Introduction
Diagnosis and treatment
Evidence-based recommendation | ||
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Level of Evidence LLA | Grade of recommendation A | Degree of consensus++ |
Peri- and Postmenopause in women aged 45 or older should be diagnosed based on clinical parameters |
Evidence-based recommendation | ||
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Level of Evidence LLA | Grade of recommendation A | Degree of consensus++ |
FSH should be used to diagnose peri- and postmenopause only in women between 40 and 45 years with climacteric symptoms or in women under the age of 40 years with suspected indicators of premature ovarian insufficiency |
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Perimenopause—women with irregular menstrual cycles and possibly vasomotor symptoms.
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Postmenopause—women without a menstrual bleeding for at least 1 year in the absence of interventions which may cause amenorrhea (e.g. oral contraceptives).
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Peri-/postmenopause—women after hysterectomy with vasomotor symptoms. In women who are using hormone replacement therapy (HRT), it may be difficult to define the menopausal status.
Symptoms
Information
Therapeutical interventions
Evidence-based recommendation | ||
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Level of Evidence 1a | Grade of recommendation A | Degree of consensus + + |
Women with vasomotor symptoms should be offered hormone replacement therapy (HRT) after information about short- (up to 5 years) and long-term risks and benefits. Women with an intact uterus may receive estradiol replacement therapy with an appropriate progestin component (EPT), women after hysterectomy may receive estradiol replacement therapy (ET) only |
Evidence-based recommendation | ||
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Level of Evidence 3 | Grade of recommendation A | Degree of consensus + + |
Serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs), clonidine, and gabapentin should not be offered as treatment of first choice for the treatment of vasomotor symptoms |
Evidence-based recommendation | ||
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Level of Evidence 1b | Grade of recommendation 0 | Degree of consensus + + |
Cognitive behavioural therapy (CBT), isoflavones, and cimicifuga preparations may be used to treat vasomotor symptoms | ||
* See “Appendix” for dissenting opinion of the GPT |
Vasomotoric symptoms
Changes of sexual function
Evidence-based recommendation | ||
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Level of Evidence 1b | Grade of recommendation 0 | Degree of consensus + + |
Peri- and postmenopausal women with loss of libido can be offered testosterone treatment after psychosexual exploration and when HRT has not been efficient. They should be informed about off-label use |
Urogenital atrophy
Evidence-based recommendation | ||
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Level of Evidence 1b | Grade of recommendation A | Degree of consensus +++ |
Women with symptomatic urogenital atrophy should be offered lubricants alone or together with a vaginal ET. The treatment duration should be individualized |
Starting and stopping HRT
Urogynecology
Urinary incontinence
Evidence-based statement | ||
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Level of Evidence 1a | Degree of consensus + + | |
Vaginal ET may improve urinary incontinence in postmenopausal women |
Evidence-based recommendation | ||
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Level of Evidence 1a | Grade of recommendation A | Degree of consensus + + |
Patients should be informed before systemic ET or EPT that these therapies may lead to occurrence or worsening of urinary incontinence |
Evidence-based recommendation | ||
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Level of Evidence 1a | Grade of recommendation A | Degree of consensus + + |
Postmenopausal women with urinary incontinence should be offered pelvic floor training and vaginal ET |
Overactive bladder
Evidence-based statement | ||
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Level of Evidence 1b | Degree of consensus +++ | |
Systemic HRT may lead to worsening of urinary incontinence. Women with overactive bladder may be offered vaginal ET |
Evidence-based recommendation | ||
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Level of Evidence 1b | Grade of recommendation 0 | Degree of consensus + + |
After exclusion of urological diseases, women with symptoms of urgency and frequency may be offered local ET |
Urinary tract infections
Evidence-based statement | ||
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Level of Evidence 2b | Degree of consensus + + | |
Changes in the vaginal milieu of postmenopausal women may predispose to urinary tract infection, especially in older women |
Evidence-based recommendation | ||
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Level of Evidence 2a | Grade of recommendation B | Degree of consensus + + |
Recurrent urinary tract infections in postmenopausal women should preferably be treated with vaginal ET instead of antibiotics |
Cardiovascular disease
Evidence-based recommendation | ||
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Level of Evidence 2b | Grade of recommendation B | Degree of consensus + + |
The risk for cardiovascular disease in peri- and postmenopausal women varies depending on their risk profile. These risk factors should be controlled optimally to exclude contraindications for HRT. Therefore, cardiovascular risk factors have to be identified and treated before HRT is initiated |
Thromboembolism
Evidence-based recommendation | ||
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Level of Evidence 2a | Grade of recommendation A | Degree of consensus + + |
Women should be informed that risk of thromboembolism is higher during oral compared to transdermal ET and EPT |
Cerebrovascular events
Evidence-based recommendation | ||
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Level of Evidence 2b | Grade of recommendation A | Degree of consensus + + |
Women should be informed that oral EPT, but not transdermal ET may increase the risk for ischemic cerebrovascular events. Absolute risk for cerebral stroke is very low in younger women |
Coronary heart disease
Evidence-based recommendation | ||
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Level of Evidence 2b | Grade of recommendation A | Degree of consensus + + |
Women should be informed that EPT does not increase their cardiovascular risk or has only a minor effect. ET does not increase cardiovascular risk or may even reduce it. HRT is not appropriate for the primary or secondary prevention of coronary heart disease. HRT should be started before the age of 60 years for the treatment of climacteric symptoms |
Osteoporosis
Evidence-based statement | ||
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Level of Evidence 1a | Degree of consensus +++ | |
HRT significantly reduces the risk for osteoporotic fractures |
Evidence-based statement | ||
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Level of Evidence 2a | Degree of consensus + + | |
The reduction of osteoporotic fracture risk by HRT is independent of treatment duration (even treatment duration of less than 1 year leads to reduction of the risk of osteoporotic fractures) and age at initiation of HRT. In addition, risk reduction seems to persist after stopping HRT |
Prevention
Treatment
Dementia, depression and mood changes
Evidence-based recommendation | ||
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Level of Evidence LLA | Grade of recommendation A | Degree of consensus +++ |
Peri- and postmenopausal women should be informed that it is unclear whether HRT before the age of 65 has an influence on the risk of dementia.Peri- and postmenopausal women should be informed that it is unclear whether HRT before the age of 65 has an influence on the risk of dementia |
Evidence-based recommendation | ||
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Level of Evidence LLA | Grade of recommendation A | Degree of consensus + + |
Pharmacological treatment of depression in perimenopausal women should be used according to current treatment guidelines. Currently, there is no evidence indicating that the efficacy of anti-depressant medications varies according to menopausal status.
There is insufficient evidence to recommend HRT or psychotherapy for the treatment of perimenopausal depression |
HRT and cancer risk
HRT and breast cancer risk
Evidence-based recommendation | ||
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Level of Evidence 1a | Grade of recommendation A | Degree of consensus + + |
Women considering HRT should be informed that HRT (EPT/ET) may lead to a small or no increased risk of breast cancer. Breast cancer risk depends on HRT formulations and treatment duration and is reduced after the end of treatment |
EPT
ET
Vaginal ET and breast cancer risk
HRT after breast cancer
Evidence-based statement | ||
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Level of Evidence 2b | Degree of consensus +++ | |
HRT may increase the risk of relapse after breast cancer |
Evidence-based recommendation | ||
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Level of Evidence 2a | Grade of recommendation A | Degree of consensus +++ |
HRT should not be used in women after breast cancer. In selected cases it may be used after ineffective non-hormonal treatments and severe limitations of quality of life |
Vaginal ET after breast cancer
HRT and endometrial cancer
Evidence-based statement | ||
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Level of Evidence 2 | Degree of consensus +++ | |
HRT containing an estrogen without a progestin is a risk factor for endometrial cancer in non-hysterectomized women. The effect is dependent on the duration of treatment |
Evidence-based statement | ||
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Level of Evidence 2 | Degree of consensus + + | |
Continuous combined HRT with conjugated equine estrogens and medroxyprogesterone acetate for an average duration of 5.6 years reduced the risk of endometrial cancer |
Evidence-based statement | ||
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Level of Evidence 2 | Degree of consensus + + | |
Continuous combined HRT for less than 5 years does not increase risk of endometrial cancer |
Evidence-based statement | ||
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Level of Evidence 3 | Degree of consensus + + | |
Long-term treatment with of continuous combined HRT for more than 6 or 10 years may lead to an increased risk of endometrial cancer |
Evidence-based statement | ||
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Level of Evidence 4 | Degree of consensus + | |
The use of progesterone or dydrogesterone in continuous combined HRT may increase the risk of endometrial cancer |
Evidence-based statement | ||
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Level of Evidence 3 | Degree of consensus +++ | |
Sequential combined HRT may increase the risk of endometrial cancer. The effect depends on duration, type and dose of progestin |
Evidence-based statement | ||
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Level of Evidence 3 | Grade of recommendation A | Degree of consensus +++ |
Sequential combined HRT for a duration of less than 5 years including a synthetic progestin does not increase the risk of endometrial cancer risk |
Evidence-based recommendation | ||
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Level of Evidence LLA | Grade of recommendation A | Degree of consensus + + |
ET should only be performed in hysterectomized women. A combined EPT in non-hysterectomized women should contain a progestin for a duration of 10, better 14 days per treatment month |
Vaginal ET and endometrial cancer risk
HRT after endometrial cancer
Evidence-based statement | ||
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Level of Evidence 2b | Degree of consensus +++ | |
The effect of HRT on the risk of relapse after treatment of endometrial cancer has not been investigated sufficiently |
Evidence-based recommendation | ||
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Level of Evidence 2b | Grade of recommendation EK | Degree of consensus + + |
In patients who have been treated for endometrial cancer, HRT may be used for the treatment of climacteric symptoms if they have severe quality of life limitations and in whom non-hormonal treatments were not effective |
Vaginal ET after endometrial cancer
Evidence-based recommendation | ||
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Level of Evidence 4 | Grade of recommendation A | Degree of consensus + + |
Patients with symptoms of vaginal atrophy after treatment of endometrial cancer should be treated primarily with moisturizers or lubricants |
Consensus-based recommendation | ||
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EK | Degree of consensus + + | |
After treatment of endometrial cancer, vaginal ET may be used if lubricants or cremes have proven to be ineffective |
HRT and ovarian cancer risk
Evidence-based recommendation | ||
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Level of Evidence 2a | Grade of recommendation A | Degree of consensus + + |
Women considering HRT should be informed that ET and EPT may increase ovarian cancer risk. This effect has been observed after treatment durations of less than 5 years and is reduced after stopping treatment |
HRT after ovarian cancer
Evidence-based statement | ||
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Level of Evidence 2b | Degree of consensus + + | |
The safety of HRT after treatment of ovarian cancer is unclear |
Evidence-based recommendation | ||
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Level of Evidence 2b | Grade of recommendation 0 | Degree of consensus +++ |
HRT may be used after treatment of ovarian cancer and appropriate consultation with the patient |
HRT and risk for colorectal cancer
Evidence-based recommendation | ||
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Level of Evidence 2a | Grade of recommendation A | Degree of consensus +++ |
Women should be informed that HRT may reduce the risk of colorectal cancer. HRT should not be used for colorectal cancer prevention |
Premature ovarian insufficiency (POI)
Evidence-based recommendation | ||
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Level of Evidence 2b | Grade of recommendation B | Degree of consensus + + |
Women with POI should be informed about the importance of HRT or combined oral contraceptives at least until the age of natural menopause if there are no contraindications against HRT or combined oral contraceptives |
Evidence-based statement | ||
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Level of Evidence 2b | Degree of consensus + + | |
There is no evidence for different treatment efficacy of HRT and combined oral contraceptives in women with POI |
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HRT might have a positive effect on blood pressure compared to contraceptive pills.
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HRT and contraceptive pills have a positive effect on bone health.
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HRT does not offer protection from pregnancies.
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Women with POI and contraindications for HRT should be advised about cardiovascular risks, bone health and alternative treatments of climacteric symptoms.
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Women with POI should be generously transferred to specialized centres.
Informing women about HRT
Events | Difference of events per 10,000 women years (95% CI)a | |
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EPT oral | ET oralb | |
Breast cancer | 9 (1 bis 19) | − 7 (− 14 bis 0.4) |
Coronary heart disease | 8 (0 bis 18) | − 3 (− 12 bis 8)c |
Stroke | 9 (2 bis 19) | 11 (2 bis 23)c |
Thromboembolism | 21 (12 bis 33) | 11 (3 bis 22)c |
Dementia | 22 (4 bis 53) | 12 (− 4 bis 41) |
Gallbladder disease | 21 (10 bis 34) | 30 (16 bis 48) |
Urinary incontinence | 876 (606 bis 1168) | 1261 (880 bis 1689) |
Bowel cancer | − 6 (− 9 bis − 1) | 2 (− 3 bis 10) |
Ovarian cancer | 2 (− 1 bis 6) | No data |
Lung cancer | 1 (− 4 bis 7) | 1 (− 4 bis 8) |
Fractures (osteoporosis) | − 44 (− 71 bis − 13) | − 53 (− 69 bis − 39) |
Diabetes | − 14 (− 24 bis − 3) | − 19 (− 34 bis − 3) |
Mortality | 1 (− 9 bis 12) | 1 (− 10 bis 14) |