M ENOPAUSE Phil Thirkell. D EFINE THE MENOPAUSE [2 MARKS ] No menstrual periods for 12 months.

MENOPAUSE

Phil Thirkell

DEFINE THE MENOPAUSE [2 MARKS]

No menstrual periods for 12 months

WHAT HAPPENS AT THE MENOPAUSE?

End of Ovulation End of Menstrual cycle Stabilising of hormones

WHAT 3 CLASSICAL SYMPTOMS ARE ASSOCIATED WITH THE MENOPAUSE?

Hot flushes Sweats (sometimes only at night) Vaginal dryness

WHAT 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

WHAT IS THE AVERAGE AGE OF THE MENOPAUSE?

51 years

WHAT CAUSES THE ONSET OF SYMPTOMS?

a) Low oestrogen?b) Rising FSH?c) Rising GnRH?d) Fluctuating oestrogen?

WHAT IS OSTEOPOROSIS?

Progressive disease Decreased bone mineral density and bone mass Increases the risk of fractures

HOW 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

WHAT 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

WHICH FRACTURES TYPICALLY OCCUR IN OSTEOPOROSIS?

Wrist Hip Vertebral body Rib

HOW IS OSTEOPOROSIS MANAGED?

Weight-bearing exercise Diet Bisphosphonates Strontium ranelate Hormone Replacement Therapy Teriparatide

recombinant parathyroid hormone Monoclonal antibodies – denosumab

MANAGEMENT OF MENOPAUSE

Do nothing Hormone Replacement Therapy Anti-depressants – flushes + mood

DO NOTHING

Symptoms bearable for many women Will resolve themselves in time

HORMONE REPLACEMENT THERAPY

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

BENEFITS OF HRT

Reduces vasomotor symptoms Improves urogenital symptoms Reduces osteoporosis risk

RISKS OF HRT

Breast cancer Venous thromboembolism Stroke Endometrial cancer Dementia Gall bladder disease Lung cancer Ovarian cancer

EARLY MENOPAUSE

Before the age of 45 (or 40) Primary ovarian failure Secondary ovarian failure

Hormonal disorders – Addison’s, Hypothyroid, Diabetes Chromosomal abnormalities

WHICH TEST CAN BE USED TO IDENTIFY EARLY MENOPAUSE?

Follicle stimulating hormone blood test

HOW 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

UNTREATED 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 biasTo 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?

AdvantagesReduces biasReduces confoundersCan show causalityGood for rare drugs/exposures

DisadvantagesCostTimeLimited to a few exposures/drugs