M i s s N i d h i Tr i p a t h i

C o n s u l t a n t O b s t e t r i c i a n a n d G y n a e c o l o g i s t

L e a d f o r M e n o p a u s e S e r v i c e s

N a t i o n a l M e n o p a u s e Tr a i n e r

S o u t h e n d U n i v e r s i t y H o s p i t a l

Management of Menopause in the Community

Why do we hesitate to prescribe HRT

Management of menopausal symptoms presents a clinical challenge mainly because of concerns about breast cancer risk

The initial data from the Women’s Health Initiative (WHI) trial in 2002, which reported 1. an increased risk in cardiovascular disease (CVD) and

2. possible early harm in women receiving combined oestrogen and progesterone. This resulted in reduced prescribing of HRT in the UK.

In 2013 Follow-up data from the same study showed no detrimental effect on CVD

With careful consideration of risks and benefits, slowly the confidence in prescribing HRT is improving both within Hospital and Community

Publishing of the NICE guidance in 2017 has possibly helped, and is a positive step to reassuring Community specialists to initiate HRT

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Hormone Replacement Therapy-Bad Press 2002

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Hormone Replacement Therapy- Good Press

Wednesday, Jun 26 2013

A wasted decade: How one

HRT scare has 'caused

thousands of women 10 years

of needless suffering' By Jenny Hope

'Wasted decade': A panel of experts believe the 2002 HRT scare has denied thousands of women the relief that hormone replacement could offer

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HRT Controversies!!! HEADLINES 2016

By Sarah Knapton, Science Editor 23 August 2016 • 12:30pm Hormone replacement therapy can triple the risk of breast cancer, the biggest ever study has found, following more than a decade of controversy.

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Is assistance available to prescribe HRT ?

Having the NICE care pathway at hand can assist GP ‘s in triaging patients. NICE Pathways bring together everything it says in an interactive flowchart to be used online.

https://pathways.nice.org.uk/pathways/menopause/menopause-overview

By using the Pathways Healthcare professionals can provide a patient-centred approach to advising women about the menopause

Provide information about the risks and benefits of menopause hormone treatment that will allow patients to make an informed choice

Not all women need to be referred to secondary care unless there are health issues or concerns related to HRT use.

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NICE Quality statements

Statement 1 Women over 45 years presenting with menopausal symptoms are diagnosed with perimenopause or menopause based on their symptoms alone, without confirmatory laboratory tests.

Statement 2 Women under 40 years presenting with menopausal symptoms have their levels of follicle-stimulating hormone measured.

Statement 3 Women with premature ovarian insufficiency are offered hormone replacement therapy or a combined hormonal contraceptive.

Statement 4 Women having treatment for menopausal symptoms have a review 3 months after starting each treatment and then at least annually.

Statement 5 Women who are likely to go through menopause as a result of medical or surgical treatment are given information about menopause and fertility before they have their treatment

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Menopause: Perimenopause Any difference?

Perimenopause is defined as irregular periods and vasomotor symptoms

Menopause is defined retrospectively as no periods for more than 12 months in the absence of hormonal contraception

Around 80 % of menopausal women experience symptoms related to oestrogen deficiency: Irregular periods, hot flushes and night sweats, vaginal dryness, mood changes, sexual dysfunction (including loss of libido), memory and concentration changes, headaches, joint and muscle complaints.

In healthy women over the age of 45 years with menopausal symptoms, menopause and the perimenopause can be diagnosed without laboratory tests.

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Diagnosing Menopause in special situations

Woman is on POP/ IUS contraception: stop at 51 years and if periods don’t come back in 3 months, perform FSH levels (>40IU/l) on two occasions more than 4–6 weeks apart.

Premature ovarian insufficiency (POI): Affects 1% of women. Diagnosed if women under the age of 40 years have infrequent or no periods and FSH levels >40IU/l on two occasions more than 4–6 weeks apart

Women without a uterus: ( surgical or medical menopause) menopause is diagnosed via symptoms alone

Additional laboratory tests, blood count or thyroid function tests, may still be needed if non-menopausal causes of symptoms are suspected.

Reducing the number of unnecessary tests will reduce stress for women, lead to potential cost savings

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Managing the menopause without menopause hormone treatment: Lifestyle factors

Minimising caffeine and alcohol

Maintaining a healthy weight

Avoidance of smoking

Women should be advised to do at least 150 minutes of moderate intensity exercise per week. ( approx. 30 min per day)

Two sessions of resistance training may provide additional benefit.

Improved metabolic function, balance, muscle strength, cognition and quality of life are observed in women who are physically active.

Additionally, cardiovascular events, breast and colon cancer, stroke and fractures are less frequent

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Vasomotor Symptoms

Offer women HRT for vasomotor symptoms after discussing with them the short-term (up to 5years) and longer-term benefits and risks.

Oestrogen and progestogen to women with a uterus

Oestrogen alone to women without a uterus.

Do not routinely offer selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors or clonidine as first-line treatment for vasomotor symptoms alone

Explain to women that there is some evidence that isoflavones or black cohosh may relieve vasomotor symptoms. However, explain that:

multiple preparations are available and their safety is uncertain

different preparations may vary, interactions with other medicines have been reported

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Alternative therapies

There is some evidence that meditation, relaxation, controlled breathing, cognitive behavioural therapy and mindfulness training could play a role in reducing hot flushes,

Acupuncture may be beneficial for vasomotor symptoms

Non-prescription treatments Lady Care Plus Magnet therapy

NICE guidance advises that isoflavones and black cohosh may alleviate vasomotor symptoms

St John’s wort is effective in relieving vasomotor symptoms however,

For women at high risk of, or who have, breast cancer, there is uncertainty regarding safe dosing.

It should also be used with caution because it can interact with other medications (e.g. anticoagulants, antidepressants and anticonvulsants

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Non-hormonal treatments

Some women will have contra-indications to HRT or choose not to use hormonal treatment.

Non-hormonal treatments are less effective than HRT for vasomotor symptoms and will not help other symptoms of oestrogen deficiency, such as vaginal dryness, joint pain and low sexual desire

Antidepressant medications: The benefit for vasomotor symptoms ranges from 20% to 60%.

Selective serotonin reuptake inhibitors (SSRIs) act upon serotonin only

Serotonin–norepinephrine reuptake inhibitors (SNRIs) e.g. venlafaxine inhibit the reuptake of serotonin and norepinephrine

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Patients ask for HRT - Why worry ?

HRT is taken for the correct reasons, i.e. to alleviate the

symptoms of the menopause.

It has a role in the prevention of osteoporosis but long

term use is often required

HRT is taken for only as long as necessary at the lowest effective dose

If women start HRT around the time of menopause the risk is very small, but there is only limited data for continued usage beyond the age of 60.

It is not usually appropriate for women over 60 to be starting HRT, this does not mean that women who started HRT earlier should have to stop it on reaching 60.

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Prescribing HRT

Discuss Risks

Lifestyle methods are important to address along with use of HRT

Vaginal symptoms respond well to local HRT use, which can be repeated if symptoms recur

Lower dose of HRT has less risks and side effects

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Routes of administration

HRT can be administered via several routes :The choice of route will depend on several factors including past medical history and patient preference.

oral,

transdermal (patches or gel), or

subcutaneous implant.

The transdermal route avoids first-pass hepatic metabolism and, hence

is not thought to be associated with any increased risk in venous thromboembolism (VTE).

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Prescribing HRT

Women with uterus

Premature Ovarian Failure: idiopathic/iatrogenic

Premature menopause

Natural menopause

Types of HRT

Cyclical

Sequential

Continuous combined regimen

Women without uterus

(Post TAH+BSO)

Oestrogen only HRT

Androgen replacement ( If symptoms related to decreased Libido)

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Prescribing in Premature and Early Menopause

Premature menopause is associated with an accelerated risk of Coronary Heart Disease (CHD) and Osteoporosis, which can be prevented by early use of HRT

HRT should normally be offered until the average age of menopause (51 yrs)

HRT should be recommended for QOL related concerns as well

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Prescribing HRT in Peri-Menopause

Dependant on symptoms with which the patient presents

1. Menstrual disturbance: a.Cyclical progestogen in second half of cycle b. IUS

2. Vasomotor Symptoms: a. Cyclical HRT

b. ORT and IUS

3. If side effects to Progestogen – 3 monthly cyclical HRT

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Prescribing to the Menopausal Woman

QOL issues need to be treated- hot flashes, night sweats, sleep disturbances, decreased libido, vaginal symptoms

Long-term sequelae such as osteoporosis and urogenital-

atrophy need to be addressed

Long term effects take importance because of our longevity and ageing society

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Combined HRT : Two Types

Sequential or Cyclical Combined HRT (sc-HRT)

This is for women who are peri-menopausal or still menstruating, and is usually taken until age 51 or for at least one year.

2 types of cyclical HRT: Monthly Oestrogen is taken every day and progestogen is taken most

commonly in the luteal phase (day 15–28) of the cycle (for women having regular periods)

Three monthly Oestrogen is taken every day and add progestogen alongside it for 14 days every 3 months ( for patients having irregular periods)

E.g. Uterogestan 200 mg once daily on days 15–26 of each 28-day oestrogen HRT cycle, alternatively Uterogestan 100 mg once daily or MPA 10mg daily for 14 days

Duration of use should be individualised and not based on arbitrary limits

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Combined HRT

Continuous combined HRT (cc-HRT) This is daily oestrogen and progestogen, and is taken 12 months after the last period, after 51 years of age or 1 year after sc-HRT.

HRT is usually prescribed within 5 years of menopause in women aged 50–59 years.

Progestogens in CCHRT:

E + Dydrogesterone: Femoston Conti

E + MPA: Indivina

E +LNG : Femseven Conti

E + NET: Ellesti duet cont, Evorel conti, Kliofem

Duration of use should be individualised and not based on arbitrary limits

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Contra-Indications to HRT (as specified by regulatory authorities)

Current, past or suspected breast cancer

Known or suspected estrogen dependant malignant tumours (i.e. endometrial cancer)

Undiagnosed genital bleeding

Untreated endometrial hyperplasia

Previous idiopathic or current VTE (DVT/PE)

Current, past or suspected breast cancer

History of Stroke

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Initiation and assessment of Treatment

REMEMBER

Lowest effective dose used for shortest duration for symptom relief

Treatment should be reviewed annually

Indication for HRT should be reconsidered

at annual check-ups

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Starting and stopping hormone replacement therapy

Explain to women with a uterus that unscheduled vaginal bleeding is a common side effect of HRT within the first 3 months of treatment.

Should be reported at the 3-month review appointment, or

Promptly if it occurs after the first 3 months

When stopping HRT offer a choice of gradually reducing or immediately stopping treatment.

Explain to women that:

Gradually reducing HRT may limit recurrence of symptoms in the short term

Gradually reducing or immediately stopping HRT makes no difference to their symptoms in the longer term.

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Altered sexual function and Urogenital symptoms

Offer vaginal oestrogen to women with urogenital atrophy (including those on systemic HRT) and continue treatment for as long as needed to relieve symptoms

Consider vaginal oestrogen for women with urogenital atrophy in whom systemic HRT is contraindicated, (after seeking advice from a healthcare professional with expertise in menopause)

If vaginal oestrogen does not relieve symptoms of urogenital atrophy, consider increasing the dose after seeking advice from a healthcare professional with expertise in menopause.

Do not offer routine monitoring of endometrial thickness or progestogen for endometrial protection during treatment for urogenital atrophy.

Advise women with vaginal dryness that moisturisers and lubricants can be used alone or in addition to vaginal oestrogen.

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Altered sexual function and Urogenital symptoms

Points to remember about treatment of urogenital atrophy :

Symptoms often come back when treatment is stopped

Adverse effects from vaginal oestrogen are very rare

They should report unscheduled vaginal bleeding to you

Can safely be used in women with breast cancer for relief of urogenital symptoms on a short course.

Consider Testosterone supplementation for menopausal women with low sexual desire if HRT alone is not effective.

NB: Currently testosterone does not have a UK marketing authorisation for this indication in women. Follow relevant professional guidance, taking full responsibility for the decision.

Informed consent should be obtained and documented

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Risks of HRT use: VTE

Consider referring menopausal women at high risk of VTE (for example, those with a strong family history of VTE or a hereditary thrombophilia) to a haematologist for assessment before considering HRT.

Consider transdermal rather than oral HRT for menopausal women who are at increased risk of venous thromboembolism, including those with a BMI over 30 kg/m2

The risk of venous thromboembolism is increased by oral HRT compared with baseline population risk

The risk of venous thromboembolism associated with HRT is greater for oral than transdermal preparations

The risk associated with transdermal HRT given at standard therapeutic doses is no greater than baseline population risk.

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CVD Risk with HRT

HRT is currently not used widely for CHD prevention.

However, evidence from clinical trials and observational studies shows clear benefit for HRT in the prevention of CHD in postmenopausal women.

The starting doses of HRT are probably crucial in determining benefit and avoiding any harm; the older the women, the lower the starting dose must be.

It is not usually appropriate for women over 60 to be starting HRT, as the WHI study shows that the risks are increased, but this does not mean that women who started HRT earlier should have to stop it on reaching 60.

HRT is not generally recommended for women with a history of stroke or deep-vein thrombosis

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Breast cancer facts & Risks of HRT

The older a woman is, the more likely she is to get breast cancer. Rates of breast cancer are low in women under 40.

They begin to increase after age 40 and are highest in women over age 70

Inherited breast cancers account for about 2% of breast cancers diagnosed annually in the UK

If family member has breast cancer : Age at diagnosis is important - the younger the relative was when she was diagnosed, the greater a woman's chance of getting breast cancer

E.g. A woman whose mother was diagnosed with breast cancer before age 40 has about twice the risk of a woman without this family history . For a woman whose mother was diagnosed at an older age, the increase in risk isn’t as high.

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Breast cancer facts & Risks of HRT

If a woman has a single first degree relative (i.e. mother or sister) or second degree relative (i.e. aunt) diagnosed with breast cancer over the age of 40, it is very unlikely that this places her at an increased risk of breast cancer and she will be considered to be at population risk.

There is no need to refer for further risk assessment.

Alcohol and Smoking changes to metabolism of female sex hormones

All types of HRT increase the risk of breast cancer within 1-2 yrs. of initiating treatment

The increased risk is related to the duration of use of HRT

→Not related to the age at which HRT is started

→ Risk disappears within 5 yrs. of stopping

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Age related Breast cancer risk

Age 50 – 59 years

10 : 1000 women have breast cancer diagnosed over 5 yr period

20 : 1000 women have breast cancer diagnosed over 10 yr period

With ORT

12 : 1000 5 yr

26 : 1000 10 yr

With Combined HRT

16 : 1000 5 yr

44 : 1000 10 yr

Age 60 - 69 years 15 : 1000 women have breast cancer diagnosed over 5 yr period 30 : 1000 women have breast cancer diagnosed over 10 yr period With ORT 18 : 1000 5 yrs 39 : 1000 10 yrs With Combined HRT 24 : 1000 5 yrs 66 : 1000 10 yrs

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Endometrial Cancer and HRT use

Unopposed ORT increases risk of endometrial cancer and this persists for many years after cessation

Endometrial Protection – only achieved in sequential or Continuous Combined regimen

IUS adequate protection

(20µgm)

Sequential treatment

This can be a monthly or a quarterly regimen 10 - 14 days/month

Concerns exist of an increased risk of endometrial cancer with long term sequential use

CC HRT

Associated with lower incidence of endometrial hyperplasia and cancer than occurs in general population.

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Use of HRT in special circumstances

Diabetic women : Use of HRT (either orally or transdermally) is not associated with an increased risk of developing type 2 diabetes.

Muscle mass and strength: There is limited evidence suggesting that HRT may improve muscle mass and strength

It is maintained through, and is important for, activities of daily living.

Dementia : The likelihood of HRT affecting their risk of dementia is unknown

Cardiovascular disease :

HRT does not increase cardiovascular disease risk when started in women aged under 60 years

Does not affect the risk of dying from cardiovascular disease.

Presence of cardiovascular risk factors is not a contraindication to HRT as long as they are optimally managed.

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HRT use in patients with Migraine

Migraine aura does not contraindicate HRT

Non-oral Bio-identical estrogen (patch or gel) should be used

Lowest estrogen dose that effectively controls vasomotor symptoms should be prescribed

Women with uterus - Continuous delivery progestogen is recommended e.g.

levonorgestrel intrauterine system

transdermal norethisterone (as in combined patches)

micronised progesterone

Women with migraine and vasomotor symptoms who do not wish to use HRT or in whom estrogens are contraindicated may benefit from escitalopram 10-20mg/day( active form of Citalopram) or Venlafaxine 37.5-150 mg/day

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Other HRT formulations

• Tibolone:

It is a synthetic form of period-free HRT which may have similar benefits to CCT. It is taken continuously in tablet form

Can assist with improving libido

Duavive MR (Pfizer) contains CCE+ Bazedoxifene acetate (3rd generation SERM)

Using CEE as ORT and Bazedoxifene, acting as an oestrogen receptor antagonist in the uterus, greatly reduces the oestrogen-induced risk of endometrial hyperplasia in non-hysterectomised women

It was licensed and launched in the UK in July 2016 for treatment of oestrogen deficiency symptoms in post-menopausal women with a uterus for whom treatment with progestogen-containing therapy is not appropriate.

Dose: 0.45/20 mg daily continuously

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Summary

Safe until age 50

Safe to use up to 5 years after age 50

Yearly checks important

ORT lowers risk of Breast cancer

Combined HRT increases risk of Breast cancer

Refer if any concerns

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