Key Facts

The menopause marks the permanent cessation of menstruation due to loss of ovarian follicular activity. The perimenopause is the transition period with fluctuating hormones. Primary care manages the vast majority of menopausal women.

Epidemiology

• Average age of menopause: 51 years in the UK
• Perimenopause typically begins 4-8 years before final menstrual period
• 1 in 100 women experience premature ovarian insufficiency (<40 years)
• 80% of women experience menopausal symptoms; 25% describe them as severe
• Vasomotor symptoms last an average of 7 years (range 2-20 years)

Aetiology

• Natural depletion of ovarian follicles with declining oestradiol and rising FSH
• Premature ovarian insufficiency: idiopathic (most common), autoimmune, iatrogenic (surgery, chemotherapy, radiotherapy), genetic (Turner syndrome, Fragile X premutation)
• Surgical menopause: bilateral oophorectomy (immediate onset)
• Risk factors for earlier menopause: smoking (1-2 years earlier), low BMI, nulliparity, family history

Pathophysiology

• Declining ovarian oestrogen production leads to hypothalamic dysregulation of the thermoregulatory centre (vasomotor symptoms)
• Oestrogen deficiency affects multiple organ systems: urogenital atrophy, bone loss, cardiovascular changes, mood/cognition
• Loss of oestrogen's protective effects on bone leads to accelerated bone loss (2-3% per year in first 5-10 years post-menopause)
• Genitourinary syndrome of menopause (GSM): vaginal atrophy, dryness, dyspareunia, recurrent UTI

Vasomotor Symptoms

• Hot flushes (sudden sensation of heat, often face/chest)
• Night sweats
• Palpitations

Urogenital Symptoms

• Vaginal dryness and dyspareunia
• Urinary frequency, urgency, recurrent UTI
• Vaginal atrophy on examination

Psychological Symptoms

• Mood changes (anxiety, irritability, low mood)
• Difficulty concentrating ('brain fog')
• Sleep disturbance
• Reduced libido

Musculoskeletal

• Joint pain and stiffness
• Muscle aches

Long-term Consequences

• Osteoporosis and fragility fractures
• Cardiovascular disease (loss of cardioprotective oestrogen effect)

Red Flags

• Postmenopausal bleeding (>12 months after last period) — requires 2-week-wait referral to exclude endometrial cancer
• Menopause <40 years — investigate for premature ovarian insufficiency
• Unilateral breast lump or bloody nipple discharge — urgent breast referral
• New vaginal bleeding on HRT after initial 6 months — investigate

Bedside

• Clinical diagnosis in women ≥45 with typical symptoms (NICE NG23) — no blood tests required
• BMI, blood pressure
• Breast examination if symptomatic

Bloods

• FSH: only required if:
  • Age 40-45 with menopausal symptoms (FSH >30 IU/L on 2 occasions 4-6 weeks apart suggests menopause)
  • Age <40 suspected premature ovarian insufficiency
  • On progestogen-only contraception making clinical diagnosis difficult
• Not required in women ≥45 with typical symptoms
• Before starting HRT: no mandatory blood tests, but consider baseline lipids, blood glucose/HbA1c

Imaging

• Pelvic USS: if unscheduled bleeding requiring investigation
• DEXA scan: if osteoporosis risk assessment needed (particularly premature ovarian insufficiency)

Special Tests

• Endometrial biopsy: if postmenopausal bleeding or abnormal bleeding on HRT
• Mammogram: as per NHS Breast Screening Programme (3-yearly, age 50-71)

Non-pharmacological

• Lifestyle advice: regular weight-bearing exercise, healthy diet, smoking cessation, moderate alcohol
• CBT: effective for vasomotor symptoms and low mood (NICE NG23)
• Layer clothing, cool environment, reduce triggers (caffeine, alcohol, spicy food)
• Vaginal moisturisers (Replens) for GSM

Pharmacological

HRT (NICE NG23):

• With uterus — combined HRT:
  • Perimenopause: sequential combined (oestrogen daily + progestogen for 12-14 days per month): e.g. Evorel Sequi patches, Femoston 1/10
  • Postmenopause (>12 months since LMP): continuous combined: e.g. Femoston Conti 0.5/2.5 or 1/5, Evorel Conti patch, Kliovance
  • Mirena IUS can provide progestogen component (licensed for 5 years as endometrial protection)
• Without uterus — oestrogen only:
  • Transdermal oestradiol patch (Evorel 50-100mcg) or gel (Oestrogel 1-2 pumps)
  • Oral oestradiol 0.5-2mg OD
• Transdermal route preferred if VTE risk factors, BMI >30, migraine, hypertension
• Vaginal oestrogen (Vagifem 10mcg pessary, Ovestin cream): for localised GSM symptoms; minimal systemic absorption; can be used alongside systemic HRT; no progestogen needed; can continue indefinitely

HRT risks and benefits (for women starting <60 years or within 10 years of menopause):

• Benefits: effective for vasomotor symptoms, bone protection, GSM, possible cardiovascular benefit
• Breast cancer risk: combined HRT — small increased risk (4 extra cases per 1,000 women over 5 years); oestrogen-only — no significant increase up to 7 years
• VTE risk: oral HRT doubles VTE risk; transdermal HRT does NOT increase VTE risk
• Cardiovascular: HRT started <60 years reduces CVD risk; HRT started >60 years may increase risk

Non-hormonal alternatives:

• SSRIs/SNRIs: fluoxetine 20mg OD, venlafaxine 37.5-75mg OD, paroxetine 7.5-20mg OD (reduce hot flush frequency by 50-60%)
• Gabapentin 300mg TDS (off-label)
• Clonidine 50-75mcg BD (limited efficacy)
• Avoid unregulated 'bioidentical' hormones and compounded preparations

Premature ovarian insufficiency:

• HRT or COCP recommended until at least age 51 (average menopause age)
• Important for bone and cardiovascular protection

Testosterone:

• For reduced sexual desire not improved by HRT alone
• Transdermal testosterone cream/gel (no UK-licensed female product; male preparations used at reduced dose)

Surgical

• Not applicable for menopause management itself

Referral Criteria

• Premature ovarian insufficiency: gynaecology/reproductive medicine
• Postmenopausal bleeding: 2-week-wait gynaecology
• Complex HRT decisions (previous breast cancer, VTE history): menopause specialist clinic
• Persistent symptoms despite optimised HRT: specialist review

• Vasomotor symptoms: average duration 7 years; some women continue beyond 10-15 years
• HRT: symptoms improve in >80% within 3 months
• Osteoporosis risk: bone density loss of 2-3%/year in first 5-10 years post-menopause; HRT prevents this loss
• Premature ovarian insufficiency: without HRT, significant increased risk of osteoporosis and cardiovascular disease
• HRT and all-cause mortality: evidence suggests no increased all-cause mortality with HRT in women starting within 10 years of menopause
• Breast cancer: risk returns to baseline within 2-5 years of stopping combined HRT

HRT Route Selection

WHI Study Context