Hormone replacement therapy (HRT) became available to women in the UK almost 60 years ago. Since then, a slew of clinical studies on its benefits and risks has resulted in a tumultuous ride in terms of popularity, both among women and prescribers.
Almost a third of women used HRT in 1995, but this dropped significantly in 2002 following first results from the Women’s Health Initiative (WHI) — a US-based randomised controlled trial — which suggested HRT had more detrimental than beneficial effects. A UK-based study in 2003 — the Million Women Study — added further support to the view that long-term use of HRT is associated with an increased risk of breast cancer.
The past few years, however, has seen a resurgence in HRT’s popularity, with demand soaring on the back of a better understanding of the risks of HRT, an increase in general awareness of menopausal symptoms — largely led by politicians and celebrities — and a “menopause revolution”, which aims to bring menopause support to everyone who needs it. This increase in demand, as well as several other factors related to manufacturing capacity and disruption of global supply chains, has led to major shortages of HRT, which are still ongoing (see Figure 1).
Benefits of HRT
HRT can relieve a wide range of symptoms associated with menopause and perimenopause (see Figure 2).
Menopausal symptoms can be confused with those of other conditions, such as:
- Recurrent urinary tract infection;
- Severe migraine;
- Memory problems.
Breast cancer risks
There have been several recent studies looking at the risk of breast cancer with HRT, including the 2019 Collaborative Group for Hormonal Risk Factors (CGHFBC) and the 2020 long-term follow-up of the WHI trials[3,4]. These, along with previous studies, have found there are different risks of breast cancer associated with different forms and/or durations of use of HRT (see Figure 3).
Risks with HRT should be considered in the context of the increased risk of breast cancer with lifestyle factors, such as smoking, drinking alcohol and being overweight, as well as the benefits of HRT detailed above, including symptom relief, improved quality of life and the protective effects for cardiovascular and bone health.
Box: When is breast cancer risk not increased?
- There is no evidence of a dosage effect on breast cancer risk with oestrogen;
- There appears to be little or no increase in risk of breast cancer for current or past users of HRT if it is used for less than one year;
- Low-dose vaginal oestrogen does not appear to be associated with an elevated risk of breast cancer;
- Oestrogen combined with micronised progesterone does not increase breast cancer risk for up to five years of use;
- HRT is not associated with an increased risk of breast cancer mortality.
Other HRT risks
Oral HRT is associated with an elevated risk of venous thromboembolism (VTE); transdermal HRT is unlikely to increase risk of VTE. There is an increase in risk of endometrial cancer with oestrogen-only HRT, which is why it is only prescribed for women without a uterus (see Figure 4).
Types of HRT
HRT can be synthetic or body identical.
Body identical HRT has the same molecular structure as the hormones produced in the body and includes estrone, 17-beta-estradiol, estriol, micronised progesterone and testosterone. Body identical progesterone is thought to minimise risk of breast cancer but choice will depend on individual circumstances.
Synthetic HRT includes ethinyl estradiol (combined hormonal contraception) and progestogens, including dydrogesterone, medroxyprogesterone acetate, norethisterone and levonorgestrel.
Bioidentical HRT is body identical HRT that is compounded for individual patients in pharmacies and is not regulated in the same way as licensed HRT. It is not recommended by the BMS.
There are two main types of HRT:
- Oestrogen-only, for females without a uterus or who are using a progestogen coil.
- Combined oestrogen and progestogen: for females with a uterus. This can be sequential (for people who still have periods) or continuous (for people who have stopped menstruating for at least 12 months).
Several different presentations are available (see Figure 5).
Editorial adviser: Paula Briggs, consultant in sexual and reproductive health at Liverpool Women’s NHS Foundation Trust and chair of the British Menopause Society.
- 1Writing Group for the Women’s Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial. JAMA: The Journal of the American Medical Association. 2002;288:321–33. doi:10.1001/jama.288.3.321
- 2Breast cancer and hormone-replacement therapy in the Million Women Study. The Lancet. 2003;362:419–27. doi:10.1016/s0140-6736(03)14065-2
- 3Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. The Lancet. 2019;394:1159–68. doi:10.1016/s0140-6736(19)31709-x
- 4Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials. JAMA. 2020;324:369. doi:10.1001/jama.2020.9482
- 5Marsden J, Pedder H. FAST FACTS: HRT and breast cancer risk. British Menopause Society. 2022.https://thebms.org.uk/wp-content/uploads/2022/12/12-BMS-TfC-Fast-Facts-HRT-and-Breast-Cancer-Risk-NOV2022-A.pdf (accessed 19 May 2023).
- 6Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2007;107:103–11. doi:10.1007/s10549-007-9523-x