The negative publicity regarding previous studies, including the Women's Health Initiative (WHI) and the Million Women Study (MWS), has led to many women being concerned and anxious about the potential risks of hormone replacement therapy (HRT).[1, 2]It is very important to explore a woman's fears and understanding of the menopause and her expectations concerning HRT.
Data accumulated from numerous studies over the period of a decade or so have shown that, in women under the age of 60 years with symptoms or other indications, initiating HRT near menopause will provide a favourable benefit:risk ratio.
See separate Menopause and its Management, Hormone Replacement Therapy (including Benefits and Risks), HRT - Initial Consultation and HRT- Topical articles.
Current evidence-based guidelines advise consideration of HRT for troublesome vasomotor symptoms in perimenopausal and early postmenopausal women without contra-indications and after individualised discussion of likely benefits and risks.There is no debate any more on the good safety profile of postmenopausal HRT in healthy perimenopausal and early postmenopausal women.
Current indications for the use of HRT are:
- For the treatment of menopausal symptoms where the risk:benefit ratio is favourable, in fully informed women.
- For women with early menopause until the age of natural menopause (around 51 years).
- For those women aged under 60 years who are at risk of an osteoporotic fracture, in whom non-oestrogen treatments are unsuitable.
For women with premature (age <40 years) or early (<45 years) menopause, current guidelines recommend HRT until the age of 51 years for the treatment of vasomotor symptoms, and bone and cardiovascular protection.[3, 5]
Starting HRT in women over the age of 60 years is generally not recommended.
After an initial three-month review, the current recommendations are for women to be reviewed on an annual basis thereafter, unless there are clinical indications for an earlier review (such as treatment ineffectiveness, side-effects or adverse events).
Components to a follow-up assessment:
- A three-month trial of HRT is suggested to achieve maximum effect.
- Improvement of symptoms should be noted and women should be asked about any residual symptoms.
Where a patient remains symptomatic, consider:
- Poor absorption - for example, due to bowel disorder.
- Drug interactions reducing bio-available oestrogen - for example, carbamazepine and phenytoin.
- Problems with patch adhesion.
- Incorrect diagnosis - hypothyroidism or diabetes may mimic some features of menopause.
- Patient expectations - these may also need to be addressed.
- The dose of oestrogen in HRT being too low.
Altering the HRT product or delivery method may help address some of these problems. The oestrogen dose may need to be increased. For example, vaginal oestrogen cream can be added if urogenital symptoms are poorly controlled.
A regular review should include the following:
- Check for side-effects - eg, breast tenderness or enlargement, nausea, headaches or bleeding - and manage appropriately (see 'Management of side-effects', below).
- Check blood pressure and weight.
- Encourage breast awareness and participation in screening mammography and also cervical screening if appropriate for age.
- A review and discussion of an individual's risk:benefit ratio concerning HRT should occur at least annually.
- If appropriate, consider switching from cyclical HRT to continuous combined HRT (see below).
The decision on whether to advise continuation of HRT should be based on symptoms and ongoing risks and benefits rather than a set minimum or maximum duration of therapy. Cessation of HRT leads to recurrent symptoms for up to 50% of women. Consider the potential impact of recurrent symptoms on quality of life. The merits of long-term HRT use should be assessed for each individual woman and the lowest dose of HRT which controls symptoms should be used.
Management of side-effects
Side-effects may be oestrogen-related (occurring continuously or randomly through a cycle) or progestogen-related (occurring cyclically during the progestogen phase).
These are usually transient and resolve spontaneously with increasing duration of use. Encourage patients to persist with a particular therapy for at least 12 weeks. Side-effects are more likely to occur or be problematic where there has been a longer interval since ovarian failure.
Oestrogen-related side-effects include:
- Breast tenderness or enlargement - this usually settles after 4-6 weeks of taking HRT. The oestrogen dose could be reduced and then increased very gradually. A change in progesterone can sometimes be beneficial. Evening primrose oil is no longer recommended.
- Leg cramps - try exercise and calf stretching.
- Nausea and dyspepsia - adjust time of dose and administer with food.
- Headaches - try transdermal oestrogen, as this usually produces more stable oestrogen levels.
These may be more problematic and are usually connected to the type, duration and dose of progestogen.
Progestogen-related side-effects include:
- Fluid retention.
- Headaches or migraine.
- Breast tenderness.
- Mood swings and depression.
- Symptoms of premenstrual syndrome.
- Lower abdominal and back pain.
Again encourage perseverance, as symptoms may improve over three months. If there is no improvement, strategies include:
- If bleeding is heavy or irregular on sequential combined HRT then the dose of progestogen can be doubled or increased in duration to 21 days. Alternatively the type of progestogen can be changed.
- Erratic bleeding can be common in the first three to six months after starting HRT.
- Women with progestogen side-effects (eg, fluid retention, mood swings, weight gain) can have the progestogen dose halved or the duration of taking progestogen reduced to seven to ten days.
- Fewer progesteronic side-effects occur with progesterone and dydrogesterone. The Mirena® intrauterine system (IUS) can be used as an alternative for endometrial protection. Its licence for this use is four years.
- Drospirenone has anti-androgenic and anti-mineralocorticoid properties.
- Micronised progesterones are natural, 'body-identical' progesterones, devoid of any androgenic as well as glucocorticoid activities but being slightly hypotensive due to their anti-mineralocorticoid activity. These appear to be the optimal progestogen in terms of cardiovascular effects, blood pressure, venous thromboembolism (VTE), probably stroke and even breast cancer.Utrogestan® is the only one currently available to prescribe in the UK.
Micronised progesterone can be prescribed with oral or transdermal oestrogen. It is commonly prescribed at a dose of 200 micrograms a day for two weeks followed by a two-week break for those women who are still having periods. For a continuous combined use, it should be prescribed as 100 micrograms daily. It is usually taken at night.
This is often given as a major reason for why women discontinue HRT but there is no randomised controlled trial evidence of HRT-induced weight gain. Reassure the patient that weight gain is common at this time of life and counter with dietary and lifestyle advice.
Monthly sequential preparations should produce regular, predictable and acceptable bleeds starting towards the end, or soon after, the progestogen phase. This pattern may be altered by:
- Drug interaction
- Gastrointestinal upset
Breakthrough bleeding is common in the first three to six months of continuous combined and long-cycle HRT regimens. Unscheduled bleeding in the first six months of HRT use does not need investigation but investigate new-onset or persistent bleeding to exclude pelvic disease.
Where pelvic pathology is excluded, strategies for tackling bleeding problems include:
- Heavy or prolonged bleeding - increase dose, duration or type of progestogen. Consider the use of the levonorgestrel-releasing IUS (LNG-IUS) combined with oral or transdermal oestrogen.
- Bleeding early in the progestogen phase - increase the dose or change the type of progestogen.
- It can be useful for some women with bleeding when taking a continuous combined regime to revert back to a cyclical regime for a few months.
- Painful bleeding - change the type of progestogen.
- Irregular bleeding - change the regimen or increase progestogen.
- No bleeding - this occurs in 5% of women and is due to an atrophic endometrium. It is necessary to exclude pregnancy in perimenopausal women and to ensure compliance with the progestogen element of the HRT regimen.
Switching from cyclical HRT to continuous combined HRT
Cyclical HRT can be changed to continuous combined HRT when the woman is considered to be postmenopausal.
- Women should be prescribed sequential combined HRT if:
- Their last menstrual period was less than one year previously.
- Women can be prescribed continuous combined HRT if:
- They have received sequential combined HRT for at least one year; or
- It has been at least one year since their last menstrual period.
Menopausal symptoms (hot flushes and sweats) last on average between two to five years but there is considerable individual difference and symptoms may last decades in some women.
A trial of withdrawal of HRT could be considered in:
- Those women symptom-free on HRT after one to two years.
- Women who have been on HRT for longer than five years.
- Women on HRT for premature menopause after the age of 51.
See the paragraph on alternatives to HRT at the bottom of the separate Menopause and its Management article.
Many women have stopped HRT themselves in the recent past as they have been influenced by the media. Many young women taking HRT needlessly stop their HRT too early. There is evidence that up to 79% of women with premature ovarian insufficiency (POI) think that taking HRT under the age of 51 years is associated with an increased risk of breast cancer.This is obviously not correct. It is extremely important that women should be given the correct information regarding the benefits and the potential risks of HRT.
Abrupt cessation or gradual withdrawal of HRT?
When stopping HRT, it is generally recommended that the dose of HRT should be gradually reduced over three to six months to minimise the chance of oestrogen deficiency symptoms returning.
On initial cessation of therapy, symptoms may return fairly soon but then resolve. Ideally, staying off treatment for two to three months should be considered before deciding whether or not to recommence.
However, if the vasomotor symptoms are severe after stopping HRT, restarting treatment may be the most appropriate course of action. The lowest dose to improve symptoms should be given.
Consider referral to a healthcare professional with expertise in menopause if:
- Treatments do not improve menopausal symptoms.
- Treatments cause ongoing troublesome side-effects.
- A woman has menopausal symptoms and contra-indications to HRT.
- There is uncertainty about the most suitable treatment options for a woman's menopausal symptoms.
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- Beral V; Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9 362(9382):419-27.
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- Sussman M, Trocio J, Best C, et al; Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records. BMC Womens Health. 2015 Aug 13 15:58. doi: 10.1186/s12905-015-0217-y.
- Gibson-Helm M, Teede H, Vincent A; Symptoms, health behavior and understanding of menopause therapy in women with premature menopause. Climacteric. 2014 Dec 17(6):666-73. doi: 10.3109/13697137.2014.913284. Epub 2014 Jul 17.
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