Menopause/perimenopause 

Pre-menopause:

• is characterised by continuation of regular menstrual cycles without any changes in the symptoms of menstruation transition or hormonal variability. 

Peri-menopause: 

• about or around the menopause.
• The average length of this stage is 5 years. 
• Usually 39 – 51 years
• Cyclic irregularities increase as women enter this stage with prolonged ovulatory and anovulatory cycles. 
• Levels of follicle stimulating hormone and oestradiol oscillate frequently with decreasing luteal function.
• 10-20% NO sx
• 10-20% severe sx, remainder … some sx

Menopause

• cessation of menses for >12 months, reduced oest/prog +  increasedFSH/LH
• range 45-55ysm average 50-51yrs

Early menopause

• menopause <45yrs; premature menopause = <40yrs

Stopping contraception at menopause

• Non hormonal – amneorrhea for 12 months can cease
• Hormonal – amneorrhea for 24 months can cease
• Estrogen or Depo should be advised to switch around age 50
• Can continue POP, implant or Mirena
• If on a progesterone only method amenorrhea is not reliable
• Decision to stop is not exact – give information to support informed choice

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; ORContinue 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;* ORSwitch 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; ORSwitch 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
  • 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
• Urogenital:
  • atrophic vaginitis
  • vaginal dryness
  • dyspareunia
  • decline in libido
  • bladder dysfunction (dysuria)
  • stress incontinence/prolapse
• MSK:
  • aches + pains
• Skin:
  • dry skin, formication, new facial hair, breast glandular tissue atrophy

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), ferrum (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 intensitypelvic 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
	HysterectomyMirena™ 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 polypAbnormal 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 massDeep 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 testsFasting 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 oestrogenTrial 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 patient

• Before menopause the ovaries (usually) release an egg each month, which then triggers the normal cascade of hormone changes that result in regular periods and cyclical changes. 
• As the ovaries ‘fail’, they begin to release their eggs erratically, which in turn causes erratic hormone levels. 
• Periods become erratic and we enter a stage of ‘hormonal chaos’ where hormone levels are unpredictable and ‘all over the place’. This is why you may have symptoms such as hot flushes (when the ovary hasn’t released an egg for a while and hormone levels drop) and then suddenly the hot flushes disappear (because your ovary spontaneously released an egg and gave you a ‘dose of hormones’ naturally). 
• This ‘spontaneous release of an egg’ is why you need to use contraception for at least 12 months from your last natural period. This period of time, called the ‘menopausal transition’, can take up to 4–5 years.
•  Very rarely do the ovaries ‘switch off’ overnight (unless they are removed surgically). Eventually, the ovaries fail completely, no eggs are released and hormone levels drop to postmenopausal levels. 
• How your body reacts to these low hormone levels is different for every woman. 
• Some women (around 20%) will have no symptoms; another 20% will have severe, disabling symptoms; and most (60%) fall in the middle. Similarly, the types of symptoms experienced will vary between women – some get hot flushes, some get mood symptoms, others may have a dry vagina; some have all symptoms! Your symptoms will also depend on whatever else is going on in your life at the time, such as whether you are stressed or have other medical or psychosocial conditions that are impacting on your menopause symptoms. 
• It is like putting everything – hormones, relationships, genetics, work, stressors, general health and lifestyle into a big pot and stirring it around and you come out as you are. Therefore, ‘fixing your hormones’ will only be a part of your overall health management plan.

• Before Menopause:
  • Ovaries release an egg monthly.
  • Regular periods and predictable hormone changes.
• Approaching Menopause:
  • Ovaries release eggs irregularly.
  • Hormone levels become unpredictable.
  • Periods become irregular.
• Symptoms During Transition:
  • Hot flushes (due to hormone level drops).
  • Symptoms may come and go (due to irregular egg release).
• Menopausal Transition:
  • Lasts up to 4–5 years.
  • Use contraception for at least 12 months after the last period.
• Post-Menopause:
  • Ovaries stop releasing eggs.
  • Hormone levels drop permanently.
• Symptoms Variability:
  • 20% of women have no symptoms.
  • 20% have severe symptoms.
  • 60% have moderate symptoms.
  • Symptoms can include hot flushes, mood changes, and vaginal dryness.
• Influencing Factors:
  • Stress, medical conditions, and lifestyle can impact symptoms.
  • Managing hormones is part of overall health management.

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 assessmentFracture 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 cmpression 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

Menopause Treatment Options:

Lifestyle and Behavioural Modifications

• Maintaining healthy weight = One study of 40 overweight/obese women showed that a 10% weight loss resulted in significant improvement in hot flushes, with a correlation between weight loss and reduction in hot flush frequency
• Physical Activity:
  • Regular physical activity has been associated with a reduction in menopausal symptoms, including hot flushes. Exercise improves overall health and can help manage weight, which in turn can reduce the severity of hot flushes (Elavsky S, McAuley E. Menopause. 2007).
• Clothing and Environment: Improving cooling through environmental control
  1. Clinical evidence does not exist to support the efficacy of cooling interventions as treatment for vasomotor symptoms.
  2. Nonetheless, small core body temperature elevations can trigger vasomotor symptoms, so it makes sense to propose environmental and lifestyle changes that lower core body temperature or that prevent it from rising.
  3. Suggested changes include: adjusting clothing, dress in layers, wear sleeveless blouses or tops, wear clothing made of natural fibres that breathe, avoid jumpers and scarves, lower the room temperature, put a cold pack under the pillow, turn the pillow over to the cool side when feeling warm, drinking cool liquids such as iced water.
• Avoiding triggers of vasomotor symptoms
  1. Specific triggers such as caffeine, alcohol, and spicy foods have been shown to exacerbate hot flushes in some women
• Mind- and body-based therapies and practices:
  • Cognitive behaviour therapy
  • Mindfulness and relaxation techniques have been found to reduce the frequency and severity of hot flushes.
  • Yoga
  • Paced breathing
  • Relaxation

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

• Alternative treatments 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
• Includes off-label use of medications primarily for hot flushes/night sweats
• Emphasis on evidence-based prescribing practices for off-label use

1. Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):
   • Indications: Hot flashes, mood disturbances, anxiety.
   • Examples:
     • Venlafaxine (Effexor): Start with 37.5 mg daily, may increase to 75 mg daily based on response.
     • Paroxetine (Paxil): Start with 10 mg daily, may increase to 20 mg daily.
     • Citalopram (Celexa): Start with 10 mg daily, may increase to 20 mg daily.
   • Evidence: SSRIs and SNRIs are shown to reduce the frequency and severity of hot flashes and improve mood symptoms in menopausal women .
2. Gabapentin (Neurontin):
   • Indications: Hot flashes, particularly nocturnal hot flashes.
   • Dosage: Start with 300 mg at bedtime, may increase to 300 mg three times daily.
   • Evidence: Gabapentin has been demonstrated to significantly reduce the frequency and severity of hot flashes in several clinical trials .
3. Clonidine (Catapres):
   • Indications: Hot flashes.
   • Dosage: Start with 0.1 mg at bedtime, may increase to 0.1 mg twice daily.
   • Evidence: Clonidine is effective in reducing the frequency of hot flashes but is associated with side effects such as dry mouth and drowsiness .

Vasomotor Symptoms/hot flushes 

Urine Symptoms

• Oxybutynin 

Vaginal dryness

• First line = non hormonal – Replens, K-Y Gel
• 2^nd line = Low dose vaginal preparations –
  • Estriol cream, estriol pessary, estradiol pessary – daily for 2 weeks then twice weekly
• Vaginal moisturisers (regular, twice weekly use): Replens®, Yes®
• Vaginal estrogen does not incrase risk CVD, VTE< developing brest cancer
• If previous breast Ca – try other first line, consider estrogen in consult with oncology team
• May also improve urinary symptoms/recurrent UTI

Natural Therapy

“Phyo-oestrogens” have no effect on decreasing hot flushes / other menopausal sx & use >5yrs increases risk of endometrial hyperplasia. Black cohosh is ax w liver failure.