HRT - Nachuntersuchungen

The British Menopause Society Tools for Clinicians is an excellent resource and regularly updated.

HRT reviews^{1 2}

Arrange to review the woman after three months if HRT has been started or changed, then annually thereafter, unless there are clinical indications for an earlier review (such as treatment ineffectiveness or adverse effects).³ Bei jeder Überprüfung:

• Reinforce information and lifestyle advice.

• Assess the efficacy and tolerability of treatment(s).

• Assess for bothersome adverse effects or persistent symptoms, and offer to adjust the HRT dose or preparation if appropriate. Options include:

  • Reduce or increase the dose of oestrogen.

  • Change the dose or type of progestogen. Mirena or micronised progesterone is the progesterone of choice for most women as it has the lowest breast cancer risk profile.

  • Alter the route of administration - for example, switch from oral to transdermal. Transdermal oestrogen is the modality of choice for the majority of women as it has the lowest VTE risk profile.

• Wenn es zu einer plötzlichen Veränderung des Menstruationsmusters, Zwischenblutungen, postkoitalen Blutungen oder neuen Blutungen kommt, die nicht innerhalb der ersten 3-6 Monate nach einer Änderung der HRT auftreten, sollte eine angemessene Beurteilung erfolgen und bei Verdacht auf gynäkologischen Krebs eine dringende Überweisung veranlasst werden. Die BMS-Richtlinien enthalten ein nützliches Flussdiagramm, das je nach Anzahl der Risikofaktoren für Endometriumkarzinom bei einer Frau die Maßnahmen anleitet. ^{4 5}

• If there are persistent symptoms despite adjustment of the HRT dose or preparation, consider an alternative cause for symptoms.

Review the duration of HRT treatment:

• If HRT was started in the perimenopause, discuss the option of changing the treatment regimen and/or changing the dose of oestrogen.

• Support the woman to make an individual decision on when and how to stop HRT. Advise that:

  • HRT should be continued for as long as benefits of symptom control and improved quality of life outweigh any risks, and there is no arbitrary limit for duration of HRT use.

  • For vasomotor symptoms, most women require 2-5 years of treatment, but some women may need longer.

  • Frauen mit premature menopause or premature ovarian insufficiency (POI) sollte in Großbritannien bis zum Alter von 50 Jahren HRT eingenommen werden, danach sollte der Bedarf an fortlaufender HRT neu bewertet werden.

  • HRT may be gradually reduced over 3-6 months, or stopped suddenly, depending on the woman's preferences. However, gradual reduction is preferable (see 'Stopping HRT' below).

  • Symptoms may recur in the short term after stopping treatment, particularly if HRT is stopped suddenly.

• If troublesome symptoms recur, options include restarting HRT at a low dose, or considering alternative non-hormonal treatments.

• Vaginal oestrogen preparations can be used long term.

HRT assessment¹

Components to a follow-up assessment:

• A three-month trial of any change in 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. Whilst HRT has been shown to improve vasomotor symptoms for 75% of women and also improve sleep and libido for some women, some of the symptoms attributed to the menopause are less successfully treated. Cognitive improvements have been shown in women at the start of the menopause but there appears to be an increase in dementia in women over the age of 65.⁶

• The dose of oestrogen in the HRT may be too low.

Eine Änderung des HRT-Produkts oder der Verabreichungsmethode kann helfen, einige dieser Probleme zu lösen. Möglicherweise muss die Östrogendosis erhöht werden. Zum Beispiel kann eine vaginale Östrogencreme hinzugefügt werden, wenn urogenitale Symptome schlecht kontrolliert werden. ⁷

An annual review should include the following:

• Check for side-effects 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.

• Eine Überprüfung und Diskussion des individuellen Risiko-Nutzen-Verhältnisses in Bezug auf HRT sollte mindestens jährlich erfolgen. Den meisten Frauen sollte geraten werden, auf die HRT mit dem geringsten Risiko umzusteigen (transdermales Östrogen plus, falls erforderlich, entweder ein Levonorgestrel-Intrauterinpessar oder mikronisiertes Progesteron). ⁸

• Kontinuierliche HRT hat ein geringeres Risiko für Endometriumkarzinom als zyklische, und daher sollten Patienten spätestens nach fünf Jahren umgestellt werden. ⁹¹⁰

• Erwägung der Notwendigkeit, menopause-spezifische KVT oder vaginales Östrogen zur systemischen HRT hinzuzufügen.

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 recurring symptoms for up to 50% of women. Consider the potential impact of these 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 HRT side-effects¹

Side-effects may be oestrogen-related (occurring continuously or randomly through a cycle) or progestogen-related (occurring cyclically during the progestogen phase).

Oestrogen-related side-effects

These are usually transient and usually 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 progestogen can sometimes be beneficial. Evening primrose oil is no longer recommended.

• Leg cramps - suggest 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.

Progestogen-related side-effects

These may be more problematic and are usually connected to the type, duration and dose of progestogen.

Progestogen-related side-effects include:

• Flüssigkeitsretention.

• Headaches or migraine.

• Brustempfindlichkeit.

• Mood swings and depression.

• Symptoms of premenstrual syndrome.

• Akne.

• Lower abdominal and back pain.

Again encourage perseverance, as symptoms may improve over three months. If there is no improvement at that point strategies include:

• If bleeding is heavy or irregular on cyclical HRT then the dose of progestogen can be doubled or increased in duration to 21 days. Alternatively the type of progestogen can be changed. However, increasing the progesterone dose over necessary levels can increase breast cancer risk.

• Erratic bleeding can be common in the first three to six months after starting HRT.

• Weniger progestogene Nebenwirkungen treten bei Progesteron und Dydrogesteron auf. Das 52mg Levonorgestrel-Intrauterinpessar kann als Alternative zum Endometriumschutz verwendet werden. Seine Zulassung für diesen Zweck beträgt vier Jahre (nur Marke Mirena®), aber jedes 52mg Gerät kann für diesen Zweck fünf Jahre lang off-label verwendet werden.

• Micronised progesterone:

  • Is a natural, 'body-identical' progestogen, devoid of any androgenic as well as glucocorticoid activities but being slightly hypotensive due to anti-mineralocorticoid activity.

  • Zusammen mit Dydrogesteron ist es wahrscheinlich ein Progesteron mit geringerem Risiko in Bezug auf das Brustkrebsrisiko.

  • It 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 'continuous' micronised progesterone use, the dose recommended in the BNF is days 1-25, with a 3-day break, rather than continuous use. This may reduce the chances of breakthrough bleeding compared to continuous use. However, continuous is commonly used in practice, is generally well tolerated, and is easier for women to remember.

  • Some women who are struggling with progestogenic side effects report benefits from using the micronised progesterone vaginally rather than orally. This is not licensed and there are no studies confirming safety but it is commonly reported to reduce side effects and improve tolerability.

Gewichtszunahme

Dies wird oft als Hauptgrund dafür angegeben, warum Frauen die HRT abbrechen, aber es gibt keine randomisierten kontrollierten Studien, die einen durch HRT verursachten Gewichtszuwachs belegen. Beruhigen Sie die Patientin, dass Gewichtszunahme in dieser Lebensphase häufig ist, und geben Sie Ernährungs- und Lebensstilberatung.

Blutung

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:

• Non-concordance.

• Drug interaction.

• Gastrointestinale Beschwerden.

Durchbruchblutungen sind in den ersten drei bis sechs Monaten kontinuierlicher kombinierter und langzyklischer HRT-Regime häufig. Ungeplante Blutungen in den ersten sechs Monaten der HRT-Anwendung müssen nicht untersucht werden, aber neue oder anhaltende Blutungen sollten untersucht werden, um eine Beckenkrankheit auszuschließen, unter Verwendung der BMS-Richtlinien. ⁵

Where pelvic pathology is excluded, strategies for tackling bleeding problems include:

• Heavy or prolonged bleeding - increase dose, duration or type of progestogen. It is safest to use the levonorgestrel intrauterine device combined with oral or transdermal oestrogen. Increasing the dose of other progestogens may increase the breast cancer risk.

• 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.

• Irregular bleeding - change the regimen or increase progestogen (with the caveats above).

• 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

Women should usually be prescribed cyclical/sequential combined HRT if their last menstrual period was less than one year previously, or if they are peri-menopausal (still having periods but having symptoms relating to the peri-menopause).

Cyclical HRT can be changed to continuous combined HRT when the woman is considered to be postmenopausal. This is advantageous to the woman as it removes the risk of endometrial hyperplasia and reduces the risk of endometrial cancer.⁹ Die Frau möchte sich möglicherweise auch nicht mehr mit einer Blutung auseinandersetzen müssen.

Frauen kann eine kontinuierliche kombinierte HRT verschrieben werden, wenn sie mindestens ein Jahr lang eine sequentielle kombinierte HRT erhalten haben, oder es ist mindestens ein Jahr seit ihrer letzten Menstruation vergangen, oder sie ist 54 Jahre oder älter. Es sollte spätestens nach fünf Jahren der Anwendung erfolgen.

The problem with starting continuous combined HRT before a woman is postmenopausal is the increased frequency of irregular bleeding, which may need further investigation if it persists for longer than 6 months, such as ultrasound assessment of endometrial thickness.

HRT referral²

At the time of review, consider arranging referral to a healthcare professional with expertise in menopause if:

• The woman has ongoing symptoms and lifestyle measures, hormonal, non-hormonal, or non-drug treatments are ineffective.

• Die Frau hat eine persönliche Vorgeschichte von Brustkrebs oder ein hohes Risiko für Brustkrebs.

• There is doubt about the diagnosis of premature ovarian insufficiency.

• The woman has persistent, troublesome adverse effects from treatment.

• There is uncertainty about the most suitable treatment option - for example, if the woman has comorbidities and/or contra-indications to treatment.

• The woman has persistent altered sexual function and hormonal and/or non-hormonal, or non-drug treatments are ineffective:

  • Seek specialist advice regarding the use of testosterone supplementation, unless you feel that you have the training to initiate it yourself.

  • Consider referral for psychosexual counselling, depending on the woman's wishes.

Stopping HRT¹

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.

• In women who have been on HRT for longer than five years.

• After the age of 51 for women who were started on HRT for premature menopause.

Alternativen zur HRT werden im separaten Abschnitt besprochen Menopause und deren Behandlung Artikel.

Abrupt cessation or gradual withdrawal of HRT?

When stopping HRT, it is generally recommended that the dose of HRT should be reduced gradually 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.

Reasons HRT must be stopped¹¹

It used to be recommended that hormone replacement therapy should be stopped if any VTEs occurred as they were assumed to be related to the HRT. With transdermal oestrogens this is not a concern and HRT does not need to be stopped.¹² Bei Frauen, die orale Östrogene einnehmen, ist es jedoch weiterhin sinnvoll, diese abzusetzen (bis zur Untersuchung und Behandlung). Diese Ereignisse umfassen:

• Sudden severe chest pain (even if not radiating to the left arm).

• Sudden breathlessness (or cough with blood-stained sputum).

• Unexplained swelling or severe pain in the calf of one leg.

• Severe stomach pain.

• Serious neurological effects including:

  • Unusual severe, prolonged headache, especially if for the first time or that is getting progressively worse.

  • Sudden partial or complete loss of vision.

  • Sudden disturbance of hearing.

  • Other perceptual disorders or dysphasia.

  • Bad fainting attack or collapse or first unexplained epileptic seizure.

  • Weakness, motor disturbances.

  • Very marked numbness suddenly affecting one side or one part of body.

• Blood pressure above systolic 160 mm Hg or diastolic 95 mm Hg.

• Prolonged immobility after surgery or leg injury.

HRT should be stopped where there is:

• Detection of a risk factor which contra-indicates treatment (for example, breast cancer).