Transcript Management of the Menopause
Management of the Menopause
Dr Tina Peers Consultant in Contraception and Reproductive Health Clinical Director SHS Surrey
A Life-changing event
Life expectancy continues to increase.
Important to support good health and reduce the incidence of disease Requirement and desirable to live as full, healthy and active a life as possible into old age-delayed retirement Majority of women are unaware of the health impact of the menopause Some simple measures and improvements in lifestyle could protect them from significant health problems later in life, and, in some cases, premature death
Healthy Options:
Sensible diet Exercise Moderate alcohol intake Smoking cessation Appropriate weight loss Blood pressure control These reduce the incidence of CVD, osteoporosis and breast cancer
Life Expectancy for women at the age of 45 (2006)
Living past the age of 50………99.06% Living past the age of 60………95.4% Living past the age of 70………86.9% Living past the age of 80………66.3% Living past the age of 90………28.32% Living past the age of 100……..2.19% At 80 1:3 have cognitive impairment At 80 1:3 have had an osteoporotic fracture For 2014 add 2.5 years
UK
>13 million women >45 in the UK 1/5 of the population A fantastic resource or a huge burden to the social care bill, and the NHS?
A Time of Change
We need; A clear government policy addressing the causes of ill health in middle-aged and older women Good access to HCP who understand affect the health of this age group the issues which Women to be positively informed BMS Statement to Government
Disadvantages Women Endure
Levels of income Pensions Fear of cancers-poorly informed Major cause of disability >45s is arthritis and osteoporosis women> men-isolation, poor quality of life and premature death AD and Dementia-women>men 2x depression in women Negative stereotypes-lack of role models generally in this age group.
Symptoms of the Menopause
Hot flushes Night sweats Poor sleep Depression Carpel tunnel syndrome Nocturia Itchy skin Dry skin Muscle weakness/fatigue/loss of volume
Symptoms continued:
Receding gums Brittle nails Low libido Vaginal dryness Bladder irritability Osteoporosis Vaginal infections Weight gain Dry eyes
Symptoms continued:
Reduction in collagen-leads to a change in appearance Aches and pains Irritability Low mood Forgetfulness Anxiety Panic attacks Lose Confidence Back ache
Effect on the Woman
Misery!
Very debilitating.
Exhaustion both mental and physical.
Detrimental to all relationships-home and work Start to feel that they have lost their identity/femininity/intimacy/control/their faculties/ability to cope/their ‘mo-jo’ Aymptomatic women have very little idea of the detrimental effect on their health the menopause can have
What is happening at the cellular level Post-menopausally?
Cardiovascular Disease: Women have a significantly less CVD than men of the same age until they are 60-prolonged protective effect of premenopausal Oestrogen Significant narrowing of the coronary arteries and atheroma formation can be detected within 7 yrs of the last menses Increase in BP Increase in Cholesterol-LDL
Osteoporosis: Osteoblastic activity is reduced and osteoclastic activity increases, resulting in osteoporosis Reduction in Collagen: 20% of the vertebral column is composed of intervertebral discs.
Fibroblastic activity reduces resulting in flattening of the discs, loss of height and loss of collagen in joints and ligaments. Fibroclastic activity increases.
Dementia: Secretase activity in the brain is reduced post menopause as it requires Oestrogen to effectively remove amyloid from the brain.
Increased incidence of both Dementia and Parkinsons Disease
Oestrogen Receptor
Consequences of Untreated POI 1
80% more likely to suffer from heart disease 50% more likely to die from heart disease Greater risk of cerebral aneurism Twice as likely to have a poor quality of life in health terms Islam R; Cartwright R.
The impact of premature ovarian failure on quality of life: results from the UK 1958 Birth Cohort.
27th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology, 3 Jul 2011 - 6 Jul 2011. 26:I108-I108. OXFORD UNIV PRESS (1 Jul 2011) Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis
Consequences of Untreated POI 2
Greater incidence of heart disease, osteoporosis and neurological disorders: Parkinsons Alzheimers Psychiatric disorders (Mayo Clinic)
Effects on connective tissue & collagen: blood vessels skin bones ligaments gum disease, tooth loss cataracts
Shuster LT, Rhodes DJ, Gostout BS,et al Maturitas. 2010 Feb;65(2):161-6. doi: 10.1016/j.maturitas.2009.08.003. Epub 2009 Sep 5. Rocca WA, Grossardt BR, Miller VM,et al Menopause. 2012 Mar;19(3):272-7. doi: 10.1097/gme.0b013e31822a9937.
WHI Study
Prescribing has reduced by >2/3 in most countries WW Especially influenced those who have qualified in the last decade Results as percentages-ie it reported a 26% increase risk of breast cancer in older women-v 1 extra case per 1000 women per year-dubious methodology Estimated > 40,000 extra osteoporotic fractures per year in the USA alone in women >50 as a result of study
Re-analysis of WHI & MWS
Shapiro S, Farmer RD, Seaman H, Stevenson JC, Mueck AO. The Collaborative Reanalysis.
Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: Part 1.
J Fam Plann Reprod Health Care. 2011 Apr;37(2):103-9. doi: 10.1136/jfprhc.2011.0078.
Shapiro S, Farmer RD, Mueck AO, Seaman H, Stevenson JC.
The Women's Health Initiative: estrogen plus progestogen Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: part 2.
.J Fam Plann Reprod Health Care. 2011 Jul;37(3):165-72. doi: 10.1136/jfprhc-2011-0090. Epub 2011 Jun 2 Shapiro S, Farmer RD, Mueck AO Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: part 3 . The Women's Health Initiative: unopposed oestrogen J Fam Plann Reprod Health Care. 2011 37(3):225-230. Shapiro S, Farmer RD, Stevenson JC, Burger HG, Mueck AO.
Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies. Part 4 : the Million Women Study.
J Fam Plann Reprod Health Care. 2012 Apr;38(2):102-9. doi: 10.1136/jfprhc-2011-100229. Epub 2012 Jan 16
MHRA
Statement from 2002 stated that “treatment should be evaluated at least annually in the light of new knowledge”
Key points
The decision whether to use HRT should be made by each woman having been given sufficient information by her health professional to make a fully informed choice.
The HRT dosage, regimen and duration should be individualised, with annual evaluation of pros and cons.
Arbitrary limits should not be placed on the duration of usage of HRT; if symptoms persist, the benefits of hormone therapy usually outweigh the risks.
HRT prescribed before the age of 60 has a favourable benefit/risk profile.
It is imperative that women with POI are encouraged to use HRT at least until the average age of the menopause.
If HRT is to be used in women over 60 years of age, lower doses should be started, preferably with a transdermal route of administration.
It is imperative that in our ageing population research and development of increasingly sophisticated hormonal preparations should continue to maximise benefits and minimise side effects and risks.
This will optimise quality of life and facilitate the primary prevention of long-term conditions which create a personal, social and economic burden
IMS Statement 2011
“
The safety of HRT largely depends on age. Healthy women younger than 60 years should not be unduly concerned about the safety profile of HRT.
”
IMS Statement 2011
“
There are no reasons to place mandatory limitations on the duration of HRT. Whether or not to continue therapy should be decided at the discretion of the well-informed woman and her health professional, dependent upon the specific goals and an objective estimation of ongoing benefits and risks.
”
HRT and CARDIOVASCULAR PREVENTION 1
• Danish Study • 1006 women, aged 45-58 yrs • Recent post menopausal • • Randomised to receive HRT or placebo Women with an intact uterus were treated with triphasic E 2 women who had undergone hysterectomy received 2 mg E 2 + NET and a day.
• • Intervention for 10 yrs – f/u for 16 yrs The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction.
(Schiebeck.LL, Rejnmark L, Tofteng CL et al. BMJ 2012; 345:e6409)
HRT and CARDIOVASCULAR PREVENTION 2
Results : • Women receiving Px early after the menopause have a significantly reduced risk of: Mortality (HR 0.57, 95% CI 0.30 to 1.08; P=0.084) Heart Failure + MI + Death (HR 0.48, 95% CI 0.26 to 0.87; P=0.015) • No apparent increased risk of: Any cancer (HR 0.92, 95% CI 0.58 to 1.45; P=0.71) Breast cancer (HR 0.58, 95% CI 0.27 to 1.27; P=0.17) Stroke (HR 0.77 95% CI 0.35 to 1.70) • DVT (HR 2.01 95% CI 0.18 to 22.16)
safety of long-term use
‘
window of opportunity
’ (Schiebeck.LL, Rejnmark L, Tofteng CL et al. BMJ 2012; 345:e6409)
• • • • • EFFECT OF COMBINED ORAL ESTROGEN/PROGESTOGEN PREPARATION (KLIOGEST) ON BONE MINERAL DENSITY, PLASMA LIPIDS AND POSTMENOPAUSAL SYMPTOMS IN HRT-NAÏVE THAI WOMEN.
Single centre RCT 120 Thai women, 45-65yrs, over 1yr Increase in spine & hip BMD Decrease in Total Cholesterol & LDL-Chol but also HDL-Chol Reduction in Climacteric Symptoms but not statistically significant Jirapinyo M, Theppisai U, Manonai J, et al LN.Acta Obstet Gynecol Scand. 2003 Sep;82(9):857-66.
EVALUATION THE EFFICACY AND SAFETY OF ESTRADIOL AND DROSPIRENONE TABLETS IN THE TREATMENT OF MENOPAUSAL SYMPTOMS AMONG POSTMENOPAUSAL CHINESE HEALTHY WOMEN:A RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL STUDY
RCT, multi-centre over 16wks 244 chinese women, 55-65yrs - 183 on Angeliq, 61 women on placebo During the trial, blood pressure in observation group was stable.
The commonest adverse event in observation group was breast tenderness which accounted for 12.0% (22/183) AE rate were low. SAEs reported in this trial were assessed as not study drug related or as unlikely study drug related Zhou YZ, Sun LZ, Lin JF, Yang Xet al 2011 May;46(5):345-9. Chinese.
Long-term safety and tolerability of continuous-combined hormone therapy in postmenopausal women: results from a seven-year randomised comparison of low and standard doses
Study design. 419 postmenopausal women Parallel treatment groups - Indivina 1/2.5mg, 1/5mg, 2/2.5mg, 2.5mg 84 cycles of 28 days in a randomised, comparative study. The first 24 month double-blind efficacy period has been previously reported. This report focuses on the open safety period after the first two years until completion of 84 treatment cycles.
Results. 275 women (65.6%) completed the seven-year study. All regimens provided good bleeding control.
No cases of endometrial hyperplasia or cancer diagnosed. Low frequency of AE, mostly occurring within the first two years - No SAEs. Very few women (n = 4) receiving the lowest dose option (1/2.5 mg) reported AEs vs other groups (p<0.009). No serious cardiovascular events. The incidence of strokes was lower than the national incidence for the age group.
Incidence of breast cancer was comparable with the national incidence (95% CI). Heikkinen J Vaheri R Timonen U Medical JBMS: September 2004 95-102
Climodien * (estradiol valerate 2 mg plus dienogest 2 mg) is safe and effective in the treatment of postmenopausal complaints.
DESIGN: Open, multinational, multicenter, non-controlled phase III study.
PARTICIPANTS:A total of 1501 women aged 52-65 years with postmenopausal symptoms of sufficient severity to require treatment over 48wks.
SAFETY OUTCOMES : TVS, EB, Mammography, thrombophilia screen, routine biochemistry, general & gynae examination CONCLUSIONS:Continuous combined estrogen-progestin therapy with Climodien is effective, safe and well tolerated in postmenopausal women, with a profile and incidence of adverse events consistent with those of existing HRT preparations
* Not licenced in the UK
Gräser T, Römer T, Wiedey KD, Janaud A.Climacteric. 2001 Dec;4(4):332-42.
Continuation beyond age 65 and starting De Novo
VTE
Risk increases with:
• • •
estrogen dose age BMI Canonico M, Plu-Bureau G, Lowe G, BMJ 2008, 336 DOI:10.1136/bmj.39555.441944 BE Greater during the 1st yr of use Oral, but not transdermal, estrogens are associated with a higher risk of recurrent VTE
• •
transdermal HR 1.0 (95% CI:0.4 -2.4) oral HR 6.4 (95% CI:1.5-27.3) Olie V, Plu-Bureau G, Conrad J et al Menopause 2011 May(18) 5:488-93
STROKE
The effects of tibolone in older postmenopausal women.
METHODS: RCT, 4538 women, 60-85 yrs T score of < -2.5 at the hip or spine or T score of < -2.0 + X-ray vertebral fracture Once-daily tibolone (1.25 mg) or placebo.
Annual spine radiographs were used to assess for vertebral fracture. Rates of cardiovascular events and breast cancer were adjudicated by expert panels.
RESULTS Decreased risk of vertebral fracture - 70 cases vs 126 cases / 1000 person-years (relative hazard, 0.55; 95% CI 0.41 0.74; P<0.001) Decreased risk of non vertebral fracture, 122 cases vs 166 cases / 1000 person-years (relative hazard, 0.74; 95% CI, 0.58 - 0.93; P=0.01) Decreased risk of invasive breast cancer (relative hazard, 0.32; 95% CI, 0.13-0.80; P=0.02) Decreased risk of Colon cancer (relative hazard, 0.31; 95% CI, 0.10 to 0.96; P=0.04) Increased risk of stroke (relative hazard, 2.19; 95% CI, 1.14 to 4.23; P=0.02) Cummings SR, Ettinger B, Delmas PD, Kenemans P N Engl J Med. 2008 Aug 14;359(7):697-708.
STROKE
Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. DESIGN Population based nested case-control study. 400 GP practices in UK contributing to the GP Research Database. Cohort of all women in the database aged 50-79 yrs, 01/1/87- 31/10/06 Each case of stroke matched to 4 controls Exposure to HRT categorised into E 2 , E+P, P only, Tibolone. Estrogens were further subdivided according to the route of administration and dose RESULTS: 15,710 cases of stroke matched to 59 958 controls. The rate of stroke in the cohort was 2.85 per 1000 per year. Adjusted rate ratio of stroke associated with current use of transdermal HRT was 0.95 (95% CI 0.75 - 1.20). The risk of stroke was not increased with use of low oestrogen dose patches (rate ratio 0.81(0.62 to 1.05)) The risk was increased with high dose patches (rate ratio 1.89 (1.15 to 3.11)). Current users of oral HRT had a higher rate of stroke than non-users (rate ratio 1.28 (1.15 to 1.42)) with both low dose and high dose.
Renoux C , Dell'ani ello S, Garbe E, Suissa S. BMJ . 2010 Jun 3;340 :c2519. doi: 10.11
36/b mj.c251
9.
Management
IUS plus transdermal oestrogen Utrogestan 200mg nocte –micronised natural progesterone Sandrena may not be absorbed by everyone Oestrogel may be better preparation for absorption Estradot patches useful.
Ensure sufficient levels to protect CVS and bones >300pmol/l-check 6 weeks after changing doses/changing regimen Check testosterone levels as well
Testosterone
Has been shown to affect the limbic part of the brain mood, energy and enthusiasm Affects muscle mass-reduction of 2-3% per annum PM if have low levels of testosterone Increases the blood flow to the vagina, vulva and clitoris.
Improves intensity of orgasms Improves libido