managing menopausal issues: options for therapy jan shepherd, md, facog

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  • Slide 1
  • Managing Menopausal Issues: Options for Therapy Jan Shepherd, MD, FACOG
  • Slide 2
  • Objectives Compare and contrast contemporary pharmacologic options for HT. Compare the pharmacology of oral HT to that of transdermal delivery systems. Identify options for management of menopausal issues with agents other than HT.
  • Slide 3
  • Slide 4
  • A 52 year-old Caucasian female, LMP 6 months ago, presents with significant hot flashes interfering with her daily activities and sleep. She has read that HT can cause breast cancer and heart attacks. If you and she decide on HT, what is your initial choice for therapy?
  • Slide 5
  • Current Options for HT
  • Slide 6
  • Fertil Steril 2001;75:1065. Lower-Dose HT Effective Reduces symptoms Protects bone Improved acceptance and safety Lower rate of breakthrough bleeding Fewer side effects Requires less progestin ? Decreased risk
  • Slide 7
  • Oral Estrogens ( in increasing order of potency ) estrone (Ogen, Ortho-Est) estradiol (Estrace, Prefest, Activella, Angelique, transdermal/vaginal preparations) conjugated estrogens (Premarin, Prempro, Premphase, Cenestin, Estratab, Menest, Enjuvia) ethinyl estradiol (Femhrt, oral contraceptives)
  • Slide 8
  • Premarin (Conjugated Equine Estrogens from PREgnant MARes urINe) Premarin (Conjugated Equine Estrogens from PREgnant MARes urINe) Sodium estrone sulfate - 50-60% Sodium equilin sulfate - 22.5-32.5% 17 - dihydro equilin sulfate Estradiol sulfate 17 - dihydro equilenin sulfate Sodium equilenin sulfate
  • Slide 9
  • Novel Delivery Systems Estrogen-only and combination patches Systemic therapy vaginal ring (Femring) Gel, cream, mist All contain estradiol Provide steady blood levels
  • Slide 10
  • Transdermal vs Oral Estrogen Bloodstream Oral Liver Liver proteins SHBG C-reactive protein Antithrombin III Factors VII, X Cells of target tissues Transdermal Stomach / Intestines Filer WD, Filer RB. Am Fam Physician. 1994;49:1639-1644. TG
  • Slide 11
  • Vaginal Preparations Minimal blood levels Used if vaginal dryness is only symptom Preparations Premarin cream Estradiol cream, tablets (10 g. lower dose now available) Estring (3-month low-dose estradiol vaginal ring)
  • Slide 12
  • Progestins In increasing order of potency Micronized progesterone* (Prometrium) Norgestimate (Prefest) Norethindrone acetate (Aygestin, Activella, Femhrt) Medroxyprogesterone acetate (MPA, Provera) * May be associated with less risk of breast cancer HormoneRelative Potency Progesterone 1.0 19-nor- testosterone 5.6 MPA 8.1 * J Clin Onc 2008;26:1260-8.
  • Slide 13
  • Continuous Combined Preparations PremPro (Premarin + Provera) Activella (estradiol + norethindrone acetate) Prefest (estradiol + norgestimate) Femhrt (ethinyl estradiol + norethindrone acetate) Angeliq (estradiol + drospirenone) Patches (estradiol + norethindrone acetate or levonorgestrel)
  • Slide 14
  • A 54 year-old female presents with persistent hot flashes on PremPro.625. Requests you check a salivary estriol level and prescribe bio-identical hormones based on the result.
  • Slide 15
  • Comparison of Pharmaceutical HT with Bioidentical HT CharacteristicPharmaceutical HTBioidentical HT Molecular structureSimilar or identical to human Identical to human FDA oversightYesNo DosageMonitored, accurate & consistent Not monitored; may be inaccurate & inconsistent* PurityMonitored; pureNot monitored; may be impure SafetyTested; risks knownNot FDA tested; risks unknown EfficacyTested & provenNot FDA tested; unproven Scientific EvidenceExistent; conclusiveInsufficient Santen, R. J. et al. J Clin Endocrinol Metab 2010;95:s1-s66. *Potency 67.5% to 268.4% of label in FDA study
  • Slide 16
  • Other Pharmacologic Options Statins and other lipid-lowering agents Bisphosphonates Centrally-acting meds for hot flashes Raloxifene a SERM
  • Slide 17
  • 60-year old g3p3, LMP age 50. No menopausal symptoms. At Health Fair, T score -1.5. No personal or FH of fractures. On HCTZ for bp, otherwise healthy. Nonsmoker, nondrinker. Ht 54, wt 135 #. Vitamin D 24 ng/ml. All other labs normal. How will you manage?
  • Slide 18
  • Treating with Bisphosphonates Treat If T score < -2.5 or < -1.5 with history of fracture If T score -1.0 to -2.5 (no fracture), treat if FRAX score 10-year probability of major osteoporotic fracture > 20% 10-year probability of hip fracture > 3% Re-evaluate at 5 years drug holiday if: Risk factors low T score > -2.5 Pt agrees to repeat DEXA in 2 years
  • Slide 19
  • http://www.sheffield.ac.uk/FRAX/tool.jsp?country=9
  • Slide 20
  • Slide 21
  • New Denosumab (Prolia) Monoclonal antibody against RANKL (cytokine leading to formation and activation of osteoclasts) 60 mg subq q 6 months Rapid response, more effective than alendronate* Rapid loss of effect when stopped Adverse events incidence similar to alendronate Indicated for osteoporotic pts at high risk of fracture *J Bone Miner Res 2009;24:153-61.
  • Slide 22
  • A 50 year old g1p1, LMP 1 year ago, history of DVT in pregnancy, presents with severe hot flashes.
  • Slide 23
  • Medications for Hot Flashes (Off-label)
  • Slide 24
  • A 54 year old on tamoxifen after lumpectomy, radiation, and chemotherapy for ER + breast cancer presents with severe hot flashes. How will you treat? What if she presents with only severe vaginal dryness/dyspareunia?
  • Slide 25
  • Raloxifene (Evista) Antagonist Breast Endometrium Hypothalamus Agonist Bone Liver Lipids Coagulation factors
  • Slide 26
  • Raloxifene Indications* Prevention and treatment of osteoporosis Prevention of invasive breast cancer Dosage - 60 mg/day *Only in Postmenopausal women
  • Slide 27
  • Raloxifene - Benefits Prevention and treatment of osteoporosis 2-3% increase in bone mineral density 30-50% reduction in vertebral fracture risk 44-71% reduction in invasive breast cancer incidence of endometrial cancer Positive effect on lipid profile triglycerides, LDL, no effect on HDL Not shown to cardiovascular mortality
  • Slide 28
  • Raloxifene - Risks DVT/VTE Risk of stroke Cause or increase hot flashes No effect on vaginal symptoms May cause leg cramps
  • Slide 29
  • Coming Soon TSECS (Aprela) Tissue Selective Estrogen Complexes A SERM (bazedoxiphene) plus conjugated estrogens Concept Antagonist to estrogens effects on breast and endometrium Preserves estrogens effects on symptoms and bone Additional effects studied DVT/PE risk = oral estrogen alone LDL, HDL, but triglycerides No effect on C-reactive protein
  • Slide 30
  • Alternative Therapies Acupuncture Phytoestrogens Soy Red clover Black cohosh Ginseng, ginkgo Omega-3 fatty acids Vitamin E None proven superior to placebo
  • Slide 31
  • Lifestyle Interventions
  • Slide 32
  • Cooler environment Weight loss Smoking cessation Aerobic exercise
  • Slide 33
  • 3 Most Important Health Measures for Postmenopausal Women Weight-bearing exercise Low-fat diet rich in fruits and vegetables Calcium 1000-1200 mg/day & vitamin D 800-1000 IU/day

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