If one thing’s clear about the data on the health effects of hormone replacement therapy after menopause, it’s that they’re confusing. But researchers are continually learning more about which women can safely use estrogen or progestin, and when.
In the latest study, published in the journal Lancet Oncology, scientists once again mined data from the Women’s Health Initiative (WHI) — the large-scale trial begun in 1991 that first looked at the relationship between hormone replacement therapy and health risks such as breast cancer and heart disease. The study looked at the effects of both combination hormone therapy, including both estrogen and progestin, and estrogen-only treatment.
In 2002, the combination-therapy arm of the study was halted when data revealed that women taking the hormone pills to treat the symptoms of menopause had a 24% increased risk of developing breast cancer. The results also showed that contrary to what doctors had thought, the hormones did not protect women from heart disease.
That led doctors to change the way they prescribed estrogen and progestin therapy for postmenopausal women, limiting its use to short periods and only to help women manage the worst symptoms of hot flashes and night sweats.
MORE: Making Sense of Hormone Therapy After Menopause
Still, the safety of estrogen-only therapy remained an open question. WHI’s combination-therapy arm included only women with an intact uterus. These women must take progestin along with estrogen in order to combat the increased risk of endometrial cancer — cancer of the uterine lining — caused by excess estrogen. That risk doesn’t apply to women who have had their uterus removed through hysterectomy, however. So, the question was, Could postmenopausal women without a uterus safely take estrogen-only therapy for menopausal symptoms? Would they show the same elevated risk of breast cancer and lack of protection against heart disease? Or would they actually benefit from the continued addition of estrogen?
In 2004, further data emerged: WHI researchers found that estrogen therapy increased women’s risk of stroke and potentially deadly blood clots, and thus, the estrogen-only arm of the trial was also halted. However, the study did not show any effect on heart disease or an increase in breast cancer risk over the seven-year follow-up. Last year, the WHI researchers published a study based on the same data, finding that the blood-clot and stroke risk disappeared after women stopped hormone therapy.
Now the scientists have looked at the data again, tracking women for an additional five years after they stopped taking estrogen, and found that after 12 years of follow-up, women taking estrogen-only therapy showed a 23% lower risk of breast cancer than those who took a placebo. Among more than 7,600 post-menopausal women who had had a hysterectomy, 151 women in the estrogen group developed breast cancer during the trial, compared with 199 women in the control group. Among the women who developed cancer, those taking estrogen were 63% less likely to die from breast cancer than non-estrogen-users during the 12 years.
“It’s a very interesting finding,” Dr. Rowan T. Chlebowski, a co-author of the study and chief of medical oncology and hematology at Harbor-UCLA Medical Center, told the Los Angeles Times. “It goes against a huge number of observational studies suggesting estrogen would increase the risk of breast cancer by itself. But this study points out that it’s much more complex than we originally thought. Estrogen alone for the period we studied seems to be pretty safe and maybe even beneficial.”
MORE: Study: More Evidence for the Harms of Hormone Replacement Therapy
But that doesn’t mean that estrogen therapy is safe for everyone. The authors note that for women with a family history of breast cancer or other risk factors that make them more vulnerable to the disease, the added hormones might not be a good idea. In the study, estrogen therapy did not reduce these women’s cancer risk. “For women who are most in need of a breast cancer [risk] reduction strategy, this approach isn’t going to work,” Dr. Garnet L. Anderson, principle investigator of the WHI Clinical Coordinating Center in Seattle, told WebMD. “These agents should not be used for breast cancer prevention, even though we clearly show a lower risk of breast cancer in these women taking hormones.”
How do the authors explain the apparent contradiction between the current findings and the initial results of the WHI? Does estrogen contribute to an increased risk of breast cancer or not? While estrogen can stimulate breast tissue growth, and therefore trigger abnormal growths that can become cancerous, the researchers say that fluctuating hormone levels may inhibit tumor growth. Estrogen declines during menopause and taking supplemental estrogen boosts the hormone, but generally not to the same levels that the body produced during menstrual cycles before menopause.
Some experts remain unconvinced by the findings. “It’s inconsistent with the totality of evidence that finds estrogen increases breast cancer risk,” Valerie Beral, director of cancer epidemiology at Oxford University, told the Associated Press, adding that while estrogen-only therapy may have a lesser breast-cancer effect than combination therapy, “to say it protects against breast cancer is wrong.”
For now, the results seem to suggest that women who have had a hysterectomy and are taking estrogen to treat symptoms of menopause can at least stop worrying about an increased risk of developing breast cancer. But it’s clear that the relationship between hormones and health is a complex one that we will only understand with more studies and better research.
MORE: Big Gulp: Juice Fasting Makes You Feel Healthy, Even if It’s Not
Alice Park is a writer at TIME. Find her on Twitter at @aliceparkny. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.