1/11/2017. Disclosure Statement. Describe the most common medical issues associated with peri-menopause and menopause. Case study:

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1 The Pharmacological Management of Peri-Menopause and Menopause Debora Bear, FNP, MSN, MPH University Of New Mexico Hospital Hormones and other Treatments Gwen Iffil, Stepmber 29, 19 to vember 14, 2016 Peabody Award-Winning Journalist Disclosure Statement Objectives: I have no real or perceived vested interests that relate to this presentation nor do I have any relationships with pharmaceutical companies, biomedical device manufacturers, and/or other corporations whose products or services are related to pertinent therapeutic areas. Following this knowledge-based presentation, the pharmacist participants will be able to: 1) Choose safe and effective contraceptive options as per CDC/WHO medical eligibility criteria 2) Choose safe and effective prescriptions among the available drug categories for vasomotor symptoms 3) Choose safe and effective prescriptions for vaginal health 4) Choose safe and effective prescriptions for bone health ) Review a variety of other medical issues and evidence for potential prevention and treatment of peri-menopausal and menopausal issues Following this knowledge-based presentation, the pharmacy technician participants will be able to: 1) Aid the pharmacist in reviewing CDC/WHO medical eligibility criteria in order to safely choose safe and effective contraceptive options 2) Review safe and effective prescriptions as well as benefits and risks of hormones nad other treatments for vasomotor symptoms 3) Review safe and effective prescriptions for vaginal health 4) Review safe and effective prescriptions for bone health ) Review safe and effective treatments for a variety of other symptoms associated with peri-menopause and menopause Describe the most common medical issues associated with peri-menopause and menopause Case study: 63 year old woman requests a refill of her bio identical hormone prescription. She takes this for her duodenitis, tendon pain, urinary incontinence, skin, hot flashes (she has tried EVERYTHING else and it is the ONLY thing that works), memory, leg swelling, varicose veins, bloating (had terrible IBS prior), osteopenia, and vaginal dryness. Does not get mammograms due to concern for radiation exposure. 1

2 When is menopause Premature < 40 (1%), For women who miss three or more consecutives menses, measure HCG, FSH, estradiol, prolactin, TSH Consider AMH level, vaginal ultrasound, Karyotype and testing for fragile x permutation, thyroid peroxidase antibodies, adrenal antibodies, fasting glucose, serum calcium and phosphorus levels If not contraindicated: consider estrogen treatment early < 40 < 4 (%) median age 2 Describe the most common medical issues associated with peri-menopause and menopause Contraception During Peri-Menopause Contraception Need for use until 12 months after FMP Methods Key Points: Vasomotor Symptoms/ Mood 60%-8% (varies by culture): treat with hormone replacement, SSRIs and SNRIs, CBT -CHC (Pills/Patch/Ring) -Progestin Only Review Medical Eligibility Criteria Option to treat hot flashes Vaginal Systemic replacement may not impact When to use/when to stop/remove Bone Estrogen & decreased risk of hip fracture -LARC Other: cardiovascular, memory, cancer Estrogen & stroke risk, memory not improved with HRT? Unopposed estrogen associated with endometrial cancer, Selective Estrogen Receptor Modulators decrease breast cancer -Barrier Methods Other Benefits from Hormonal Contraception Femcap, Diaphragm, condoms Treats irregular uterine bleeding, reduce vasomotor symptoms, decrease ovarian and endometrial cancer, maintain bone mineral density United States Medical Eligibility Criteria (US MEC) for Contraceptive Use, 2016 Contraception: Case Study A Fifty two year old woman presents for her annual. She is on a CHC and has menopause questions. 2

3 In a 2 year old woman, what testing can be offered to know when to A. FSH while on the CHC B. FSH at the end of the placebo time off the CHC C. Stop the CHC and wait to see if there is no menses for 12 months stop the CHC? For how long do you do you recommend to continue a CHC? A. Stop before or at least by age 2 B. Review medical eligibility criteria and continue through menopause C. Offer a non-hormonal method of contraception Response Counter D. Both b and c Response Counter Treatments for Vasomotor Symptoms Hormones SSRI/SNRI Gabapentin Clonidine Others: Isoflavones Botanicals Acupuncture Behavioral Estrogen most effective treatment Contra-indications (heart disease, breast cancer, active liver disease, thromboembolic disease) Shortest duration (< 4 yrs) Low dose: < 0.3mg CE, < mg oral micronized estradiol < 0.2 μg transdermal estradiol, or < 0.2 μg ethinyl estradiol Progestogen required for women with a uterus -Paroxetine(SSRI) 7.mg-2mg (not w/tamoxifen) Venlafaxine XL(SNRI) 37., 7, 10mg 900mg mg Studies are poor to good showing these are not effective more than placebo May help some women May provide relief when done for 20min 3xa day Beliefs about what is Natural Natural= Believed to be plant derived, not synthesized. Made without chemicals. Associated with fewer or no risks or adverse effects. It is equally or more effective than conventional hormone therapy Treats & prevents osteoporosis & has no heart disease risk Fewer than 1 in 3 women choose to take conventional hormone treatment At least 36% of Americans use some form of complementary/alternative medicine (> 60% if prayer & megavitamins for health factored in) The media, and not women s healthcare practitioners, have been the primary source of information concerning hormone benefits and risks The end product, physiologic effect, should be the concern 3

4 What are Hormones Diosgenin extrated from high-yield soy and Mexican (Dioscorea) and chemically converted into progesterone History: 1930s the first BH preparations were both natural and bioidentical, they were derived from human pregnancy urine Estriol (biest/triest): currently component in most BHT. Considered by proponents to be gentler and protective Claim to Individualize therapy based on hormone levels Saliva tests provide poor reproducibility, lack evidence supporting the stability of samples in storage and handling, and are subject to large interassay variability. Hormone levels in saliva may vary depending on diet, time of day, the hormone being tested, and changes in other variables such as secretion rate. Much of the physiological effects are determined at the cellular level and not the sera level High failure rate of progestin which is solely prescribed to protect women from estrogen-associated effects on endometrial tissue Generic Brand Available Strength (mg) Name Branded hormone therapeutics Estrogen alone Route of Indications Dosing Source of active Administration Generic Brand name Available Strength (mg) Route of administration Indications Dosing Source of active Conjugated Genestin Conjugated synthetic Enjuvia Moderate-severe VmS daily Moderate-severe VmS daily and and Mexican Yams Estraderm Estring 2 delivers 7.μg/day Transdermal Vaginal ring Moderate-severe Vms; moderate-severe vulvar and vaginal atrohophy; Prev. o st. Moderate-severe vulvar and vaginal atrhophy twice weekly q90 days from Mexican from Mexican Conjugated Premarin 0.3 moderatesevere vulval and vaginal atrophy daily Vaginal cream Atrophic vaginitis; kraurosis vulvae Esterified Menest 0.3 atrophic (estrone, equiline) 0.62 vaginitis; kraurosis vulvae daily Micronized estradiol Estrace 0. (estrone, equiline) 1 atrophic vaginitis; kraurosis daily 2 vulvae Prev.o st. Pregnant mares urine and and cypionate Transdermal Moderate-severe Vms; moderate-severe vulvar twice weekly from Mexican and vaginal atrohophy; Prev. o st. Vaginal ring Moderate-severe VmS q3- months (prodrug converts to estradiol) Moderate-severe VmS (prodrug converts to estradiol) Injection Moderate-severe VmS Synthetic? (prodrug (in oil) Q3-4 weeks converts to Cyclic estradiol) Vivelle 0.02 Vivelle Dot Femring /day Femtrace Depo- 1 Estropipate Ogen moderate-severe vulvar and vaginal atrophy; Prev.o st. from Mexican hemihydrate Estrasorb 8.7 (two 1.74-g pkgs) deliver 0./day Topical emulsion (micellar nanoparticle) Moderate-severe VmS daily Estropipate Ortho-Est moderate-severe vulvar and vaginal atrophy; Prev.o st from hemihydrate Vagifem 0.02 Vaginal tablet Atrophic vaginitis daily for 2 weeks twice weekly after Alora Climara Transdermal Transdermal moderate-severe vulvar and vaginal atrophy; Prev.o st moderate-severe vulvar and vaginal atrophy; Prev.o st Synthetic? Twice weekly Once weekly valerate valerate Delestroge n Valergen- 10,20, or Injection (in oil) Moderate-severe VmS q4 weeks cyclic Injection (in oil) Moderate-severe VmS q4 weeks cyclic Synthetic? (prodrug converts to estradiol) Synthetic (prodrug converts to estradiol) Generic Brand name Available Strength (mg) Route of Indications Dosing Source of active administration Generic Brand name Available Strength (mg) Route of Indications Dosing Source of active administration Etinyl estradiol Estinyl 0.02 Moderatesevere VmS Syntehsized and Branded hormone therapeutics: Progestogens Medroxyprogesterone endometrial continuous Amen 10 To reduce risk of Cyclic or hyperplasia in postmenopausal Medroxyprogesteron taking estrogen continuous Cycrin 2. women who are Cyclic or 10 and have an intact uterus Medroxyprogesteron continuous Provera 2. oral Cyclic or Secondary amenorrhea 10 Abnormal Micronized Crinone 4% w/w (4); 8% Vaginal gel Cyclic from uterine bleeding progesterone w/w (90) continuous Mexican due to hormonal imbalance Micronized Prometrium 100 Cyclic from progesterone 200 continuous Mexican rethindrone Aygestin Cyclic Branded hormone therapeutics: Estrogens + progestogens Conjugated PremPhase CE MPA Moderatesevere VmS; Cyclic Pregnant mares urine moderatesevere vulval Medroxyprogesterone atrophy; Prev. 0 and vaginal and Ost. Congugated PremPro CE MPA Pregnant mares urine combined Medroxyprogesteron and Esterified EstraTest 1.2 Moderate-severe VmS in combined patients not responsive to and estrogen alone 2. Methyltestosteron e and Esterified EstraTest 0.62 Moderate-severe VmS in combined HS patients not responsive to and estrogen alone Methyltestosteron 1.2 e and Activella 1 combined moderate-severe vulval and and vaginal atrophy; Prev. Ost. 0. rethindrone Combi moderate-severe vulval and 0.0/0.14 or E2 NETA Transdermal combined vaginal atrophy from 0.0/0.2/E2/ NETA per day rethindrone Mexican cycling is achieved using Vivelle OrthoPref Tablet 1 Tablet 2 Pulsed Tablet 1 (days est 1 1 moderate-severe vulval and 1-) Tablet 2 (days 4-6) vaginal atrophy; Prev. Ost. and repeat rgestimate Ethinyl estradiol Femhrt EE NETA Prev. Ost rethindrone Branded hormone therapeutics: Testosterone Testosterone Androderm 2. Transdermal NAMS: low libido Testosterone Androgel 2 Transdermal NAMS: low libido 0 Testosterone Testoderm 4 6 Transdermal NAMS: low libido mg/day Synthetic? 4

5 Generic Brand name Available Strength (mg) Route of administration Indications Dosing Source of active Testosterone cypionate Depo-testosterone metabolized into 100 mg/ml IM Low libido Twice/month Synthetic (prodrug is BH) Testosterone enanthate Delatestryl 100mg/mL IM Low libido Twice/month Synthetic? (prodrug is 200mg/mL metabolized into BH) Compounded hormone therapeutics: Estrogens, progesterone, testosterone Customized, trans-dermal; Claims vary Estriol Compounded (usually 1.2, 2., ) sublingual, vaginal Assumed: twice daily Estrone Customized for moderatesevere be less (Claimed to (triest) each patient, VmS/moderatesevere vulvar used due to commonly saliva, sera levels, or symptoms and vaginal Estrone (usually 1.2, 2., ) atrophy content Generic Brand name Available Progesterone Strength (mg) Customized for each patient, saliva, sera levels, or symptoms Route of administrati on, transdermal; sublingual, vaginal, injectable Indications Dosing Source of active Claims vary : cyclic or protection from estrogenassociated endometrial hyperplasia and adenocarcino mas Estriol (biest) Estriol Compounded Customized for each patient, saliva, sera levels, or symptoms (usually 1.2, 2., ) Customized for each patient, saliva, sera levels, or symptoms, trans-dermal; sublingual, vaginal, trans-dermal; sublingual, vaginal Claims vary Assumed: moderatesevere VmS/moderatesevere vulvar and vaginal atrophy Claims vary Assumed: moderatesevere VmS/moderatesevere vulvar and vaginal atrophy twice daily, commonly 1.2 mg BID Testosterone Testosterone propionate Customized for each patient, saliva, sera levels, or symptoms Customized for each patient, saliva, sera levels, or symptoms, transdermal; sublingual, vaginal, injectable IM Claims vary NAMS: decreased libido; NAMS does not recommend the use of product Monthly Twice/month and IM only Synthetic? (prodrug is metabolized into BH) Vasomotor: Case Study A fifty three year old woman presents for an annual check-up. She is two years post-menopausal, is currently taking Paroxetine for well controlled depression. She has no other chronic medical problems and was referred by her primary to talk about potential treatments for hot flashes. Vital signs include b/p 112/62 and bmi of 2. She has had yearly mammograms that are normal. The patient would like to know what is the most effective method for vasomotor symptoms A. estrogen B. Black Cohosh C. Vaginal estrogen D. Paroxetine For women with breast cancer who are taking Tamoxifen, what can be prescribed for vasomotor symptoms? A. Sertraline B. Venlafaxine C. Paroxetine D. Estrogen Response Counter

6 Vaginal: vulvar & vaginal atrophy (dryness, dysparenunia, and atrophic vaginitis) Treatments OTC Water/Silicone based moisturizers & lubricants Use moisturizers daily, use lubricants with sex Topical Hormones Ospemifene (Selective Estrogen Receptor Modulator) Ring may be absorbed less systemically Treats moderate to severe dyspareunia, associated with hot flashes, stroke & thromboembolic events Vaginal Case Study Sixty-One year old woman with Rheumatoid arthritis. History of frequent clinic visits for dysuria and negative lab studies to support urinary infections. Had not been having sex for years. Vaginal exam with pale, dry introitus, rugae not present. BMI 42 What options are available to treat her atrophic vaginitis? A. Water or silicone-based moisturizers and lubricants B. Topical vaginal C. SERMs D. All of the above Response Counter 6

7 Bone Estrogen Decreased risk of hip fracture? Consider use for prevention Selective Estrogen Receptor Modulators: Raloxifene and Bazedoxifene (use with CE in women with a uterus) Calcium Vitamin D Increasing calcium intake, through calcium supplements or dietary sources, should not be recommended for fracture prevention Other Cardiovascular Cognitive 7

8 References: Case study: 63 year old woman requests a refill of her bio identical hormone prescription. She takes this for her duodenitis, tendon pain, urinary incontinence, skin, hot flashes (she has tried EVERYTHING else and it is the ONLY thing that works), memory, leg swelling, varicose veins, bloating (had terrible IBS prior), osteopenia, and vaginal dryness. Does not get mammograms due to concern for radiation exposure. Alternative Medicine for Menopause. Endocrine Society Association of Reproductive Health Professionals Bio-Identicals: Sorting Myths from Facts. U.S. Food and Drug Administration Hormone Therapy: A Review of the Evidence. Journal of Women s Health. 2007; 16() Calcium intake and risk of fracture: systematic review. The BMJ 201; 31 Charting a Course Through Changing Tides: An Evidence-Based Examination of Hormone Therapy in Women s Health. Compounded hormone therapy: time for a reality check? Andrew Kaunitz, Menopause, September 201 Contraception. journal.org. Official Journal of Association of Reproductive Health Professionals. Vol 94,Number6, December 2016 The Endocrine Society Re-Issues Position Statement on Hormones, April, 2016 Global Consensus State Hormone Therapy. Endocrine Society The Kronos Early Estrogen Prevention Study. Women s Health (1): care-recommendations NIH Asks Participants in Women s Health Initiative Estrogen-Alone Study to Stop Pills, Begin Follow-up Phase. Barbara Alving. March 2, Perspectives in Prevention From the American College of Preventive Medicine U.S. Medical Eligibility Criteria for Contraceptive Use, 2016 The Women s Health Initiative: The Role of Hormonal Therapy in Disease Prevention, Robert Wallace, 3(1), 200 8