Hormone Replacement Therapy

Dr Annice MukherjeeConsultant and Lecturer in Endocrinology

Salford Royal NHS

Definition of Menopause

Failure of steroid production and ovulation and the final cessation of menstruation

Average age 51 yrs Incidence of natural

premature ovarian failure before age 40 is estimated as 1%

Menopause facts

70% women suffer with symptoms

Symptoms may occur before menopause is biochemically or clinically evident

Symptoms spontaneously improve over 2-5 years

Symptoms of Menopause

Menstrual irregularity indicating failing ovulation

Vasomotor symptoms - hot flushes/flashes, night sweats

Sleep disturbance Vaginal symptoms Mood changes Joint pains Physical

Skin/body habitus/weight changes Sexual dysfunction

Eleanor

46, menopause began last year Has had fractured humerus and pelvis after

trivial injuries in past Otherwise very healthy BMI 19, FH osteoporosis Tolerating menopause well with few

symptoms

The Effect of Age on Peak Bone Mass

Attainment ofpeak

bone mass

Consolidation Age-related bone mass

Males

Females

Menopause

Fracture threshold

Years0 10 20 30 40 50 60 70

Eleanor

Has she had BMD checked??

High risk of osteoporosis from history

Would benefit form HRT even in absence of symptoms in terms of bone protection

Vicky

33 year old female, married, no children Menses stopped 18 months ago, several

pregnancy tests negative, Bloods LH 70, FSH 50, Oestradiol 42 She wants to know if she can have children She also complains of vaginal dryness and

itching even thought she has had treatment for thrush

Premature Menopause Requires estrogen replacement until age of

natural menopause Symptoms may be more severe than natural

menopause Urogenital and sexual problems also impact Cardiovascular risk increased Osteoporosis Fertility

Vicky

Consider doing autoantibody screen ?Family history prem. menopause/

behavioural problems in boys (-fragile X syndrome)

Estrogen replacement required for well being and bone protection-risk of osteoporosis

Can use high doses of HRT in this context Pregnancy possible with egg donation

Menopause Aims of Management

To maximise the quality of life of hypogonadal women by:

Reducing the impact of menopausal symptoms

Addressing the increased risk of osteoporosis

Treatment options

Lifestyle Exercise, stop smoking, limiting alcohol, caffeine &

stress, adopting a healthy diet

Natural herbs & remedies Placebo treatment reduces hot flushes by 50%

HRT Other prescription therapies

Natural herbs & remedies Phytoestrogens (Red clover)

Structural similarity to oestradiolEfficacy data insufficient

Black cohosh Buttercup family Flushes & other symptoms Data insufficient to date

Progesterone creams Acupuncture

Yvonne 62 year old housewife Severe MSK pain, hot flushes, sleep

disturbance low libido, mood swings Despirate for symptom control! BMI 40, BP 160/95 Tx for hyperlipidaemia Strong FH of IHD & 2 sisters with

breast cancer Biochemistry- post-menopausal

Prescription Remedies

HRT preparations Progestogens Venlafaxine and Paroxetine Clonidine Gabapentin

Yvonne

62 year old housewife Identify ranking of symptoms Is she depressed? Would significant weight loss help well

being? If main symptom is flushing consider SSRI-

upto 70% improvement in flushes/sweating She may wish to start with a natural remedy

The Role of HRT Natural menopausal symptoms Premature menopause Surgical menopause Other causes of oestrogen deficiency

under age of 50 yrs Menopausal women at significant risk of

osteoporotic fracture Consider contraindications risks carefully

Risks of combined HRT

Breast cancer (1.24) Stroke(1.41) DVT (1.95) IHD (1.24) Billiary disease (1.59) Ovarian cancer (1.2) Malignant melanoma ?

Risks of oestrogen Only HRT

•Breast Cancer (0.77)

•Stroke (1.39)

•DVT (1.47)

•IHD (0.77)

•Billiary disease (1.67)

•Ovarian cancer (1.2)

•Malignant melanoma ?

After women’s Health Initiative StudyAfter women’s Health Initiative Studythe number of women using HRT the number of women using HRT

fell by almost halffell by almost half

Benefits of HRT

Vasomotor symptomsMood changes and insomniaOsteoporosisUrogenital symptomsSexual dysfunction

Use of HRT Start during perimenopause in natural

menopausal (earlier the better) Most women use HRT for less than 5 years Vaginal oestrogen is effective for urogenital

symptoms Merits of long term HRT should be assessed for

each individualPremature menopauseOsteoporosis

HRT preparations/combinations

Oestrogen oral/patches/gels With progestogen for women with an intact

uterus Sequential preparations (bleed) Continuous combined preparations (non-bleed)

Intrauterine progestogen

HRT; Dose and route

Use lowest dose for the shortest possible time in women with natural menopause

Women with premature menopause will need higher doses

Transdermal has less metabolic effect and probably safer

Tibolone

Synthetic steroid with oestrogenic, progestogenic and androgenic actions

Relieves symptoms Protects bones Improves sexual function Shares some of HRT risks although

possibly not all

Jenny

50 yr old police officer Menopausal symptoms++ Had TAH for endometriosis 4 years before Now feels so bad that she can’t work, thinks

she will lose her job soon. Can’t afford to be un-employed

Has maternal aunt who died of breast cancer age 45

Relative contraindications

Breast cancer Thromboembolic disease Coronary heart disease Stroke Gall bladder disease Dementia Migraine

Jenny

Difficult problem Quality of life vs. uncertain cancer risk Could have trial of low dose oestrogen only

transermal HRT with close monitoring & referral to breast cancer family history clinic

Spell out risks versus benefits

Joan

52 year old cleaner Menses stopped 1 year ago Reduced libido, low mood no flushes Worried her partner is going to leave

her Tried HRT no benefit

Somboonporn W et al. Testosterone for peri-and postmenopausal women (review), Oct 2005, Cochrane Library

Hormone Therapy (HT) vs. HT + Testosteroneon sexual function

p=0.002p=0.002

p=0.0008p=0.0008

p=0.0007p=0.0007

p=0.008p=0.008

p=0.0006p=0.0006

p=0.0004p=0.0004

p=0.009p=0.009

p=0.0008p=0.0008

Sexual Dysfunction(PHSDS)

Indications for Androgen Therapy

Progressive loss of libido and sexual enjoyment associated with non specific tiredness, loss of drive, motivation and sense of well being

Exclude clinical depression or other explanation

Joan

52 rear old cleaner management? Is she depressed? Is the reduced libido lack of interest or physical

(vaginal discomfort/pain) or both If complex psychosexual issues consider referral

to specialist clinic Consider topical oestrogen Consider testosterone/HRT combination

Oral restandol/intrinsa patches

Urogenital Atrophy

10 - 40% of hypogonadal women are symptomatic

Oestrogens effective in the management Most convincing evidence being in support

of local treatment Doses lower than conventionally used

Conclusions

HRT has well recognised benefits and well publicised risks

Consider the indications and risk carefully and discuss them with the patient

Tailor the treatment offered to the needs of the individual patient

Thank-You!