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Hormone replacement therapy: an update

Kathy Abernethy
MClinSci RN
Clinical Nurse Specialist
Northwick Park Hospital

In 2011, what has changed with regard to hormone replacement therapy (HRT)? What do we know about HRT that will reassure health professionals and what advice should be offered to women needing advice?

It is now nearly 10 years since the initial results of the Women's Health Initiative Studies were published.1 This and subsequent studies led to a change in the perceived safety of hormone replacement therapy (HRT) by health professionals and women in the UK.

There was wide debate as to the relevance of these studies to UK women and repeat analysis of the results in an effort to extrapolate safety data in the typical UK user (mainly women under 60 years of age and healthy with moderate-to-severe menopausal symptoms). Nonetheless, at the time, many women stopped HRT without medical advice and many more were encouraged not to use HRT because of the perceived risks.

Why use HRT?
Short-term symptom relief
It is estimated that around 75% of women experience menopausal symptoms at the time of the menopause and that, for over half of these, symptoms last for more than five years. In around 10% of women, vasomotor symptoms may last in excess of 10 years.2 Given the troublesome nature of some of these symptoms, it is unsurprising that women seek advice in order to alleviate them. See Box 1 for a list of typical menopausal symptoms.

[[Box 1 HRT]]

HRT remains the most effective medication for the relief of moderate-to-severe vasomotor symptoms. Once HRT is started, women will usually notice an improvement in flushes and sweats within three to four weeks. If the dose is appropriate, you can expect to see the complete resolution of symptoms by about 10-12 weeks. Of course, only those symptoms that are truly hormonal in origin will be improved; although improvement in general wellbeing may be recognised as women begin to feel better, particularly if this includes sleep patterns and relationships. The dose of oestrogen needs to be tailored to the individual, with many women getting adequate symptom control on quite low doses.

Urogenital symptom relief
Vaginal dryness and other urogenital symptoms, such as bladder frequency and urgency, respond well to oestrogen therapy, whether given systemically or locally. It may take longer for these symptoms to improve than flushes and sweats and treatment will need to be continued long term for maximum benefit.

Long-term benefits
Osteoporosis prevention
HRT has been shown from randomised, controlled trials to reduce the risk of both spine and hip fractures as well as other osteoporotic fractures. Historically, doses of oestrogen or bone preservation have been higher, but current evidence suggests that even low doses may conserve bone mass. Following publication of the Women's Health Initiative (WHI) Studies, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK advised that HRT should not be used as a firstline treatment to prevent postmenopausal osteoporosis, as risks may outweigh benefits.  Given the costs and potential side-effects of alternatives (mainly bisphosphonates), this conclusion has been vigorously challenged, particularly for younger women.3

Colorectal cancer
The WHI oestrogen-only arm (but not the combined arm) demonstrated a reduced risk of colorectal cancer. There is no information about HRT in high-risk populations and current data do not suggest treatment recommendations in this group.4

Risks associated with HRT
Venous thromboembolism
The risk of venous thromboembolism (VTE) increases with use of HRT, particularly in the first year. With a two-fold increase in risk and a small background risk in women over 50, the absolute risk remains small. Transdermal oestrogen is associated with lower risk and is the recommended route if risk of VTE is an anxiety. Increasing age, obesity and underlying thrombosis will increase risk further.

Endometrial cancer
It has been known for many years that unopposed oestrogen therapy increases endometrial proliferation and thus risk of endometrial cancer. It is for this reason that progestogens are given concurrently to women who are not hysterectomised. While both cyclical and continuous progestogens offer endometrial protection, it is recommended that women switch to continous progestogens at around the age of 54 years for maximum protection.4

Breast cancer
The WHI and Million Women studies confirmed previous evidence that prolonged use of HRT (over seven years) is associated with an increased risk of breast cancer.5 Interestingly, the WHI data confirmed that oestrogen-only HRT (as used for hysterectomised women) conferred a lesser risk than when combined with progestogen. On stopping HRT, breast cancer risk falls and after five years has returned to untreated levels. The overall increased risk of breast cancer with HRT is low and is similar to the risk associated with obesity or alcohol intake over 2 units/day.4 Nonetheless, it is important that women are advised of this risk if continuing HRT for more than about five years after the age of 50.

Heart disease and stroke
HRT is not recommended for prevention of coronary heart disease but the data relating to safety for those women using it for symptom relief are reassuring. In re-analyses of the WHI data, it was observed that the increased risk of chronic heart disease (CHD), seen initially, occurred principally in older women and those many years beyond the menopause. Thus, no increased risk of heart disease was seen in women between the ages of 50 and 59 years or in those within 10 years of menopause. The data provide reassurance regarding the cardiovascular safety of HRT for bothersome hot flushes and night sweats in otherwise healthy women at the time of the menopausal transition.6 It may well be that risk is dose dependent, which is why lower doses are used with advancing age.

Routes and regimens
For many women, the choice of route will be based on convenience and often on cost/formulary restrictions (see Box 2). Women with pre-existing medical conditions may be advised to use the non-oral route first line as there may be a lesser impact on concurrent conditions, eg, diabetes, risk of thrombosis, gastrointestinal conditions.4 Women themselves often opt for patches or gels as they perceive them to be 'more natural'.

[[Box 2 HRT]]

Oestrogen therapy is given to women on a continuous basis (ie, without a break) and progestogen (for those women with a uterus) on a cyclical, tricyclical or continuous basis. Pre-packaged products make prescribing simple, but occasionally HRT needs to be tailored to the individual. A variety of doses, types and routes are available and can be easily compared either in the British National Formulary (BNF) or in MIMS, where tables are available explaining the content of each HRT product.

Side effects are common, especially in the early days and, occasionally, weeks. Women should be warned of the possibility of experiencing breast tenderness, leg cramps and nausea, and reassured that these usually subside spontaneously. Occasionally, a change is needed in the type of oestrogen or progestogen, the route is given by or the regimen in which it is used. Women can be reassured that studies have not demonstrated marked weight gain with HRT. Progestogenic side-effects, which may include headaches, mood swings and irritability, may not resolve without a change of treatment. In women over 54 years it is worth considering a change to a continuous regimen to avoid cyclical side-effects.
There is certainly a place for offering HRT to women who are experiencing troublesome menopausal symptoms. For most it will be used in the short term and at low doses.

Nurses, particularly those in primary care, are well placed to offer support and education to women so that they are able to make an informed, evidence-based decision. It is vital that nurses are well educated in issues relating to menopausal health and fully understand the risks and benefits of HRT when applied to an individual woman.


  1. Writing Group for the Women's Health Initiative Investigator. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.
  2. Politi MC, Schleinitz MD, Nananda F  (2008) Revisiting the Duration of Vasomotor Symptoms of Menopause: A Meta-Analysis. Journal of General Internal Medicine 2008;23(9):1507-13.
  3. British Menopause Society Council. Prevention and treatment of osteoporosis on women. Menopause International 2007;13:178-81.
  4. Rees M et al. Management of the menopause, 5th edition. London: RSM Publications; 2009.
  5. Million Women Study Collaborators (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;326(9382):419-27.
  6. Manson JE, Hsia J, Johnson KC et al. Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523-34.

Your comments (terms and conditions apply):

"I do wish more women took HRT as their quality of life would often be improved. I can't bear to see women 'battling on' and am a firm believer that HRT is a vital but underused treatment" - Lynn Butterworth, Staffs

"Good article - going through the menopause is very disabling at times and as professional this report did not look at the memory problems and cognitive part of the effects the menopause has on women" - Jackie Hutchinson, Durham