Hormone Replacement Therapy

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 Consolidation Age-related bone mass Attainment of peak bone mass Males Females Fracture threshold Menopause 0 10 60 70 30 40 50 20 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 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. Risks of combined HRT Risks of oestrogen Only HRT • Breast cancer (1.24) • Stroke(1.41) • DVT (1.95) • IHD (1.24) • Billiary disease (1.59) • Ovarian cancer (1.2) • Malignant melanoma ? • 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 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) p=0.0008 p=0.009 p=0.0004 p=0.0006 p=0.008 Hormone Therapy (HT) vs. HT + Testosterone on sexual function 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!