Navigating the Change: Leading Patients Through Menopause

Transcription

1 4:30pm - 5:30pm: Breakout 5 - Women s Health Option A: Navigating the Change: Leading Patients Through Menopause ACPE UAN L01-P 0.1 CEU/1.0 Hr. Activity Type: Application-Based Program Objectives for Pharmacists: Upon completion of this program, participants should be able to: 1. Review the physiological factors associated with menopause. 2. Explore the treatment options for menopausal symptoms. 3. Compare the risks and benefits of various hormone and non-hormone medication treatments. 4. Discuss bioidentical hormone therapy and its place in treatment. 5. Describe the role of the pharmacist in leading patients through menopause. Speaker: Jim Hoehns, PharmD, BCPS, is an Associate Clinical Professor with the University of Iowa College of Pharmacy and Research Director at the Northeast Iowa Family Medicine Residency in Waterloo, Iowa. Dr. Hoehns has been at this site since 1995 and has been involved with over 100 clinical drug trials during that time. He has been involved with resident physician education for over 14 years. He has written several publications. His practice and research interests include cardiovascular therapeutics, osteoporosis, and diabetes. Speaker Disclosure: Jim Hoehns reports he has no actual or potential conflicts of interest in relation to this program. The speaker has indicated that off-label use of medications will be discussed during this presentation.

2 Navigating the Change: Leading Patients Through Menopause Faculty Disclosure Jim Hoehns reports he is a speaker s bureau member for for Sanofi-Aventis Jim Hoehns has indicated that off-label use of medication will be discussed during this presentation. Jim Hoehns, Pharm.D., BCPS Associate Professor (Clinical) University of Iowa College of Pharmacy Research Director Northeast Iowa Medical Education Foundation Learning Objectives Upon completion of this program pharmacists (or pharmacy technicians) will be able to: 1. Review the physiological factors associated with menopause. 2. Explore the treatment options for menopausal symptoms. 3. Compare the risks and benefits of various hormone and non-hormone medication treatments. 4. Discuss bioidentical hormone therapy and its place in treatment. 5. Describe the role of the pharmacist in leading patients through menopause. Pre-Assessment Questions 1. What physiologic changes accompany menopause? 2. Which hormone therapy options are appropriate for menopausal symptoms? 3. What potential risks are associated with hormone therapy? 4. What nonhormonal drug therapies are effective in treating menopausal symptoms? Menopause Menopausal transition Usually develops over 4-7 years Average onset: 47 years Variation in menstrual cycle length Example: 24 days instead of 31 days Skipped menstrual cycles Endocrine changes FSH elevation Symptoms Menopause Anchor point after 12 months of amenorrhea Average: 51 years Stages of Reproductive Aging Length decreases -2 days Menopause 2001;8(6): Stages of Reproductive Aging Workshop. Menopause 2001.

3 Neuroendocrine Links in Postmenopausal Women Hypothalamus Disinhibition Decreased production of inhibin Anterior Pituitary GnRH FSH +++ Atrophic Ovary Disinhibition LH ++ Decreased production of estradiol Atrophic Ovary Symptoms of Menopausal Transition Changes in menstrual patterns Vasomotor symptoms Hot flushes, night sweats Psychological disturbances Irritability, mood swings Sexual dysfunction Vaginal dryness, painful intercourse Somatic symptoms Dizziness, palpitations, dry skin Vasomotor Symptoms Occur in 12-60% of women Begin average of 2 years before menopause 85% will last for >1 year 25-50% will last for 5 years 15% may experience >15 years Physiologic changes Peripheral vasodilation rise in skin temperature Perspiration Elevated SBP and heart rate Pathophysiology of Vasomotor Symptoms Dysfunction of thermoregulatory center in hypothalamus Correlated with estrogen withdrawal or rapid fluctuation in levels Altered neurotransmitters narrow thermoregulatory zone Williams Gynecology Hot Flashes Lifestyle Modifications Lowering air temperatures Physical activity? fewer and less severe episodes BMI obese women have more hot flashes Smoking risk increases with amount smoked Relaxation techniques Paced respiration, yoga Menopause 2004;11:11-33.

4 HRT Regimens no uterus E uterus E P OR E P OR E P (Ortho-Prefest) daily E daily E + cyclic P daily E + P daily E + pulsatile P WHI Study Summaries Clinical Event WHI (E+P) WHI (E) CHD events 1.29 ( ) 0.91 ( ) Stroke 1.41 ( ) 1.39 ( ) Pulmon. emb ( ) 1.34 ( ) Breast CA 1.26 ( ) 0.77 ( ) Colon CA 0.63 ( ) 1.08 ( ) Hip fracture 0.66 ( ) 0.61 ( ) Death 0.98 ( ) 1.04 ( ) JAMA 2004;291: Vasomotor Symptoms HALT Trial 1 year, double-blind, placebo controlled RCT (N=351) black cohosh 160mg/d multibotanical Black cohosh, alfalfa, boron, ginseng, dong quai, etc. multibotanical + soy diet counseling CEE 0.625mg/d ± 2.5mg MPA Placebo Inclusion yrs, late menopausal transition or post 2 VMS/day over 2 weeks P=0.016 Ann Intern Med 2006;145:

5 Black Cohosh - Hepatotoxicity Herbal remedy Terpene glycoside, alkaloids, flavonoids, tannins Eight reported cases of hepatotoxicity Six required transplantation Rat model: toxic to hepatocyte mitochondria Antidepressants for Hot Flashes Individual patient pooled analysis 10 studies (7 antidepressants, 3 gabapentin) Primary end point Change in hot flash activity from baseline to week 4 Occurrence of 50% reduction in activity MJA 2008;188: J Clin Oncol 2009:27: Venlafaxine Fluoxetine Fluoxetine: 13% Paroxetine Sertraline Gabapentin Paroxetine: 13-41% Sertraline: 3-18% Venlafaxine: 33% Venlafaxine and hot flashes Gabapentin: 35-38% Loprinzi et al. Lancet 2000.

6 Antidepressants for Hot Flashes Venlafaxine and paroxetine appear to be more effective than sertraline and fluoxetine Onset of activity apparent in 1 week Gabapentin looks similar in efficacy to the antidepressants NAMS Position Statement Cochrane meta-analysis ET/EPT Hot flash frequency: 77% Hot flash severity: 87% Systemic ET/EPT is the gold standard for efficacy Alternatives Progestogens IM DMPA: 60-70% efficacy PO MPA: similar efficacy; 20mg/d used Megestrol acetate: 20mg BID All: may take up to 4 wks Menopause 2004;11: NAMS Position Statement Alternatives Clonidine (PO or transdermal) Efficacy: 35-45% Start: 0.05mg BID AE s: fatigue, dizziness, dry mouth, nausea, drowsiness Methyldopa ( mg/day) Not rec. Efficacy: 30% AE s: hemolytic anemia, hepatic disease, sedation, edema Bellergal spacetabs Not rec. Phenobarbital, ergotamine, belladona Efficacy: variable ( 9-38%; placebo adjusted) AE s: visual disturbance, dry mouth, addiction Menopause 2004;11: NAMS Position Statement Moderate to severe hot flashes ET/EPT Starting dose: 0.3mg CEE, mg estradiol, 0.025mg estradiol patch Increase dose if not effective BID dosing of half-doses? stability of estrogen may be more important than attainment of an absolute level Transdermal patch Vaginal estrogen ring (Femring) Nonhormonal Venlafaxine ( mg/day) Paroxetine ( mg/day) Gabapentin (start at 300mg/day) Femring (estradiol vaginal ring) Dosage: 0.05 or 0.1mg/day Used for 3 months; replace Systemic progestins needed if intact uterus Cost: 4 rings: $ (~$60/month) Transdermal Hormonal Products Drug Dosage Cost ($) Estraderm 0.05mg/day (8 patches) 60 Climara 0.025mg/day (4 patches) 76 Climara Pro 0.045/0.015mg (4 patches) 69 Vivelle 0.05mg/day (8 patches) 50 Estrogel 50g bottle 75 Drugstore.com 12/23/09

7 Bioidentical Hormone Therapy Hormones identical to endogenous hormones Biest (estradiol 20% + estriol 80%) Triest (estrone 10% + estradiol 10% + estriol 80%) progesterone Mixed by compounding pharmacies Administered by various routes Transdermal, sublingual, peri-vaginal Saliva testing for hormones commonly done Bioidentical Hormone Therapy - Pro Cohort study 12 months; 189 females, mean age: 53.7 yrs Biest (estradiol 1mg + estriol 4mg/g) cream, 0.5g twice daily Progesterone mg SL QPM Testosterone cream peri-vaginal QHS (N=125) DHEA 25mg QD (N=146) Results 97% had some symptom control 60% pts lost weight (mean: 14.8 lbs) Poorly described study and methods Gynecological Endocrinology 2009, early online 1-5. Bioidentical Hormone Therapy - Con Unsubstantiated health claims protects against heart disease, prevents Alzheimer s disease BHT/ natural implies safety to consumers Estriol stimulates breast cancer cell lines Unopposed estriol associated with endometrial hyperplasia Saliva testing is highly variable, poor correlations with serum levels Safety is unknown Bioidentical Hormone Therapy My Thoughts Impossible to claim superior safety Micronized progesterone Favorable aspects Topical: unreliable to protect endometrium 5 of 6 studies with serum or plasma levels showed insufficient levels Estriol conflicting evidence Patients should be informed of same risks and benefits as with other hormone products J Gen Intern Med 2007;22: , FDA consumer updates April 2008, NAMS Testosterone Therapy 1/3 ½ of testosterone comes from ovaries Gradual decline with aging SHBG with transition Free T stays same or slight increase No clear association of sexual function and testosterone concentrations Lab testing of testosterone not useful for diagnosing deficiency 9 of 10 RCTs show improved sexual desire and activity Efficacy & safety of testosterone therapy without concomitant estrogen is not established No data beyond 6 months of use AE s: hepatotoxicity, HDL, hirsutism, acne, Hct Summary Vasomotor Symptoms ET/EPT remain the clear gold standard for moderate to severe symptoms Lowest dose, shortest period Short-term risks are minimal Herbal remedies No convincing efficacy for any Alternatives Venlafaxine, paroxetine, gabapentin preferred Menopause 2005;12:

8 Pharmacists Role Be engaged with your patients Ascertain symptom frequency and severity Be cognizant of absolute and relative conrtraindications for hormone therapy Educate patients on risks and benefits of available options Personal preference of patient should drive decision Address other potential chronic health problems Osteoporosis Post-Assessment Questions 1. Which of the following physiologic changes take place during the menopausal transition? A. Decreased GnRH B. Increased FSH C. Increased testosterone D. Increased ovarian follicular structures Post Assessment Questions 2. A 48 y.o. female is evaluated for frequent hot flashes and night sweats. She has not menstruated for 8 months. She is seeking a speedy resolution. Medical history is noncontributory. Which is most appropriate treatment? A. Black cohosh B. Clonidine C. Low dose hormone therapy D. Gabapentin Post Assessment Questions 3. A 49 y.o. female presents with vasomotor symptoms. She inquires about risks. Which of the following conditions is not associated with long-term hormone (E+P) use? A. Stroke B. Breast cancer C. Coronary heart disease D. Endometrial cancer Post Assessment Questions 4. Which of the following nonhormonal alternatives is reasonable for treatment of vasomotor symptoms? A. Sertraline B. Paroxetine C. Dong quai D. Black cohosh Continuing Pharmacy Education (CPE) To receive your CPE Statement of Credit: Log-on to the CEI Website Enter your user name/password or click on New to CEI to create a portfolio; Click on MY PORTFOLIO Enter the Access Code: (case sensitive) Pharmacists - Technicians -