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How well does HRT work?

HRT is currently the most effective treatment for troublesome vasomotor symptoms.

Large randomised controlled trials have confirmed that HRT also significantly reduces fracture risk, improves vaginal dryness and sexual function, and may also improve sleep, muscle aches and pains, and quality of life in symptomatic women.

The relative efficacy of tibolone compared with conventional HRT is not well established.

Clinical indications for HRT

The key indication for HRT or tibolone is the presence of troublesome vasomotor symptoms (hot flushes and night sweats, with or without awakening). HRT may be indicated when menopausal symptoms are adversely affecting quality of life.

Current evidence based guidelines advise consideration of HRT for troublesome vasomotor symptoms in perimenopausal and early postmenopausal women without contraindications and after individualised discussion of likely risks and benefits. Starting HRT in women over age 60 years is generally not recommended.

HRT reduces fracture risk, but increased risk of osteoporosis alone is not an indication for HRT. Similarly, although HRT may also improve mood and libido, these are not primary indications for treatment. Vaginal symptoms alone do not require systemic HRT and can be managed with local oestrogens.

How safe is HRT?

HRT and thromboembolic disease

Oral HRT (combined oestrogen and progestogen, and oestrogen only) increases the risk of venous thromboembolism, pulmonary embolism, and stroke. These risks increase with age and with other risk factors, such as obesity, previous thromboembolic disease, smoking, and immobility.

HRT and stroke

Overall, HRT increases the risk of stroke. In older women (>65 years) tibolone increases the risk of stroke.

HRT and cardiovascular disease

The relation between HRT and cardiovascular disease is controversial, but the timing and duration of HRT, as well as pre-existing cardiovascular disease, are likely to affect outcomes. In the estimated risks for younger women (aged 50-59 years there was no statistically significant cardiovascular risk or harm for HRT. HRT is generally avoided in older women (>60), who are more likely to have established cardiovascular disease

HRT and breast cancer

Combined HRT

Combined HRT (oestrogen plus progestogen) increases the risk of a breast cancer diagnosis or breast cancer mortality.

The risk of breast cancer with tibolone is not established, but large observational studies suggest an increased risk.

Oestrogen-only HRT

Data are conflicting over the risk of breast cancer with oestrogen-only HRT. Studies are consistent in showing a greater risk of breast cancer with combined HRT than with oestrogen alone.

HRT and endometrial cancer

In women who have an intact uterus, unopposed oestrogen may lead to endometrial hyperplasia and increases the risk of endometrial cancer. For this reason women who retain their uterus and use oestrogen should also take progestogen. Combined continuous HRT does not increase the risk of endometrial cancer provided that adequate duration and dose of progestogen are used, but sequential HRT may increase risk. Tibolone does not increase the risk of endometrial hyperplasia or cancer.

HRT and gallbladder disease

Large randomised controlled trials have shown that HRT increases the risk of cholecystitis. Observational data (the Million Women Study) show that this risk may be reduced by using transdermal rather than oral HRT, avoiding one cholecystectomy in every 140 users.

What are the precautions for HRT?

No consensus has been reached on absolute contraindications to HRT. However, on the basis of the above data, we advise avoiding or discontinuing HRT in patients with the following:

• A history of breast cancer, as HRT may increase the risk of breast cancer recurrence and of new breast cancers. Tibolone also increases the risk of breast cancer recurrence. Exclude breast disease and investigate any abnormalities before starting HRT. Counsel women considering HRT that it may increase their risk of an abnormal mammogram and that combined HRT may increase their risk of breast cancer after four to five years of use
• A personal history or known high risk of venous or arterial thromboembolic disease, including stroke and cardiovascular disease, as HRT may further increase risk. Tibolone increases stroke risk in older women. If HRT is prescribed, a transdermal preparation with minimal oestrogen is preferred. In the absence of personal or family history, screening for inherited thrombophilias is not indicated before starting HRT
• Uncontrolled hypertension.

Other conditions that require caution with use of HRT include:

• Abnormal vaginal bleeding. HRT should not be started in women with undiagnosed abnormal vaginal bleeding. Combined HRT may often cause unscheduled bleeding in the first six months of use. Persistent or new onset (after six months) unscheduled bleeding on HRT requires investigation to exclude pelvic disease
• Abnormal liver function. Avoid oral HRT products since these are metabolised in the liver
• Migraine. This does not seem to be exacerbated by HRT so migraine is not a contraindication, but low dose transdermal preparations may be preferable
• History of endometrial or ovarian cancer. Seek specialist review before considering HRT
• High risk of gallbladder disease. Advise that HRT may increase this risk further, although the risk may be lower with transdermal therapy.

Before HRT is started

• Consider HRT in perimenopausal or recently postmenopausal symptomatic women with low risk factors for cardiovascular or thromboembolic disease.
• Consider the nature and severity of menopausal symptoms and their impact on function and quality of life, the woman’s age and health status, as well as her wishes for treatment.
• It is reasonable to advise younger, healthy postmenopausal women that HRT is unlikely to increase their risk of cardiovascular disease. However, HRT is not currently indicated in women at any age for preventing or treating cardiovascular disease.
• Discuss with women any modifiable risk factors for cardiovascular disease, such as alcohol, smoking, diabetes and hypertension control. Avoid prescribing HRT in women with established cardiovascular or cerebrovascular disease or at high risk of these conditions
• Consider whether anxiety and/or depression may be contributing to the symptom burden. Somatic symptoms of menopause, such as palpitations and sleep disorder, may be difficult to distinguish from those of depression and anxiety. HRT may reduce palpitations and improve sleep and may improve mood but is not a treatment for clinical anxiety or depression.
• Ensure breast and cervical screening are up to date and investigate any abnormal vaginal bleeding.

Continuing or ceasing HRT

Base the decision on whether to advise continuation of HRT 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 risks of HRT may be related to duration of HRT use—for example, the risk of venous thromboembolism is greatest in the first year of use, but the risk of breast cancer increases with duration of use.

[Link to free BMJ article for full text, images, and references]