Menopause Dr Beverley Lawton ( Wellington JULY 2013) Women’s Health Research Centre, Wellington Menopause Clinic
www.otago.ac.nz/whrc
Women’s Health Research Centre
University of Otago, New Zealand
Useful info • www.menopause.org.au • www.menopausetoday.com • E-book Dr Beverley Lawton “Menopause: A Guide for Every Woman” • www.wellingtonmenopauseclinic.co.nz • AMS conference September 2014 Auckland
Women’s Health Research Centre
University of Otago, New Zealand
Menopause is the gateway to healthy aging
Women’s Health Research Centre
University of Otago, New Zealand
Opportunity • • • •
Wellness Successful aging Healthy Aging Maintenance or enhancement of QoL with increased years • Chronic disease prevention
Women’s Health Research Centre
University of Otago, New Zealand
Overview • What is it? • Treatment? • Prescription medications • HRT • Prescribing Woman with fan
Women’s Health Research Centre
Amedeo Modigliani
University of Otago, New Zealand
The Menopause – What Is IT! Simply means stopping of periods
Women’s Health Research Centre
University of Otago, New Zealand
Menopause • It represents a significant endocrine (hormone) change in a women. • Average age is 51. • The ovaries make several hormones including estrogen, progesterone and testosterone • Hormonal soup -stories Women’s Health Research Centre
University of Otago, New Zealand
Women’s Health Research Centre
University of Otago, New Zealand
At the Menopause • The follicle production becomes erratic. • Symptoms can occur 2-5 years before the last period. • Eventually no more follicles are produced. • Estrogen levels fall. • FSH and LH levels rise and can be tested.
Women’s Health Research Centre
University of Otago, New Zealand
Some History • 1700’s treated by leeches • 1800’s treated by surgical removal of the uterus and ovaries –strongly advised against sexual activity during and after the menopause • 1900’s depression related to loss of fertility Women’s Health Research Centre
University of Otago, New Zealand
Perspectives can differ In 1818, Elizabeth Wirt, a Virginia-born woman then living in Washington, D.C., had her last child and entered menopause. Her husband, U.S. Attorney General William Wirt wrote an oblique letter to a physician asking about her health. Elizabeth wrote a letter to her mother expressing her joy
Women’s Health Research Centre
University of Otago, New Zealand
Vasomotor Symptoms • Hot flushes • Night sweats • Palpitations • Menopause is associated with an increased risk of osteoporosis
Women’s Health Research Centre
University of Otago, New Zealand
Symptoms ? • • • • • • • • •
Joint and muscle pains Mood Memory Self Esteem Skin Hair Headaches Libido Sleep
Women’s Health Research Centre
University of Otago, New Zealand
Who gets symptoms ?
Women’s Health Research Centre
University of Otago, New Zealand
Sleep Disturbance • Increases the risk of accidents • May decrease work place performance • Affects family life 1
Sleeping Woman
Henri Matisse
• Associated with increased risk of illness such as obesity, diabetes, hypertension and diabetes 2, 3 1. Rosenthal M. Menopause2003;10(1):4-5. 2. Ayas NT,et al. Arch Intern Med 2003;163(2):205-209. 3. Gottlieb DJ et al Arch Intern Med 2005;165(8):863-867.
Women’s Health Research Centre
University of Otago, New Zealand
Help With Hot Flushes • • • • • •
Open Windows Reduce coffee Avoid hot spicy foods Avoid alcohol Plan clothes -layering Fan
Women’s Health Research Centre
University of Otago, New Zealand
The Dilemma…why treat at all?! • Common reason for seeking medical advice 1 • Significantly affect QoL for 25% of women • For 10-20% of women these symptoms persist for more than 10 years 2 1. Haimov-Kochman et al (2005) Acta Obstet Gynecol Scand 84 972-979 2. Position Statement, Menopause.11(1):11-33, 2004
Women’s Health Research Centre
University of Otago, New Zealand
Complementary and Alternative Medications (CAMS)
Women’s Health Research Centre
University of Otago, New Zealand
“Natural is good marketing ”
Women’s Health Research Centre
University of Otago, New Zealand
All therapeutic agents have: • Risks • Benefits • Side-effects • Interactions Dilemma in not treating: • Opportunity Costs Placebo effect
Women’s Health Research Centre
University of Otago, New Zealand
Prescription Medicines Antidepressants Venlafaxine, Paroxetine, Fluoxetine • Shown to have variable affect on vasomotor symptoms. Generally fast acting 1 • May be useful in breast cancer and/or presence of depression • Nine month RCT - citaloprim and fluoxetine showed no effect on flushes compared to Placebo 1 1. Suvanto-Luukkonen Menopause.12(1):18-26,2005
Women’s Health Research Centre
University of Otago, New Zealand
Antidepressants • Caution as regards side-effects • Small numbers and short duration of trials to date • Venlafaxine has been associated with hepatitis 1
1. Phillips B Ann. (2006) Pharmacoth 40(2): 323-327
Women’s Health Research Centre
University of Otago, New Zealand
Paroxetine • Paroxetine (Brisdelle) SSRI paroxetine mesylate Low dose (7.5mg) • Only non-hormonal treatment for hot flashes approved FDA (2013) • 2 studies (12 week, 24 week) • Side effects headache, fatigue and nausea vomiting • Not to be used with Tamoxifen http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm35 9030.htm Women’s Health Research Centre
University of Otago, New Zealand
After breast cancer • Tamoxifen -Venlafaxine, citaloprim, clonidine and gabapentin.( avoid fluoxetine and paroxetine ) • Do not use CAMS such as St Johns wart, phytoestrogens and black cohosh
Women’s Health Research Centre
University of Otago, New Zealand
Clonidine • May be helpful • Side-effects limit use – – – – – –
Drowsiness Tiredness Constipation Dry mouth Headache Dizziness
Women’s Health Research Centre
University of Otago, New Zealand
Gabapentin • An RCT of 59 women showed reduction of hot flushes by 45% compared to 29% placebo 1 another as effective as oestrogen 3 • Adverse effects - somnolence, headache, dizziness, ataxia, fatigue, disorientation and nystagmus (1 in 4) • Safe and effective for short term use 2 • Not approved by FDA for flushes due to sideeffects 1. Guttuso T,Obstet,Gynecol 2003;101:337-345 2. Fugate S Ann Pharmacother 2004;38:1482-99 3. Siresha Y, Obstet,Gynecol 2006;108, NO1 Women’s Health Research Centre
University of Otago, New Zealand
Stellate ganglion blocks • Used for 60 yrs for pain syndromes and vascular insufficiency; • 0.5% bupivicaine is injected on the right side of the anterolateral aspect of the C6 vertebra under fluoroscopy • An effective block confirmed by the presence of Horner’s syndrome. • Initial trials reduces flushes
Women’s Health Research Centre
University of Otago, New Zealand
Bio-identicals, NHRT • • • •
www.otago.ac.nz/whrc Compounded therapies Often contain mixtures of powerful hormones Efficacy, safety and pharmaco-kinetics unknown1 Must be considered experimental therapies
Position Statement, Menopause.11(1):11-33, 2004
Women’s Health Research Centre
University of Otago, New Zealand
Progesterone Cream • • • • •
Conflicting efficacy data Variable uptake No bone protection Limited safety data for the uterus Long term safety data needed
Davis SR et al, J Endocrinol (2005) 185, 207-222 www.otago.ac.nz/whrc
Women’s Health Research Centre
University of Otago, New Zealand
Don’t forget what we sit on! • • • •
Vaginal dryness is common Intercourse can be painful if not impossible Vaginal lubricants can help In most cases topical or oral oestrogen will be needed • Libido
Women’s Health Research Centre
University of Otago, New Zealand
Women’s Health Research Centre
University of Otago, New Zealand
Vaginal treatments • Ovestin - oestriol • Vagifem - oestradiol vaginal tablet • 80-90% achieve improvement in symptoms1 • Caution when using with Aromatase inhibitors2 NAMS, Menopause 2007 14:3 Kendall 2006 Ann Onc 17:584-587
Women’s Health Research Centre
University of Otago, New Zealand
Dilators
Women’s Health Research Centre
University of Otago, New Zealand
Women’s Health Research Centre
University of Otago, New Zealand
Universal HRT 1949-oral estrogens 1966 Feminine Forever 1975 endometrial ca 1995 PEPI 1998 HERS no benefit secondary prevention 2002 WHI EPT 2007 WHI –age ? Women’s Health Research Centre
University of Otago, New Zealand
HRT for menopausal symptoms • Oestrogen-containing HRT is the most effective treatment for menopausal symptoms (Maclennan et al 2002) – Reduces hot flushes by 70% – Also improves vaginal dryness
Women’s Health Research Centre
University of Otago, New Zealand
WHI Hormone Program Design
YES
Conjugated equine estrogen (CEE) 0.625 mg/d
N= 10,739 Placebo Hysterectomy
NO
N= 16,608
CEE 0.625 mg/d + medroxyprogesterone acetate (MDA) 2.5 mg/d Placebo
Women’s Health Research Centre
University of Otago, New Zealand
WHI Chronic Disease Prevention• Average age 63 • Largely asymptomatic • Majority well past menopause Results • Increased risk of cardiac events • Increased stroke risk • Increased risk breast cancer – E+P nonstatistical • Possible increased Alzheimer’s disease. Women’s Health Research Centre
University of Otago, New Zealand
Selected Risks and Benefits after 5 Years of combined estrogen and progestogen HRT for all women aged 50-79 (WHI Study, 2002) OESTROGEN WITH PROGESTOGEN 10,000 Women Years
* Not statistically significant
15 Breast Cancer s 8
Pulmonary Embolism Stroke
CVD *
8
8
7
Increase
0 Decrease
8
-15
Women’s Health Research Centre
Bowel and Uterine Cancers
10 Fractures Hip and Spine University of Otago, New Zealand
Selected Risks and Benefits after 7 Years of estrogen only HRT for all women aged 50-79 (WHI Study, 2004) OESTROGEN ONLY 10,000 Women Years
15 Stroke
* Not statistically significant
12 Pulmonary embolism* Bowel Cancer 3 * 1
Increase
0 Decrease
5 8 CVD* Breast Cancers*
-15
Women’s Health Research Centre
12 Fractures andNew Spine University of Hip Otago, Zealand
Window of Opportunity for HRT • Risk modified by years since menopause.1 • Supported by animal studies and observational studies. •