Menopause

• Menopause


  • Occurs when oestrogen levels decline and menstruation ceases
  • The finite number of ovarian follicles becomes depleted
  • Oestrogen and progesterone levels fall and LH and FSH increase in response
  • Diagnosed retrospectively in women over 45-years-old who have not has a period within the last 12 months (and are not using hormonal contraception)
  • Also in women without a uterus who have menopausal symptoms
• Perimenopause


  • Symptoms can start several years before the final menstrual period, there is erratic bleeding and vasomotor symptoms such as hot flushes and night sweats
  • Caused by fluctuating, decreasing oestrogen levels
• Premature ovarian insufficiency


  Menopause occurs before the age of 40-years-old and affects 1% of women
• Early menopause


  Occurs between the ages of 40—45-years-old
• Factors associated with onset of the menopause

  • Smoking
  • Low socio-economic factors
  • Some ethnic groups experience menopause at slightly different ages
  • Family history – age at which mother experienced menopause is likely to affect the age at which the menopause occurs for the patient
• Menopausal symptoms


  • Vasomotor symptoms such as hot flushes and night sweats
  • Joint and muscle pain
  • Menstrual irregularity
  • Urogenital symptoms (dyspareunia, vaginal dryness and discomfort, incontinence)
  • Sleep disturbance secondary to vasomotor symptoms or psychological
  • Psychological or mood changes, cognition problems ("brain fog")
  • Osteoporosis (oestrogen is protective against bone loss)
  • Coronary heart disease
  • Redistribution of body fat to abdomen
• Lifestyle interventions


  • Minimise caffeine and alcohol
  • Maintain a healthy weight
  • Avoid smoking (damages ovaries and can lead to earlier menopause)
  • 150 minutes of moderate intensity exercise per week
• Benefits of lifestyle interventions


  • Improved metabolic function, balance and muscle strength
  • Improved cognition and quality of life is observed in women who are physically active
• Alternative therapies


  • Cognitive behavioural therapy (CBT)
  • Mindfulness, yoga etc.
  • Acupuncture
• Herbal treatments


  • Isoflavones
  • Black cohosh
  • St John's Wort
• Non hormonal treatments


  • Only treat vasomotor symptoms and are normally less effective than HRT but generally act fairly quickly
  • Will not help with other symptoms of oestrogen deficiency such as vaginal dryness, libido etc.
  • Not recommended as first line for vasomotor symptoms by NICE
• Clonidine


  • An alpha-adrenergic agonist that works as an antihypertensive, causing peripheral vasodilation therefore helping hot flushes/night sweats
  • Some women do experience significant benefit but not commonly used due to many side effects e.g. constipation, nausea, postural hypotension and sleep disorders
  • Not suitable for patients with a low baseline BP
• SSRIs/SNRIs


  • Examples include fluoxetine (SSRI) and venlafaxine (SNRI)
  • Antidepressants that can help vasomotor symptoms
  • No clear evidence that they will help with low mood in menopausal women who have not been diagnosed with depression
  • Some can interact with tamoxifen and reduce its efficacy
  • Can also be associated with significant side effects and withdrawal effects
• Pregabalin and Gabapentin


  • Can help neuropathic pain, migraine and vasomotor symptoms including night sweats and hot flushes
  • Significant side effects including sedation
  • Risk of addiction
• HRT


  • The most effective treatment for menopausal symptoms
  • Also licensed for prophylaxis and treatment of osteoporosis
  • Need to consider a lot of different factors when deciding whether to start HRT including risks and benefits, special consideration for women with current or history of breast cancer, choice in women with/without uterus, routes of administration, length of time treatment can be safely used for
• For most women, when prescribed before the age of 60-years-old, HRT has a favourable risk/benefit profile
• Types of HRT


  • Oestrogen only
  • Sequential combined oestrogen and progestogen
  • Continuous combined oestrogen and progestogen
• Oestrogen only HRT


  Carries a significant risk of endometrial hyperplasia which can result in cancer, therefore only used in women without a uterus
• Sequential combined HRT


  • For women who still have periods (i.e. perimenopausal) or are within one year of last period
  • Consists of oestrogen every day and progestogen taken in luteal phase (day 15-28) which helps to regulate bleeding
• Continuous combined HRT


  • Daily oestrogen and progestogen
  • For women without periods i.e. more than 12 months after last period
• Routes of administration


  • Oral
  • Transdermal (patches, gel)
  • Vaginal (cream, pessary, ring)
• Vaginal HRT


  Fewer risks associated and can be used alone or alongside systemic HRT for urogenital atrophy
• Side effects of HRT

  • Unscheduled vaginal bleeding especially early in treatment
  • Oestrogen related – bloating, breast tenderness, nausea, leg cramps, swelling and headaches
  • Progestogen related – caused by activation of aldosterone and androgen receptors e.g. bloating, weight gain, mood disturbance and acne
• Reasons to stop HRT

  • Sudden severe chest pain
  • Sudden breathlessness
  • Cough with blood stained sputum
  • Unexplained swelling or severe pain in calf of one leg
  • Severe stomach pain
  • Serious neurological effects e.g. unusual severe headache, vision or hearing problems, unexplained seizure, motor disturbance, numbness of one side
  • Hepatitis, jaundice, liver enlargement
  • Blood pressure >160/95mm/Hg
• Benefits of HRT


  • Symptom relief
  • Improvements in bone strength/prevention of further bone loss
  • Enhanced self esteem and quality of life
• Risks of HRT


  • Increased risk of some cancers, venous thromboembolism and cardiovascular disease but very much linked to individual patient history and concomitant risk factors
• HRT is recommended to be used for maximum of 5 years due to risks and the minimum effective dose for the shortest possible time
• History of HRT and the HRT debate

  • Million Women Study
  • Women's Health Initiative
  • Institute of Cancer research Study
  • HERS/HERS II
• Million Women Study


  • 1996-2001 Observational Study
  • Initial findings: Current users of HRT were more likely than people who had never used HRT to develop breast cancer
  • Past users who had since stopped were not at an increased risk
  • Higher risk associated with combined oestrogen and progestogen preparations
  • Risk of breast cancer increased with increasing duration of use
• Studies in the 1990s and early 2000s identified possible risks related to the use of HRT
• Million Women Study


  Observational study from 1996-2001 that initially aimed to follow up users and non-users of HRT for cancer incidence and death
• Million Women Study findings

  • Current users of HRT were more likely than people who had never used HRT to develop breast cancer
  • Past users who had since stopped were not at an increased risk
  • Higher risk associated with combined oestrogen and progestogen preparations
  • Risk of breast cancer increased with increasing duration of use
• Women in the Million Women Study had significantly different lifestyles to women of previous generations, including higher levels of smoking, use of oral contraceptives as teenagers/adults and obesity
• Women's Health Initiative


  Study from 1997 that aimed to investigate the hypothesis that HRT would reduce the risk of cardiovascular disease in women following the menopause
• Women's Health Initiative findings

  • No benefit for prevention of cardiovascular disease but increased risk of breast cancer
  • Women recruited were older than average, overweight and smokers
  • Further complicated by use of synthetic progestogens which are not usually used in UK
• Major findings of Women's Health Initiative

  • Increased risk of breast cancer, coronary heart disease, stroke, pulmonary embolism
  • Decreased risk of colorectal cancer, vertebral factors
• A 2013 paper found a more complex pattern of risk and benefit, with no increase in cardiovascular disease risk in women under 60-years-old using HRT but not recommended over 60-years-old
• Specific risks of HRT - Breast cancer

  • All types of HRT increase the risk of breast cancer but especially oestrogen plus progestogen
  • Increased risk is related to duration of use
  • Risk decreases once HRT stopped but some excess risk continues for more than 10 years after stopping
  • Vaginal oestrogen preparations are not associated with an increased risk
• Effect of HRT on breast cancer

  • Oestrogen leads to development and growth of breast tissue, stimulating growth and inhibiting apoptosis of cells
  • Progestogens can inhibit oestrogen-induced apoptosis of breast cancer cells and have oestrogenic properties which can stimulate breast cancer cell growth
• Specific risks of HRT - Endometrial cancer

  • Increased risk when using oestrogen only HRT
  • Risk of endometrial cancer is reduced by the addition of progestogen in combined preparations
  • Risk is reduced by cyclical (sequential) use and excess risk eliminated when progestogens are used continuously in combined preparations