Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Menopause VETERANS HEALTH ADMINISTRATION Objectives Define menopause and perimenopause Appropriately assess women presenting with menopause-like symptoms Review common symptoms and discuss management options VETERANS HEALTH ADMINISTRATION 2 Case Study 1 A 45-year-old woman Veteran presents at your clinic complaining of severe and frequent hot flushes. She’s also noticed several months of irregular menstrual cycles. She wonders if she is in menopause. VETERANS HEALTH ADMINISTRATION 3 Initial Assessment Make sure it is not… Identify Triggers • Cardio-Pulmonary • Infection • Hypoglycemia • Med reaction • Thyroid VETERANS HEALTH ADMINISTRATION • Determine impact on the Veteran - Physical - Emotional - Psychosocial 4 Premature Menopause • Loss of menstrual cycles before age 40 Perimenopause • Transition from regular ovulatory cycles toward permanent infertility • Begins at different ages, even in the 30’s. May last for years. Includes 1 year after last cycle. Menopause Menopause • Permanent cessation of menstruation resulting from loss of ovarian function • No menses for >12 months in women over 45 • Average age is 51 5 Menstrual Changes in Peri-Menopause “Normal” menstrual flow Menstrual changes • 21-35 days apart • Experienced by 90% of women • Occur 4-8 yrs before menopause • Flow ranges from very scant to • Duration: 3-7 days − Avg 2.4 tbsp of fluid − Normal range 1-6 tbsp • Contains blood, cervical mucus, vaginal secretions, endometrial tissue • Reddish-brown, slightly darker than venous blood very heavy, bright red bleeding • • Duration: 1 day to 10-12 days • Cycles are often anovulatory Cycle length/frequency: may stretch to every 60-90 days or shorten to every 20 days 6 Pregnancy is still possible… 7 Peri-Menopausal and Menopausal Symptoms VETERANS HEALTH ADMINISTRATION 8 Vasomotor Symptoms • Experienced by 50% to 82% of women • Duration of 4 to 10.2 years – 15% report severe flushes for >15 years • Feelings of intense heat for 30 seconds to 10 minutes • Greatest frequency is 2-4 years after menopause • Risk factors: – – – – Smoking Physical inactivity Obesity Race (most common in African-American woman, least common in women of Japanese/Chinese descent) – Surgical menopause 9 Urogenital Atrophy Physical exam changes • Loss of labial/vulvar fullness • Pale epithelium with less folds • Decreased vaginal secretions • pH >4.5 Vaginal dryness, irritation, +/- discharge Dyspareunia (painful intercourse) Urinary sx (frequency, dysuria, incontinence) 10 Other Menopausal Symptoms Mood Swings Loss of Libido Poor Concentration Anxiety Irritability Feelings of dread Depression Memory Lapses Headache 11 Insomnia Hair Changes Managing Vasomotor Symptoms with Hormone Therapy 12 13 1960. Estrogen is Fountain of Youth! 1970s. Poison! (linked to endometrial Ca) 1980s: Good! (prevents osteoporosis) 1990. Use expands! (protects heart) 2002. Poison! (WHI study) 2014 ? VETERANS HEALTH ADMINISTRATION 14 Hormone Therapy (HT) • Estrogen therapy seemed logical based on the hypothesis that menopause: - Decreased estrogen - Accelerated cardiovascular disease Thus… giving estrogen will protect the heart 15 Women’s Health Initiative (WHI) • Prospective study of estrogen + progesterone (Prempro) or estrogen alone on risks for CHD, breast cancer, hip fracture ─ E+P for women with intact uterus ─ E alone for women without VETERANS HEALTH ADMINISTRATION 16 WHI Results E+P vs. placebo Hazard ratio E only vs. placebo Hazard ratio CHD 164 vs. 122 1.29 177 vs. 199 0.91 Stroke 127 vs. 85 1.41 158 vs. 118 1.39 DVT/PE 151 vs. 67 2.13 101 vs. 78 1.33 Breast cancer 166 vs. 124 1.26 94 vs. 124 0.77 Colon cancer 45 vs. 67 0.63 61 vs. 58 1.08 Hip fracture 44 vs. 62 0.66 38 vs. 64 0.61 231 vs. 218 .98 291 vs. 289 1.04 Death Rossouw et al. JAMA, 2002; Anderson et al. JAMA, 2004. 17 WHI Findings • CHD, DVT/PE, and breast cancer risk all increased with E+P • DVT/PE risk increased in both groups • Similar increased risk of stroke for E+P and estrogen alone • No beneficial effect of HT on cognitive function in older post-menopausal women when administered for up to 5 years Rossouw et al. JAMA, 2002; Anderson et al. JAMA, 2004. VETERANS HEALTH ADMINISTRATION 18 Further Analyses of WHI Data • Both arms re-analyzed to look for trends in the effect of HT on CHD, stratified by age and years since menopause • Women who initiated HT closer to menopause tended to have reduced CHD risk vs. the increase in CHD risk seen in women more distant from menopause – This trend not statistically significant Rossouw et al. JAMA, 2007. VETERANS HEALTH ADMINISTRATION 19 Timing of HT and CHD • Majority of women in the WHI had been menopausal for at least a decade - These older women likely had more extensive subclinical atherosclerosis • Hypothesis: prothrombotic and proinflammatory effects of estrogens manifest primarily in women with subclinical lesions - Conversely, women with less arterial damage who start HT early in menopause may derive cardiovascular benefits Rossouw et al. JAMA, 2007. VETERANS HEALTH ADMINISTRATION 20 Additional Studies • Kronos Early Estrogen Prevention Study (KEEPS) - No beneficial or harmful effect on atherosclerosis progression with HT vs. placebo after 4.8 years • BMJ TRIAL - After 10 years of follow up, women receiving HT early after menopause had a reduced risk of mortality without any apparent increase in breast cancer or stroke • Both studies provide more reassurance about the safety of HT on the heart if started early in menopause (still not for appropriate for primary prevention of heart disease) KEEPS Report, NAMS Annual Meeting, 2012; Schierbeck et al. BMJ, 2012. VETERANS HEALTH ADMINISTRATION 21 Extended Follow-up of WHI Data • Neither regimen significantly affected all-cause mortality during or after the intervention phase – CEE-alone group: Subset of women aged 50 to 59 had fewer MI and significantly lower all-cause mortality – Combination HT has a harmful effect on CHD risk among older women, results in younger women are inconclusive • Risk–benefit ratio of HT is most favorable when initiated in younger menopausal women – Most risks and benefits from hormone therapy dissipate after stopping Manson JE, et al. JAMA,2013 22 Breast Cancer Risk with HT • Per WHI, risk for breast cancer is higher with E+P when used longer than 5 years; no risk for estrogen alone • Multiple follow-up studies support “gap” hypothesis: breast cancer risk increases when HT is started shortly after menopause vs. after several years delay • So, timing for breast cancer risk is direct opposition to HT and CAD Chlebowski et al. JAMA, 2003; NAMS position statement. Menopause, 2012; Beral et al. J Natl Cancer Inst, 2011. VETERANS HEALTH ADMINISTRATION 23 HT and Shared Decision-Making • Ultimately, it comes down to risks/benefits: - Most women who want HT will want it within 5 years - With E + P <5 years, absolute cancer risk is very low (lower than 1 alcoholic drink/day) - Many more women will die of CAD rather than breast cancer - If woman is of average cancer risk with significantly impairing hot flushes, recommend HT initiation when symptom control is needed most (early!) VETERANS HEALTH ADMINISTRATION 24 Current Indications for Hormone Therapy • Moderate to severe vasomotor symptoms related to menopause in healthy women • Patient request/quality of life issues • Not for chronic disease prevention • Do not start HT if >10 years after menopause • Systemic hormones for short-term use only (<5 years) Individualized decision should be based on risks for CVD, breast cancer, and osteoporosis as well as quality of life issues VETERANS HEALTH ADMINISTRATION 25 Hormone Therapy Initiation • All routes of systemic therapy are equally effective - Transdermal estrogen has lower risk of VTE vs. oral route • Use lowest effective dose - CEE 0.625 mg per day oral (estradiol 50 mcg) or lower • For women with a uterus, add progesterone - 2.5 mg of MPA per day • Continuous regimen is associated with fewer hot flushes - Women on this regimen are typically amenorrheic NAMS position statement. Menopause, 2012; Laliberte et al. Menopause, 2011. VETERANS HEALTH ADMINISTRATION 26 Hormone Therapy Discontinuation • No optimal approach for immediate cessation vs. taper • Try prolonged 6-12 month taper if symptoms recur after an abrupt stop • North American Menopause Society suggests that extended use of HT is reasonable for women who feel that benefits of symptom relief outweigh the risks VETERANS HEALTH ADMINISTRATION 27 Compounded Bioidentical Hormones • Typically custom-compounded formulations similar in chemical composition to those made endogenously • May combine several hormones and use non-standard routes of administration - Estradiol, estrone, and estriol - Often utilize salivary testing — inaccurate and unreliable • No rigorous randomized controlled trials to test safety or efficacy; under-dosage and over-dosage possible because of variable bioavailability and bioactivity • No more effective than traditional HT with similar risks/side effects; inform patients in same manner as FDA-approved HT VETERANS HEALTH ADMINISTRATION 28 Alternatives to Estrogen for Hot Flushes 29 Decrease in hot flush score Medications Venlafaxine (Effexor): antidepressant 37.5 - 150 mg 27-61% Desvenlafaxine (Pristiq): antidepressant 100 & 150mg 60-65% Fluoxetine (Prozac): antidepressant 20 mg 40-50% Paroxetine (Paxil): antidepressant 10 - 25 mg FDA-approved to treat menopausal hot flushes 38-62% Escitalopram (Lexapro): antidepressant 10 - 20 mg 47% Citalopram (Celexa): antidepressant 10 - 30 mg 23-55% Gabapentin (Neurontin): anti-seizure, 300 - 2400 mg 45-65% ACOG practice bulletin no. 141. Obstet Gynecol 2014; Casper et al. UpToDate, 02/14/11, lit review through 03/14. 30 Vitamin and Herbal Remedies Vitamin E No effect Black cohosh (can harm the liver) No effect Evening primrose oil No effect Ginseng (may help with mood, insomnia) No effect Wild yam (“natural progesterone”) No effect Phytoestrogens: isoflavones (soy, red clover) No effect Phytoestrogens: lignans (crushed flaxseed) No effect Chasteberry No effect Dong quai (bleeding problems with blood thinners) No effect Licorice root No effect Kava (may ease anxiety, can damage the liver) No effect *Note: Many herbs are estrogenic and the risks are unclear 31 Mind-Body Therapies Treatment Efficacy Paced respiration Mixed results Acupuncture Mixed results Yoga Possibly effective? Exercise Negative effect on flushes. Positive effect on sleep. Stress management No effect Relaxation therapy No effect Homeopathy/ magnet therapy No effect 32 Comment Small pilots, 1 randomized controlled trial Raises core body temp, thus triggering flushes Lifestyle Changes • Identify triggers and avoid them if possible – Spicy foods, alcohol, caffeine, chocolate, stress, hot places • • • • • • Dress in layers and remove the top layer as necessary Sip a cold drink when flushes occur Adjust room temperatures Use fans at home or in the workplace Consider losing weight to decrease flush frequency Don’t smoke VETERANS HEALTH ADMINISTRATION 33 Smoking and Menopause • Women who smoke >10 cigarettes per day are 40% more likely to go into menopause earlier than nonsmokers – Early menopause → heart disease, stroke, osteoporosis • Smokers have more severe hot flushes and sleeping difficulties • Women who smoke are 35% more likely to break a hip after menopause than nonsmokers – Former smokers have a 15% greater risk of hip fracture Employ motivational interviewing: Is it ok if I give you information about how smoking affects you during menopause? What are some reasons why you might think about quitting? What are some things that you can do to cut down on your smoking? 34 Summary: Hot Flush Management • Systemic HT is most effective approach for treating moderatesevere vasomotor symptoms • Risks for combined systemic HT = thromboembolic disease, breast cancer – Non-oral approach safer (no RCT evidence) • Use lowest effective dose in continuous regimen; re-evaluate annually – Estrogen + progesterone for women with a uterus • Consider non-hormonal alternatives – Venlafaxine, gabapentin, paroxetine – Encourage smoking cessation, weight loss VETERANS HEALTH ADMINISTRATION 35 Managing Vaginal & Urinary Symptoms 36 Common Symptoms Vaginal Dryness Pruritus Dyspareunia +/- Thin watery discharge Dysuria (painful urination) Urinary urgency or incontinence Frequent urinary tract infections VETERANS HEALTH ADMINISTRATION 37 Sexual Function and Menopausal Symptoms • 75% of middle-aged American women consider sexual activity to be of moderate to extreme importance • Common menopausal symptoms are associated with diminished libido: depressive symptoms (P = .003), poor sleep (P = .02), and night sweats (P = .04) • Large cohort studies report: - Prevalence of vaginal dryness… 27% - 55% of women - Prevalence of dyspareunia… 32% - 41% Cain et al. J Sex Res, 2003; Reed et al. Am J Obstet Gynecol, 2007; SOGC clinical practice guidelines no. 145. Int J Gynecol Obstet, 2005. VETERANS HEALTH ADMINISTRATION 38 Vaginal Atrophy • Clinical Diagnosis – Appearance of external genitalia and vaginal mucosa • Loss of labial/vulvar fullness • Pallor of urethral/vaginal epithelium • Decreased vaginal secretions – pH >4.5 VETERANS HEALTH ADMINISTRATION 39 Vaginal Atrophy Management Treatment Pros Lubricants OTC • Eases pain during • Astroglide intercourse • K-Y Jelly • Olive oil Moisturizers OTC • Eases symptoms • Replens (on VA • Improves vaginal formulary) epithelium • Vagisil Vaginal estrogen Rx • Eases symptoms • Premarin cream • Improves vaginal • Estring epithelium • Vagifem • No systemic effects 40 Cons Doesn’t change vaginal tissue Expensive option Not for women with breast cancer? Vaginal Atrophy: Systemic Estrogen • Systemic estrogen is not recommended for vaginal symptoms • Disadvantages ─ Need to add progesterone to protect the uterus ─ Increase in sex hormone binding globulin (SHBG) can decrease free testosterone • Transdermal estrogen may have less of an effect Why incur systemic risks for a local problem? NAMS position statement. Menopause, 2012. VETERANS HEALTH ADMINISTRATION 41 Vaginal Atrophy: Local Estrogen Advantages • Relieves atrophy and may improve sexual function • Low dose is effective and all preparations equally effective • Progesterone generally not indicated when low-dose vaginal estrogen is administered. Endometrial safety data not available for use longer than 1 year. • Can simultaneously treat urinary incontinence Disadvantages • May not be appropriate for women with hx of breast cancer NAMS position statement. Menopause, 2013; Suckling et al. Cochrane Rev, 2006 Oct 18. VETERANS HEALTH ADMINISTRATION 42 Vaginal Estrogen Comparison Cream Ring* *Non-formulary Tablet* Dose 0.5-2gm dose 5-10 mcg daily 10 mcg Frequency Nightly for 2 wks then twice/wk Replace every 3 months Nightly for 2 wks, then twice/wk Safety No reports of endometrial CA No endometrial No reports of proliferation at 1 year endometrial CA Comments Can achieve systemic estrogen levels No rise in serum estrogen No systemic or endometrial absorption Note: Estring provides local effects only; Femring achieves systemic levels, which requires adding progesterone to protect the uterus. NAMS, ©2012. http://www.menopause.org/htcharts.pdf 43 Summary: Vaginal Atrophy Management • First-line therapies include nonhormonal lubricants with intercourse and, if indicated, regular use of long-acting vaginal moisturizers • Estrogen therapy is advised for moderate-severe atrophic vaginal symptoms or if no response to lubricants and moisturizers • Ospemifene is another option for dyspareunia – SERM targeting vaginal tissues • Spotting or bleeding in a postmenopausal woman with an intact uterus requires a thorough evaluation ACOG practice bulletin no. 141. Obstet Gynecol, 2014; NAMS 2012, 2013. VETERANS HEALTH ADMINISTRATION 44 Urinary Incontinence and Estrogen • Prevalence during menopausal transition is 8% - 56% • Urinary incontinence may improve with use of local estrogen therapy - No evidence whether benefits continue after stopping treatment - No information on long-term effects • Randomized trials show oral estrogen worsens incontinence Cody et al. Cochrane Database Syst Rev 2012 Oct 17. VETERANS HEALTH ADMINISTRATION 45 Urinary Tract Infections & Estrogen • Oral estrogens do not reduce UTIs compared to placebo • In 2 studies, vaginal estrogens reduced the number of UTIs in postmenopausal women with recurrent UTI • Intravaginal estrogen may be reasonable for postmenopausal women with 3+ recurrent UTIs/year, especially when resistance to multiple drugs limits efficacy of antimicrobial prophylaxis Perotta et al. Cochrane Database Syst Rev, 2008 Apr 16; Stamm WE. J Infect Dis, 2007. VETERANS HEALTH ADMINISTRATION 46 Summary • Menopause symptom management should be based on an in-depth conversation between patient and provider • Critical to identify patient’s biggest concern • Tailor treatment based on impact of symptoms on daily life, taking into consideration patient’s cardiovascular and cancer risk factors VETERANS HEALTH ADMINISTRATION 47 Resources North American Menopause Society. Information on menopause and educational materials. http://www.menopause.org/edumaterials.aspx PubMed Health. Fact sheet: menopause. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004974/ U.S. DHHS. Menopause and menopause treatments fact sheet. http://www.womenshealth.gov/publications/our-publications/factsheet/menopause-treatment.cfm U.S. DHHS. Menopause symptom relief and treatments. http://www.womenshealth.gov/menopause/symptom-relieftreatment/ VETERANS HEALTH ADMINISTRATION 48 Resources NHLBI. Facts about menopausal hormone therapy. http://www.nhlbi.nih.gov/health/women/pht_facts.pdf NIA. Hormones and menopause: tips from National Institute on Aging. http://www.nia.nih.gov/sites/default/files/TipSheet_HormonesAnd Menopause_0.pdf NCI. Fact sheet: Menopausal hormone therapy and cancer. http://www.cancer.gov/cancertopics/factsheet/Risk/menopausalhormones National Center for Complimentary and Alternative Medicine. Herbs at a glance. http://nccam.nih.gov/health/herbsataglance.htm VETERANS HEALTH ADMINISTRATION 49 Author Rachel Bonnema, MD, MS Nebraska Western Iowa VA Health Care System VETERANS HEALTH ADMINISTRATION 50