POST MENOPAUSAL HORMONE REPLACEMENT Dr Jonathan Ruby Assistant

POST MENOPAUSAL HORMONE REPLACEMENT Dr. Jonathan Ruby Assistant Residency Director Lake Cumberland Family Medicine Residency Program

NOTHING TO DISCLOSE UNFORTUNATELY

THERESA W. Patient is 49 year old who comes in to establish care. She is experiencing nightly hot flashes that interfere with sleep. Patient requests “hormones” Her last menstrual period was over a year ago. She has no chronic medical conditions. No history of hypertension/VTE/migraines She smokes 1 ppd Last PAP was in 2005, normal with no history of dysplasia She has never had a mammogram

DIAGNOSIS OF MENOPAUSE Mean age is 51 with 95% of women menopausal at 45 -55 years Women > 45 years Irregular menstrual cycles Menopausal symptoms (hot flashes, mood changes, sleep disturbances, etc) No further diagnostics necessary FSH may be misleading if still having irregular menses However, if patient is looking for reassurance or sexually active with no reliable birth control use or clinical features of thyroid disease or hyperprolactinemia consider: FSH (>25 IUL/ml indicative of menopause) TSH, prolactin, Hc. G may also be reasonable

DIAGNOSIS OF MENOPAUSE Women between 40 -45 years of age If patients are having irregular menstrual cycles, with or without menopausal symptoms Recommend checking: FSH TSH Prolactin Women less than 40 Will need workup for premature ovarian failure

DIAGNOSIS OF MENOPAUSE Special considerations: Contraception use OCP’s in non-smoking women have been found to be safe up to age 50 Recommend checking FSH. If >25 IU/L, highly suggestive of menopause. But no value diagnostic Post hysterectomy/endometrial ablation FSH > 25 IU/L suggest transition to menopause

THERESA W. Patient is 49 year old who comes in to establish care. She is experiencing nightly hot flashes that interfere with sleep. Patient requests “hormones” Her last menstrual period was over a year ago. She has no chronic medical conditions. No history of hypertension/VTE/migraines She smokes 1 ppd Last PAP was in 2005, normal with no history of dysplasia She has never had a mammogram

INDICATIONS FOR HORMONE REPLACEMENT THERAPY (HRT) Management of menopausal symptoms • Vasomotor symptoms (hot flashes) • Mood liability/depression • Vaginal atrophy • AKA-Genitourinary syndrome of menopause • Joint aches and pains

NOT INDICATIONS FOR HRT Not for prevention of cardiovascular heart disease (CHD) Not for prevention of osteoporosis Not for treatment or prevention of cognitive decline/dementia

CONTRAINDICATIONS FOR HRT Breast cancer CHD Previous thromboembolic event Active liver disease Unexplained vaginal bleeding High risk endometrial cancer Transient ischemic attacks

THERESA W. Patient is 49 year old who comes in to establish care. She is experiencing nightly hot flashes that interfere with sleep. Patient requests “hormones” Her last menstrual period was over a year ago. She has no chronic medical conditions. No history of hypertension/VTE/migraines She smokes 1 ppd Last PAP was in 2005, normal with no history of dysplasia She has never had a mammogram

BENEFITS OF HORMONE REPLACEMENT Decrease in mortality of nearly 30% for women age 50 -59 Decrease osteoporotic fractures Reduce the risk of Type II diabetes Moderate improvements in mental health and well being 60% reduction in cataract formation

RISKS FOR HORMONE REPLACEMENT Women’s health Initiative clearly demonstrated increased risks in the older menopausal patient > 60 years of age Coronary Heart disease related to progestin no increase seen in unopposed estrogen risk is less if <60 years

RISKS FOR HORMONE REPLACEMENT Stroke 30% increased risk of ischemic stroke Venous thromboembolism (VTE) Gallbladder disease Breast cancer No increase and possible a decrease with unopposed estrogen felt to be related to progestin

RISKS OF HRT-COMBINED ESTROGEN/PROGESTERONE • Coronary heart disease (CHD) – 2. 5 additional cases • Invasive breast cancer – 3 additional cases • Stroke – 2. 5 additional cases • Pulmonary embolism – 3 additional cases • Colorectal cancer – 0. 5 fewer cases • Endometrial cancer – no difference • Hip fracture – 1. 5 fewer cases • All-cause mortality – 5 fewer events Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015

RISKS OF HRT-ESTROGEN ONLY • CHD – 5. 5 fewer cases • Invasive breast cancer – 2. 5 fewer cases • Stroke – 0. 5 fewer cases • Pulmonary embolism – 1. 5 additional cases • Colorectal cancer – 0. 5 fewer cases • Hip fracture – 1. 5 additional cases • All-cause mortality – 5. 5 fewer events Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015

THERESA W. Patient is 49 year old who comes in to establish care. She is experiencing nightly hot flashes that interfere with sleep. Patient requests “hormones” Her last menstrual period was over a year ago. She has no chronic medical conditions. No history of hypertension/VTE/migraines She smokes 1 ppd Last PAP was in 2005, normal with no history of dysplasia She has never had a mammogram

STARTING ESTROGEN Route Oral Greater effect on liver due to first pass effect More favorable effect on lipid profile - EXCEPT triglycerides Increases Sex Hormone Binding Globulin (SHBG)/Triglycerides/HDL/clotting factors Preparations Conjugated equine estrogens (Premarin) 17 -beta estradiol (micronized) Esterified estrogens (Menest) Ethinyl estradiol (OCP’s) Estropipate (Ortho-Est)

STARTING ESTROGEN Route Transdermal Lower incidence of VTE and stroke (compared or oral route) More favorable lipid profile (compared to oral route) 50 mcg/day equivalent to 0. 625 oral conjugated estrogens Topical Gel preparations dosed in metered dose pumps (1. 25 gm/day, delivers 0. 75 mg estradiol/day) Gel packets (estradiol 0. 25 mg, 0. 5 mg and 1. 0 mg / day) Topical spray (1. 53 mg estradiol/day) caution around children/pets

STARTING ESTROGEN Route Vaginal Effective at low doses for management of vaginal atrophy (now called Genitourinary Syndrome of Menopause, GSM) Preparations Vaginal cream (Premarin, Estrace cream) Vaginal tablet (Vagifem, Yuvafem) Vaginal rings (Femring, Estring)-good for 3 months

PROGESTERONE Must have on board in women with intact uterus Medroxypregesterone acetat (MPA) is most common Can dose cyclically (5 -10 mg a day) or continuously (1. 25 -2. 5 mg/day) Progesterone Little impact on lipids Dose Cyclic (200 mg/day X 12 days) or continuous (100 mg/day)

PROGESTERONE Levonorgestrel-releasing intrauterine device Not approved in US for endometrial protection in menopause but being used overseas and some are using it off label Bazedoxifene-Evista selective estrogen receptor modulator (SERM) "progestin-free" MHT for women with a uterus Increased risk for VTE

COMBINATION ESTROGEN-PROGESTIN Oral Preparations Oral conjugated equine estrogen/medroxyprogesteron (Prempro) Oral conjugated equine estrogen/ bazedoxifene (Duavee) estradiol/norgestimate (Prefest) estradiol/norethindrome (Activella, Amabelz, Mimvey) estradiol/drospirenone (Angeliq) ethinyl estradiol/norethindrone (Fem. HRT, Jevantique Lo)

COMBINATION ESTROGEN-PROGESTIN Transdermal Preparations 0. 045 mg estradiol/0. 015 mg levonorgestrel-Climara Pro 0. 050 mg estradiol/0. 14 mg norethindrone - Combipatch

REFERENCES Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321. Worzala K, Hiller R, Sperduto RD, et al. Postmenopausal estrogen use, type of menopause, and lens opacities: the Framingham studies. Arch Intern Baker VL. Alternatives to oral estrogen replacement. Transdermal patches, percutaneous gels, vaginal creams and rings, implants, other methods of delivery. Obstet Gynecol Clin North Am 1994; 21: 271. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100: 3975 ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol 2014; 123: 202. Nelson HD, Walker M, Zakher B, Mitchell J. Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U. S. Preventive Services Task Force recommendations. Ann Intern Med 2012; 157: 104.