Hormone Therapy for Menopausal Symptoms

1 APPROACH TO THE Menopausal PATIENT&CURRENT MANAGEMENTof Menopausal SymptomsMOA AUTUMN CONFERENCENOVEMBER 17, 2018 DAVID J BOES, DO, NOTHING TO DISCLOSE RELATIVE TO THIS PRESENTATION NO STOCK IN PHARM2 LEARNING OBJECTIVES Understand the impact and duration of Menopausal Symptoms on women, as well as morbidities associated with post- menopause Understand treatment options for Management of Menopausal Symptoms Understand the "timing hypothesis" relative to the timing of initiation of Hormone Therapy , and potential cardiac risks or benefits Understand the risks and benefits of various treatment options and individualization of Therapy based on a women's risk-benefit ratio3 Goals Discuss/Understandrole of HRT (HT, ET) For whom, how long Systemic?

2 Oral vsTransdermal Which Progestin? Bioidentical? Discussrisks and benefits: relative to menopause & treatment Heart Breast Bone Genito-Urinary Discuss critical window hypothesis Discusshow do you help the patient decide? (SHARED DECISION MAKING) Discuss:Howdo you educate your patient beyond the media-hype? Become familiar with MenoPro(NAMS) app4 GOALSE ducate Clinicians & Eliminate Fear Since early 2000s , the Practice and Art of HT for post Menopausal care has been abandoned or minimized. We as leaders in women s health need to; understand theevidence, individualizetherapy, and understand possible treatment options, and provide our female patients with toolsto assist in app (FREE) North American menopause Society (NAMS) To help clinician & patient work together to personalize treatment decisions on the basis of a your personal preferences ( Hormone vsnonhormoneoptions)

3 , taking into account patient medical history and risk factor status Facilitates shared decision making The MenoProapp Calculate patient 10-year risk of heart disease and stroke Has links to online tools that assess your risk of breast cancer and osteoporosis/ fracture. AIDS IN DECISION FOR HT OR ALTERNATIVES 6 MenoPro appMenoProwas developed in collaboration with NAMSand includes links to NAMS education materials, including a downloadable MenoNoteon behavioral and lifestyle modifications to reduce hot flashes, and information pages on the pros and cons of Hormone versus nonhormonetherapy options, a discussion of pill versus patch Therapy , and information on treatment options for vaginal dryness and pain with sexual activities, --with links to tables with information about different medications.

4 These pages can be printed out or directly accessed from your phone or tablet. Helps make informed choices about managing menopause Symptoms . MenoProcontains no advertising and was developed without any industry or pharmaceutical company support. 7menopro8 Number of Postmenopausal Women in the United States Is Continually Increasing*Projected Census Bureau. Statistical Abstract of the United States. 2000 Census Bureau. National population projections. Available at: Accessed January 3, 65 years60-64 years55-59 years50-54 years45-49 years010,00020,00030,00040,00050,00060,0 0070,00080,00090,000100,00020002010*2020 *2030*2040*2050*Age[Data from US Census Bureau]9 STAGES OF REPRODUCTIVE AGINGSTAGES.

5 REPRODUCTIVE PERIOD Menopausal TRANSITION menopause /POSTMENOPAUSE(PERIMENOPAUSE) (years)Estrogen Secretion40455055606570 75 Development of subclinical diseaseEstrogen Loss and Manifestations of Health Risks Over TimeUrogenital symptomsCardiovascular diseaseShort-term SymptomsLong-term DiseasesCognitive decline (Alzheimer s disease)Hot flushesMood, sleep, and/or acute cognitive changesOsteoporosis11 Patient: HF 52 year old Caucasian female, G4 P 3013, presents with c/o Hot Flashes and Night Sweats, with increasing severity over past 6 : 9 months ago. Increased spacing between periods over past 2-3 History: Tobacco, 25 pack year history.

6 Quit: 1 year ago Etoh: 4-6 glasses wine /week Hyperlipidemia (controlled with Statin)PMH: no major problems PSH: NONEV itals: BMI : 30 BP: 134 : normal12 Case HF : Management Options? Where is she in the stages of reproductive aging? What therapywould you offer her? What are optionsof management? How would you counsel her? Does she have any contraindications to HT ? Is she a candidate for HT? What if there is a family history of breast carcinoma?13 FACTORS TO CONSIDER Symptoms & SIGNS OF MENOPAUSEM enstrual Cycle Alterations Beginning at approxage 40 a woman may notice shortening or lengthening of her cycles The luteal phase remains constant (13-14 days) whereas the follicular phase changes Frequency of ovulation decreases from 13-14 times per year to 11-12 times per year With advancing reproductive age, ovulation frequency may decrease to 3-4 times/year average age menopause = years duration of Symptoms ?

7 7-10 years +14 menopause Review Average age of menopause : 50-52 Age Range : 45-56 Earlier onsetwith: Smoking, lower SE status, malnutrition, maternal hxof early menopause Duration: 10 years +/-average15 Symptoms & SIGNS OF MENOPAUSEHot flushes and Vasomotor Instability Hot flushes are the 1stphysical manifestation of decreasing ovarian function and estrogen production. It is a symptom of vasomotor instability Hallmark sign of perimenopause Hot flushes = recurrent, transient episodes of flushing, perspiration, and a sensation ranging from warmth to intense heat on the upper body and face, sometimes followed by chills Night sweats = when they occur during sleep and are associated with perspiration Typically last less than 3 minutes Resolve with Hormone Therapy (HT) in 3-6 weeks16 Symptoms & SIGNS OF MENOPAUSES leep Disturbances Latent phase of sleep (time required to fall asleep)

8 Is lengthened and the actual period of sleep is shortened One of the most common and disabling effects of menopause17 Symptoms & SIGNS OF menopause Mood Changes Depression Apathy Crying spells These Symptoms may be related to menopause , sleep disturbances, or both18 Hormone Therapy --TIMELINE: 19 Hormone Therapy ---2000 Prevailing View: HT was a low-risk intervention Immediate value for symptom relief Probably conferred long term protection against the major chronic diseases post Menopausal 20 What happened on a HOT SUMMER night in 2002??WHI E-P ARM: discontinued due to reported risks and released to media before published or notification to physiciansCEE/MPA RX21 WHI WHAT DID WHI TELL US?

9 EPT ET Quick review of WHI Important to understand & demystify findings Much Consternation over how decision was made to stop and release informationReview: The evidence base for HRT: what can we believe. Langer, Climacteric, 2017. vol20, #2, 91-9622 Hormone Therapy :Women s Health Initiative Large RCT to determine if hormones prevent heart disease, breastand colorectal cancer, and osteoporotic fractures in postmenopausal women Enrolled women ages 50-79 (average age 63) One arm of trial (11,000 women) continuous, combined E-P vs placebo Other arm (16,000 women) estrogen only Was scheduled to be completed in 2005, but both arms terminated early Prescriptions for HT decreased by approx.

10 38% in the first year post-WHI23 Initial data, non abjudicated90% > age 602425 WHI: Limitations and Criticisms Older population (mean age 63) Heavier women (BMI>30) 50% pts were current or past smokers-tobacco Only one route of administration Only one formulation of estrogen and progestogen (HIGHER DOSE CEE,.625MG &MPA, ) Should NOTbe extrapolated to pts with premature ovarian failure OR premenopausal oophorectomy High crossover (from intention to treat), & dropout rates26 WHI: Limitations and Criticisms Conclusions---were not stratified by age/decade or time since menopause Reanalysis of data suggests that HT/ET in younger postmenopausal women may not be as detrimental, and in fact, benefits > risks Many experts called for studies to evaluate Hormone Therapy in newly Menopausal women Large observational studies (such as Nurses Health Study) did not corroborate some of WHI findings27 REEVALUATING WHIW here do we stand in 2018?