Emerging Consensus on HRT Suggests the Benefits Far Outweigh the Risks

For years, doctors have generally avoided prescribing hormone replacement therapy (HRT) for premature menopause resulting from surgery for uterine or ovarian cancer.

Such therapy, many believed, could cause a relapse or even invite breast cancer.

But the taboo of prescribing hormone replacement therapy for cancer survivors is giving way to mounting evidence that HRT is not only safe and effective in many cases—but it could also save lives.

Menopause itself can endanger women. According to a 2020 study published by the journal Pathology & Oncology Research, if left unchecked, menopause can decrease life expectancy by years—about 2 for every 17 of menopause—by compromising bone and heart health through hormone deficiency. Additionally, a 1996 study in The Lancet found every year menopause is delayed, the risk of death from heart disease decreases by 2 percent.

"Denying HRT 'just to be on the safe side' is unacceptable," stated the authors of the Pathology & Oncology Research article.

Helping breast cancer patients

Hormone replacement therapy comes in systemic form—pills, skin patches, gel or cream, rings, spray foam—and low-dose, including vaginal creams, tablets and rings.

Just as with ovarian and uterine cancer survivors, breast cancer patients can benefit from hormone replacement therapy because they, too, can lose estrogen and experience symptoms of menopause—theirs as a result of chemotherapy.

But, just as HRT had long been taboo for ovarian and uterine cancers, this was also the case for breast cancer survivors because estrogen can fuel the growth of breast tumors. Prescribing HRT to breast cancer patients can be tricky, depending on estrogen and progesterone receptor status, and some people suffering from breast cancer would not be a candidate for HRT. However, doctors are now finding that in some cases, estrogen therapy can help control metastatic breast cancer. A daily dose of estrogen stopped the growth of tumors or shrunk them in one-third of women with metastatic breast cancer who had become resistant to estrogen-lowering therapy, according to doctors at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis.

50,000 unnecessary deaths

Much of the concern over hormone therapy can be traced to a 2002 study by the Women's Health Initiative (WHI) that was understood to have found significant increases in heart disease, stroke and breast cancer among women treated with estrogen and progestin.

The report caused HRT use worldwide to drop. Before 2002, estrogen therapy was standard practice for women 50 to 69 who had undergone a hysterectomy. In more than 90 percent of hysterectomies, HRT was used to treat symptoms of menopause and prevent osteoporosis and other diseases related to menopausal hormone deficiency. Today, only about 10 percent of these women use estrogen.

Attitudes toward hormone replacement therapy are now starting to change amid mounting evidence it's relatively safe.

Widespread rejection of estrogen therapy in the 10 years following the WHI report likely led to almost 50,000 unnecessary deaths, according to a 2013 study by Yale researchers.

Attitudes toward hormone replacement therapy are now starting to change amid mounting evidence it's relatively safe. In May 2017, the Canadian Medical Association Journal reported that initial results linking hormone replacement therapy to breast cancer and heart attacks may have been misleading.

Doing harm by doing no harm

There are still acknowledged risks of using hormone therapy, depending on the type of therapy, the dose, how long the medication is taken and an individual's health risks, according to the Mayo Clinic. HRT should be tailored to individual patients and continually reevaluated. But the benefits can outweigh the risks if HRT is done right, experts say.

In 2013, investigators from the Women's Health Initiative Hormone Trials concluded that while hormone therapy isn't recommended for the prevention of chronic disease, minimal doses are an option for the short-term management of menopausal symptoms for younger women.

An article in the September 2015 issue of the Journal of Clinical Oncology concluded doctors could "feel comfortable offering patients HRT after the treatment of epithelial ovarian cancer to manage postmenopausal symptoms." The article analyzed the results of one multinational randomized clinical trial that showed women with epithelial ovarian cancer who were treated with estrogen-only hormone replacement therapy lived longer than women who were not.

HRT should be tailored to individual patients and continually reevaluated. But the benefits can outweigh the risks if HRT is done right, experts say.

The 2020 report in Pathology & Oncology Research referenced earlier in this article stated that the Women's Health Initiative study led to "an irrational fear of female hormone replacement, both by the general population and medical professionals."

Many doctors made a mistake by reasoning that in not prescribing HRT, they were doing no harm, according to the report.

It had seemed the logical and safe conclusion to many physicians to avoid HRT, believing this decision definitely caused no harm, whereas the decision to prescribe estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication.

However, it "was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects," stated the authors of the 2020 study.

In conclusion, although there are unanswered questions, such as the mechanisms of how estrogen improves overall survival, oncologists are beginning to feel comfortable again offering patients HRT as needed after cancer treatment.