Management of menopause - key guidelines

Frequently asked questions about
common menopause professional queries

• Basics of prescribing

  Basics of prescribing

  For patients who have not had a total hysterectomy, progesterone is required to protect the endometrium. You should start with a low/medium oestrogen dose and titrate according to response; older patients may require a low or ultra-low dose. High doses of oral oestrogen are not usually recommended due to VTE risk.

  BMS tables of oestrogen and proportionate progesterone doses taken from BMS guidance

  

  

  Transdermal oestrogen should be chosen in the following patients;

  • High risk of VTE, previous history of VTE or family history of VTE
  • BMI >30
  • Migraine
  • Poorly controlled hypertension
  • Poor absorption due to GI disorder
  • Enzyme inducing drugs
  • Gall bladder disease

  Please use the Devon Formulary to guide you in which preparation to prescribe and follow their prescribing flowchart.

• Testosterone

  The only current evidence-based indication for the addition of testosterone to standard HRT is for persistent low sexual desire in postmenopausal patients, despite optimised transdermal systemic HRT, after all other contributory factors have been addressed (relationship factors, genital syndrome of menopause, etc.). Claims regarding the effect of testosterone on cognition, mood, strength and wellbeing are not currently supported by evidence.

  How to prescribe testosterone

  • Follow BMS Testosterone replacement in menopause guidance-
  • Test total testosterone prior to treatment
  • If in normal range or low, commence a trial of treatment. You can prescribe either Tostran 1 pump of 0.5g (10mg testosterone) on alternate days – each canister should last 240 days  – or Testogel 2.5g sachets, 1/8 of a sachet/day = approx. 5mg testosterone/day i.e. each sachet should last 8 days.
  • Document that you have made the patient aware that this treatment is off licence.
  • Repeat total testosterone at 2-3 months and then annually to ensure still in female physiological range.
  • If there is no impact on sexual desire at 6 months testosterone should be stopped.

  When prescribing testosterone advise the patient to rotate the sites where they apply the gel, and always apply below the waist in case there is any resultant excess hair growth. Side effects of clitoromegaly, hirsutism, acne and voice deepening are very rare if testosterone is within physiological range, but patient should be counselled regarding these and treatment stopped should they occur.

• Genitourinary Syndrome of Menopause

  Genitourinary Syndrome of Menopause (GSM), also known as urogenital atrophy, occurs due to oestrogen levels dropping systemically and also vaginally during menopause. For 25-30% of patients, systemic HRT will not penetrate to the vaginal mucosa. Low oestrogen levels cause vaginal and urethral atrophy and a decrease in vaginal secretions and lubrication leading to symptoms such as vaginal dryness, irritation, painful intercourse and increased UTIs. It is useful to offer examination of these women if there is uncertainty about their symptoms or response to treatment.

  Use of locally acting vaginal oestrogens containing either estradiol (Vagirux/Vagifem) or the less potent estriol cream is supported by NICE.

  It can take up to 3 months for vaginal oestrogens to work fully. There is usually an initial loading period followed by maintenance dosing. After the loading period there is very little systemic absorption of vaginal oestrogens.

  Some systemic side effects, such as abdominal cramping and headache, may occur in the loading period due to the poor skin barrier allowing systemic absorption. Usually the side effects improve after 6-8 weeks of continued administration. The use of vaginal oestrogens should be alongside vaginal moisturisation. There are multiple brands available. A moisturiser with at least pH 3 and osmolality below 380 mOsm/kg is recommended. Vaginal lubricants are also recommended to provide short term relief from vaginal symptoms and help prevent pain during sex. If the patient does not use condoms then an oil-based lubricant alongside a water based one can be used for optimum effect.

• Managing GSM in a patient with a history of breast cancer

  A low pH, low osmolality moisturiser should be used at least twice weekly. Decisions about using vaginal oestrogen after breast cancer should always be discussed with the patient’s breast team. As systemic absorption of vaginal oestrogen is low, use when other modalities have failed is supported by NICE and the British Menopause Society. Preparations containing low dose estriol (Estriol 1mg/g cream, ‘Blissel’ gel or ‘Imvaggis’ pessaries) are less potent and cannot convert to the more potent estradiol so are preferable.

   

  In patients on aromatase inhibitors, any oestrogen exposure is not advised. These patients should be discussed with the breast team- a change to a SERM like tamoxifen may be possible if the urogenital atrophy represents a serious quality of life issue. Vaginal oestrogen will not interfere with tamoxifen.

   

• Using vaginal oestrogen after gynaecological cancers

  It is recommended to follow BMS and BGCS guidance.

  • Ovarian/fallopian/primary peritoneal cancer: Vaginal oestrogen has been deemed safe in all subtypes excluding low grade serous cancers stage 2+. In the stage 2+ low-grade serous ovarian cancers initiation should be discussed with the cancer specialist team and non-hormonal alternatives be offered first line.
  • Endometrial cancer: It is reasonable with low and intermediate risk endometrial cancers to discuss both systemic and vaginal oestrogen with patients. Those with high risk cancer should be discussed with oncology.
  • Cervical, vulval and vaginal cancers: Both systemic and vaginal oestrogens are deemed safe.
  • Uterine sarcoma: Both systemic and vaginal oestrogens are contra-indicated.
• Non-hormonal treatments for menopause management

  The majority of patients can have HRT, however there will be a body of patients in whom it is contraindicated or in patients who choose not to have it for other reasons. There are several different options to support this. If a patient has contraindications to HRT use, but wishes to be considered for this please consider writing to Devon Menopause Service for advice and guidance.

  The BMS makes recommendations for alternatives to HRT. SSRI/SNRI’s, gabapentin, pregabalin and oxybutynin can all be used off licence as options. Some SSRIs can interfere with cytochrome p450 which can affect some active cancer therapies such as tamoxifen.

  CBT has been shown to reduce anxiety and mood effects as well as the perceptions of severity of vasomotor symptoms. Talkworks covers Devon, excluding Plymouth, and Livewell covers Plymouth patients.

  Herbal treatments lack evidence, regulation and safety data and some will not be suitable for patients with previous breast or oestrogen driven cancers. Some, for example St John’s Wort, acts as enzyme inducers and Black Cohosh can also interact with tamoxifen. If a patient chooses to take herbal treatments, recommend a product with the Traditional Herbal Remedy stamp as it assures that the product meets strength and quality standards.

• Premature Ovarian Insufficiency

  Defined as menopause before the age of 40yrs, this will be experienced by up to 4% of patients. It can be spontaneous or iatrogenic due to surgeries or cancer treatments. Aside from impact on fertility, POI increases the risk of cardiovascular disease, osteoporosis and cognitive impairment. Receiving a diagnosis of POI can be very distressing The Daisy Network offers support for those with POI.

  To diagnose POI follow NICE recommendations. Elevated serum follicle-stimulating hormone (FSH) levels (more than 30 IU/L) on two blood samples taken 4–6 weeks apart.

  Patients with POI should be advised to take HRT at least until age 51, whether they are experiencing menopause symptoms or not. The aim for hormonal treatment is to achieve a pre-menopausal physiological state and offered mitigation of the risks on cardiovascular and bone health. This could be in the form of standard HRT, with vaginal oestrogen if required. However, combined hormonal contraception can also be used although this may be less beneficial to bone health. Contraception is still recommended as 5% of patients with a diagnosis of POI will spontaneously conceive due to intermittent ovarian activity and sporadic ovulation.

  Patients with POI have a higher risk of osteoporosis therefore a baseline DXA should be considered at diagnosis and then repeated after 2-3 years to assess adequacy of treatment. HRT rather than bisphosphonates should be the first line treatment for the management of osteoporosis in patients with POI.

• Bone Health and HRT

  The reduced oestrogen levels after menopause disrupt the balance between bone resorption and bone formation. This leads to a progressive loss of bone density which increases the risk of fractures and osteoporosis

  NOGG support the use of HRT as osteoporosis prevention in patients under 60 years of age with high fracture risk and remains the recommended option for bone protection in primary ovarian insufficiency. For those over 60 years of age it is advisable to treat with bisphosphonates if appropriate as per formulary.

  If HRT is prescribed, patients should be aware the benefit for bone mineral density is only present whilst they are using it. The following doses are thought to give adequate bone protection: 2mg oral oestradiol, 2 pumps of oestradiol gel, a 50mcg oestradiol patch or 3 sprays of Lenzetto. After 3 months check the oestradiol level to confirm adequate absorption. There is no evidence to recommend length of time for HRT use in terms of bone protection. Risks of prolonged HRT use vs bone protection need to be considered.

  Other recommendations to improve bone health in menopause are;

  • A healthy, nutrient-rich balanced diet with an adequate intake of calcium (700- 1000mg daily) and vitamin D (800-1000IU).
  • Smoking cessation.
  • Moderation of alcohol intake to ≤ 2 units/day.
  • Regular weight-bearing and muscle strengthening exercises.

   

• HRT and VTE

  The background population risk DVT/PE is 1.7 per 1,000 women aged over 50. There are several factors that increase background risk of developing VTE for example:

  • BMI >30 increases the risk up to 4 fold (BMI 25-30 also holds an increase risk from baseline)
  • Age- baseline risk doubles for each decade of life.
  • Smoking
  • Family history of VTE or hereditary thrombophilia
  • Previous VTE or inflammatory conditions that increase VTE risk for example Lupus, inflammatory bowel disease.
  • Reduced mobility/sedentary lifestyle
  • Hospitalisation

  When prescribing in these patients follow Devon Formulary guidance. The general recommendation is transdermal oestrogen and micronized progesterone or a 52 mcg Levonogestrel intrauterine device.

  Transdermal oestrogen has no increased risk above that noted in with non-users of HRT. The progestogen component of the HRT may also play a role with the VTE risk with synthetic type progestogens, Norethisterone and Medroxyprogesterone acetate, being higher risk than dydrogesterone or micronized progesterones. The 52 mcg Levonorgestrel intrauterine device has minimal systemic absorption and is thought to have low VTE risk. Tibolone does not increase VTE risk although has a noted stroke risk.

  Oral oestrogens increase the risk of VTE 2-4 fold. The highest risk being in the first year after initiation. Higher doses of oestrogen are associated with higher VTE risks. Preparations with conjugated equine oestrogen were associated with higher risks than preparations using oestradiol.

• Cardiovascular disease, MI, Stroke and HRT

  There is evidence that there is a reduction in cardiovascular disease in patients who initiate HRT under the age of 60 years. After that, it appears to be ‘risk-neutral’ although the dose and preparation have an impact. Patients with premature ovarian insufficiency have worse cardiovascular outcomes if they are not treated with HRT up to the age of 51.

  BMS makes recommendations for managing patients with cardiovascular disease. Individualised assessment is required and can be supported through Devon Menopause Service advice and guidance. In general, the recommendation for prescribing after MI or stroke in patients younger than 60 years of age or who are less than 10 years after menopause is to use a low dose transdermal oestrogen (25mcg patch/one pump oestrogen gel/one spray Lenzetto) alongside micronized progesterone in patient who have not had a total hysterectomy.

  HRT should not be discontinued post-MI (if the patient still requires it for menopause symptoms) as there is ongoing benefit to the cardiovascular system but dose and preparation adjustments may be needed. HRT can increase the risk of atrial fibrillation, so caution should be considered in patients with arrhythmia. Studies have shown reduced morbidity and mortality in patients on HRT after MI.

  Oral oestrogen and tibolone increase the risk of stroke and should be avoided in a patient with a history of stroke or with multiple risk factors for stroke. Studies have demonstrated no increased risk of stroke in transdermal oestrogen users versus non-users.

• HRT and Migraine

  In those patients whom have no evidence of aura and assuming no other risk factors for oral products, the full spectrum of HRT or combined hormonal contraception could be considered.

  In patients with a history of aura, combined hormonal contraceptives are contraindicated  due to increased risk of cerebrovascular events and VTE, oral oestrogen HRT is not recommended for the same reason. BMS recommends transdermal oestrogens (patch, gel or spray) will not increase this risk and will be safe to use in this group.

  Where progestogen is required, a continuous combined method is better suited in migraine as there are less absorption spikes. The decision will be led on patient preference as well as stage in menopause transition and need for contraception. Progestogens of choice would be levonorgestrel intrauterine device, transdermal norethisterone (combined patches) or micronized progesterone.

  Oestrogen patch is preferable to other formulations to provide a steady level of hormones without absorption spikes. Oestrogen should be started at a low dose and slowly titrated for example 25mcg patch twice weekly increased as tolerated after 2-4 weeks. The patient should be warned that migraine can be exacerbated in the initiation phase.

  In patients unable to take HRT, who require support for their menopause as well as migraine, the use of Venlafaxine (MR) 37.5mg – 150mg, or Escitalopram 10-20mg daily could be considered as off label options.