1. Hormone Replacement Therapy
Dr Annice Mukherjee
Consultant and Lecturer in Endocrinology
Salford Royal NHS

2. 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%

3. Menopause facts 70% women suffer with symptoms
Symptoms may occur before menopause is biochemically or clinically evident
Symptoms spontaneously improve over 2-5 years

4. 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

5. 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

6. The Effect of Age on Peak Bone Mass
Attainment of
peak
bone mass
Consolidation
Age-related bone
mass
Males
Females
Fracture threshold
Menopause 10 20 30 40 50 60 70
Years

7. 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

8. 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

9. 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

10. 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

11. 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

12. Treatment options Lifestyle Natural herbs & remedies HRT
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

13. Natural herbs & remedies
Phytoestrogens (Red clover)
Structural similarity to oestradiol
Efficacy data insufficient
Black cohosh
Buttercup family
Flushes & other symptoms
Data insufficient to date
Progesterone creams
Acupuncture

14. 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

15. Prescription Remedies
HRT preparations
Progestogens
Venlafaxine and Paroxetine
Clonidine
Gabapentin

16. 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

17. 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

18. After women’s Health Initiative Study the number of women using HRT
Risks of combined HRT
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 ?
Breast cancer (1.24)
Stroke(1.41)
DVT (1.95)
IHD (1.24)
Billiary disease (1.59)
Ovarian cancer (1.2)
Malignant melanoma ?
After women’s Health Initiative Study
the number of women using HRT
fell by almost half

19. Benefits of HRT Vasomotor symptoms Mood changes and insomnia
Osteoporosis
Urogenital symptoms
Sexual dysfunction

20. 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 individual
Premature menopause
Osteoporosis

21. 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

22. 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

23. 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

24. 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

25. Relative contraindications
Breast cancer
Thromboembolic disease
Coronary heart disease
Stroke
Gall bladder disease
Dementia
Migraine

26. 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

27. 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

28. Sexual Dysfunction (PHSDS) Hormone Therapy (HT) vs. HT + Testosterone
on sexual function
Testosterone for peri- and postmenopausal women.
Somboonporn W, Davis S, Seif MW, Bell R.
BACKGROUND: : The value of adding testosterone to hormone therapy (HT) for the management of peri- and postmenopausal women is controversial and has not been systematically reviewed. OBJECTIVES: : To determine the benefits and risks of testosterone therapy for peri- and postmenopausal women taking hormone therapy. SEARCH STRATEGY: : We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (1st November 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to 1st November 2003), EMBASE (1980 to 1st November 2003), Biological Abstracts (1969 to 2002), PsycINFO (1972 to 1st November 2003), CINAHL (1982 to 1st November 2003), and reference lists of articles. We also contacted pharmaceutical companies and researchers in the field. SELECTION CRITERIA: : Studies that were randomized comparisons of testosterone plus hormone therapy versus hormone therapy alone in peri- or postmenopausal women. DATA COLLECTION AND ANALYSIS: : Two review authors assessed the quality of the trials and extracted data independently. Where it was necessary, the corresponding authors of eligible trials were contacted for additional information. For dichotomous outcomes Peto odds ratios and 95% confidence intervals were calculated. For continuous outcomes non-skewed data from valid scales were synthesized using a weighted mean difference or standardized mean difference. If statistical heterogeneity was found, a random-effects model was used and reasons for the heterogeneity were explored and discussed. MAIN RESULTS: : Twenty-three trials with 1957 participants were included in the review. The median study duration was 6 months (range 1.5 to 24 months). Most of the trials were of adequate quality with regard to randomization and concealment of allocation sequence. The major methodological limitations were attrition bias and lack of a washout period in the cross-over studies. The pooled estimate from the studies suggested that the addition of testosterone to HT regimens improved sexual function scores for postmenopausal women. A significant adverse effect was a decrease in high-density lipoprotein (HDL) cholesterol levels. The discontinuation rate was not significantly greater with testosterone therapy (Peto odds ratio 1.01, 95% confidence interval 0.76 to 1.33) than with HT alone. There was insufficient evidence of a treatment effect for perimenopausal women or for other outcomes. AUTHORS' CONCLUSIONS: : Only a limited number of studies could be pooled in the meta-analyses. This limited the power of the meta-analysis to provide conclusions about efficacy and safety. However, there is evidence that adding testosterone to HT has a beneficial effect on sexual function in postmenopausal women. There was a reduction in HDL cholesterol associated with the addition of testosterone to the HT regimens. The meta-analysis combined studies using different testosterone regimens. It is, therefore, difficult to estimate the effect of testosterone on sexual function in association with any individual hormone treatment regimen.
Cochrane Database Syst Rev Oct 19;(4):CD Review.
p=0.0007
p=0.0008
Somboonporn W et al. Testosterone for peri-and postmenopausal women (review), Oct 2005, Cochrane Library
p=0.002

29. 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

30. 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

31. 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

32. 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

33. Thank-You!