The Menopause and HRT

The Menopause and HRT

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

Objectives

The menopause What is it? What are the symptoms? How should it be investigated?

HRT Indications Choice Risks Side effects

Alternatives to HRT

The Menopause

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

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 20-

30 follicles start to develop each time. Eventually the supply of responsive oocytes in the

ovaries runs out

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

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 Mar2) Politi MC, Grimm C, Bentz EK et al; J Gen Intern Med. 2008 Sep

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

Symptoms

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

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

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

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

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, Sep2) Di Donato P et al;. Maturitis, 2005, Nov

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

Investigations

Generally not required, but blood tests include:

TFT FBC ?FSH LH, oestrogen and progesterone levels not

normally helpful

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.


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

Treatment - HRT

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

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


Choice

Oestrogen + progestogen Oestrogen alone Tibolone

Routes of delivery

Oral tablets Patches Creams/gels Nasal sprays IUS Oestrogen releasing vaginal ring S/C implants

Which preparation?

Questions:

1. Does the women have an intact uterus?

2. Are symptoms primarily vaso-motor or urogenital?

3. Systemic or local treatment?

4. Combined or oestrogen only?

5. Cyclical (oestrogen with progestogen from day 12-14) or continuous?

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

She has no uterus

Symptoms mainly vasomotor – systemic oestrogen only HRT

Symptoms mainly urogenital – local oestrogen OR systemic oestrogen only HRT

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) 1) Al-Azzawi et al; Obstet Gynecol 1999 Feb2) 2) Kenemans P et al; Lancet Oncol 2009 Feb

HRT Snap!

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

What are the risks?

Venous thromboembolism Coronary heart disease Stroke Breast cancer Endometrial cancer Ovarian cancer

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

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

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):


Combined HRT

50-59 4 5 5

60-69 9 12 12

What are the risks?

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 5 years


Combined HRT

50-59 10 12 16

60-69 15 18 24

Over 10 years


Combined HRT

50-59 20 26 44

60-69 30 39 66

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

yearsOestrogen

only HRT – 5 years

No HRT – 10 years

Oestrogen only HRT –

10 years

50-59 2 6 4 36

60-69 3 9 6 54

What are the risks?

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 5 years


Combined HRT

50-59 2 2 2

60-69 3 3 3

Over 10 years


Combined HRT

50-59 4 5 5

60-69 6 8 8

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

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

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

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)

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)

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!

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

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

But before changing treatment!

Pelvic examination – including visualising cervix

Confirm smears up to date TV USS

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

HRT Snap!

Treatment - Alternatives

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)

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

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

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

References

As detailed on slides + www.gpnotebook.co.uk www.patient.co.uk www.bnf.org NHS CKS RCOG British Menopause Society

Documents

The Menopause and HRT