M ENOPAUSE Phil Thirkell

D EFINE THE MENOPAUSE [2 MARKS ] No menstrual periods for 12 months

W HAT HAPPENS AT THE MENOPAUSE ? End of Ovulation End of Menstrual cycle Stabilising of hormones

W HAT 3 CLASSICAL SYMPTOMS ARE ASSOCIATED WITH THE MENOPAUSE ? Hot flushes Sweats (sometimes only at night) Vaginal dryness

W HAT OTHER SYMPTOMS ARE ASSOCIATED WITH THE MENOPAUSE ? Headaches Migraine Palpitations Sleep disturbance Cystitis Urinary frequency Urinary incontinence Loss of concentration Poor memory Irritability Loss of libido Skin thinning Hair loss Brittle nails Osteoporosis Central adiposity

W HAT IS THE AVERAGE AGE OF THE MENOPAUSE ? 51 years

W HAT CAUSES THE ONSET OF SYMPTOMS ? a) Low oestrogen? b) Rising FSH? c) Rising GnRH? d) Fluctuating oestrogen?

W HAT IS OSTEOPOROSIS ? Progressive disease Decreased bone mineral density and bone mass Increases the risk of fractures

H OW IS OSTEOPOROSIS DIAGNOSED ? Dual-energy X-ray absorptiometry (DEXA) scan Fragility fracture  DEXA WHO definition 2.5 standard deviations below the mean peak bone mass

W HAT ARE THE RISK FACTORS FOR OSTEOPOROSIS ? Age (men and women) Menopause (drop in oestrogen causes increased bone resorption) Smoking Malnutrition Vitamin D deficiency Family history Drugs – steroids Cushings

W HICH FRACTURES TYPICALLY OCCUR IN OSTEOPOROSIS ? Wrist Hip Vertebral body Rib

H OW IS OSTEOPOROSIS MANAGED ? Weight-bearing exercise Diet Bisphosphonates Strontium ranelate Hormone Replacement Therapy Teriparatide recombinant parathyroid hormone Monoclonal antibodies – denosumab

M ANAGEMENT OF M ENOPAUSE Do nothing Hormone Replacement Therapy Anti-depressants – flushes + mood

D O NOTHING Symptoms bearable for many women Will resolve themselves in time

H ORMONE R EPLACEMENT T HERAPY Oestrogen ± progesterone – if they have a uterus, progesterone inhibits proliferation of endometrium and decreases risk of endometrial cancer SERMs – selective estrogen receptor modulators Act as a partial agonist/antagonist at different oestrogen receptors Femarelle Prevents hot flushes and bone mineral loss Doesn’t increase risk of breast/uterine cancer Doesn’t increase clots or change the lipid profile

B ENEFITS OF HRT Reduces vasomotor symptoms Improves urogenital symptoms Reduces osteoporosis risk

R ISKS OF HRT Breast cancer Venous thromboembolism Stroke Endometrial cancer Dementia Gall bladder disease Lung cancer Ovarian cancer

E ARLY MENOPAUSE Before the age of 45 (or 40) Primary ovarian failure Secondary ovarian failure Hormonal disorders – Addison’s, Hypothyroid, Diabetes Chromosomal abnormalities

W HICH TEST CAN BE USED TO IDENTIFY EARLY MENOPAUSE ? Follicle stimulating hormone blood test

H OW TO TREAT EARLY MENOPAUSE ? Treat with hormones until the average menopausal age – 51 If a woman reaches menopause early, her bones will start to resorb and bone density will be decreased, leading to greater risk of osteoporosis/fractures Keep hormone replacement going until 51 Although increased risk of breast cancers etc. the woman isn’t getting extra oestrogens, just replacing what she should have had at this age

U NTREATED PREMATURE MENOPAUSE CAUSES INCREASED RISK OF …? Osteoporosis Cardiovascular disease Dementia etc.

A patient of yours is asked if she would like to take part in a trial of a new drug for the menopause. It claims to reduce the number of hot flushes but without any of the side effects of oestrogen. She agrees and will be entered into a randomised controlled trial, comparing the new drug with existing HRT. i. Define what is meant by randomised in this context. ii. Give TWO reasons why it being randomised is an important feature of this type of trial. iii. Define what is meant by controlled in this context.

i. random allocation of treatment equal chance of being assigned to either group analogous to flipping a coin not the choice of researchers or patient ii. To minimise bias To minimise confounding factors iii. The group receiving treatment are matched for a parallel group receiving the standard treatment/ a different treatment/ placebo/ no treatment etc.

Give and explain TWO ethical issues you will consider when advising the patient about this type of trial.

Clinical Equipoise – reasonable uncertainty about which treatment is better Scientifically robust – is the study big enough to generate useful data? Informed consent – written, informed, free to withdraw from trial etc.

The trial is extended nationwide and all menopausal women are invited. The incidence and prevalence of menopausal women has been calculated. Define incidence and prevalence.

Incidence – the number of new cases of a condition occurring in a defined population in a set time period. Prevalence – the number of existing cases of a condition in a defined population at a specific time

What are the advantages of an RCT? What are the disadvantages ?

Advantages Reduces bias Reduces confounders Can show causality Good for rare drugs/exposures Disadvantages Cost Time Limited to a few exposures/drugs