1. Menopause and HRT

2. Aims and Objectives Aims Objectives
To be able to diagnose menopause and know when it is appropriate to investigate
To feel confident in discussing the management of menopausal symptoms with patients
To be able to prescribe HRT safetly
Objectives
Review subject of menopause
Discuss management of menopausal symptoms
Look in more depth at HRT preparations
Look at the first consultation for HRT
Discuss clinical scenarios

3. Menopause Definitions
Menopause is defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity.
Amenorrhoea for 1 year in patients > 50 or for 2 years in patients <50
Perimenopause is the period leading up to the menopause when the features of menopause commence
Premature menopause occurs under age 45 years
World health organisation
It is the date of the last menstrual period
It can only be diagnosed with certainty after 12 months spontaneous amenorrhoea
Therefore it is a retrospective diagnosis.
Premature menopause, menopause that occurs more than 2 standard deviations under the mean age. In practice this is usually said to be 45 years in developed countries. Developing countries tend to use age 40 as a cut off.

4. Physiology
Each ovary has a certain number of oocytes from birth which steadily decreases until we are approximately 50 years old when the stock becomes exhausted
During the perimenopause follicular activity fails, oestrogen levels decrease and the pituitary gland produces increased amounts of LH and FSH due to negative feedback.
Cycles become anovulatory, follicular development stops, the endometrium is no longer stimulated and amenorrhoea occurs
It is the low oestrogen levels that cause the menopause symptoms
Eventually the postmenopausal pattern of low oestrogen and high fsh and lh is established

5. Ovarian follicular activity falls, oestrogen and progestogen levels decrease, rise in FSH and LH due to negative feedback to pituitary.

6. Communication
‘A natural menopause occurs because as you get older, your ovaries stop producing eggs and make less of the main female hormone oestrogen. The symptoms you are experiencing are due to low levels of oestrogen’
‘It signals the end of the fertile phase of a woman’s life’

7. Urinary incontinence is more likely to be due to mechanical factors, such as obesity, gynaecological surgery, or multiparity, than to be associated with the menopause [Sherburn et al, 2001].
Mood changes, including anxiety, irritability, and depression, have been associated with the menopause. These symptoms are more likely to be associated with past problems and life stresses than to be due to the menopause alone. General population studies suggest that most women do not experience major changes in mood during the menopause transition [Hickey et al, 2005; Nelson et al, 2005; Rees and Purdie, 2006a; Roberts, 2007]. Exclude depression.
Cognitive disturbance, such as forgetfulness or difficultly concentrating. Cross-sectional studies suggest that these symptoms are unlikely to be related to the menopause [Nelson et al, 2005].
Loss of libido can be attributed to androgen deficiency. However, non-hormonal factors, such as conflict between partners, insomnia, inadequate stimulation, life stresses, or depression, are also important contributors and should not be overlooked [Rees and Purdie, 2006a].
Muscle and joint pains. Pain and swelling resulting in restriction of mobility most often affects the small joints of the hands and feet, as well as the knees, elbows, and the cervical spine. These symptoms have been linked to a decrease in oestrogen, but osteoarthritis, rheumatoid arthritis, and mechanical trauma are common causes [Panay et al, 2004; Lauritzen and Studd, 2005].
Skin changes. Soon after the menopause, skin collagen content and skin thickness decrease, and skin laxity and wrinkling increase abruptly. Skin elasticity also decreases. It is difficult to separate age-related skin changes, smoking, and sun exposure from changes related to declining hormonal secretion and menopause [SOGC, 2006].
Weight gain is unlikely to be due to the perimenopause or the menopause. Body weight in women tends to increase with age, especially beginning at or near the menopause. The average weight gain ranges from 2.25–4.19 kg. Body fat redistribution to the abdomen also occurs with age (independently of weight gain). This centralized abdominal fat distribution is an independent risk factor for cardiovascular disease in women [SOGC, 2006]. A longitudinal study of 418 women found that weight gain was more likely to be due to alcohol consumption and lack of exercise

8. Incidence of Symptoms What proportion of women;
experience some menopausal symptoms in their lifetime?
80%
find their menopausal symptoms distressing?
45%
experience hot flushes?
experience vaginal symptoms in the early postmenopausal period?
30%
experience vaginal symptoms in the late postmenopausal period?
47%
seek medical advice?
10%
This is effected by racial, cultural and sociological factors
Western women report high levels of symptoms
Japanese women have a low incidence of symptoms. There is no Japanese word for hot flushes. ?due to high soya content of diet.

9. Symptoms of Menopause Natural history; Menstrual irregularity
Symptoms start and increase from 2 years prior to the final menstrual period, peak at one year following it and return to normal after 5 years
Varies widely
Menstrual irregularity
Hot flushes and sweats
Sleep disturbances
Vaginal dryness
Urinary symptoms
Mood changes
Loss of libido
Osteoporosis and CVD and stroke risk increase
Menopause symptoms are usually self limiting. Usually last between 2-5 years. May last longer.
Menstrual irregularity - length of cycle can shorten or lengthen. Often become more heavy
Hot flushes – sudden feeling of heat in the upper body spreading upwards and downwards with patchy flushing of the skin followed by palpitations and sweating. Should last a few minutes.
Sleep disturbance – often due to night sweats, can lead to irritabilty, problems with short term memory and concentration.
Vaginal symptoms such as discomfort, dryness, dyspareunia and recurrent utis. Symptoms of atrophy may appear up to 10 years after the last period.

10. Investigations Not necessary in most cases FSH
Levels vary in perimenopause so single measures unreliable.
>30 IU/L – postmenopausal range
>12 IU/L – raised in women still menstruating
Other hormone tests – not useful
TFTs
Diagnosis should be made clinically based on age and symptoms with no need for investigations.
FSH levels vary almost daily in perimenopause stages so unreliable test.
Normal results do not exclude menopause
An increased level indicates ovarian failure but does not indicate an inability to concieve
Other hormone tests are unhelpful unless investigating for other secondary causes of amenorrhoea, polycystic ovary syndrome, or infertility

11. When is FSH Helpful? Premature menopause Measure on day 3-5 of cycle
If amenorrhoeic take 2 samples 2 weeks apart
Hysterectomy with conservation of ovaries
Measure on 2 or more occasions at least 1-2 months apart
Women using hormonal contraception
Must be off COCP for at least 6 weeks before testing. Can start progestorone only preparation.
A level in the menopause range in 2 or more occasions suggests ovarian failure
May still be at risk of becoming pregnant!
Hysterectomy with conservation of ovaries – have up to a 50% chance of their ovaries failing within 5 years ?because blood supplt to uterus is cut off
Should we be testing FSH in these women annually?

12. Premature Menopause Defined as menopause before age 45 Causes;
Primary ovarian failure
Surgically induced menopause
Radiation induced
Chemotherapy induced
May be linked with smoking, lower socioeconomic groups, BMI, family history
Refer any women under 40
Prescribe HRT for osteoporosis prevention
Stop HRT at normal age of menopause (50)
Primary ovarian failure – may occur at any age and usually no cause is found. May be linked to chromosomal abnormalities, autoimmune disease, enzyme deficiencies. Affects 1% of women age < 40 and 0.01% <30.
5-15% of women with primary ovarian failure may retain intermittent ovarian function for years and spontaneous ovulation and pregnancy are possible

13. Management of Menopause
Reassurance
Education, lifestyle changes
HRT
Alternatives

14. Lifestyle changes Hot flushes and night sweats Sleep disturbances
Regular exercise, lighter clothing, sleep in a cooler room, stress management
Avoid triggers
Sleep disturbances
Avoid exercise late in the day
Maintain regular routine
Mood and anxiety
Adequate sleep, regular exercise, relaxation exercises
Cognitive symptoms
Adequate sleep, regular exercise
Triggers – spicy foods, caffiene, alcohol, smoking
Smoking and obesity linked with increase in hot flushes

15. Benefits of HRT Effective for;
Treating vasomotor symptoms
Treating urogenital symptoms
Treating sleep or mood disorders if associated with flushes or night sweats
Preventing osteoporosis
Reducing risk of colon cancer
Improves quality of life and sexual function in symptomatic women

16. Side Effects Oestrogen related Progestogen related
Nausea, headaches, breast tenderness, fluid retention, headaches
If side effects occur advise to persist for 3/12
Try reducing dosage
Try swapping oestrogen types (estradiol/conjugated oestrogens)
Try changing mode of delivery
Progestogen related
Bloating, Mood swings, headaches, backache
Less androgenic progestogens produce less side effects
Change to continuous therapy if postmenopausal
If problem is bleeding then change to more androgenic progestogen or increased progestogen dose
Side effects often improve after 3 months
Consider reducing oestrogen content of HRT if persist
Increased bleeding may be due to the preparation, may wish to consider mirena to deliver progestogen if menorrhagia

17. Risks Risk Age range (years)
Background incidence per 1000 women in Europe not using HRT
Additional cases per 1000 women using oestrogen only HRT (estimated)
Additional cases per 1000 women using combined (oestrogen-progestogen) HRT (estimated)
Over 5 years
Over 10 years
For 5 years’ use
For 10 years’ use
Breast cancer
50–59 10 20 2 6 24
60–69 15 30 3 9 36
Endometrial cancer 4 32 NS 48
Ovarian cancer
<1 1
Venous thromboembolism 5 7 8
Stroke
Coronary heart disease
70–79
29–44
HRT prescribing fell by 50% between 2001 and 2005, probably due to the womens health initiative (2002) which highlighted safety concerns.
Risk of breast cancer returns to baseline after stopping for 5 years
Risk of ovarian cancer returns to baseline after stopping for a few years
Stroke – older women have a greater absolute risk of stroke on HRT. This seems to also be dose dependant
CHD – trials are on older women. Lack of evidence for younger. Overall the risk for younger women is probably low given their already low baseline risk

18. Contraindications Breast cancer Endometrial cancer
Untreated endometrial hyperplasia
Undiagnosed vaginal bleeding
Thromboembolic disease
Arterial disease
Active thrombophlebitis
Liver disease where LFTs not returned to normal
Pregnancy and breastfeeding
Stop 4-6 weeks prior to surgery and restart when fully mobile

19. Which Type of HRT??
HRT
With Uterus
Without Uterus
Urogenital Symptoms
Perimenopausal
Postmenopausaal
Cyclical Combined
Continuous Combined
Unopposed Oestrogen
Local Oestrogen
Start at lowest dose possible for shortest period of time

20. Systemic Oral HRT Cyclical combined Use in perimenopause
Have monthly withdrawl bleeds
Eg Prempak C, Elleste Duet
Continuous combined
Use if >1 year after last period
No bleed
If bleeding beyond 3-6 months, needs further ix
Eg Premique, Nuvelle continuous
Unopposed oestrogen
Only use if no uterus
Eg Elleste solo, Premarin
Continuous tends to be more convenient as don’t bleed

21. Other Preparations Transdermal patches Vaginal preparations
Available as unopposed oestrogen, cyclical and continuous
May have a lower thromboembolic and stroke risk
May have skin reactions
Apply to buttock
Vaginal preparations
Pessaries, creams, rings
Eg vagifem tablets, premarin
Implants, gels
Patches just as effective as tablets – may have lower thromboembolic and stroke risk but needs further research
Vaginal creams – can take months to respond well and are often needed long term. Systemic absorbtion is minimal so no need to use rogestogen

22. Alternatives
There are over 200 preparations available

23. Alternatives General rule is to advise against herbal medications.
Many may contain oestrogenic compounds.
Women may be taking more hormones by using these than they would with HRT.
They are often not regulated by a governing body.
Some studies suggest diet high in soy and isoflavones reduces severity and frequency of symptoms. They are safe.
Foot massage, reflexology – no evidence
Evening primrose oil – no evidence
Black Cohosh – limited evidence
Red Clover – limited evidence, no health concerns
Dong Quai – no evidence
RCOG – SAC Paper 6 – alternatives to HRT for the management of symptoms of the menopause
Herbal – most have placebo effect
Isoflavones – found in soy and linseed
May even reduce incidence of breast, ovarian, endometrial cancer, cv disease

24. Medical Alternatives
Tibolone – synthetic steroid with weak oestrogenic, progestogenic and androgenic properties.
Clonidine – alpha 2 agonist which helps with vasomotor symptoms. Useful for patients with hx of breast cancer.
SSRIs can reduce vasomotor symptoms.
Gabapentin reduces severity and frequency of hot flushes
Progestogens – may improve hot flushes but there are concerns about risk of breast cancer
Replens – vaginal bio adhesive moisturiser
Clonidine enhances the effects of anxiolytics and should not be used with alcohol
SSRI – 60% compared to 30% for placebo
Gabapentin – reduces frequency by 45% and severity by 54%

25. First Consultation History Examination confirm menopause clinically
LMP
Symptoms
Gynae history – smears, mammograms
Risk factor for osteoporosis
PMH/FH breast ca/CHD/thromboembolism
Contraception
Examination
Blood pressure
Height and weight
Breast exam?

26. First Consultation Ctd
ICE – Depression, anxiety, effect on life
Investigations?
Management
Lifestyle changes
If starting HRT
discuss benefits, risks, side effects
Ensure no contraindications
Discuss different preparations
Discuss contraception
Alternatives
Safety net – investigate PCB, bleeding 1 year after LMP
Arrange follow up

27. Follow Up Reassess after 3 months then annually
Follow up consultations should cover;
Assessing effectiveness
Enquiring about side effects
Ask about bleeding pattern
Check weight and BP
Ensure she examines her breasts regularly
If on cyclical treatment, consider changing to continuous if she is considered to be postmenopausal. This is usually considered to be
If she is over 54 years or;
If they have had previous raised FSH levels or amenorrhoea or;
If they have been on cyclical regimes for at least 2 years

28. Stopping HRT
General rule is to stop after 1-2 years to see if symptoms have gone.
If they recur, can try lower dose or try different method.
Stop HRT 4-6 weeks prior to major surgery.
If started for early menopause, stop at age 50.

29. Scenario 1
Deidre (54) has been on continuous combined HRT for a year. She describes an episode of postmenopausal bleeding.
You should reassure her that breakthrough bleeding on HRT is normal. T/F
False
If the bleeding occurred in the first 2 months you could....
Reassure
Consider changing to a more androgenic progestogen-containing HRT
Consider changing to transdermal route
Consider changing to cyclical to make more predictable
Combine with the IUS
Breakthrough bleeding is common in the first few weeks or months but if there is any bleeding after 4 months it should be investigated
Unpredictible bleeding is the most common reason patients choose to discontinue HRT

30. Scenario 2
Susan (49) presents with pain on intercourse. She had a total abdominal hysterectomy with oophorectomy 8 years ago. She currently takes 1mg estradiol. O/E – atrophic vaginitis
Topical oestrogen is contraindicated as she is already taking oral oestrogen. T/F
False
What are your treatment options?
Vaginal lubricants
Vaginal moisturisers
Topical oestrogen
Topical oestrogen can be used for a maximum of 5 years. T/F
She re-presents complaining of reduced libido. Treatment options include;
Psychosexual counselling
Change HRT to a patch
Testosterone replacement?
Vaginal oestrogens – minimal absorbtion.
They often need to be used long term as symptoms may recur. Vagifem is licensed for long term use if there is long term benefit. Should be reviewed annually and attempts made to stop.
Reduced libido is seen in up to 25% postmenopausal women.
Oral HRT may decrease the amount of free testosterone. Changing to a patch may help.
Testosterone may improve sexual function. Can be used in a patch. Particularly useful in premature menopause. Refer to specialist centre.

31. Scenario 3
Peggy (67) comes to see you for a repeat prescription of her HRT. She has been using Premique for 15 years. She also takes bendroflumethiazide for hypertension.
You must stop her HRT immediately. T/F
False
What could you do?
Trial decreased oestrogen dose
Change to a patch
Stop HRT gradually
Continue with current dose with annual review
Should she have annual mammograms?
No – continue routine screening every 3 years. Will need to continue with screening as long as remains on HRT.
Oestrogen requirements decrease as you get older so it is likely that she will still respond to a lower dose.
Patch - ?lower thromboembolic and stroke risk.

32. Scenario 4
Bianca (31) presents with a 6 months history of amenorrhoea after stopping her pill. She is otherwise well and denies any stress or other symptoms. She wants to try to get pregnant.
Amenorrhoea in should be investigated after;
6 weeks
6 months
1 year
2 years
Appropriate investigations include
FSH/LH
TFTs
Prolactin
Pregnancy test
FSH is found to be 45. What should you do?
Refer
Offer HRT or COC
Note – she could still become pregnant.
Ovarian function may resume so could become pregnant. HRT is not a contraceptive!

33. AKT Question Which statements are correct regarding menopause?
Defined as >18 months since last period
Diagnosed if >6 months since last period
Clonidine can be used to treat hot flushes
Diabetes is an absolute contraindication to HRT
Breakthrough bleeding whilst on HRT is of no concern
Increased frequency of UTIs occur
Decreased risk of IHD
Increased risk of osteoporosis
Can cause depression
3,6,8,9

34. Help for patients British Menopause Society
Daisy Network Premature Menopause Support Group
National Prescribing Centre website for risk charts (decision aids)

35. Summary
Menopause symptoms can be managed with lifestyle advice and medical treatment
HRT is the most affective treatment but is associated with risks so should be used at the lowest dose for the shortest time necessary
Women should be allowed to make an informed decision regarding starting and continuing HRT
More data is needed on complementary therapies