Menopause/perimenopause 

Stages of Menopause:

• Pre-Menopause:
  • Characterized by regular menstrual cycles.
  • No changes in symptoms or hormonal fluctuations related to the menopausal transition.
• Peri-Menopause:
  • Definition: The transitional period “around menopause.”
  • Average Duration: Approximately 5 years.
  • Typical Age Range: Between 39 and 51 years.
  • Cycle Changes: Increased cyclic irregularities, including prolonged ovulatory and anovulatory cycles.
  • Hormonal Changes:
    • Levels of follicle-stimulating hormone (FSH) and oestradiol oscillate, with declining luteal function.
  • Symptoms:
    • 10-20% experience no symptoms.
    • 10-20% experience severe symptoms.
    • The remainder have varying levels of symptoms.
• Menopause:
  • Definition: Cessation of menstruation for over 12 months.
  • Hormonal Changes: Reduced oestrogen and progesterone; increased FSH and LH.
  • Typical Age Range: Between 45-55 years.
  • Average Age: 50-51 years.
• Early Menopause:
  • Definition:
    • Early Menopause: Menopause occurring before 45 years.
    • Premature Menopause: Menopause occurring before 40 years.

Stopping Contraception at Menopause:

• Non-Hormonal Contraceptives:
  • Can be stopped after 12 months of amenorrhea.
• Hormonal Contraceptives:
  • Can be stopped after 24 months of amenorrhea.
  • It is advisable to switch from estrogen-containing methods or Depo around the age of 50.
  • Progesterone-only pills (POP), implants, or Mirena can continue if suitable.
  • Amenorrhea is not always reliable as an indicator in women on progesterone-only methods.
• Supporting Informed Choice:
  • The decision to stop contraception is not exact.
  • Provide patients with the information needed to make an informed choice regarding contraception use during the menopausal transition.

Advice on stopping contraception for women aged 50 years and older according to method
Method	Advice
LNG-IUD, POP, ENG implant	Amenorrhoeic for ≥12 months: Check 2 x FSH levels at least six weeks apart and if both are ≥30 IU/L advise that contraception is only required for another 12 months; OR Continue until aged ≥55 years
Cu-IUD and barrier methods	Stop method after 12 months of amenorrhoea
DMPA	Generally not recommended beyond 50 years of age. Either: Switch to a non-hormonal method until amenorrhoea for 24 months;* OR Switch to an alternative progestogen-only method and follow method-specific advice for stopping
CHC: includes COCP and vaginal ring	Generally not recommended  beyond 50 years of age. Either: Switch to a non-hormonal method until amenorrhoea for 12 months; OR Switch to LNG-IUD, POP or ENG implant and follow method-specific advice for stopping
*As prolonged amenorrhoea can occur after stopping DMPA, it is necessary to wait 24 months before a woman can be assumed to be no longer fertile. CHC, combined hormonal contraception; COCP, combined oral contraceptive pill; Cu-IUD, copper intrauterine device; DMPA, depot medroxyprogesterone acetate; ENG, etonogestrel; FSH, follicle stimulating hormone; LNG-IUD, levonorgestrel intrauterine device; POP, progestogen-only pill

SYMPTOMS

• Vasomotor:
  • hot flushes – typically lasts 5-7 years, but can persist for 10+ years in some women.
  • night sweat
  • palpitations
  • lightheadedness/dizziness
  • migraine
• Psychogenic:
  • irritability, depression
  • anxiety/tension
  • tearfulness, loss of concentration
  • poor memory, unloved feelings, sleep changes, loss of self confidence
  • Typically lasts for 1-2 years around menopause, but for some can persist longer.
• Urogenital:
  • atrophic vaginitis
  • vaginal dryness
  • dyspareunia
  • decline in libido
  • bladder dysfunction (dysuria)
  • stress incontinence/prolapse
  • Symptoms can continue indefinitely, particularly if related to vaginal dryness, which often requires ongoing treatment.
• MSK:
  • aches + pains
• Skin:
  • dry skin, formication, new facial hair, breast glandular tissue atrophy
• Weight Gain and Metabolic Changes:

Symptoms potentially present at menopause and differential diagnoses
Assessment	History and examination findings		Could this be due to…?	Investigations in specific circumstances (some may be specialist initiated)
General menopausal symptoms	Flushes	Excessive or not relieved with oestrogen Associated factors: weight loss, hypertension, diarrhoea, anxiety, goitre, thyroid nodule	Thyroid disease Phaeochromocytoma Carcinoid syndrome	Thyroid stimulating hormone (TSH) 24 hour urinary catecholamines 24 hour urinary 5 HIAA
	Night sweats	Lymphadenopathy Hepatosplenomegaly Weight loss	Malignancies (eg. lymphoma, myeloma)	Appropriate blood work up, chest X-ray, node biopsy, serum and urine protein electrophoresis
	Palpitations	Associated cardiac symptoms	Cardiac arrythmia	Electrocardiogram (ECG), 24 hour Holter monitor
	Formication (‘ants crawling on skin’)	Presence of rash New sexual partner (ie. risk sexually transmissible infections [STIs])	Scabies Dermatitis	Skin examination
	Myalgia and arthralgia	Associated joint swelling, inflammation	Rheumatological disorders arthritis	ESR. CRP.  autoimmune serology, joint X-ray
	Migraine/headaches	Unusual, focal neurological symptoms and signs	Intracranial lesion	CT MRI brain
Gnaecological symptoms	Menorrhagia	Persistent (ie. not a one-off heavy bleed) Flooding at night Clots Anaemia or iron deficiency	Fibroid Uterine polyp Endometrial hyperplasia Uterine cancer Adenomyosis Thyroid dysfunction Coagulopathies	Transvaginal ultrasound  Endometrial sampling (Pipelle biopsy, hysteroscopy) Full blood examination (FBE), Fe studies, TSH, coagulation profile
	Amenorrhoea	Recent unprotected intercourse Associated factors, eg: galactorrhoea, headache, visual field defects thyroid symptoms androgen excess recent weight changes, eating disorders, exercise intensity, pelvic pain, mass	Pregnancy Hypothalamic dysfunction Pituitary dysfunction Ovarian tumours Thyroid disease Polycystic ovary syndrome (PCOS)	Beta human chorionic gonadotrophin (HCG) Transvaginal ultrasound CT/MRI brain/pituitary TSH, androgen screen, prolactin
	Hysterectomy Mirena™ IUD in situ	Oestrogen deficiency symptoms	Menopause	Follicle stimulating hormone (FSH) and oestradiol (if not on oral contraceptive pill [OCP] or HT; measured ~ day 3 of cycle)
	Postcoital bleeding	Cervical polyp Abnormal Pap smear/history	Cervical cancer	Biopsy
	Family history	Relevant family history of cancer (CA): ovary, breast, uterus, bowel	Cancer ovary, uterus (familial)	Transvaginal ultrasound CA 125, inhibin, genetic testing
	Pelvic pain	Palpable mass Deep dyspareunia Per vaginal (PV) discharge, febrile Known history endometriosis	Cancer ovary/uterus Endometriosis/ adenomyosis Ovarian cyst Pelvic inflammatory disease (PID)	Transvaginal ultrasound Laparoscopy Swabs
Genitourinary symptoms	Incontinence	Stress incontinence Urge incontinence Faecal incontinence	Pelvic floor dysfunction Detrusor instability Fistula	Urodynamics Physiotherapy assessment
	Urinary symptoms	Fever, dysuria, haematuria Polyuria/oliguria Polydipsia	Urinary tract infection Renal insufficiency Diabetes	Midstream specimen of urine (MSU) Renal function tests Fasting blood glucose
	Vulval irritation	Vaginal discharge Superficial dyspareunia Abnormal vulval appearance: lichenification, absent labia minora, inflammation, lesions	Vaginal infections: thrush, STI Lichen sclerosus Candidiasis Vulval cancer	Swabs Vulval biopsy
Sexual symptoms	Loss of libido	Relationship issues Associated lethargy, tiredness, depression Bilateral oophorectomy Superficial dyspareunia Use of medications (eg. selective serotonin reuptake inhibitors [SSRIs], OCP, oestrogen)	Androgen insufficiency syndrome Mood disorder Atrophic vaginitis Medication side effects Relationship breakdown	Sensitive testosterone (T), sex hormone binding globulin > calculated free T (measured in morning, ~ day 7 of cycle)Trial of local oestrogen Trial off/change medication
	Sexual partner	New partner, not using condoms Partner in another sexual relationship	STI	STI screen: serology syphilis, HIV, hepatitis, urine PCR for chlamydia
Breast symptoms	Family history	Relevant family history of breast or ovarian cancer	Breast cancer (familial)	Diagnostic mammogram +/–Ultrasound Genetic testing
	Breast changes	Palpable lump or skin distortion Nipple discharge/eczema Abnormal screening mammogram	Breast cancer Fibroadenoma Breast cyst/abscess Mammary duct ectasia	Diagnostic mammogram Ultrasound Biopsy (eg. fine needle, core, excisional)
Psychosocial symptoms	Depression/anxiety	Family/past history mood disorders including premenstrual syndrome (PMS) postnatal depression (PND) Panic attacks phobias sleep disturbance Loss of motivation loss of libido appetite suicidal thoughts Current use of medications (eg. SSRIs)	Major depressive disorder Generalised anxiety disorder Specific phobias Panic disorder Bipolar disorder Schizophrenia	Psychological assessment
	Memory loss	Poor concentration Disorientation	Cognitive disorder Dementia	Mini Mental State Examination Neuropsychological testing

CLINICAL APPROACH

aim of the assessment of the menopausal woman is to:

1. manage acute menopausal symptoms (eg. hot flushes)
2. manage complications of menopause (eg. osteoporosis)
3. avoid risk factors for complications (eg. fracture, thromboembolism)

Explaining Menopause to a Patient:

• Before Menopause:
  • Ovaries typically release an egg each month.
  • This triggers regular hormone changes that result in monthly periods and cyclical bodily changes.
• Menopausal Transition:
  • As ovaries begin to ‘fail’, egg release becomes erratic.
  • This causes unpredictable hormone levels, leading to:
    • Irregular periods.
    • Symptoms like hot flushes (due to low hormone levels when an ovary fails to release an egg).
    • Symptom relief when ovaries spontaneously release an egg, temporarily increasing hormone levels.
  • This phase is often referred to as a period of “hormonal chaos”.
  • You will need contraception for at least 12 months after your last natural period due to spontaneous egg releases.
  • The transition phase can last up to 4–5 years.
• Ovarian Failure:
  • Ovaries rarely stop functioning suddenly, except when surgically removed.
  • Eventually, the ovaries will completely stop releasing eggs.
  • Hormone levels drop to what is considered postmenopausal levels.
• Symptoms During Menopause:
  • Every woman experiences menopause differently:
    • About 20% of women have no symptoms.
    • Another 20% experience severe, disabling symptoms.
    • The majority (60%) experience moderate symptoms.
  • Types of symptoms vary:
    • Hot flushes, mood changes, vaginal dryness, or a combination.
  • Symptoms are also influenced by lifestyle and other factors, including:
    • Stress levels, medical conditions, psychosocial factors.
• Holistic Management:
  • Menopause is influenced by multiple factors: hormones, relationships, genetics, stressors, and overall health.
  • Managing menopause symptoms involves more than just addressing hormone levels—it requires a comprehensive health management approach considering all aspects of your life.

Investigations

• For women less than 45 years of age, FSH testing is  Recommended
• but for women older than 45 diagnostic blood tests including FSH are not necessary

Risk assessment in midlife women
Risk assessment	Significant risk factors	Possible additional investigations (some may be specialist initiated)
Cardiovascular	Family history of ischaemic heart disease (IHD), Family history of ischaemic heart disease (IHD), stroke, cardiovascular disease (CVD) risk factors Past history of IHD, stroke Diabetes, hypertension, hyperlipidaemia, obesity, smoker Sleep apnoea	Glucose tolerance test Urine microalbumin, renal function tests 24 hour blood pressure monitor Chest X-ray ECG echocardiogram Sleep study Absolute cardiovascular risk calculator
Osteoporosis risk assessment Fracture risk	Past history of fragility fracture: site, spontaneous or fall related Family history hip fracture Age over 65 years Low body mass index (BMI) Low T-score on DXA >3 months corticosteroid use High fall risk: frail, visually impaired, neuromuscular disorders, sedative use Lifestyle: sedentary, prolonged immobilisation, smoker, more than three units of alcohol per day, low calcium and/or, vitamin D intake Chronic disorders: rheumatoid arthritis, type 1 diabetes mellitus, hyperthyroidism, liver disease, chronic renal failure Hyperparathyroidism, hypogonadism (including premature menopause and secondary amenorrhoea), malabsorption syndromes (including coeliac disease), multiple myeloma	Exclusion of secondary causes of osteoporosis: – calcium – phosphate – parathyroid hormone – vitamin D – liver function tests – creatinine, urea and electrolytes – TSH – ESR – urine and serum protein electrophoresis – coeliac serology Plain X-ray spine to exclude compression fracture if back pain, loss of height Bone scan if osteoporosis very localised Bone turnover markers – used to assess treatment rather than risk NB: FRAX® WHO Fracture Risk Assessment Tool calculates percentage likelihood that an individual will sustain a fracture in the next 10 years using clinical risk factors in conjunction with bone density measurements, providing opportunity for more accurate targeting of therapies to prevent fractures based on probability rather than simply T-score: www.shef.ac.uk/ FRAX/
Thrombophilia	Family history of deep vein thrombosis (DVT), pulmonary embolism (PE), genetic thrombophilia Past history DVT, PE – what circumstances, ie. spontaneous, related to surgery or pregnancy, young age Known thrombophilia, ie. Factor V Leiden mutation Older age (>60 years) High BMI,  Smoker Recent hospitalisation/surgery/hip, leg fracture, immobilisation, travel Past history recurrent miscarriages Systemic lupus erythematosus, cancer Medications – tamoxifen, raloxifene	Thrombophilia screen – activated protein C resistance (APCR) – Factor V Leiden – prothrombin gene mutation – homocysteine – protein C&S – antithrombin III – coagulation profile – Antiphospholipid antibodies: anticardiolipin Ab, lupus anticoagulant
Cancer	Breast cancer Increasing age, increasing weight Nulliparous, later age at birth of first child, no breastfeeding, early menarche High mammographic breast density More than three alcoholic drinks per day Ashkenazi Jewish ancestry Past history invasive cancer breast, DCIS, atypical ductal hyperplasia Family history breast cancer (depends on degree, number, age) Past or family history ovarian cancer Family or personal history hereditary nonpolyposis colorectal cancer (HNPCC) Known family or personal BRCA1 or BRCA2 gene mutations Diethylstilbestrol (DES) use in pregnancy/in utero Ovarian cancer Older age (>65 years) Nulliparous or first child after 30 years, early menarche, late menopause Family history ovarian cancer Known family or personal BRCA1 or BRCA2 gene mutations Family or personal history HNPCC Endometrial cancer Aged >50 years Nulliparous Taking tamoxifen, anastrozole, unopposed oestrogen Endometrial hyperplasia Family or personal history HNPCC	Transvaginal ultrasound Tumour markers: – CA 125 – inhibin Genetic testing Laparoscopy

MANAGEMENT

Lifestyle and Behavioural Modifications for Menopausal Symptoms

• Maintaining Healthy Weight:
  • A study involving 40 overweight/obese women showed that a 10% weight loss significantly improved hot flushes.
  • Weight loss correlated with a reduction in the frequency of hot flushes.
• Physical Activity:
  • Regular physical activity is linked to reduced menopausal symptoms, including hot flushes.
  • Exercise improves overall health, helps with weight management, and can reduce hot flush severity.
    • (Reference: Elavsky S, McAuley E. Menopause. 2007)
• Clothing and Environment:
  • Cooling Strategies:
    • Though no definitive clinical evidence supports cooling interventions for vasomotor symptoms, reducing core body temperature can help.
    • Suggested changes include:
      • Wear light, breathable clothing (layers, natural fibers).
      • Avoid heavy clothing like jumpers and scarves.
      • Lower room temperature.
      • Use a cold pack under the pillow or flip the pillow to the cooler side.
      • Drink cool liquids like iced water.
• Avoiding Triggers of Vasomotor Symptoms:
  • Certain triggers can exacerbate hot flushes for some women, including:
    • Caffeine, alcohol, and spicy foods.
• Mind- and Body-Based Therapies:
  • Cognitive Behaviour Therapy (CBT):
    • Helps manage the psychological and physical symptoms of menopause.
  • Mindfulness and Relaxation Techniques:
    • Can reduce the frequency and severity of hot flushes.
  • Yoga:
    • Promotes relaxation and helps manage menopausal symptoms.
  • Paced Breathing:
    • Controlled breathing exercises to aid in relaxation.
  • Relaxation Techniques:
    • General relaxation practices can provide symptom relief.

Menopausal Hormone Therapy (MHT)

1. Oestrogen Only Menopausal Hormone Therapy
   • Suitable for women with troublesome menopausal symptoms
   • Effective for hot flushes, vaginal dryness, loss of libido, irritability, sleep disturbances, and muscle/joint pains
2. Combined Menopausal Hormone Therapy
   • Recommended for women with an intact uterus to prevent endometrial hyperplasia and cancer
   • Includes both oestrogen and progestogen
   • Benefits: Symptom relief and bone loss prevention
   • Risks: Increased risk of breast cancer, thrombotic events, and adverse cardiovascular changes
3. Tibolone
   • Synthetic hormone therapy for post-menopausal women
   • Relieves menopausal symptoms and prevents osteoporosis

Non-Hormonal Pharmacotherapy for Menopause Symptoms

• Suitable for Women Who:
  • Do not find relief with lifestyle changes.
  • Cannot use hormones due to medical conditions.
  • Prefer to avoid hormones due to potential health risks.
• Key Considerations:
  • Includes off-label use of medications, especially for managing hot flushes/night sweats.
  • Emphasis on evidence-based prescribing for off-label use.
• Selective Serotonin Reuptake Inhibitors (SSRIs) & Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):
  • Indications: Hot flashes, mood disturbances, anxiety.
  • Examples & Dosage:
    • Venlafaxine (Effexor): Start at 37.5 mg daily; may increase to 75 mg daily.
    • Paroxetine (Paxil): Start at 10 mg daily; may increase to 20 mg daily.
    • Citalopram (Celexa): Start at 10 mg daily; may increase to 20 mg daily.
  • Evidence: Shown to reduce frequency/severity of hot flashes and improve mood in menopausal women.
• Gabapentin (Neurontin):
  • Indications: Hot flashes, particularly nocturnal hot flashes.
  • Dosage: Start at 300 mg at bedtime; may increase to 300 mg three times daily.
  • Evidence: Demonstrated to significantly reduce hot flash frequency and severity in multiple clinical trials.
• Clonidine (Catapres):
  • Indications: Hot flashes.
  • Dosage: Start at 0.1 mg at bedtime; may increase to 0.1 mg twice daily.
  • Evidence: Effective in reducing hot flashes but often associated with side effects (e.g., dry mouth, drowsiness).

Vasomotor Symptoms/hot flushes 

Urinary Symptoms and Vaginal Dryness

• Urine Symptoms:
  • Oxybutynin can be used for urinary symptoms.
• Vaginal Dryness Management:
  • First Line (Non-Hormonal Options):
    • Replens or K-Y Gel as lubricants for vaginal dryness.
  • Second Line (Low-Dose Vaginal Hormonal Preparations):
    • Estriol cream, estriol pessary, or estradiol pessary:
      • Use daily for 2 weeks, then reduce to twice weekly.
    • Vaginal Moisturisers (use twice weekly):
      • Examples include Replens® and Yes®.
  • Safety of Vaginal Estrogen:
    • Vaginal estrogen does not increase the risk of:
      • Cardiovascular disease (CVD)
      • Venous thromboembolism (VTE)
      • Developing breast cancer
    • If Previous Breast Cancer:
      • Start with non-hormonal treatments.
      • If symptoms persist, consider vaginal estrogen in consultation with an oncology specialist.
  • Additional Benefits:
    • Vaginal estrogen may also improve urinary symptoms and help prevent recurrent UTIs.
• Natural Therapy Considerations:
  • Phytoestrogens:
    • No proven effect on reducing hot flushes or other menopausal symptoms.
    • Long-term use (>5 years) is associated with an increased risk of endometrial hyperplasia.
  • Black Cohosh:
    • Associated with the risk of liver failure; caution is advised.