stopped and, after the initial results were published, the popularity of HRT plummeted. 

Why the early studies on HRT aren’t clear cut  

The initial conclusions, while concerning, aren’t as clear cut as researchers thought. Here’s why.

The trials didn’t make a distinction between age groups or how many years subjects were from entering menopause. 

  • Newer analyses of the same data from the WHI found that the treatment did not cause an increase in coronary heart disease in women who used HRT within 10 years of menopause (6,9,10).

  • There was even suggestion that HRT may prevent heart disease for this population, as the early observational data suggested, though these numbers were not strong enough to draw a definitive conclusion (9,10). 

The trials did not consider whether subjects had previously received HRT, before beginning the study (6).

The trials did not take into account what type of HRT subjects were using, or whether or not they had had a hysterectomy (6). 

  • Initial WHI reports claimed that the results from their study were applicable to all people using all forms of HRT; however, these initial results really only applied to a specific form of HRT that contained a specific estrogen and progestin. Estrogen-only HRT seems to affect the body differently than the combined form of HRT, and there are other forms of combined HRT that the results don’t necessarily apply to, given that there are many forms of estrogen and progestins (6).

  • Further, the estrogen-only HRT trials focused on women with hysterectomies, whose risk of developing breast cancer and heart disease from the treatment were not found to be as high. These trials continued for another two years (6). 

The media also played a role in misrepresenting data to the public. While the study found a 24% increased risk of breast cancer linked to HRT use, some outlets incorrectly reported a 24-fold increased risk—the equivalent to 2,300% increased risk (6, 11).

Current opinions on HRT

Now, almost 20 years since the WHI trials, more studies have been conducted and researchers better understand the impact that a person's age, the timing of HRT use, and type of HRT have on the health benefits and risks of HRT. 

Accepted Benefits of Oral HRT

  • Relief of hot flashes and night sweats (1,6)

  • Prevents osteoporosis and bone fractures (1, 6, 12) (1,6,14)

Possible Benefits of Oral HRT 

  • Reduction of depressive mood, irritability, and sleep troubles (6)

  • Lower risk of death due to coronary heart disease in younger women (primarily those close to menopause and/or younger than 60) especially with treatments containing only estrogen (6,7,13)

  • Lower risk of all-cause death (5,6,9) for younger women (60 years or younger) and/or for those beginning treatment within 10 years of menopause 

  • Decreased risk of colon and rectal cancer (6,8,11,14) 

  • Lower risk of invasive breast cancer for women who have had a hysterectomy and use treatments that contain only estrogenhowever, the results are mixed and some studies show the opposite association (6,15,16)

Risks of Taking Oral HRT

  • Breast tenderness, bloating, changes in mood, increases in blood pressure, and uterine bleeding (6)

  • Increase in risk of coronary heart disease in women older than 60, as well as in younger women with established coronary heart disease or elevated cardiovascular risk, particularly in the first two years of use (6)

  • Increased risk of stroke by about a third (6,17,18) 

  • Doubled risk of developing a blood clot, just like with oral contraceptives. This risk decreases with time (6).

  • Risk of breast cancer is slightly increased for those using treatments combining estrogen and progestin (6).

  • Increased risk of uterine cancer is associated with treatments containing only estrogen, in women who have not undergone a hysterectomy (6).

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Should I take HRT?

If you are experiencing negative effects of menopause at the onset of your transition, and are low risk for coronary heart disease and breast cancer, then HRT may be right for you. 

Other forms of HRT, like vaginal estrogen, can be used directly in the vagina as a cream or tablet, and do not impact cardiovascular or breast cancer risk (21). 

While there is some evidence indicating that HRT may be useful for decreasing the risk of death, coronary heart disease, and osteoporosis, the treatment is not currently recommended for this use (22). 

New research surrounding HRT is constantly being published, so speak to your healthcare provider to learn more about your risks, as well as other treatment options, that might be better for you.

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