by Huntsman Cancer Institute

Credit: Pixabay/CC0 Public Domain

For millions of American women, hormone replacement therapy (HRT) has provided relief from side effects of menopause. As the ovaries stop releasing eggs, a woman’s body also stops producing the hormones progesterone and estrogen. This change often affects quality of life due to hot flashes, mood swings, vaginal dryness, and a loss of bone density. HRT replenishes the hormones lost during this process and alleviates the discomfort.

However, many breast and gynecological cancers are driven by changes in hormone levels, leading to widespread fear that HRT increases cancer risk.

“Most breast cancers are ‘fed’ by hormones,” says Cindy Matsen, MD co-leader of the Breast and Gynecologic Cancer Center at Huntsman Cancer Institute and associate professor of surgery at the University of Utah (the U). “Anytime you’re manipulating hormones, there’s going to be effects on breast tissue.”

But does HRT directly affect a woman’s likelihood of getting cancer? Matsen says the answer is complicated.

The Women’s Health Study

Concerns about HRT and cancer first appeared in the early 2000s. The Women’s Health Study, a landmark trial that began in 1993, has followed tens of thousands of women to track the development of heart disease, osteoporosis, and breast and colorectal cancer.

Initial results, published in 2003, suggested the use of HRT led to an alarming risk of breast and uterine cancer. These findings attracted a significant amount of media attention, and patients and physicians quickly moved away from the use of HRT.

In the Journal of the American Medical Association, researchers estimated that doctors wrote 89 million prescriptions for HRT in 2002. The next year—right after the Women’s Health Study results were published—projected use had fallen to 57 million.

Decades later, Matsen says, scientists are revisiting those early results.

“In more recent years, as the researchers have continued to follow these women and analyze the data more critically over time, it turns out that not every HRT regimen increases cancer risk. It’s only specific combined regimens of progesterone and estrogen,” says Matsen. “I do think that the risk has been a bit overblown. Because of that, a lot of women probably suffered.”

Considering the risks and benefits

However, taking HRT in the form of progesterone or estrogen alone is not without drawbacks. Artificial progesterone, known as progestin, can increase breast cancer risk. Taking estrogen alone, while protective against breast cancer, may contribute to the development of uterine cancer.

“We are at odds here. From a breast cancer standpoint, we don’t want women to take progesterone. When it comes to uterine cancer, doctors don’t want women to take estrogen,” says Matsen. “So, it gets very complicated and confusing for people, and it’s really important to have some careful discussions around personal risk.”

Factors to consider are age and family history. Breast cancer, Matsen notes, is also more common than uterine cancer. The American Cancer Society estimates that 310,720 women will be diagnosed with breast cancer in 2024. Their projection for new uterine cancer diagnoses is 67,880—a 128% difference.

Matsen adds that women going through menopause should consider how much they are suffering.

“If you’re going to have terrible side effects from going through menopause, it really may be worth it to go on HRT for a period of time. Usually, doctors will recommend the lowest dose possible for the shortest amount of time possible,” says Matsen. “It’s really a matter of having a careful discussion with your providers about what you’re going through and what might help.”

Those who decide to use HRT should not feel self-blame if they are diagnosed with breast cancer. Matsen says the breasts are influenced by many hormonal changes throughout a person’s life.

“If you get breast cancer, there’s always going to be thoughts of, ‘what could I have done to prevent this from happening?'” says Matsen. “And in the end, we can’t know for sure. What I generally tell people is to make the best decision you can based on the information you have at the moment. Cancer doesn’t happen just because you took HRT. There is no personal responsibility for people who get breast cancer.”

Gender-affirming care

Transgender people who are interested in HRT as part of gender-affirming care should also consider these pros and cons, Matsen says, though there are currently no major studies examining the long-term health effects of HRT on the transgender community.

“In general, anytime you are using any hormone replacement, there is going to be an increased risk of some kind of cancer,” says Matsen. “But I would not deny gender care based on increased risk. It would just be part of the conversation around what the trade-offs are.”

Journal information:Journal of the American Medical Association

Provided by Huntsman Cancer Institute