HRT, menopause and cancer: What women need to know before hormone therapy

Deciding on which Hormone Replacement Therapy (HRT) to choose to alleviate menopausal symptom, or whether to take it at all, can be a minefield especially as much of the evidence from previous medical trials has been conflicting, particularly in terms of cancer risk.

Fortunately, definitive results of a major international trial presented at the 2024 American Society of Clinical Oncology (ASCO) meeting this week have provided some welcome clarity, even though the findings may not make the decision-making process any easier.

Researchers performed a 20-year follow-up analysis of two major randomised clinical trials that ran from 1993 to 1998 as part of the Women’s Health Initiative (WHI) which involved nearly 30,000 participants. In these studies, women who had passed through menopause, who did not have pre-existing cancer, were randomised to either a placebo, an oestrogen only or a combined oestrogen and progesterone HRT pill.

Participants in the study were a good representation of different ethnic groups; their age ranged between aged between 50 and 80 years old, about half still had a uterus, and the others had undergone a hysterectomy to remove their uterus for various medical reasons, other than cancer.

In accordance to national guidelines, the type of pill women were given was stratified depended on whether they had their uterus removed or not. This is because previous studies have already demonstrated that oestrogen-only pills can increase the risk of cancer of the uterus but pills combining oestrogen with progesterone did not.

In this new study therefore, half the women who had a hysterectomy received an oestrogen-only pill and the other half received a placebo. Of the women who still had a uterus, half received an oestrogen and progesterone combination pill and the other half a placebo.

Key findings of this new study

Women taking oestrogen alone were twice as likely to develop ovarian cancer and nearly three times more likely to die from ovarian cancer than those who received the placebo.

Women taking the combined oestrogen and progesterone pills did not have an increased risk of developing or dying from ovarian cancer compared to those who received the placebo. In fact, those who received the combination pill had a 28 per cent lower risk of developing uterine cancer than those who received the placebo.

What we know from previous studies

It has already been established that all HRT pills increase the risk of blood clots. The oestrogen-only pill increases the risk of stroke and cancer of the uterus but slightly reduces the risk of breast cancer. Pills which provide continuous oestrogen and progesterone pills increase the risk of breast cancer but trials have also shown that HRT which vary the level of progesterone over the month have a lower risk. There is also emerging evidence that natural over synthetic progesterone does not increase the breast cancer risk.

This data, unfortunately, does not make the decision for women any easier. Women without a uterus considering oestrogen-only HRT now have to trade off a lower risk of breast cancer with a higher risk of ovarian cancer. On the other hand, women with a uterus considering combined oestrogen progesterone HRT have to trade off a lower risk of uterine, no increased risk of ovarian cancer with a potential higher risk of breast cancer, although this can be mitigated with careful selection of the type of progesterone.

It is important to note that many postmenopausal women gain considerable benefits from HRT particularly by reducing menopausal symptoms including hot flushes, low libido and improving mood and bone health.

In conclusion, although these trials have confirmed a measurable influence on the risk of cancer of the ovary, breast, and uterus, depending on the variety of HRT, compared to women taking placebo, the absolute risk of cancer was still low in both groups. While this new information is an important part of patient counselling and education, given the low risks, this data should not necessarily impact a woman’s decision to take HRT if their quality of life is significantly impacted by their menopausal symptoms.

What’s more, when considering relative risks, it’s useful to consider other crucial lifestyle factors which can significantly reduce the risk of cancer, blood clots and stroke including:

• Taking daily physical activity and avoiding long periods of sedentary behaviour
• Quitting smoking
• Eating less meat and particularly processed meat
• Eating more phytochemical rich herbs, fruit, nuts and veg
• Drinking less alcohol
• Ensuring adequate vitamin D levels
• Ensuring adequate essential mineral intake
• Reducing processed sugar intake
• Looking after your gut health
• Keeping a normal weight
• Avoiding environmental carcinogens