There is no such thing as a risk-free medication. The important thing when considering a treatment is to make sure that it provides greater benefits than adverse effects. Often, this benefit-risk balance is relatively straightforward to assess. For some medications, however, it is more complex. This is the case with menopausal hormone therapy (MHT).

— The messages surrounding menopause and MHT are quite varied and contradictory. This leaves many women confused, unsure whom to believe or what to think about these treatments. The key component of MHT is estrogen. There are generally two hormones involved. Estrogen affects both menopausal symptoms and the risk of various diseases. These treatments have been used since the 1960s. MHT was once seen as a cure-all with nothing but benefits. It was thought to prevent aging, protect against cardiovascular disease, and prevent osteoporosis. Many benefits, few drawbacks. Before the 2000s, 50% to 70% of postmenopausal women used menopausal hormone therapy, which they were advised to continue for the rest of their lives. In 2002, a US trial unexpectedly showed that menopausal hormone therapy increased cardiovascular risk, whereas the opposite had been expected. It also showed an increased risk of breast cancer. This brought MHT prescribing to an abrupt halt, in France and around the world. Prescriptions plummeted and continued to decline until recently. The findings of the 2002 trial still tarnish the reputation of MHT in France today. They have since been widely criticized.

— The results of the WHI study cannot be directly applied to France. It included relatively older women. Today, the women we treat are not 60 or 65 years old. We treat them at the very beginning of menopause, at around age 50 on average. And we use different compounds in France: not the same estrogens as in the US trial, and different progestogens as well. We often use estrogen administered through the skin, in the form of a patch or gel. In the US, in the WHI study, it was administered orally. This also changes the impact of these compounds on the risk of cancer or cardiovascular disease. Only a minority of women in France use MHT, but prescriptions are increasing again. These medications do have real benefits.

— The known benefits of MHT include the near-total or complete disappearance of menopausal symptoms: hot flashes, night sweats, vaginal dryness, and so on. That is what leads women to seek these treatments. Other benefits, in France and elsewhere, include a degree of protection against osteoporosis and fractures. Despite this, taking MHT can also lead to significant adverse effects.

— The risks occur over the longer term. We have quite a lot of data on the risks of breast and ovarian cancer and venous thrombosis. But all of this needs to be brought together to determine where the balance lies. It is difficult to know what weight to give, for example, to breast cancer compared with hot flashes. There is a trend toward rehabilitating—or, as we often hear it, “re-establishing confidence in”—menopausal hormone therapy. I think it may be premature to adopt a very reassuring message that could minimize the risks. We do not have enough information to say which side of the balance—risks or benefits—comes out ahead. To try to answer this question, Agnès Fournier is working with data from the E3N cohort, the largest epidemiological study dedicated to women’s health in France. Launched by Inserm more than 35 years ago, this cohort includes 100,000 women born between 1925 and 1950. To ensure long-term follow-up, participants complete lengthy questionnaires every two or three years.

— This is the first E3N questionnaire that was sent to the women. Obviously, things have evolved with technology. Today, our questionnaires look more like this. We repeatedly focus on many of the same risk factors. We ask women to regularly report their weight and medical history. They must report whether they have developed cancer during the follow-up period. At the beginning, we asked them about the number of children they had, their age at each birth, and which hormone treatments they had taken. The data collected are digitized, cleaned, and then entered into statistical analysis software. The aim? To assess the contribution of each factor to the development of diseases, particularly cancers.

— In the E3N study, we found that the risk of breast cancer associated with French hormone therapies was not, or was only very slightly, increased for treatment durations of less than five years. On the other hand, these treatments increase the risk of endometrial or ovarian cancer. These cancers are less common but are associated with poorer survival. How do we take into account and assess breast cancer, which is more common but less often fatal, on the one hand, and ovarian or endometrial cancer, which are much less common but associated with higher mortality, on the other? This is where the choice becomes very difficult, because it is individual and genuinely complex. It depends on how bothersome the hot flashes, night sweats, and other symptoms are. An asymptomatic woman has little reason to take this treatment unless she is very much willing to take a risk—developing one disease in the hope of avoiding another. Menopausal hormone therapies have been used since the 1960s. Perhaps we are not moving fast enough to build up knowledge about these treatments. It would be good to accelerate that process. The EPI-PHARE research group is working on an overall assessment of the benefit-risk balance of MHT using health insurance data. While we await those results, expected in 2027, what should we take away from French research on these controversial medications? Today, the official recommendations for menopausal hormone therapy are to use it for the shortest possible duration and at the lowest effective dose. This means that, for short-term treatment—several months or years, depending on the need—the risks are very low, while the main benefit is an improvement in quality of life through relief from menopausal symptoms. I would prefer MHT to be a cure-all; that would make things much simpler. But it isn't. We have to accept that and work with what we know.