Introduction

• Menopause is the permanent cessation of the menstrual cycle
• Menopause usually occurs between the ages of 45 and 55
• Typical age is 51.5
• Premature menopause is defined as menopause before the age of 40 – aka premature ovarian insufficiency
• The process of going through the menopause can be split into the premenopause – a time of irregular periods, and menopause – the time when the periods cease. The total time spent passing through these changes varies between 2 and 5 years
• Postmenopause is said to begin at 12 months after the final period
• Menopause has many physiological effects, but one of the main pathological consequences is the predisposition for osteoporosis
• As well as being a physiological process, menopause is induced by surgical removal of the ovaries, or by damage to ovarian function with radiotherapy or chemotherapy

Physiology

• As the menopause approaches, the number of primary follicles declines
• Levels of FSH and LH rise dramatically
• The ovary produces very little oestrogen or progesterone, but continues to produce androgens
• Diseases for which risks increases after menopause:
  • Osteoporosis
  • Cardiovascular disease
  • Diabetes
  • Cancer
    • Breast
    • Ovary
    • Cervix
• Premature menopause occurs in
  • About 1% of women <40 years as a result of genetic or autoimmune disease. These patients require specialist investigation
  • About 5% of women <40 due to oophorectomy or chemotherapy
  • Women age 40-45 have physiologically significant “premature menopause” and don’t necessarily require further work-up

Presentation

The symptoms of menopause are due to tissue sensitivity to lower oestrogen levels. This mainly affects the brain. Symptoms vary widely – some women experience none at all, whilst other are severe debilitated by their symptoms. About 80% of women will experience some symptoms. 50% of women will experience some symptoms for at least 7 years.

• Hot flushes – 80%
• Night sweats – 70%
• Palpitations – 30%
• Dizziness
• Lethargy / tiredness
• Migraine / other headaches
• Psychological
  • Irritability
  • Depression
  • Anxiety
  • Poor short term memory
  • Sleep disturbance
• Urogential
  • Vaginal dryness (45%)
  • Atrophic vaginitis
  • Dyspareunia (pain on sexual intercourse)
  • Reduced libido
  • Bladder dysfunction
  • Stress incontinence (e.g. frequency, dysuria)
  • Prolapse
• Skin
  • Dry skin
  • Sensation of insects crawling on skin (formication)
  • Facial har
  • Breast tissue atrophy

The oestrogen deficiency symptoms are hot flushes and the urogenital symptoms. These are important to elicit in the history, as these are the symptoms most effectively treated with HRT.

• Vasomotor symptoms (hot flushes and night sweats) are at their height in the perimenopause and early post menopausal stage, before resolving with time
• Urogenital atrophy symptoms tend to worsen with age

Investigations

In a typical-age patient (age 45-55), no specific investigations are required – the diagnosis is usually clinical. However, several investigations may be performed to rule out other differentials. Differentials include:

• Thyroid disorders
• Dysfunctional uterine bleeding
• Anaemia
• Depression

Investigations to help discern these differentials would include:

• Urinalysis
• FBC
• TSH
• LFTs
• Iron studies
• B-hCG (!)

Investigations are not necessary to confirm diagnosis of menopause in women aged >45.

In possible early menopause (age <45), the following hormonal test may confirm the diagnosis:

• Serum FSH – high – (around 25 U/L))
• Serum oestradiol – low – (<100 pmol/L)
• Two readings should be taken 6 weeks apart (or 3 months apart if has a mirena (IUD))
• These investigations are NOT intended to diagnose menopause in women >45
• FSH is not always elevated early in the perimenopausal period

Other investigations to consider around the perimenopausal period include:

• Fasting lipid profile (for cardiovascular disease risk)
• Mammogram – particularly remember to consider this 3 months after starting HRT
• Hysteroscopy – if abnormal uterine bleeding
• Pap smear and mammography
• Bone density – if risk factors (consider using risk calculator – such as FRAX)

Management

Patient education

• Emphasis that the menopause is a natural physiological process
• Some lifestyle factors can trigger the vasomotor symptoms – including caffeine, alcohol, spicy foods
• Lifestyle factors have been shown to reduce the severity of symptoms
  • Healthy diet
  • Healthy weight
  • Regular exercise
  • Smoking cessation
  • Reduce caffeine intake
  • Alcohol intake within recommended safe limits
  • Stress reduction and relaxation (consider mindfulness)
• Screen for anxiety and depression and treat these if present
• Give advice about bone health
  • 1300mg calcium per day
  • 150 minutes of moderate intensity exercise weekly
  • Vitamin D – either supplementation or sun exposure
  • Smoking cessation
  • Safe drinking limits (alcohol)

Sex

• Advise it is normal to need additional vaginal lubrication
• Advise to continue contraception for 12 months after the last period in women >50 and 2 years in women <50
• The combined oral contraceptive pill (low dose preparations) can be used up to the age of 50 if there are no contraindications (see UKMEC guidelines for contraindications). After the age of 50, condoms and progesterone only preparations are recommended.

Hormone replacement therapy

Hormone replacement therapy (HRT) should be considered for any patient with moderate to severe vasomotor symptoms (hot flushes, night sweats, palpitations).

For patients with urogenital symptoms – consider topical oestrogen preparations:

• e.g. – Oestradiol 1mg/g with applicator
  • Once at night for three weeks, then 2-3x per week thereafter
  • OR
  • Oestradiol 10mg pessary – at night daily for 3 weeks, then x2 per week at night after that

These topical vaginal preparations will:

• Reduce vaginal dryness, itching and pain
• Reduce dyspareunia
• Reduce risk of recurrent UTIs
• Take 6-8 weeks to be effective
• Avoid added progestins – can increase the risk of endometrial cancer
• Contraindicated in undiagnosed vaginal bleeding, endometrial cancer
• Some gynaecologists recommend against their use after a diagnosis of breast cancer

For vasomotor symptoms, consider preparations with systemic effects (e.g. oral medications, patches, implants, gels). Use the smallest dose possible to receive symptoms. 

Examples of oestrogen preparations include:

• Patches – applied weekly – typical dose 50mcg
• Transdermal topical gel applied to the skin
• Implant – 50-100mg – given every 3-12 months
• Oral preparations – no need to stop dosing for one week each month (unlike in pre-menopausal women)
  • Oral oestrogen carries significant VTE risk and should not be used in those with personal history or 1st degree relative history of VTE
  • Non-oral oestrogen does NOT have these contraindications and can still be used in these patients

However – unopposed oestrogen (i.e. without progesterone) therapy causes hypertrophy of the uterus and a 5-10x increased risk of endometrial carcinoma.

• As a result, any woman on HRT who still has her uterus should be on a progestin
• Can be given as a 14 day on-off cyclical regimen – however this often causes withdrawal bleeds which many post-menopausal women would prefer to avoid
• Can also be given continually
• The sole purpose of giving a progestin is to prevent endometrial hypertrophy and reduce risk of endometrial carcinoma
• Examples of progestins include:
  • Dydrogesterone 10-20mg daily
  • Medroxyprogesterone acetate 10 mg daily
  • Norethisterone 1.25mg – 5mg daily

Many preparations come as combined oestrogen and progestin combinations. Some of these are cyclical (best in perimenoapusal women) and other are continuous best in post menopausal women – i.e. >12 months since the last period. The most commonly prescribed method is transdermal patch. These may cause localised skin irritation. Transdermal methods of oestrogen are generally preferred because they have a reduced risk of VTE compared to oral preparations.

HRT improves quality of life in the short term. It has widespread and complicated risks for various disease – some increased and some decreased.

In 2002, the Women’s Health Initiative (WHI) trial results were released. This raised concerns amongst prescribers around the world, as it showed that in women who used oestrogen containing oral HRT preparation for >5 years there is an increased risk of:

• Breast cancer – 1.26x risk
• Coronary heart disease – 1.29x risk
• Stroke – 1.41x risk
• Pulmonary embolus – 2.13x risk

and also reduces the risk of:

• Bowel cancer
• Osteoporosis
• Fractures

Prior to this study, HRT was much more widely used. In the wake of this study, new recommendations advised to:

• Not use HRT solely for osteoporosis prevention in asymptomatic women
• Women using HRT should slowly reduce their dose over 2-3 months when stopping treatment
• It is advisable to limit treatment to <5 years
  • There is no proven associated risk of an increase in breast cancer in women who use HRT <5 years
• Risks are greatest in women >60 using HRT

Principles of HRT

• If perimenopausal – use the combined oral contraceptive pill (if <50) or the IUD
• If menopause – use specific HRT preparations (as above and table below)
  • Combined therapy for all women with a uterus
  • Oestrogen only therapy for women without a uterus
  • Start with a small dose and titrate upwards
• Perform mammography 3 months after starting treatment
• Then, review at 6 monthly intervals
• Duration of treatment
  • Aim to cease treatment at 2 years
  • If unable to tolerate symptoms at this point – continue for up to 5 years. Be aware that up to 50% of patient swill suffer vasomotor symptoms (at least temporarily) on cessation of treatment
  • Balance risk vs benefits if you plan to continue past 5 years – ensure informed consent

• E = Oestrogen
• P = Progesterone
• Patches may be preferred over pills due to lower VTE risk

Contraindications to HRT

• Oestrogen dependent tumours
  • Endometrial carcinoma
  • Breast cancer
  • Ovarian cancer
• VTE
  • Contrainidcation for oral oestrogen preparations only
  • Personal or first degree relative history
• Ischaemic heart disease / coronary artery disease
• Previous TIA / CVA
• Uncontrolled HTN
• Undiagnosed vaginal bleeding
• Liver disease
• SLE
• Pregnancy (!)

Examples of HRT preparations

HRT therapies containing both an oestrogen and progestin are known as ‘combined HRT’. There are two types – cyclical and non-cyclical. Cyclical should be used in those who are perimenopausal (<12 months since last period) and non-cyclical can be used in those who are menopausal.

Some examples include (don’t worry about memorising this table – but perhaps know a couple of options):

NB – based on brands available in Australia in 2020. 

Testosterone

• May be given to relieve reduced libido
• Usually given as a 50mg implant – which lasts 3-12 months
• Should be given with concurrent 50mg oestrogen implant
• Limited data as to its safety

Tibolone

• A synthetic hormone with combined oestrogen, progestin and testosterone effects
• Can be used in post-menopause women – particularly useful in patients without a uterus and those whose last period was >12 months ago
• Useful for vasomotor symptoms (but probably less effective than conventional HRT)
• Useful for low libido (better than conventional HRT)
• Less likely to cause bleeding than conventional HRT
• In perimenopausal women may cause irregular bleeding – so avoid

“Bioidentical hormones”

• Available at some private clinics and unregulated online
• Variable preparations and strengths of oestrogen and progesterone
• Marketed as being “safer” than traditional HRT
• There is no evidence that they are safer – and in fact due their unregulated nature are inherently less safe and not well studied
• No evidence that they are more effective than conventional HRT
• Frequently raised by patients who are struggling with menopausal symptoms

Correcting bleeding problems

• Heavy bleeding – reduce oestrogen
• Breakthrough bleeding – Increase progestrogen
• Irregular bleeding – investigate
• Patient can’t tolerate bleeding – use continual regimen
• No bleeding – normal

SSRIs

• Should be considered as second line – and are particularly effective for treatment of hot flushes (vasomotor symptoms)
  • Contrary to some belief – they are not recommended in menopause because of their mood boosting efects
• More effective than placebo in clinical trials
• E.g.:
  • Venlafaxine 37.5mg increasing to 75mg daily
  • Paroextine 10mg increasing to 20mg daily

Other non-hormonal medications

• Gabapentin 100 – 300mg PO OD, slowly can increase dose to maximum of 300mg TDS
• Clonidine 25mcg PO BD, can increase to 50mg BD after 2 weeks

When to refer

Refer to gynaecology if:

• Patient aged <40 and symptoms of menopause, OR
• Pharmacological treatment is required in menopausal women whose menopause is secondary to cancer or chemotherapy

Flashcard

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Menopause – Health Pathways
• HRT – Health Pathways
• Menopause – patient.info

Read more about our sources

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