Heavy Menstrual Bleeding (HMB) Dysmenorrhoea / Endometriosis Endometrial Hyperplasia HRT

Heavy Menstrual Bleeding (HMB) Dysmenorrhoea / Endometriosis Endometrial Hyperplasia HRT Janesh Gupta Professor of Obstetrics and Gynaecology Birmingham Women s Hospital

Heavy Menstrual Bleeding (HMB)

Menorrhagia Aetiology Menorrhagia: 20% of reproductive age women worldwide Biochemical Anatomic Endocrinologic Haematologic Iatrogenic Prostaglandins Endometriosis Fibroids / polyps Adenomyosis Infection (Pre) malignancy "Hormone imbalance" Brain / Ovary Thyroid / Adrenal Clotting diseases Leukaemia Anticoagulants Exogenous hormones Intrauterine devices Hysterectomy Hysterectomy Hysterectomy Hysterectomy Hysterectomy 50% No cause found

Heavy Periods Affects up to 30% of women of reproductive age 12% result in secondary care referrals with up to 50% surgical intervention rate Two thirds result in hysterectomies and endometrial ablations 50% of hysterectomies are normal uteri

Number of procedures England Hospital Episodes Statistics (HES) in Hospital Episode Statistics (HES) in NHS Hospitals NHS Hospitals in England in England Hospital Episode Statistics (HES) in NHS Hospitals in England 0000 0000 0000 0000 0000 0000 0000 0000 0000 0 0000 0000 0000 0000 0 80000 70000 60000 50000 40000 30000 20000 1998-10000 1999-99 0 00 1998-99 2000-01 1999-00 2001-02 2000-01 2002-03 2001-02 2003-04 2002-03 1998-99 1999-00 2000-01 2001-02 2002-03 2003-04 All hysterectomies Endometrial ablation Total All hysterectomi Endometrial abl All hysterectomies Total Endometrial ablation Total 2003-04

ECLIPSE TRIAL Effectiveness and Cost effectiveness of Levonorgestrel containing Intrauterine system (LNG-IUS) in Primary Care against Standard Treatment for menorrhagia RCT trial design in primary care Recruitment completed with 571 patients NIHR HTA Funding 1.6 million - 5 years

Results of primary outcome: Menorrhagia Multi-Attribute Scale (MMAS) overall score Excluding women who crossed over between treatment groups increased the treatment benefit of LNG-IUS over usual medical treatment to 17.8 points (95% CI, 14.1 to 21.5 points; p<0.001)

Time to first treatment change (cross-over or stop treatment) to two years Reasons for changing treatment Lack of effectiveness Irregular / prolonged bleeding LNG-IUS 37% (29/79) 28% (22/79) Usual medical treatment 53% (87/163 )

Surgical intervention by 2 years Endometrial Ablation Hysterectomy LNG-IUS 4% (12/300) 6% (16/267) Usual medical treatment 6% (16/267 ) 6% (16/267)

Conclusions Both LNG-IUS and usual medical treatments reduce the adverse impact of HMB on women s lives over two years But LNG-IUS is the more effective Largest randomised trial Recruited the target sample Ethnically representative of the UK population over 60 centres used increasing generalisability Low loss to follow-up Outcomes over two years but 5 and 10 year follow up is intended

Acknowledgements

Dysmenorrhoea / Endometriosis

Primary dysmenorrhoea Definition pain soon after menarche no organic or psychological cause can be found Mechanism local release of prostaglandins uterine spasm usually associated with ovular cycles Clinical features colicky abdominal pain onset shortly after or at onset of menses tends to improve with age and after pregnancy

Primary dysmenorrhoea Management exclude organic causes by history and examination - usually normal findings explanation reassure no pelvic disease runs in families Treatment options simple analgesics e.g. paracetamol prostaglandin synthetase inhibitors such as mefenamic acid combined oral contraceptive pill to suppress ovulation surgery like forced cervical dilatation and presacral neurectomy are never indicated

Secondary dysmenorrhoea Definition painful periods for which an organic or psychosexual cause is demonstrated Features commences in adult life begins several days before menses

Secondary dysmenorrhoea Causes endometrosis adenomyosis chronic pelvic inflammatory disease Management laparoscopy can be helpful mainstay of treatment is to deal with underlying cause

Endometriosis present in 10-25% women Common Condition Benign Cancer 10-70% symptomatic women Chronic Pelvic Pain costs 158m/year to the NHS Symptoms are NOT related to stage of disease

Definition Endometriosis presence of endometrial tissue in sites other than the uterine cavity Common sites pelvic peritoneum such as uterosacral ligaments ovary causing endometriomas (chocolate cysts) fallopian tubes uterine muscle called adenomyosis

Sites of Endometriosis J K Gupta, Senior Lecturer

Features Endometriosis reproductive years but usually between 30-40 years 50-70% nulliparous women and remaining majority of low parity high social class Symptoms - severity NOT correlated with disease stage heavy, often irregular menses secondary dysmenorrhoea deep dyspaurenia (painful intercourse) pelvic pain subfertility

Speculum Examination for Endometriosis J K Gupta, Senior Lecturer

J K Gupta, Senior Lecturer

Adenomyosis Endometrial tissue found deep in uterine muscle Occurs in older more multiparous women increasing severe menorrhagia secondary dysmenorrhoea gradually enlarging tender uterus Virtually impossible to diagnose without first removing uterus and getting histology

Investigations

Medical Management Expensive Short-term (<6 months) options which have side-effects are: Danazol GnRH Analogues ± Add-Back Therapy Synarel Zoladex Prostap

Medical Management Temporary Effect by Inducing Amenorrhoea Cheaper Long-term (>12 months) Options are: Continuous COC Mirena Coil Progestogens i.e. Desogestrel Dienogest (19-nortestosterone derivative and in the same class as norethisterone, levonorgestrel, desogestrel, gestodene. Potent oral bioavailability and highly selective for progesterone receptors)

Management in Primary Care Ultrasound to exclude gross endometriosis Use for 6 months continuously If pain settles = endometriosis If pain continues = likely bowel symptoms If pain settles continue COC / POP indefinitely until pregnancy

Endometrial Hyperplasia

Incidence of endometrial cancer in England and Wales / 100,000 cases 70 60 50 40 30 20 10 0 20-24 25-29 30-34 25-39 40-44 45-49 50-54 55-59 60-64 65-69 Age Range Source: Series MB1 no. 34 ONS Cancer statistics Registrations 2003

Endometrial Hyperplasia? Medical Treatment Normal variation 5% risk of progression Simple Hyperplasia Non-Atypical Hyperplasia Atypical Hyperplasia Endometrial Cancer 40% risk of progression TAH+BSO reasonable

Endometrial Hyperplasia Risk factors Age BMI DM HTN Exogenous hormones Oestrogens More than 40% have BMI >30

Management Mirena as 1 st line choice compared to oral progestogens Regression rates are around 80% Need to biopsy (for at least 2 years) on a yearly basis If there is persistence then for hysterectomy

HRT

Menopause Symptoms Vasomotor: hot flushes, night sweats CNS : depression, agitation, insomnia, concentration Urogenital atrophy: vaginal dryness, dyspareunia, recurrent UTIs

Menopause Treatments Systemic HRT Women with uterus: oestrogen with progestogen (combined HRT) Women without uterus: require oestrogen only HRT (oestrogen only HRT)

Menopause Treatments To protect uterus from unopposed oestrogen, combined HRT is achieved by:- i. Cyclical progestogen for the last 14 days of cycle (period giving, cyclical combined HRT) ii. Continuous oestrogen and progestogen (period-free, continuous combined HRT) iii. Specific drug with E2/Progestin/Androgen iv. activity (Tibilone, period-free) LNG-IUS (Mirena ) in uterus and oestrogen only HRT (period-free)

Menopause Treatments Local (vaginal) oestrogen cream or impregnated rings treat urogenital atrophy Non-HRT osteoporosis prevention: Calcium, bisphosphonates vasomotor symptoms: clonidine, homeopathic lifestyle measures: weight loss

Pre-requisites before starting HRT Clinical indications Moderate-to-severe vasomotor symptoms (systemic HRT) Urogenital symptoms [but HRT does not improve urinary incontinence] Low libido (use Tibolone or add in androgens) If premature menopause - continue HRT until age 50 years to reduce risks of osteoporosis, Coronary Heart Disease. May also restore fertility

Pre-requisites before starting HRT Documented detailed counselling on risks vs. benefits

Risks of Breast Cancer in combined HRT users Incidence of breast cancer Never-users 50-70 years old 45 per 1000 women Ever-users Began use at age 50 and used it for 5 years 47 per 1000 women (2 extra) 10 years 51 per 1000 women (6 extra) 15 years 57 per 1000 women (12 extra) Virtually no extra increased risk with oestrogen only HRT Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997;350:1047-1059

Prevention and Treatment of Osteoporosis A healthy lifestyle at any age Not smoking Not exceeding recommended limits of 14 units/week for women, 21 units for men Regular weight bearing exercise e.g. walking, skipping or sports such as tennis or jogging. Swimming is less effective for bones although very good for the heart and muscles A good calcium intake is important at all ages - at least 700mg (roughly the equivalent of a pint of milk any sort) HRT which also treats hot flushes and other symptoms For women with an early menopause HRT is usually recommended until the average age of menopause around 50yrs in order to protect the bones

Drug treatments for the prevention and treatment of osteoporosis

Alternative and Complementary Therapies Phytoestrogens: plant substances similar to oestrogens e.g. soy milk containing isoflavones and lignans Herbalism Black cohosh, Kava Kava, Evening primrose, Dong quai, Ginkgo biloba, Ginseng Others - Wild yam cream, St John's Wort, Agnus Castus (Chasteberry), Liquorice root and Valerian root Steroids e.g. DHEA (dehydroepiandrosterone) and progesterone transdermal creams Diet and supplements e.g. vitamins E and C Homeopathy: acupressure, acupuncture, Alexander technique, Ayurveda, osteopathy, hypnotherapy, reflexology, Reiki and Tai Chi

Conclusions Employ strategies to reduce adverse risks HRT for short duration (<6 months) Use lowest effective dose (risks of breast cancer greater if >5yr HRT) Avoid combined preparations. Consider using Mirena coil and oestrogen only HRT Use local oestrogen if treating urogenital symptoms only Regular (at least annual) treatment review Mammograms and breast self-examination Use non-hrt alternatives for osteoporosis (e.g. Raloxifene - oral selective oestrogen receptor modulator (SERM) with oestrogenic actions on bone and anti-oestrogenic actions on the uterus and breast) Lifestyle measures (e.g. reduce weight) if appropriate