MENOPAUSE & HRT Nicola Stewart 28/02/2018

Physiology & Clinical Features 1.5 million oocytes at birth. 1/3rd lost by menarche. Peri-menopause – increased anovulatory cycles. Clinical Features: (affects 2/3rd woman) Menstrual irregularity Vasomotor Musculoskeletal Psychological Urogenital Cardiovascular Osteoporosis Breast disease Menstrual irregularity – cycle can lengthen or shorten. Period can be heavy. 10% have periods that suddenly stop. Vasomotor – hot flushes, warmth, sleep disturbance. Affects 85% menopausal woman. 8-15 times per day lasting for 4-5 mins. Due to release of GnRH. Most improve within a few months, and 90% resolved within 4-5 yrs. Clonidine can help. MSK – joint aches and pains due to reduced oestrogen Urogenital – Oestrogen dependent organs thin causing dyspareunia, bleeding, increased vaginal and urinary dryness and infections, urgency, nocturia and dysuria, UTIs, low libido Psychological – mood, depression, irritable, confused, lethargy, memory, libido, depresison, sleep disturbance. Osteoporosis – bone density decreases, increased risk of fractures. Breast Disease – rate increases with age, but rate of increase slows after menopause

Case Study 1 43 year old Asking if she is peri-menopausal? Mirena coil for 2 years Presenting with: Inter menstrual and post coital bleeding Increased anxiety, snapping No hot flushes or night sweats, not low in mood, no change to libido No FH of early menopause Asking if she is peri-menopausal? Asking to have a blood test?

Diagnosis Diagnosis should be based on clinical symptoms if >45 Perimenopause – vasomotor Sx & irregular periods Menopause – no period for 12m & not taking contraception (Sx if no uterus) Consider FSH if… >45 years with atypical symptoms 40-45 years with Sx and change in periods <45 years and suspecting premature menopause Laboratory results Consistently raised FSH >30IU/l. Raised LH Low serum oestrdiol. Cannot use blood tests to diagnose menopause if taking hormonal treatment. So, in this case unable to.

Assessment of Menopause Assess symptoms and their severity Assess risk of cardiovascular disease (Qrisk) Assess risk of osteoporosis Discuss her expectations Only carry out investigations if… Sudden change in menstrual pattern (IMB, post coital) Personal or FH of DVT High risk of breast cancer Evidence of arterial of other gynaecological disease

Case Study 2 34 year old Asking if she should be tested for this? Has not had a period for 7 months FH of premature menopause Nil other symptoms Asking if she should be tested for this? Asking what management might be required?

Premature Menopause Menopause <40 years (1%). Risk of osteoporosis and IHD Diagnosis – FSH >30 with raised LH and low oestrogen on two occasions 4-6 weeks apart Management Should have hormonal treatment with HRT or combined hormonal contraceptive until age of natural menopause & 5-10 yrs after HRT can benefit BP/ CVS risks, but both HRT and combined contraceptive offer bone protection. HRT not a contraceptive Prior to diagnosing premature menopause, other helpful tests to exclude causes for secondary amenorrhoea include: Pregnancy test, TFTs, Prolactin, testosterone, Blood glucose, Blood cholesterol and triglycerides, Cervical screening and mammograms, A pelvic scan Premature meonpause is elevated gonadotrophins and oestrogen deficiency. Early menopause is 40-45 years. Average age of menopause is 51.

Case Study 3 52 year old Would like to discuss HRT. Suffering from hot flushes, night sweats and loss of libido Last period was 8 months ago Would like to discuss HRT. Benefits and risks? If there are things she can also adjust herself? What she should start?

HRT Indications Contraindications Relief of vasomotor or other menopausal symptoms Prevention of osteoporosis Premature ovarian failure Contraindications Pregnancy, undiagnosed abnormal PV bleeding Active thromboembolic disorder or MI Breast disease or endometrial cancer Active liver disease

HRT Modifiable lifestyle factors Benefits Healthy balanced diet Calcium supplements Smoking, alcohol and caffeine Optimise management of their co-morbidities Benefits Reduce vasomotor symptoms Improved sleep, joint pain, quality of life Reduced psychological symptoms Reduce vaginal dryness and improve sexual function Improve bone mineral density

Counselling Points Irregular bleeding is common in first 3-6 months (Bleeding > 6mnths/ after amenorrhoea requires Ix) Importance of adherence with treatment Remind peri-menopausal women that HRT is not a contraceptive Can stop contraception at 1 year after period if >50 yrs and 2 years if <50yrs or 56yrs No evidence that HRT causes weight gain

Risks (over 5 years) Breast cancer Ovarian cancer Endometrial cancer <50yrs on HRT no extra risk Background risk is 15/1000. 2-6/1000 extra cases Ovarian cancer Background risk is 2/1000. <1 extra case over 5 yrs Endometrial cancer Combined HRT protects endometrium B/G risk is 2/1000. 4 extra cases over 5 yrs (oestrogen only) Venous thromboembolism Background risk is 5/1000. 2 extra cases over 5 yrs Cardiovascular disease No increased risks

Risks (in perspective) Breast cancer <>2-3 units alcohol per day increases risk by 1.5x Post menopausal obesity increases risk by 1.6x First pregnancy >30 years increases risk by 1.9x 5 years of HRT increases risk by 1.35x

Management Algorithm HRT Guidance and Treatment Pathway

Case Study 4 54 yr old has read the PIL on HRT and decided that she does not want to accept the potential risks. Suffers from hot flushes and would like to know what she can try? Finding sex uncomfortable, would like to know what she can try?

Alternative Treatments Vasomotor symptoms Fluoxetine, citalopram, venlafaxine or clonidine Vaginal dryness Vaginal lubricants Sexual dysfunction Seek specialist advice re; testosterone Psychological symptoms CBT, antidepressants Tibolone Beta blockers, gabapentin, complementary therapies Clonidine S/E: Dry mouth, sedation, fluid retention and depression. No clear evidence that anti-depressants help mood in woman who have not been diagnosed with depression. Tibolone (SERM) – combines oestrogenic and progesteronic activity, with weak androgenic activity. Complementary therapies: black Cohosh (risk?), evening primrose oil, acupuncture, phyto-oestrogen (nuts, wholegrain cereals, soy beans).

Case Study 5 57 year old Menopausal symptoms LMP: 2 yrs ago. PMH: DVT following laparotomy. Asking if she can start HRT?

Management of Co-Morbidities With or high risk of breast cancer Non-hormonal and non-pharmacological treatment St Johns Wart (Tamoxifen) Refer for further specialist input Risk of VTE Transdermal rather than oral Refer to haematologist if high risk Cardiovascular disease Can use HRT. Manage risk factors Type 2 diabetes Can use HRT. No effect of glucose control

Case Study 6 51 year old What options would you give her? Presenting with mastodynia (worse over 3-4 months) and symptoms of hot flushes, night sweats and tearfulness Estradiol for 15 months. Mirena for 3 years. No periods Has tried St Johns Wort and primrose oil What options would you give her?

Poor Symptom Control Check compliance and allow time Usually 3 months before making any changes Poor patch adhesion or skin irritation Change brand Inadequate oestrogen dose Increase dose or change route Unrealistic expectations Counsel Drug interactions

Side Effects

When to Refer Persistent side effects Difficulty in diagnosis Loss of libido causing significant distress Premature menopause Patient request Difficulty in knowing when to stop HRT (usually consider at 5 yrs as they enter menopause) Complex medical history

Review Follow up at 3 months Then annual review Effectiveness, s/e, dose, route, pros and cons BP, cervical and breast screening, osteoporosis Roughly for around 5 years after onset of symptoms There is no mandatory limitations HRT should be withdrawn slowly