1. The Menopause and HRT

2. Aims
Gain an understanding of what is meant by “menopause”, and how it is diagnosed
Gain an understanding of the treatment options
Think about the risks and benefits of HRT

3. Objectives The menopause HRT Alternatives to HRT What is it?
What are the symptoms?
How should it be investigated?
HRT
Indications
Choice
Risks
Side effects
Alternatives to HRT

4. The Menopause

5. The menopause – what is it?
From the British Menopause Society:
Permanent cessation of menstruation
Only diagnosed after 12 months spontaneous amenorrhoea – a retrospective diagnosis
Climacteric/perimenopause – period of change leading up to the menopause

6. The menopause – why does it happen?
Women are born with around 1.5m oocytes
1/3 are lost by the time of menarche.
Most women menstruate about 400 times, and follicles start to develop each time.
Eventually the supply of responsive oocytes in the ovaries runs out

7. The menopause – hormonal changes
Ovarian follicular activity begins to fail as responsive oocytes run out
Leads to reduction in oestrogen and progesterone levels
Low level of oestrogen causes disruption of cycle and menopausal symptoms
-ve feedback loop causes rise in levels of luteinising hormone and follicle stimulating hormone

8. 2) Politi MC, Grimm C, Bentz EK et al; J Gen Intern Med. 2008 Sep
Epidemiology – UK
Final menstrual period usually occurs between the ages of 40 and 58, with an average age of 511
Final menstrual period below the age of 40 is considered to be premature menopause1
Evidence suggests that in the average woman symptoms start to increase from 2 years before the last menstrual period, reach a peak at 1 year following it, and have resolved by 8 years2
1) Nelson H; Lancet, 2008 Mar
2) Politi MC, Grimm C, Bentz EK et al; J Gen Intern Med Sep

9. How common are symptoms?
80% of women experience menopausal symptoms1
45% of these find the symptoms distressing1
Most women manage the symptoms themselves – 10% seek medical advice for their symptoms2
1) RCPE, 2003
2) Roberts; BMJ, 2007

10. Symptoms Menstrual irregularity Hot flushes/sweats
Urinary/vaginal symptoms
Sleep disturbance
Mood changes
Loss of libido
Others

11. Menstrual irregularity
Cycle may lengthen to months, or shorten to weeks1
Increase in blood loss is common1
Majority of women experience irregularities, but 10% have a sudden cessation of menstruation2
1) Nelson H; Lancet, 2008 Mar
2) “Menopause”; Clinical Knowledge Summaries

12. 2) “Menopause” Clinical Knowledge Summaries
Hot flushes/sweats
Common 70-80% of peri-menopausal women1
Tend to affect head, neck, face and chest.
Usually last for a few minutes but can happen multiple times during the day and night.
Most common in the first year after the last menstrual period2
1) RCPE 2003
2) “Menopause” Clinical Knowledge Summaries

13. Urinary/vaginal symptoms
Dyspareunia
Vaginal discomfort/dryness
Recurrent UTI
Urinary incontinence
Occur in 30% in early post-menopausal period, rising to 47% later in life1
1) Grady; NEJM, 2006

14. Sleep disturbance and mood change
Sleep disturbance – commonly reported symptom, probably related to mood changes – anxiety, depression, memory loss, poor concentration1
Development of psychological symptoms has been linked to high BMI, and low amounts of physical activity2
1)Young T et al;. Sleep, 2003, Sep
2) Di Donato P et al;. Maturitis, 2005, Nov

15. Loss of libido/other changes
Loss of libido may be related to hormonal changes, but also psychological factors, vaginal dryness, partner
Others (probably due to low oestrogen):
Brittle nails
Thinning of skin
Hair loss
Generalised aches and pains

16. Investigations Generally not required, but blood tests include: TFT
FBC
?FSH
LH, oestrogen and progesterone levels not normally helpful

17. 1) “Menopause” Clinical Knowledge Summaries
FSH1
Only needed if doubt about diagnosis – eg. in premature menopause
Can be very variable during peri-menopause – single measures are unreliable, and levels should be checked when women are not using any oestrogen containing medications (including COCP)
FSH > 30 is generally taken as post-menopausal range.
1) “Menopause” Clinical Knowledge Summaries

18. 1) British Menopause Society
Associated problems1
Increased risk of cardiovascular disease + stroke
Increased risk of osteoporosis
Redistribution of body fat
?Alzheimer’s Disease – more common in women so may be hormonal link, but no evidence HRT reduces risk
1) British Menopause Society

19. Treatment - HRT

20. HRT Effective treatment for menopausal symptoms
Previously used widely and for prolonged periods
However:
Women’s health initiative (2002) – increased risk of coronary heart disease, stroke, breast cancer, PE
Million women study (2003) – increased risk breast and ovarian cancer

21. 1) “Menopause” Clinical Knowledge Summaries
Indications for HRT1
Treatment of menopausal symptoms where the risk benefit ratio is favourable, in fully informed women, in the lowest possible dose needed to control symptoms and for the shortest possible time
In women with premature menopause until the age of natural menopause (50)
For prevention of osteoporosis in women unable to use other medications
1) “Menopause” Clinical Knowledge Summaries

22. Choice
Oestrogen + progestogen
Oestrogen alone
Tibolone

23. Routes of delivery Oral tablets Patches Creams/gels Nasal sprays IUS
Oestrogen releasing vaginal ring
S/C implants

24. Which preparation? Questions: Does the women have an intact uterus?
Are symptoms primarily vaso-motor or urogenital?
Systemic or local treatment?
Combined or oestrogen only?
Cyclical (oestrogen with progestogen from day 12-14) or continuous?

25. She has a uterus Symptoms mainly vasomotor:
Perimenopausal – Systemic cyclical combined HRT
Postmenopausal – Systemic continuous combined HRT
Symptoms mainly urogenital:
Perimenopausal – local oestrogen OR systemic cyclical combined HRT
Post menopausal – local oestrogen OR systemic continuous combined HRT

26. She has no uterus
Symptoms mainly vasomotor – systemic oestrogen only HRT
Symptoms mainly urogenital – local oestrogen OR systemic oestrogen only HRT

27. Tibolone Selective oestrogen receptor modulator
Oestrogenic, progestogenic and androgenic properties
Can be used if intact uterus and no bleeding for >1yr
Evidence for improvement in sexual function and vasomotor symptoms1
Increased risk of stroke and breast cancer, especially in over 60s2
Less risk with DVT and IHD
1) Al-Azzawi et al; Obstet Gynecol 1999 Feb
2) Kenemans P et al; Lancet Oncol 2009 Feb

28. HRT Snap!

29. Contraindications to HRT1
Pregnancy and breast-feeding
Undiagnosed vaginal bleeding
VTE
Active/recent angina or MI
Suspected, current, or past breast Ca
Endometrial Ca
Active liver disease with abnormal LFTs
1) “Menopause”; Clinical Knowledge Summaries

30. What are the risks? Venous thromboembolism Coronary heart disease
Stroke
Breast cancer
Endometrial cancer
Ovarian cancer

31. What are the risks? Venous thrombo-embolism
Increased risk of DVT and PE; highest risk in the first year of use.
Number of women having VTE/1000 over 5 years (figures from BNF):
No HRT
Oestrogen only HRT
Combined HRT
50-59 5 7 12
60-69 8 10 18

32. Rossouw JE et al; JAMA 2007, Apr
What are the risks?
Coronary heart disease
Evidence for protection from CHD is lacking
Increased risk of heart disease for women starting combined HRT more than 10 years after the menopause (extra 15 cases/1000 women over 5 years)1
Rossouw JE et al; JAMA 2007, Apr

33. What are the risks? Stroke
Small increased risk of stroke for younger women on HRT, rising in older women
Number of women having stroke/1000 over 5 years (figures from BNF):
No HRT
Oestrogen only HRT
Combined HRT
50-59 4 5
60-69 9 12

34. What are the risks? Breast cancer
Over 5 years
No HRT
Oestrogen only HRT
Combined HRT
50-59 10 12 16
60-69 15 18 24
Breast cancer
Increased risk is proportional to the duration of treatment
Risk returns to untreated levels after 5 years
Number of women having breast cancer/1000 over 5 and 10 years (figures from BNF):
Over 10 years
No HRT
Oestrogen only HRT
Combined HRT
50-59 20 26 44
60-69 30 39 66

35. Oestrogen only HRT – 5 years Oestrogen only HRT – 10 years
What are the risks?
Endometrial cancer
Substantial increased risk with oestrogen only HRT
Use of progestogen eliminates risk, but needs to be weighed against increased risk of breast cancer
Number of women having endometrial cancer/1000 over 5 and 10 years (figures from BNF):
No HRT – 5 years
Oestrogen only HRT – 5 years
No HRT – 10 years
Oestrogen only HRT – 10 years
50-59 2 6 4 36
60-69 3 9 54

36. What are the risks? Ovarian cancer
Over 5 years
No HRT
Oestrogen only HRT
Combined HRT
50-59 2
60-69 3
Ovarian cancer
Small increased risk of ovarian cancer, rises with duration of use
Number of women having ovarian cancer/1000 over 5 and 10 years (figures from BNF)
Over 10 years
No HRT
Oestrogen only HRT
Combined HRT
50-59 4 5
60-69 6 8

37. 1) “Menopause”, Clinical Knowledge Summaries
Follow-up1
Initial follow up after 3 months
Thereafter, a minimum of annual checks
Check effectiveness
Side-effects
BP + weight
Breast examination – if appropriate
Pelvic examination – if appropriate
Review of risks/benefits
1) “Menopause”, Clinical Knowledge Summaries

38. Follow-up Effectiveness – if symptom control not good consider:
Poor absorption – eg. Bowel problem
Drug interaction – eg. Carbemazepine, phenytoin
Incorrect diagnosis – eg. Hypothyroidism, diabetes
Patient expectations
Consider – increasing oestrogen dose, altering brand, changing delivery method

39. What are the side-effects?
Oestrogen:
Breast tenderness
Leg cramps
Bloating
Nausea
Headaches
Bleeding – cyclical preparations produce regular and predictable bleeds, usually towards the end of the progestogen phase
Progestogen:
Breast tenderness
Backache
Depression
Pelvic pain

40. Oestrogen related side-effects
More likely to occur and be problematic when there has been a longer duration of ovarian failure
Often resolve with continued use
Consider –
Breast tenderness – low fat, high carbohydrate diet
Leg cramps – exercise and calf stretches
Nausea, bloating – adjust timing of dose, take with food
Headaches – try patches (may produce more stable oestrogen levels)

41. Progestogen related side-effects
May be more problematic; may be connected to type, dose and duration of progestogen
Consider –
Changing progestogen type
Reducing dose
Altering route to something other than oral
“Long-cycle” HRT – (progestogen for 14 days every 3 months – only suitable if periods have stopped).
Continuous combined therapy or tibolone (if post-menopausal)

42. Managing bleeding
Heavy/prolonged bleeding – increase dose or duration of progestogen ?IUS
Bleeding early in progestogen phase – increase dose, change type of progestogen
Painful bleeding – change type of progestogen
Irregular bleeding – increase progestogen
No bleeding – may occur in 5% due to atropic endometrium; confirm compliance and remember to exclude pregnancy!

43. Bleeding – when to refer?
Perimenopausal woman with intact uterus
Change in pattern of withdrawal bleeds
Breakthrough bleeding persisting for more than 6 months, or does not reduce on “long-cycle” HRT
Persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks

44. Bleeding – when to refer?
Postmenopausal women with an intact uterus
Breakthrough bleeding persists for more than 6 months after starting HRT
Bleeding occurs after amenorrhoea
Persistent or unexplained bleeding after cessation of hormone therapy for 6 weeks

45. But before changing treatment!
Pelvic examination – including visualising cervix
Confirm smears up to date
TV USS

46. And don’t forget contraception!
HRT does not suppress ovulation – contraception is still needed
If an intact uterus:
>50 – for one year after LMP
<50 – for two years after LMP

47. HRT Snap!

48. Treatment - Alternatives

49. Lifestyle measures1 Regular aerobic exercise
Avoid triggers – caffeine, alcohol, smoking, spicy food
Wear light clothing
Good sleep hygiene
Weight loss
1) Alternatives to HRT for management of symptoms of menopause; ROCG (2006)

50. 1) Nelson HD et al; JAMA, 2006 May
Medications1
SSRIs/SNRIs – fluoxetine, paroxetine, citalopram and venlafaxine have been shown to reduce symptoms; unlicensed for this use
Clonidine – evidence of efficacy in treating hot flushes, but high frequency of side-effects
Gabapentin – evidence of efficacy for treating hot flushes; for specialist use
1) Nelson HD et al; JAMA, 2006 May

51. Complementary therapies
Many OTC preparations available
Black cohosh
Evening primrose oil
Dong quai
Ginkgo biloba
Ginseng
St John’s Wort
Limited evidence of efficacy and long term safety
Some preparations contain oestrogens
Some preparations can interact with other medications and may have other adverse side effects

52. Summary The menopause is a natural and inevitable part of life
Menopausal symptoms are very common but most women never seek advice regarding management
Although HRT carries risks, it is a good and effective treatment for symptoms
Patients should be fully informed and allowed to make the decision themselves about whether to commence HRT

53. References As detailed on slides + www.gpnotebook.co.uk
NHS CKS
RCOG
British Menopause Society