Menopause & HRT. Luke Williams & Kelly Walters

Menopause & HRT Luke Williams & Kelly Walters

Menopause Lack of menstruation for more than 12 months, associated with cessation of ovarian function and reproductive capacity. Average age is 51. Premature menopause: menopause before the age of 40 years. [1]

Physiology Occurs when a women's finite number of ovarian follicles are depleted. Oestrogen and progesterone hormone levels fall, and reduced negative feedback causes LH and FSH to rise.

Premature ovarian failure Estimated to affect approximately 1% of women < 40, and 0.1% < than 30 years of age Not synonymous with menopause: approximately 5-15% of women with presumed primary ovarian failure may retain intermittent ovarian function for years. Spontaneous ovulation and pregnancy is possible.

Premature ovarian failure May occur at any age and in most cases it is idiopathic. Known causes include genetic e.g. Turner s syndrome, Fragile X syndrome Autoimmune disease e.g hypothyroidism, Addison's disease FSH receptor mutations Congenital adrenal hyperplasia Metabolic galactosemia

Iatrogenic premature ovarian failure Chemotherapy: can cause either temporary or permanent ovarian failure. Long term treatment with small doses > toxic than short term acute treatment. Particularly in those > 30 years. Radiotherapy Bilateral oophorectomy: results in immediate menopause which can be very symptomatic. Hysterectomy without oophorectomy: area of controversy. Diagnosis can be difficult (absence of amenorrhoea as a sign).

Signs and symptoms Perimenopause: transition phase leading up to the menopause. Usually begins with change to menstrual pattern. Attributed to tissue sensitivity to lower oestrogen levels. Most common symptoms are: Hot flushes Night sweats Vaginal dryness Sleep disturbance

Hot flushes Sudden feeling of heat in the face, neck and chest which last a few minutes. Flushing of the skin is followed by sweating and palpitations. Smoking and a high BMI may predispose a woman to more severe or frequent hot flushes.

Urinary and vaginal symptoms Arise directly from loss of the trophic effect of oestrogen. Symptoms of urogenital atrophy may not appear until 5/10 years after the menopause. Include: Dyspareunia Vaginal discomfort and dryness Recurrent lower UTI s

Investigations Often off little value and not routinely recommended for diagnosis: Measurement of FSH levels: fluctuate markedly from pre- to postmenopausal values on an almost daily basis during the perimenopause. May be helpful if premature menopause is suspected. FSH levels of greater than 30 IU/L suggest ovarian failure. Measurement of LH, estradiol, progesterone, or testosterone is of no value in diagnosing ovarian failure.

Hormone Replacement Therapy Restore hormonal levels to relieve the symptoms of the menopause Hot flushes Mood swings Vaginal dryness Not recommended over the age of 60 For women with early menopause, current guidelines recommend HRT until the age of 51. Detailed counselling required prior to initation.

Benefits Best for treating vasomotor symptoms (87% decrease in severity compared with placebo within 4 weeks) [3] Preserves BMD whilst on treatment Urogenital symptoms i.e. dryness (esp. with topicals) HRT may also improve sleep, muscle aches and pains and QOL in symptomatic women. [4] Short-term HRT may improve mood and also depressive symptoms.

Types available There are several ways HRT can be taken, including: Tablets Transdermal Patches An implant Oestrogen gels Pessary Vaginal Ring Nasal spray

Which to prescribe? Duration of treatment? No more than 5 years (if more than 10, discuss individual risks at GP annual review) Depends on pt preference (post counselling) Non-oral preparations (ie patches or gels) are often more suitable for: Women who experience side-effects such as nausea with oral preparations. Women with liver disease or gallstones. Women with a history of malabsorption. Women who are at risk of thrombosis. Women with diabetes. Women taking enzyme-inducing drugs. Those women with a history of migraines (oral medication can trigger migraines in some women). Low-dose vaginal oestrogen (tablet, cream, pessary, or vaginal ring) may be preferred if symptoms are primarily urogenital. [5] The levonorgestrel-releasing intrauterine system (Mirena ) plus oestrogen component may be used if: Progestogen side-effects are experienced with other progestogen preparations and delivery routes. Contraception is still needed. There is persistent heavy bleeding on cyclical combined HRT and normal investigations.

Contraindications? Breast/ovarian/endometrial cancer (ERdependent types) a history of VTE a history of heart disease or stroke untreated high blood pressure liver disease (abnormal LFTs) Current pregnancy/breast feeding Undiagnosed PV bleeding

Symptoms/Side effects Hormones used in HRT can have associated side effects, including: fluid retention bloating breast tenderness or swelling headaches indigestion depression

Oestrogen Vs Progesterone Oestrogen-only HRT substantially increases the risk of endometrial cancer (so + progest.) The Mirena intrauterine system (IUS) can be used as an alternative for endometrial protection. (Liscenced for 4 years). Women with progestogen side-effects (eg, fluid retention, mood swings, weight gain) can have the progestogen dose halved or the duration of taking progestogen reduced to 7-10 days

Safety? Cardiovascular risk (WHI) Venous thromboembolic risk (x2-3 oral) Cancer risk (particularly breast) Can also reduce the sensitivity of mammograms

Trial data Womens Health Initiative Million women study Discredited: age, selection

Alternatives to HRT Healthy Lifestyle Aerobic exercise, reduce caffeine and alcohol consumption, smoking cessation, adequate calcium intake Antidepressants: Venlafaxine, fluoxetine, citalopram, paroxetine (unliscened for treating hot flushes) Vaginal lubricant for dryness Tibolone? A selective oestrogen receptor modulator (SERM) which combines oestrogenic and progestogenic activity with weak androgenic activity.

Conclusion Current guidelines state that the benefits outweigh the risks as over a short time period (& low dose) i.e favorable benefit:risk ratio Important to titrate doses to tailor for womens changing needs throughout the menopause. Limit doses of hormone by prescribing appropriate delivery methods

Question 1 What is a clear contraindication for HRT? A) Currently medicated for hypertension B) Thyroid hyperplasia C) Hx of Lung Ca D) Hx of Breast Ca E) Premature Ovarian Failure

Question 2 What age does the average woman in the UK undergo the menopause? A) 49 B) 58 C) 65 D) 51 E) 55

Question 3 At what point is a woman defined to have undergone the menopause? A) After the age of 51 B) After missing 2 consecutive periods C) After 12 months of no periods D) Irregular menstruation after age 50 E) Following extended episodes of hot flushes

Question 4 Which hormone used in HRT can precipitate endometrial cancer? A) Progesterone B) Testosterone C) Oestradiol D) Combined therapy only E) Oxytocin

Question 5 What % of women recruited to the Women s Health Initiative were between 50-54 years of age (target age-range for HRT) A) 72% B) 7.2% C) 53% D) 20% E) 3.5%

Question 6 What is the FSH level that is considered to be in the postmenopausal range? A) >50 IU/L B) >30 IU/L C) >20 IU/L D) >60 IU/L E) >40 IU/L

Question 6 What is the FSH level that is considered to be in the postmenopausal stage? A) >50 IU/L B) >30 IU/L C) >20 IU/L D) >60 IU/L E) >40 IU/L

Question 7 What is the most reliable investigation to diagnose menopause? A) FSH level B) LH level C) Estradiol D) Progrestrone E) No reliable investigation

Question 8 Premature menopause is regarded as onset of menopause in western society before the age of: A) 30 years B) 35 years C) 40 years D) 45 years E) 50 years

Question 9 The most common cause of premature ovarian failure is: A)Genetic abnormalities B) Autoimmune disease C) Iatrogenic D) Idiopathic

Question 10 Which of the following statements are false? A) Vaginal pessaries give less systemic side effects than oral B) HRT provides long term bone protection following cessation of treatment C) Paroxetine can be used to treat hot flushes in the menopause D) Personal history of DVT s is a C/I for HRT E) 1 st degree relative with DVT s is a relative C/I for HRT

References [1] NHS CKS Menopause. Available at: http://cks.nice.org.uk/menopause#!background [2] Venous Thromboembolism and Hormone Replacement Therapy (Green-top Guideline No. 19). Available at: https://www.rcog.org.uk/en/guidelines-researchservices/guidelines/gtg19/ [3] Panay N et al; British Menopause Society & Women s Heath Concern recommendations on hormone replacement therapy, May 2013 [4] Hickey M, Elliott J, Davison SL; Hormone replacement therapy. BMJ. 2012 Feb 16;344:e763. doi: 10.1136/bmj.e763 [5] http://www.patient.co.uk/doctor/hrt-initial-consultation [6] http://www.nhs.uk/conditions/hormone-replacementtherapy/pages/introduction.asp