Understanding Menopause: Pharmacotherapy and Treatment Options
School
Thomas Jefferson University**We aren't endorsed by this school
Course
NU 560
Subject
Nursing
Date
Dec 11, 2024
Pages
26
Uploaded by HighnessAntelopePerson3341
C O L L E G E O F N U R S I N GPharmacotherapy of Women’s HealthPart 2:MenopauseSara Arn, MSN, CRNP, AGPCNP-BC
•Define menopause and its pathology•Differentiate between therapies used in treatment of post menopausal syndromes (vasomotor and genitourinary) including:•Hormonal, nonhormonal, and alternative methods; dosages; side effects; contraindications; correct use•Understand how to select the most appropriate agent to treat menopausal syndromes.Learning Objectives
Menopause
•Permeant cessation of menstruation resulting from loss of ovarian function•Mean age of menopause in US is 51, ranging from 41-58•Early menopause risk factors include: hx of irregular menses, blacks, tobacco use, weight reduction diets, hysterectomy•Postmenopausal chronic disease conditions (from decreased levels of estrogen/progesterone)•Coronary heart disease, stroke, hip fx, breast cancer, colorectal cancer, endometrial cancer, Alzheimer dxMenopause Overview
Pathophysiology•Menopause is the age-related loss of ovarian function resulting in decrease in estrogen secretion by ovarian follicular unit•Perimenopause- starts around 2 years prior to final menstrual period FMP•Changes in time span from one cycle to the next•Decreased or increased amount of menstrual flow and number of bleeding days•Skipped cycles with amenorrhea lasting 60 days or more•Menopause is reached after 1 full year of amenorrhea from final menstrual period •Postmenopausal- after menopause is reached
Estrogen Function•Maintains body temp & delays memory loss•Regulates metabolism and body weight•Prevents reduction in skin collagen•Encourages stimulation of hair growth•Conserves integrity of mucous membranes •Decreases buildup of plaque in coronary arteries•Supports maturation of breasts•Regulates liver production of cholesterol•Maintains lubricated/thick vaginal lining•Regulates menstrual cycle•Maintains epithelial lining of the bladder•Enhances urethral resistance•Preserves bone density
Symptoms of Low EstrogenTrouble concentratingMoodiness and irritabilityDry skinHot flashes and night sweatsTender breastsDecreased BMDVaginal atrophyAmenorrhea Weight gainHeadaches Decreased sex drive DyspareuniaFatigueInsomniaRecurrent UTI’sOveractive bladder
Vasomotor Symptoms (VMS)•Approximately 87% affected•Hot flashes, flushes, perspiration, chills, and clamminess•Transient from 1-5 min up to 10 times per day•Affects mood and sleep•Risk factors associated with occurrence and severity of VMS•Obesity, Tobacco use, depression, anxiety, sedentary lifestyle, low socioeconomic status, race (blacks)
Genitourinary Syndrome of Menopause (GSM)•Approximately 40% affected•Vaginal dryness, itching, burning•Dyspareunia•Recurrent UTI’s•Overactive bladder
Goals of therapyReduce symptom severity and frequencyImprove quality of life
Agents to Treat Menopausal SymptomsHormone Therapy (estrogen, progestins, or combination)Estrogen Agonist/AntagonistTissue Selective Estrogen ComplexSSRIs & SNRIsGabapentinClonidine
•Mechanism of action: minimizes VMS and GSM related to estrogen deficiency by repleting estrogen levels.•Important note: Progestins are added to systemic estrogen formulations (oral and transdermal) in women who have a uterus because estrogen alone lead to endometrial hyperplasia, increasing risk of Endometrial cancer•Contraindications: Estrogen dependent neoplasia (breast, Endometrial), thrombophlebitis or thromboembolic disorder, pregnancy, undiagnosed vaginal bleeding, uncontrolled hypertension, acute liver disease•Side effects: N/v, breakthrough bleeding, edema, weight changes, swollen/tender breasts, HTN, depression, hair loss, changes in libido, VTE•Long Term Side effects: breast cancer, CHD, VTE•Interactions: Corticosteroids, barbiturates, phenytoin, rifampin, tobacco use, alcohol useHormone Therapy
•Use at lowest effective dose for shortest duration possible•VMS•Transdermal Patches- 0.025mg•Oral- 0.3mg•GSM (atrophy, recurrent UTI, OAB)•Vaginal Tablets: 10mcg daily x 2 weeks then twice per week•Vaginal Ring: 7.5mcg released daily over 90 days•Vaginal Cream: 2-4 gram of cream vaginally per day for 1-2 weeks followed by 1 g of cream vaginally 1-3 x per week•Transdermal and vaginal formulations- lower risk of VTE compared to oral formsHormone Therapy
•Estrogen w/ or w/o progestogen•Prevents postmenopausal bone loss•Increases bone mass•Decreases risk of hip/vertebral fx•Increases mammogram density •Increases risk of gallbladder disease•Estrogen w/ progestogen•Lowers risk of colon cancer•Estrogen alone•Increases risk of Endometrial cancer in those with uterus•Risk of VTE doubled w/ HT and even higher in those with increased BMI, thrombotic disorders, surgery, immobilizationAdditional HT information
•Estrogen Only HT•Alora (Estradiol)- patch•Estrace (Estradiol)- Pill, vaginal cream•Femring (estradiol acetate)- vaginal ring•Premarin (conjugated estrogens)- Pill, vaginal cream, injection•Vagifem (estradiol)- Vaginal tablet•Progestin Only HT (Given to lower change of Endometrial cancer in those with a uterus)•Prometrium (micronized progesterone)- pill•Provera (medroxyprogesterone acetate)- pill•Combination Estrogen/Progestin HT•Combipatch (estradiol/norethindrone acetate)- patch•Prempro (conjugated estrogen/medroxyprogesterone)- pillCommon HT meds seen in practice
Estrogen Agonist/Antagonist•Nonestrogen alternative for GSM (dyspareunia)•Weak estrogen activity in uterus & has antiestrogenic activity in breast tissue (no increase in breast cancer or Endometrial cancer risk)•Reduces bone turnover rate•Mechanism of action: Binds to both estrogen receptor alpha and estrogen receptor beta.•Triethylene derivative (similar to tamoxifen)-•Osphena (Ospemifene)- oral- 60mg daily with food•12 -52 weeks to reach clinical effectiveness •Contraindications: Undiagnosed/abnormal vaginal bleeding, known estrogen dependent neoplasia, hx of active thromboembolic disease•Adverse Events: Vaginal discharge, muscle spasm, hot flashes, hyperhidrosis•BOXED WARNING: VTE events, CV disease, endometrial cancer•Interactions: Should not be used with drugs inhibited or induced by CYP-450 system, Diflucan, rifampin
•Approved for severe VMS•Mechanism of action: Acts as an estrogen antagonist in urerine tissue (reducing risk of endometrial hyperplasia) and an estrogen agonist in bones (minimizes bone loss). •Combination with bazedoxifen further reduces BMD loss, reduction in VMS, and no greater increased VTE ( as opposed to CEE & Progestin)•Duavee (CEE /bazedoxifen)- Oral- 0.45mg OR 0.625mg / 20mg daily•Up to 80% reduction in severity and frequency of hot flashes in 12 weeks•Contraindications: Hx of VTE, arterial thrombotic disorder, hx of breast cancer, hepatic impairment, protein C/S or antithrombin deficiency. •Adverse events: Comparable to placebo treatment groups (N/diarrhea, abdominal pain, muscle spasms, dizziness)•Interactions: Avoid use with ospemifene. Should not be used with drugs inhibited or induced by CYP-450 system.Tissue Selective Estrogen Complex
•Reduce VMS•Mechanism of action: reestablishes NTs in thermoregulatory center of hypothalamus•Only Brisdelle (Paroxetine) FDA approved for moderate to severe VMS•Others used include:•SSRI: Paxil (paroxetine)- 7.5mg daily, Zoloft (sertraline)- 50mg daily, Celexa (citalopram)- 10-30 mg daily, Lexapro (escitalopram)- 10-20 mg daily•SNRI: Effexor (venlafaxine)- 37.5- 75mg daily, Pristiq (devenlafaxine)- 100mg daily•30-75% show reduction in VMS after 4-8 weeks of treatment•Contraindications: Do not use within 14 days of MAOI’s•Adverse events: Nausea, dizziness, dry mouth, nervousness, constipation, sexual dysfunction •Interactions: MAOI’s, carbamazepine, cimetidine, NSAIDSSSRI’s, SNRI’s
•Reduce VMS•Mechanism of action: Unknown•Dosage: 600-900mg in divided doses to a total of 2700mg daily•VMS reduced in frequency and severity by 45% within 4-12 weeks•Contraindication: Hypersensitivity to gabapentin or components•Adverse Events: Somnolence, fatigue, dizziness, rash, edema•Interactions: Antacids reduce absorption (take gaba 2 hours after)Gabapentin (Neurontin)
•Reduce VMS•Mechanism of action: Unclear, ? Related to central activity and potential impact on thermoregulatory center in hypothalamus. •Dosage: 0.1mg daily•Clinical improvement reached by 4-6 weeks•Contraindications: Low blood pressure•Adverse events: dry mouth, insomnia, drowsiness, increased risk for hypotensionClonidine
•Follow up 4-8 weeks after starting therapy and then every 3-6 months•Decision to continue HT reviewed yearly•Note any vaginal bleeding, ensure mammograms/ PAPs/DEXA UTD•Height/weight, lipids, BP, breast exam, full pelvic exam•Should be d/c’d in 1-3 years after menopause •Discontinue gradually (4–6-week intervals) to reduce rebound symptoms•Use beyond 3-5 years is not recommended d/t increase risk of breast cancerMonitoring patient response to HT
•Drug info•May take up to 4 weeks or more before clinical response noted•Communicate any adverse side effects •Never double dose when a dose is missed•Advise the safest is lowest necessary dose for the shortest duration possible•Discontinuation should occur gradually Patient Education
•Vaginal Atrophy•Long-acting vaginal moisturizers and lubricants•Hot flashes•Black Cohosh 40-200mg/d < 6 months (SE: Gi upset, hypotension)•Soy 20-40mg/d (SE: flatulence)•Mood swings- St. John wort 300mg TID (SE: sun sensitivity) •do not take w/ any antidepressantComplementary and Alternative Medication
•Arcangelo, V.P. & Petersen, A.M. (2022) Pharmacotherapeutics for Advanced Practice: A Practical Approach. 5th Ed. Lippincott, Williams and Wilkins.References