Menopause management seminar

Management of Management of MenopauseMenopause

Dr Yusmadi Abdullah

Life After Menopause Life After Menopause

Age at menopause : 51.7 (average)

1900 : life expectancy at 40 years old



(Malaysian women - 75.4 years)

“Women now live a third of their lives

after menopause”

8th International Congress on Menopause, Sydney 1996

MenopauseMenopause Menopause Menopause is the permanent is the permanent

cessation of menstruation that cessation of menstruation that results from loss of ovarian follicular results from loss of ovarian follicular activity.activity.

Menopausal age :Menopausal age : 45 – 55 years45 – 55 years Mean age ( M )Mean age ( M ) : : 50.7 years50.7 years Premature menopausePremature menopause < 45 years< 45 years Late menopauseLate menopause > 55 years> 55 years

is the cessation of menstruation is the cessation of menstruation that follows surgical removal of that follows surgical removal of both ovaries or both ovaries or iatrogenic ablation iatrogenic ablation of ovarian functionof ovarian function by by chemotherapy, radiotherapy or chemotherapy, radiotherapy or treatment with GnRH analogues.treatment with GnRH analogues.

Induced /surgical menopauseInduced /surgical menopause

PerimenopausePerimenopause

Is the period beginnning with the first clinical, biological and endocrinological features of the approaching menopause such as vasomotor symptoms and menstrual irregularity

Can be 1 or 2 years and for some as long as 7 to 10 year

Diagnosis Diagnosis

For those 50 years and above : For those 50 years and above : 12 consecutive month of 12 consecutive month of amenorrhoea is diagnostic.amenorrhoea is diagnostic.

For those below 50 years :For those below 50 years :

* * FSHFSH > 30 IU/l> 30 IU/l

Consequences of menapause Consequences of menapause

Vasomotor symptoms

Psychological symptoms

Sexual dysfunction

Osteoporosis Cardiovascular

Disease Urogenital Atrophy

Vasomotor SymptomsVasomotor Symptoms

Hot flushes and night sweats are experienced by as many as 85% of women around the menopause.

Most would experience these symptoms for < 5 years, however about 25% would experience it for more than 5 years.

Sexual Dysfunction Sexual Dysfunction

The underlying problem for female sexual dysfunction are usually multifactorial.

Oestrogen deficiency can lead vaginal dryness and dyspareunia,

Non hormonal factors such as conflict between partners, insomnia, inadequate stimulation, life stresses can also lead to sexual dysfunction.

Depressed mood, anxiety, irritability, mood swings, lethargy and lack of energy have been associated with the menopause.

General population studies suggest that most women do not experience major mood changes during the menopause.

Psychological SymptomsPsychological Symptoms

Prospective epidemiological Prospective epidemiological studies studies

‘ psychological problems experienced during the menopause are likely to be associated with past problem and current life stresses’

Osteoporosis Osteoporosis

Affects 1:3 women. Risk factors include family history of fracture,

low BMI, early menopause, cigarette smoking, alcohol abuse, sedentary lifestyle, corticosteroids, hyperthyroidism.

Common sites for osteoporotic fracture are lower end of radius (wrist/Colles’ fracture), proximal femur (hip) and vertebrae.

Cardiovascular DiseaseCardiovascular Disease

common cause of death in women after the age of 60 years.

Risk factors for myocardial infarction are abnormal FLP, smoking, depression and stress.

Incidence of stroke increases with age. Risk factors are hypertension, smoking,

diabetes, hyperlipidaemia, obesity.

Urogenital AtrophyUrogenital Atrophy

Oestrogen and progestrone receptors are present in the vagina, urethra, bladder and pelvic floor musculature.

Oestrogen deficiency after menopause cause atrophic changes in the urogenital tract and is associated with urinary symptoms which may co-exist with symptoms of vaginal atrophy.

Treatment OptionTreatment Option

Making lifestyle changes - healthy diet, exercise and stress reduction.Hormone replacement therapy.Complementary and alternative therapies.

Hormone Replacement Hormone Replacement TherapyTherapy

How to approach? How to approach?

CounselingHealth screening – history ,

examination and investigationKnowledge??

Hormone Replacement Hormone Replacement Therapy Therapy

combine regime- estrogen and progestogen in women with uterus

Oestrogen /ERT only – women with no uterus

OestrogensOestrogens

Natural : oestradiol, oestrone and oestriol which are chemically synthesised from soya beans or yams; conjugated equine oestrogen (CEE) consisting primarily of estrone sulphate and equilin sulphate,obtained from urine of pregnant horses,

Synthetic : ethinyl oestradiol and mestranol (less suitable for HRT)

ProgestogensProgestogens

High androgenic potency marked adverse effects on lipoproteins! negates beneficial effects of estrogen eg. 19-nor progestogens, norgestrel,

norethisterone Moderate androgenic potency

some effects on plasma lipids eg. Medroxyprogesterone acetate (MPA)

No androgenic potency no effect on blood lipids Eg dydrogesterone (Duphaston)

Eg - Femaston

Routes of AdministrationRoutes of Administration

Oral-most widely used-well tolerated-highly effective-rapid onset-‘first-pass’ effect

(beneficial changes in HDL:LDL)

Transdermal-patches or gels-messy, time consuming-redness/itchiness-need of oral progestogen:

low compliance

Intravaginal-vaginal rings, pessaries, cream-no effects on vasomotor

symptoms, osteoporosis or CVD

-creams or tablets:messy-need oral progestogen: poor

compliance Subcutaneous

-surgically inserted pellets-hormone release varies-treatment can’t be

reversed-estrogen effects persist

Prescribing RegimensPrescribing Regimens Estrogen therapy may be

cyclical :administered for first 21 days of the cycle)

continuous :administered throughout the cycle)

Progestogens therapy may be sequentially :added for last 10 - 14 days of

the cycle (induces a withdraw bleed) continuously (to eliminate withdrawal bleed)

HRT CHART HRT CHART link

Weight Gain and Android Fat Distribution in Menopause

% change from baseline after 24 months (n=26, n=28, n=26)

Hänggi W et al. Endocrinology 1998;48:691-699.

Effect of HRT on Body Weight and Fat Distribution

-2

0

2

4

6

Total Body Fat Mass

Trunk Fat mass

Total Body Weight

Controls

Tibolone

femoston 2/10

*

*p<0.05 vs. baseline

* *

% c

han

ge

fro

m b

asel

ine

Sequential TherapySequential Therapy

Mimics the menstrual cycle.

Regular, monthly periods.

Periods often lighter.

Appropriate for perimenopausal women with irregular bleed.

Continuous Combined Regime Continuous Combined Regime

A continuous-combined regime is to eliminate wihdrawal bleeding.

Use should be avoided within the first 12 months after the last menstrual bleed.

Spottings may occur during the first 3 - 4 months in most women.

Appropriate for postmenopausal women who do not wish for any regular withdrawal bleed.

Duration of Systemic Duration of Systemic TreatmentTreatment

Vasomotor symptoms - up to 5 years and then evaluate as some women do experience symptoms for more than 5 years.

Prevention or treatment of osteoporosis - needs to be continued for life as BMD falls when treatment is stopped. However other option should be discussed as long term HRT is associated with other risk.

Premature menopause - usually advised to continue until the natural age of menopause ~ 51 years. There after need to reevaluate what is the endpoint of treatment.

Treatment of Local Treatment of Local SymptomsSymptoms

Treatment is usually long term if not life long as symptom return on cessation of treatment.Synthetic oestrogens or CEE should be avoided as they are well absorbed from the vagina.The options available are low dose natural oestrogen e.g vaginal oestriol by cream or pessary or oestradiol by tablet or ring.With the recommended dose regimen, progestogen need not be added for endometrial protection.

- effective in treating hot flushes and improvement is usually seen within 4 weeks with maximum effect achieved by 3 months.

- treatment should be continued for at least 1 year.

Vasomotor symptomsVasomotor symptoms

Percentage of menopausal symptoms in 186 women during a 52 week period of femoston 2/10 treatment

Baseline

6 weeks

52 weeks0

10

20

30

40

50

60

70

80

Hotflushes

Nightsweats

Sweatingattacks

Vaginaldryness

Painfulintercourse

Per

cen

tage

of

wom

en

Amy JJ. Eur Menop J 1995;2 (Suppl.):16-22

Relief of Menopause Symptoms with femoston® 2/10

Urogenital symptoms and sexualityUrogenital symptoms and sexuality

- vaginal dryness, superficial dyspareunia, urinary frequency and urgency respond well to oestrogens

- urinary incontinence, however, is not improved

- reduces the risk of spine, hip and other osteoporotic fracture.

- need lifelong treatment to be effective in preventing fracture.

- not recommended as a first-line treatment as risks outweigh benefits.

- standard dose for bone protection are CEE 0.625mg, oestradiol 1-2mg and transdermal 25-50µg.

OsteoporosisOsteoporosis

Bone Mineral Density % Change

Stevenson JC et al. Maturitas 2001;38:197-203.

Significant increase in BMD of the lumbar vertebrae and hips

1 mg estradiol plus 5, 10 or 20 mg continuous dydrogesterone, N=177, 1 year treatment duration

* p<0.01 vs. baseline

0.0%

1.0%

2.0%

3.0%

4.0%

L2-4 Vertebrae Femoral Neck

Ward's Triangle

Trochanter

3.6%*

1.16%* 1.62%*

2.83%*

% in

crea

se f

rom

bas

elin

e

Prevention and Treatment of Prevention and Treatment of OsteoporosisOsteoporosis

Biphosphonates- shown to reduce both vertebral and non-vertebral

fractures- principal side-effect : irritation of upper GIT so

given weekly/monthly to reduce this. Eg - alandroanate

SERMs (Raloxifene)- shown to reduce vertebral fracture.- does not treat vasomotor symptoms, cause

transient side effects such as hot flushes and leg cramps.

- Has an equal propensity with HRT to cause VTE

Prevention and Treatment Prevention and Treatment of Osteoporosisof Osteoporosis

Calcitriol- active metabolite of vitamin D and facilitates the

intestinal absorption of calcium. Calcium- in postmenopausal women not on HRT 1.5 gram/day

and in those on HRT 1.0 gram/day of elemental calcium is needed to preserve bone health.

Vitamin D- oral supplementation of 700-800IU/day seem to

reduce risk of vertebral and non-vertebral fractures in ambulatory or institutionalized elderly people.

Colorectal cancer Colorectal cancer

- reduces risk of colorectal cancer by about one-third

HRT AND Breast cancerHRT AND Breast cancer

- risk of breast cancer is dependent on the regimen prescribed, greatest with combined oestrogen-progestrogen replacement.

- Risk of breast cancer minimal after 5 years of usage

- The WHI found : risk in the oestrogen-alone group was 23% lower than in the placebo group.

Nurses' Health Study (January 2006Nurses' Health Study (January 2006))

Data suggest that timing of hormone initiation in relation to age of onset of menopause might influence coronary risk; women beginning HT/ET near onset of menopause had a significantly reduced risk (30% less) of CHD;

no significant correlation between HT/ET and CHD risk was observed among women who initiated therapy 10 years or more after menopause.

Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Women's Health. 2006;15:35-44.

Effects of unopposed estrogen and risk of invasive Effects of unopposed estrogen and risk of invasive breast cancer (Nurses' Health Study, May 2006) breast cancer (Nurses' Health Study, May 2006)

Data indicate that use of estrogen alone did not increase the risk of invasive breast cancer until 20 years of use and beyond, and risk was increased at 15 years for estrogen receptor and progesterone receptor-positive cancers.

Chen WY, Manson JE, Hankinson SE, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med. 2006;166:1027-1032.

Breast DisorderBreast Disorder Benign breast disease - no convincing

evidence to show that the risk of breast cancer is increased in patients with benign breast disease

Previous breast cancer - studies on systemic HRT showed contradictory results with some showing adverse outcome and some showed no further increase risk. However, low dose vaginal oestrogen are not contraindicated for vaginal symptoms.

HRT AND Endometrial cancerHRT AND Endometrial cancer

- unopposed oestrogen therapy increased the risk of endometrial cancer and risk is still increased for 5 years or more after discontinuation of therapy.

- addition of progestogen reduces this risk but not completely with sequential progestogens especially if used for more than 5 years.

- no increase risk is found with combined continuous regimen.

HRT and HRT and Venous Venous thromboembolic diseasethromboembolic disease

- highest risk occurs in the first year of use.

- however, absolute risk is small as VTE occurs in 1.7 per 1000 in women older than 50 years who are not taking HRT and mortality is low (1-2%).

- limited data suggest that transdermal HRT is associated with a lower risk than the oral route.

HRT and CANCERHRT and CANCER

Cervical and ovarian cancer - not contraindicated except for endometrioid ovarian cancer where some doubt exist and progestogen addition is recommended.

Endometrial cancer - need to be given with progestogen.

Cardiovascular DiseaseCardiovascular Disease

Hypertension - no evidence shows that oestradiol-based HRT increases blood pressure or has an adverse effect in women with hypertension. Rarely CEE may cause severe hypertension which returns to normal upon stopping treatment.

Hyperlipidaemia - depends on type of HRT used. Venous thromboembolism - relative contraindication.

If still need to give as benefits outweighed risks then the transdermal route might be safer (limited evidence)

HRT and surgery - to stop 4 weeks prior to elective surgery or to continue HRT with thromboprophylaxis.

Endocrine DiseaseEndocrine Disease

Diabetes Mellitus - HRT seems to improve the glycaemic control with varying results depending on the type and route of administion.

Thyroid disease - dose of thyroxine may need to be increased as oestrogen can can increase the concentration of thyroxine-binding globulin.

Non-oestrogen Based Treatment Non-oestrogen Based Treatment

Menopausal symptoms- progestogens such as NET 5mg/day or

megestrol acetate 40mg/day- Clonidine - 50-75mg bd, of limited value

and effectiveness- SSRI, gabapentin Vaginal atrophy- lubricants, moisturisers

What are other options?What are other options?

Exercise – yoga, Taichi, meditationsHealthy food – increase fruits and

vegetable intakeAlternative – black cohosh, red

clovers, etc

Case StudiesCase Studies

Case Study 1Case Study 1

45 year old woman, para 3, complains of:

irregular bleeding (not heavy) vasomotor symptoms (hot

flushes, night sweats)

What would you advise her ?What would you advise her ?


1.1. Health ScreenHealth Screen

• Detailed history of general health status including family history

• Physical examination: BP, Anemia, Thyroid, CVS, Lung, Breasts, Pelvic examination including Pap Smear.

• Blood Examination: Hb, Lipid profiles, FBS, Others if indicated.

• Other investigations: Mammography, BMD (Dexa)

2. Treatment …

If all tests are normal the choices are:

• Combined Cyclical HRT (regular-bleed)


2. …Treatment

Combined Cyclical HRT (regular-bleed)

• Short-term

• Pregnancy?

Rees M, Purdie DW (2002), Management of the Menopause. Pg 112


50 year old woman, posthysterectomy 3 years (ovaries not removed), has menopausal symptoms. She wants to know what are her options for: hot flushes night sweats Dryness of vagina

Dyspareunia



1.1.Health ScreenHealth Screen

• Baseline workup as is case 1

2. Treatment

• If normal mammogram and no contraindication, estrogen only therapy can be started

• For fast relieve of vaginal symptoms, local application of vaginal cream can be used for short term


3. Weigh the benefits and risks

What are my risks ?

• Cardiovascular disease

no protection

If coronary artery disease present, higher risk of mortality in the first year

• Breast Cancer

Increased risk (MW study)

No increase in risk (WHI Study)

Increase mortality from breast cancer (MW Study)


4. Alternative therapy if there are other risk factors

What are my options?

• Prozac/Effexor

• Antihypertensives (Aldomet)

• Unproven therapy

Black Cohosh

Phytoestrogens

Advise on spritual exercise yoga, taichi etc


60 year old woman, has taken HRT for 10

years is seeking your advice whether she

should stop or continue taking HRT ?


Counseling risk outweigh benefitHealth screeningOffer non pharmacological treatment now consider HT rather than HRT?

Nonpharmacological treatment of postmenopausal symptoms

Article first published online: 11 JAN 2013

© 2013 Royal College of Obstetricians and Gynaecologists Issue The Obstetrician & Gynaecologist Volume 15, Issue 1, pages 19–25, January 2013

http://onlinelibrary.wiley.com/doi/10.1111/tog.2013.15.issue-1/issuetoc

Where are we now?Where are we now?

ACOG: State-of-the-Art Guide to Hormone ACOG: State-of-the-Art Guide to Hormone TherapyTherapy

Combined hormone therapy should not be used for prevention of diseases such as cardiovascular disease, due to the small but significant increased risk of conditions such as breast cancer, heart attack, stroke, and blood clots;

Estrogen-alone therapy, used for women who have had a hysterectomy, should also not be used for prevention of diseases, due to increased risks of blood clots and stroke. Although ET carries fewer risks than combined HT, women with a uterus should not use estrogen alone due to their increased risk of uterine cancer;

ACOG: State-of-the-Art Guide to ACOG: State-of-the-Art Guide to Hormone TherapyHormone Therapy

Hormone therapies are appropriate for the relief of vasomotor symptoms, so long as a woman has weighed the risks and benefits with her doctor; and

Women on combined HT or ET should take the

smallest effective dose for the shortest possible time and annually review the decision to take hormones.

NAMS (North American Menopause Society – NAMS (North American Menopause Society – Sept 2003)Sept 2003)

The primary indication for systemic hormone therapy is moderate and severe menopausal symptoms: Hot flashes, night sweats/insomnia, mood swings

When treating moderate and severe urogenital atrophy (vaginal dryness, dyspareunia, urinary frequency, and incontinence), local estrogen preparations are preferred.

2. HRT for treating menopausal symptoms Treatment is justified since the benefits outweigh

the risks.

4. HRT for managing osteoporosis Consider alternative therapies such as calcium,

biphosponates and the selective estrogen receptor modulators. (SERMs)

3. HRT for preventing cardiovascular diseases 3.1 Conventional HRT should not to be used for primary

prevention however a low dose HRT and transdermal therapy can be considered to be used.

3.2 HRT should not be used for secondary prevention against heart disease.

3.3 Women at risk of cardiovascular disease who wish to discontinue HRT should consider dietary and lifestyle changes (weight loss, regular exercise, stop smoking) as well as the use of drugs to lower cholesterol and blood pressure.

Menopause management seminar

Health & Medicine

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