Hormone Replacement Therapy (HRT) & Cancer Risk

HRT does not carry one cancer risk. Treating it as a single substance is the main reason this topic feels so contradictory. Before any number means anything, you need four details. Which hormone? Is a progestogen included, and at what dose? How is it delivered? And for how long, starting at what age?

Those four do not just change the size of the risk. For breast cancer, they change its direction.

In the Women's Health Initiative, combined oestrogen-plus-progestogen therapy raised breast cancer risk. NCI notes that the raised risk lasts for at least a decade after use stops. The trial also linked this regimen to stroke, blood clots, heart attack, and dementia in those aged 65 and over. It also found increased breast density, which makes mammography less effective, and a higher risk of death from lung cancer.

The progestogen is not there by chance. It protects the lining of the uterus, which oestrogen alone would stimulate.

The WHI also ran an oestrogen-alone trial in women who had had a hysterectomy. There it found a lower risk of breast cancer. It also found a lower risk of death from breast cancer during treatment. That points the opposite way from the combined regimen, and it is the finding most often lost in general coverage.

The trade-off is real. Oestrogen without a progestogen raises endometrial cancer risk in anyone who still has a uterus. That is why the choice of regimen follows your anatomy rather than your preference.

Relative risks are where this topic gets distorted. So here are the absolute ones, from the 2019 individual-participant meta-analysis published in The Lancet.

Take women of average weight in Western countries. About 6.3 per 100 develop breast cancer between ages 50 and 69 with no hormone therapy at all. Five years of therapy starting at age 50 changes that to:

• 8.3 per 100 for oestrogen plus daily progestogen, an excess of about 1 in every 50 users
• 7.7 per 100 for oestrogen plus intermittent progestogen, about 1 in every 70
• 6.8 per 100 for oestrogen-only, about 1 in every 200

Two further findings from the same analysis matter. Some excess risk lasted more than 10 years after stopping. But if therapy was used for less than a year, little excess risk remained afterwards. And every type of MHT except topical vaginal oestrogens was linked to higher breast cancer risk. That makes local vaginal treatment a genuinely different proposition from systemic therapy.

Body weight mattered too. Oestrogen-only therapy had little effect in women with obesity.

These are two separate questions, and they get mixed up constantly.

The US Preventive Services Task Force recommends against combined oestrogen and progestogen for the primary prevention of chronic conditions in postmenopausal people. It recommends against oestrogen alone for that purpose too. Both are Grade D recommendations. That is a clear position, and it is also a narrow one. The USPSTF says plainly that this advice does not apply to people considering hormone therapy for menopausal symptoms such as hot flushes or vaginal dryness.

So "do not take HRT to prevent heart disease or bone fractures" is not the same as "do not take HRT for severe hot flushes." Only the first is supported. For symptom treatment, FDA guidance is to use the lowest dose for the shortest time that controls symptoms.

Nothing here is a reason to start or stop a medication on your own. If you already take HRT, stopping suddenly because of something you read has its own consequences. That is a conversation to have, not a decision to make alone.

Some facts genuinely shift the balance, and they are worth having ready. How disruptive are your symptoms, and what do they cost you day to day? What is your age now, and your age at menopause? Do you have a uterus? What is your family history of breast, endometrial and ovarian cancer? Have you had clots, a stroke or heart disease? How is your bone health? And how long do you expect to use it?

Ask which formulation and route is being proposed. Then ask what the numbers are for that one. Ask whether a local vaginal treatment would handle your main symptom. And agree a date to review whether to carry on. Duration is one of the few parts of this you can keep adjusting.

• NCI — Menopausal Hormone Therapy and Cancer Fact Sheet
• Collaborative Group on Hormonal Factors in Breast Cancer, The Lancet 2019 — Type and timing of menopausal hormone therapy and breast cancer risk (PubMed)
• USPSTF — Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons
• IARC Monographs — Combined Estrogen–Progestogen Menopausal Therapy (Volume 100A)