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9/27/15

LEARNING OUTCOMES

• Analyze the treatment options for hypogonadism in men • Evaluate specific treatments for erectile dysfunction • Discuss BPH and urinary incontinence and compare and contrast available treatments • Review contraceptive methods and choices of therapy • Discuss special considerations during pregnancy and lactation • Determine the pharmacotherapy needs of women suffering from menopause UPDATE AND REVIEW OF • Identify appropriate treatment options for osteoporosis MEN’S AND ChristinaWOMEN’S M. Madison, HEALTH Pharm.D ., BCACP, AAHIVP • Compare and contrast health maintenance recommendations for both Associate Professor of Pharmacy Practice Men and Women Roseman University of Health Sciences Clinical Assoicate Professor – Department of Internal Medicine University of Nevada School of Medicine September 27th, 2015

DISCLOSURE

• I am on the Speaker Bureau • Merck, Inc. • I am Advisory Board Member • Gilead Sciences

MEN’S HEALTH

HYPOGONADISM HYPOGONADISM Testosterone Replacement “Low T” (decreased testosterone) OR Male Menopause § Dosage Forms • Definition – a condition in which the body no longer produces enough testosterone § Buccal, Intramuscular, Subcutaneous, Topical, Transdermal • Hypogonadism can be seen at birth or develop later on in life due to many factors but the major cause § Available Products is aging § Androderm • Signs and Symptoms § Androgel • Erectile dysfunction § Striant • Infertility • Decrease in body hair and beard growth § Testim • Decrease muscle mass § Testro AQ • Development of breast tissue (gynecomastia) § Testopel Pellets • Bone loss (osteoporosis) § Axiron • Fatigue § Fortesta • Decease sex drive § Adverse Effects – increased aggression, acne, blood dyscrasias, dyslipidemia, viralization (in • Difficulty concentrating women) • Hot flashes § Monitoring – Serum Testosterone, Liver Function Test, Lipid Concentrations, Hemoglobin and • Mental and emotional changes Hematocrit, Prostate Cancer Risk (Increased)

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ERECTILE DYSFUNCTION ERECTILE DYSFUNCTION

Cause of erectile dysfunction (ED) is reduced blood flow to Common drugs that cause ED the penis § Antipsychotics – haloperidol, chlorpromazine, fluphenazine, • Types of ED thioridazine • Low serum testosterone concentrations § Antidepressants – SSRIs and SNRIs • Increased concentrations of serum prolactin § Drugs that treated BPH (finasteride, dutasteride, silodosin) • Includes one of the following designations § Chemotherapy agents – leuprolide (Lupron®) • Persistent – at least 6 months of inability to achieve or maintain an § Cimetidine erection § Opioids – methadone • Psychological § Nicotine – smokers • Organic • Mixed

ED TREATMENT ERECTILE DYSFUNCTION Nonpharmacologic treatment Treatment of Erectile Dysfunction by controlling risk factors • Vacuum pump devices • May cause some adverse effects such as pain and bruising § Smoking cessation § Control diabetes mellitus • Venous constriction rings • May cause adverse effects such as pain and bruising § Control hyperlipideimia § Control hypertension Testosterone Replacement • Oral testosterone should not be used due to potential for liver toxicity § Decreased alcohol intake • Depot intramuscular injection of testosterone enanthate § Discontinue illicit drugs • Transdermal patch placed daily – Androderm and Testoderm TTS § Lose weight • Testosterone gel § Exercise • Topical solution § Check for medication causes • Implanted (Testopel) § Stabilize cardiovascular disease • Striant buccal system Adverse Effects – increase in BP, acne, enlarged prostate, liver toxicity , cholesterol changes, polycythemia

ED TREATMENT ED TREATMENT Phosphodiesterase Type 5 Inhibitors (PDE5) Alternative agents (Second-line therapy) • First line agents for the treatment of ED in men without contraindications to use § Caverject (injectable) • Inhibits PDE-5 in the penile tissue, preventing the breakdown cGMP thus increasing § Alprostadil (Muse®) – inserted transurethral smooth muscle relaxation in the corpora cavernosa and enhances penile rigidity § Effects may last 30-90 minutes § Sidenafil (Viagra®) – given one hour prior to intercourse § Adverse Effects § Vardenafil (Levitra®) - given one hour prior to intercourse § Penile pain, cavernosal scarring, priapism, hypotension § Drug Interactions – DO NOT USE with PDE inhibitors § Talalafil (Cialis®) - given one hour prior to intercourse, can also be used daily (lower dose – 2.5 to 5 mg) § Yohimbine § Derivative of the African Yohimbe tree, alpha-2 antagonist § Side effects (For All) – headache, flushing, runny nose, stomach pain, priapism, § Efficacy is controversial, not recommended according to American Urological sudden vision loss, bluish haze (green blue), loss of hearing, ringing in the ears Association Guidelines § Contraindications – those individuals using nitrates for angina , cardiovascular § Adverse Effects – headache, dizziness, insomnia, and anxiety disease, hypotension, uncontrolled HTN, MI/Stroke with 6 months, life-threatening arrhythmias, penile deformities, renal/hepatic dysfunction, and degenerative retinal ** Treating the underlying cause disorders

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BENIGN PROSTATIC HYPERPLASIA (BPH) BENIGN PROSTATIC HYPERPLASIA (BPH) Treatment Etiology § Alpha Blockers • Non-malignant growth of the prostate epithelial/glandular tissue, leading to physical obstruction § Terazosin (Hytrin®) and Doxazosin (Cardura®) at the bladder neck, and agonism of alpha-receptor within the prostate, bladder neck, and § Side effects – orthostatic hypotension, worsening of ED, dizziness, HA urethra. This leads to lower urinary symptoms and bladder outlet obstruction § Selective alpha blockers Symptoms § Tamsulosin (Flomax®), alfuzosin (Uroxatral®), silodosin (Rapaflo®) § Hesitant, interrupted, weak stream of urine, Urgency and leaking or dribbling, Frequent urination § Side effects and precautions – dizziness, fatigue, hypotension, HA, QT at night prolongation, use in caution in patients with CrCl < 30 ml/min § Normal to slightly elevated PSA values § 5-α reductase inhibitors § Enlarged prostate § Finasteride (Proscar®) and Dutasteride (Avodart®) § Digital rectal examination § Side effects – pregnancy category X, sexual dysfunction (decrease libido, § Ultrasonograpy ejeculation, impotence) Management Adverse Effects (range depending on the agent used) – dizziness, hypotension, • Goal – reduce urinary symptoms, delay progression, prevent complications, and need for surgery syncope, asthenia, headache, edema, dyspnea, fatigue/somnolence, URI/nasal congestion, abnormal ejaculation

URINARY INCONTINENCE URINARY INCONTINENCE

Urinary incontinence physiology Treatment and Management • Activation of the detrusor smooth muscle of the bladder causes the bladder to contract • Treat underlying cause • Detrusor contraction increases pressure within the bladder and with the urethral sphincter • Goal – reduce or eliminate symptoms, increase quality of life, and prevent negative relaxation, bladder emptying occurs consequences of having incontinence • Monitoring of treatment effectiveness should be related to goals of therapy Types of Incontinence Non-pharmacologic Treatment § Functional Incontinence § Behavior modification § Stress Incontinence § Scheduled/timed voiding § Overflow Incontinence § Pelvic floor exercise (Kegel exercises) § Urge Incontinence § Drugs (avoid those that can exacerbate incontinence § Mixed Incontinence Pharmacologic Treatment Reversible Causes (DIAPPERS) § Based on type of incontinence being treated • Delirium, Infection, Atrophic urethritis, Psychiatric disorders, Pharmacologic agents, Excessive § Agents include – oxybutynin (Ditropan/Oxytrol), tolterodine (Detrol), fesoterodine (Toviaz), tropium (Sanctura), solifenancin (VESIcare), darifenacin (Enablex),and mirabegron (Myrbetriq) urine output (diabetes, heart failure), restricted mobility (Parkinson’s Disease, Osteoarthritis, § Adverse effects – dry mouth, constipation, dizziness, and vision changes Stroke, Alzheimer's disease), and Stool impaction

MENSTRUAL CYCLE

§ Average menstrual cycle is 28 days § Menstrual cycle is under the control of the following WOMEN'S HEALTH hormones Follicle stimulating hormone (FSH) Luteinizing hormone (LH)

Reference: embryology.med.unsw.edu.au

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MENSTRUAL CYCLE PRIMARY CONTRACEPTIVE METHODS AMONG WOMEN Types of Estrogen Types of Progestin AGE 15 TO 44 YEARS: UNITED STATES 1995, 2006-2010 § Natural § Natural Progestin § 17β-, estrone, and estriol § Progesterone § Synthetic estrogen (several exist) § Synthetic Progestin § Frequently used include § Norethindrone § Ethinyl estradiol § § § § Dienestrol § Dionegest §

www.cdc.gov MMWR December 21, 2012 / 61(50);1031

CONTRACEPTIVE OPTIONS Two types of methods § Barrier or Hormonal Commonly used methods of reversible contraception include: § Barrier § Intra-uterine Devices (IUD) § Diaphragm § (male and female) CONTRACEPTIVE § Hormonal § Oral contraceptives § Long acting injectable or implantable progestin § Intra-uterine contraceptive (IUC) OPTIONS § Other § § Withdrawal § Outer-course/Abstinence

Non-reversible methods (Male and Female) include: § Tubule ligation § ® procedure §

CHOOSING A METHOD CHOOSING A METHOD

Top 10 Questions to Ask • Affordability • Protection against 1. What are your contraceptive goals? Do you ever plan to get pregnant? When? sexually transmitted 2. Are you currently having sex with a male partner? • Convenience 3. Have you tried any contraceptive methods? Which ones? • Duration of action diseases 4. What did you like/dislike about that method(s)? • Efficacy • Reversibility and time to 5. Do you take pills well? return of fertility 6. How often do you forget to use the method(s)? • Effect on uterine bleeding 7. Are there any methods you have heard of and would like to try? • Frequency of side effects 8. How important is spontaneity of use? 9. Is protection from sexually transmitted infections an important consideration in your and adverse events current life situation? 10. Is cost an issue? Does your health insurance plan cover any contraceptive method(s)?

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CONTRACEPTION Types § Barrier Method § Condoms (Male/Female) § Diaphragm § § § (IUD’s) – contains copper § Hormonal Contraceptives § Oral Contraceptives – Loestrin Fe®, Yaz®, BeYaz®, Yasmin® § Transdermal Contraceptives - OrthoEvra® Patch § Injectable - Depo-Provera® (IM/SQ) § Intravaginal - NuvaRing® § - Implanon® or Explanon® § Intrauterine Contraceptive - Mirena® and Skyla® - FDA approved Feb 2013

COMBINATION HORMONAL THERAPY

CONTRAINDICATIONS CONTRAINDICATIONS — Breast Cancer — Liver disease — Pregnancy — Current or history of Deep — Age >35 years of age (Precaution) Vein Thrombosis (DVT) — Smoker(15 or more cigarettes a — Current or history of day) < 35 years of age (Precaution) cerebovascular accident or — Smoker >35 years of age (15 or Coronary Artery Disease more cigarettes a day) OTHER METHODS (CAD) — Surgery with prolonged — Diabetes with nephropathy, immobilization or any surgery on neuropathy, retinopathy, or the legs — Structural heart disease other vascular disease complicated by afib, pulmonary — Migraine Headache hypertension, or history of acute — Hypertension (>160/100mm bacterial endocarditis Hg) or with vascular disease

OTHER METHODS OTHER METHODS

Withdrawal “” § Requires the man to withdraw from the vagina before ejaculation § Can be reversible but should be considered permanent (product/ § Failure occurs if timing is not accurate or pre-ejaculation fluid contains sperm procedure dependent) § Failure rate – 18-20% § Includes: Tubal Obstruction/Ligation or Vasectomy Lactation Amenorrhea Method (LAM) § Women who breastfeed have delayed postpartum ovulation (Women) § Due to prolactin-induced inhibition of gonadotropin-releasing hormones § Prevention of tubal patency § Dependent on the following factors § Pregnancy after the procedure is uncommon § Less than 6 months postpartum § § Exclusively breastfeeding If it does occur it will most likely by a ectopic pregnancy (return of fertility is unlikely if reversed) § Amenorrehic Essure® procedure (Women)*** Sterilization § Requires no other contraceptive action after the procedure § Preformed in a trained doctors office (non-surgical) § Insertion of a soft, flexible insert into the fallopian tubes to create a natural barrier that is permanent and non-reversible Vasectomy (Men) § Ligation of the vas deferens § Highly effective § Procedure should be considered permanent but fertility will return if reversed

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INITIATION OF THERAPY INITIATION OF THERAPY

OC’s can be started at anytime during the menstrual cycle 2. Sunday Start There are several possible methods § Backup method is required for the first 7 days § Quick Start Method, Sunday Start, and First Day Start § Full contraceptive effects are not immediate 3. First Day Start 1. Quick Start Method § OC’s is started on the first day of menses § If pregnancy is excluded § Provides the maximum contraceptive effect in the first cycle § Backup method is required for the first 7 days § No back up method is required § Full contraceptive effects are not immediate 2. Sunday Start Disadvantages of the Sunday and First Day Start § OC’s are started on the first Sunday after period begins § Can be confusing to patients § Most pill packets are arranged for a Sunday start (avoid § Pt’s will not fill the prescription right away withdrawal bleeding on the weekend) § Pregnancy can occur before OC is started OC’s can be given monthly or extended cycle

INITIATION OF THERAPY COMBO THERAPY EFFICACY

Hormonal contraception can be continued until the age of Efficacy 99.8 – 99.9% menopause (50-55 years of age) § With perfect use § In healthy non-smoking women § 94 -97% with typical use ***Exception § Non-adherence is likely (16-47%) § Natazia® COC’s do not interfere with intercourse and have few side effects § Minimum of 9 days is required for back up method § NO STD PROTECTION!!!! (regardless of method used) Usually effective with in one week of starting therapy Improves menstrual regularity Decrease menstrual flow and less cramping Can be decreased by vomiting, diarrhea, and drug interactions § Effects are usually transient once symptoms are or agent stop

HORMONAL EFFECTS OF ORAL CONTRACEPTIVES EFFECTS OF HORMONAL IMBALANCE WITH COC’S Estrogenic Effects Androgenic Effects Estrogen Excess Common - nausea, dizziness, edema, bloating, cyclic weight gain, § Nausea § Increase appetite/weight gain uterine cramps, heavy menses, fibroid growth, irritability, depression, fat § Increased breast size § Depression, fatigue, tiredness deposition, hypertension, breast tenderness, increased breast size, suppressed lactation § Weight gain/fluid retention § Decreased libido Serious – stroke, thrombophlebitis, myocardial infarction § Hypertension § Acne, oily skin Estrogen Deficiency Irritability, nervousness, vasomotor symptoms (menopause), early-mid- § Thromboembolic risk § Increased breast size and cycle breakthrough bleeding/spotting, light menses, decreased libido, tenderness headaches, depression, dry vaginal mucosa, atrophic vaginitis, § Increase growth of breast dyspareunia, uterine prolapse neoplasia § Decreased carbohydrate tolerance Progestin Excess Moodiness, non-cyclic weight gain, fatigue, depression, decreased sex Estrogen/Progesterone Effects drive, hirsutism, acne, hair loss, decreased menstrual bleeding (may § Breast tenderness § Increased insulin resistance result in amenorrhea), insulin resistance, hypertension, breast § Lipid abnormalities tenderness, decreased breast size (breast regression), swelling of § Headache arms/legs § Pruritus § Hypertension Progestin Deficiency Late breakthrough bleeding/spotting, delayed onset of menstrual § Myocardial infarction bleeding, hypermenorrhea

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PRECAUTIONS DRUG INTERACTIONS CYP-450 The following conditions should be considered for benefit before § Hepatic enzyme inducers decrease efficacy of oral contraceptives initiation of hormonal contraceptive therapy Other drugs decrease CHC efficacy (different MOA) § Causing spotting, breakthrough bleeding, or pregnancy § Anemia's Drugs that Barbiturates, carbamazepine, All patients should be notified of low potential § Sickle Cell decrease CHC’s oxcarbazepine, phenobarbital, phenytoin, interactions with other anti-infectives **ACOG states that PCN, ampicillin, doxycyline, efficacy modafinil, pioglitazone, rifamycins (including Rifampin), and Antiretroviral - fluconazole, miconazole, metronidazole, FQs, § Iron Deficient – use precaution with IUDs (may cause protease inhibitors ( liponivir, ritonovir) and tetracycline DO NOT interact with hormone increased bleeding) levels § High risk for HIV Drugs that Atorvastatin, More adverse effects associated with Increase Effects of Atazanavir, Indinavir (Antiretroviral) concomitant use § HIV infection (positive status) CHC’s § AIDS diagnosis Herbals that St. John’s wort Avoid using herbal products if possible decrease the § Use IUD with caution (risk may out weight the non- effect of CHC’s contraceptive benefits) Drosperinone Potassium-sparing diuretics, potassium Increased risk of hyperkalemia supplements, ACE-I, ARBs § Increased risk of abnormal cervical cells that could lead to ONLY cancer Metabolism or Acetaminophen, antidepressants Interaction not clearly understood but known Clearance Altered (tricyclic), aspirin, benzodiazepines, beta possibility increased effects of non- by CHC’s blockers, caffeine, corticosteroids, contraceptive agent with long term cyclosporine, lamotrigine, theophylline concomitant use

COMBO THERAPY: SIDE EFFECTS COMBO THERAPY: SIDE EFFECTS Irregular bleeding or Spotting (breakthrough bleeding) Serious side effects (Rare) § More common with low-dose or triphasic/quadrphasic CHCs § VTE including DVT and/or PE (dose related- high dose § Increase Estrogen estrogen) § If occurring in the beginning of the cycle § Myocardial infarction (MI) § Increase Progestin § High-dose estrogen § If occurring at the end of the cycle § Migraine Nausea/Vomiting, weight gain, moodiness, breast tenderness § Stroke (very low risk) § Most common within first 3 months (after starting a new pack) § Hypertension § Usually due to estrogen excess (High-Dose) § Premenopausal breast cancer § Risk of weight can is generally low § Highest risk in women who use for a duration of ≥ 4 years § Most women will not take combo CHC’s b/c of this reason (~40%) before first full-term pregnancy

COMBO THERAPY: SIDE EFFECTS FDA ALERT AND LABELING CHANGE Factors that increase the risks Serious SE Include § Smoking Food and Drug Administration (FDA) April 10, 2012 § Hypertension Conducted a observational (epidemiologic) study regarding risk of blood clots in women receiving § Age > 35 years -containing pills § Based on this review the FDA concluded that drospirenone-containing birth control pills may be § Not seen as frequently with Progestin-ONLY products associated with an increased risk of blood clots than other progestin-containing pills Note: new reports linking Yaz®/BeYaz®/Yasmin® to Recommendation increased risk of gallbladder disease § Women should discuss the risks and benefits of drospirenone containing birth control pills before starting on this method § Specifically the drosperinone containing products § Request that manufactures change the labeling of these products to account for the increased risk seen in observation study

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EMERGENCY CONTRACEPTIVE

AKA: postcoital contraception and the morning after pill Definition: the use of a drug or device as an emergency measure to prevent pregnancy due to: EMERGENCY § Recent unprotected sex § Failure of a contraceptive method CONTRACEPTION Intended for occasional or back-up use § NOT as primary contraceptive

EMERGENCY CONTRACEPTION Mechanism of Action (can very among agents used) Up to the minute information about emergency contraception: § www.not-2-late.com 1. Levonorgestrel § By Princeton University faculty § Progestin ONLY (Plan B One-Step ®, Next Choice®) Educate patients/health care providers to prevent barriers to receiving EC 2. Ulipristal (Ella®) when needed 3. Ethinyl estradiol plus levonorgestrel (Yuzpe regimen) Changes regarding age restriction for OTC Plan B One-Step® and Next Choice® § April 5th, 2013 a US District Judge reversed the age restriction decision for OTC emergency § No longer commercially packaged in the US contraceptives 4. Copper intrauterine contraception (*Skyla FDA approved EC) § The government has 30 days to comply and allow the unrestricted sell of the drug § Stating that the 2011 decision by Health and Human Services Secretary to overrule the recommendations of the FDA was unreasonable and politically motivated § 2011 statement by the FDA “after rigorous study, it was safe to sell Plan B One-Step® (levonorgesterol) over the counter to all ages”.

EMERGENCY CONTRACEPTION

Method Dose Reported efficacy Progestin ONLY 0.75 mg given twice, 12 hours apart 89% of pregnancies PREGNANCY Plan B®, Plan B One- 1.5 mg single dose (Plan B One-Step®) prevented Step®, Next Choice™ Levonorgestrel AND

Selective Progestin 30mg x 1 dose (with in 120 hours of ~ 90% of pregnancies Receptor Modulator contraceptive failure) prevented LACTATION Ella® (Ulipristal)

Intrauterine Device Inserted with in 120 hours after intercourse 99% Copper Intrauterine device (Paraguard®) *Skyla (levonorgestrol containing q3 years) (Combination Estrogen/ 100 microgram ethinyl estradiol plus 0.5mg 75% -80% pregnancies progesterone) levonorgestrel, each given twice, 12 hours prevented Yuzpe Regimen apart

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PREGNANCY TESTING PREGNANCY TESTING Designed to detect the presence of human chorionic gonadotripin (hCG) in urine § Using monoclonal or polyclonal antibodies (enzyme immunoassay) Patient Counseling Points Pregnancy cannot be detected before implantation has occurred § Check the expiration date of the § Implantation will usually occur before the expected menstrual period (can be later) test Highest sensitivity § Choose a simple test if possible § First day of missed menses is 90% § Some boxes contain more than one test § One week after missed menses, accuracy is 97% § Most tests include a control § Accuracy may be as low as 50 – 75% § If directions are not followed § Read all the instructions carefully § Urine is needed to perform the test § If you have questions – call the 1-800 number on the box § Wait the needed amount of time § Morning urine is usually most accurate (detecting hCG levels) § Retest in one week if negative (and menstruation has not returned)

PREGNANCY CATEGORIES PREGNANCY CATEGORIES • Problems with FDA system • Problems with FDA system • FDA is recommending more detail in the product labeling • Drugs available prior to 1979 were “grandfathered” into the regarding risk in pregnancy system • Within category C especially • Assumptions are made that drugs within the same class have equal risk (typically inaccurate) • Manufacturers must describe the types of studies that have been conducted and the study results • As of 2001, only 40% of all drugs carried a classification designation • Current pregnancy categories have been replaced by the RULE § Category A - 0.7% on pregnancy and lactation § Category B - 19% § Category C - 66%

§ Category D - 7% § Category X - 7% • No designation of the differences in risk throughout the different stages of pregnancy

PREGNANCY CATEGORIES TERATOGENIC AGENTS Classification Description Medication Examples • Retinoid • Lithium and Category derivatives • “Statins” cholesterol lowering agents A Adequate, well-controlled studies in pregnant women have Levothyroxine • Anticonvulsants not shown an increased risk of fetal abnormalities to the Prednisone • ACE inhibitors fetus in any trimester of pregnancy • Coumadin • Tetracyclines B Animal studies have revealed no evidence of harm to the Claritin, Keflex • Anti-cancer fetus, however, there are no adequate and well-controlled Tylenol (APAP) medications • Misoprostol, studies in pregnant women Metformin • Diethylstibestrol C Animal studies have shown an adverse effect and there Keppra (Anticonvulsant) (RU-486) are no adequate and well-controlled studies in pregnant Cyclosporine (DES) women Clonidine • Thalidomide • Anti-thyroid **Tylenol (APAP) – IV medications formulation • D Adequate well-controlled or observational studies in Lisinopril (in 2nd and 3rd pregnant women have demonstrated a risk to the fetus Trimester)

X Adequate well-controlled or observational studies in Methotrexate animals or pregnant women have demonstrated positive Accutane evidence of fetal abnormalities or risks. Thalidomide The use of the product is contraindicated in women who are or may become pregnant

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TERATOGENIC AGENTS COMPLICATIONS DURING PREGNANCY Retinoid Derivatives (iPLEDGE) Requirements of patients Smoking § Once pregnancy has occurred adverse outcomes to the mother and fetus are likely § Go to laboratory for monthly pregnancy test § Damage can lead to damage of the fetal brain, heart, and nervous system § Answer monthly “quiz” questions on iPLEDGE web site § Also associated with decrease fetal birth weight (average decrease of 200g) § Long-term consequences § Provides the two birth control methods being used § Mental disabilities Requirements of pharmacies § Possible nicotine addiction § Exposure to second hand smoke § The pharmacy must interface with the iPLEDGE clearninghouse database to § Associated with adverse effects such as low birth weight and intrauterine growth determine patient eligibility retardation § The pharmacy must fill prescription within 7 days of pregnancy testing (this § Quitting smoking any time during the pregnancy is beneficial may or may not correspond with the date the prescription was written). § Cessation prior to conception is key or shortly after conception § FDA approved smoking cessation products have not been study for safety and efficacy § If > 7 days, patient must restart the process in pregnant women § The patient can get the prescription only once every 30 days § Counseling and behavior modification is required

COMPLICATIONS DURING PREGNANCY FETAL ALCOHOL SYNDROME

Substance Abuse (Alcohol) Fetal Alcohol Syndrome § Alcohol readily crosses the placenta § Incidence: 5 – 10 cases per 10,000 live births (higher in Native Americans) § “Classic” syndrome more likely if exposure occurs early in gestation § Late gestation exposure more likely to result in developmental and behavioral manifestations § Higher risk with large, binge amounts of alcohol compared to long term “social” use § 10% of all infants are exposed to the equivalent of 2 – 3 oz. of liquor per day A characteristic pattern of mild facial anomalies, including small eye openings (i.e., short palpebral fissures), a thin upper lip, or flattened ridges between the base of the nose and the upper lip (i.e., a flattened philtrum) associated with FAS.

Source: Warren, K.R., and Foudin, L.L. Alcohol-related birth defects—The past, present, and future. Alcohol Research & Health 25(3):153–158, 2001.

FETAL ALCOHOL SYNDROME COMPLICATIONS DURING PREGNANCY

Substance Abuse (Illicit Drugs) Ninety percent of women who abuse illicit drugs are of childbearing age § Substance abuse is associated with other high risk behaviors that can lead to complications during pregnancy § STD infection and HIV transmission Can cause the following fetal risk § Low birth weight, small head circumference, prematurity, developmental delay Common substances abused § Cocaine, marijuana, amphetamines, opioids, tobacco, and alcohol Women who use illicit drugs are usually polysubstance abusers § Isolating specific effects may be difficult

Areas of the brain that can be damaged in utero by maternal

alcohol consumption Source: Mattson, S.N., et al. MRI and prenatal alcohol exposure: Images provide insight into FAS. Alcohol Health & Research World 18(1):49–52, 1994

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IMMUNIZATIONS DURING PREGNANCY COMPLICATIONS DURING PREGNANCY Vaccine Before pregnancy During pregnancy After pregnancy Type of vaccine Substance Abuse (Illicit Drugs) § Cocaine Hepatitis A If at high risk for disease If at high risk for disease If at high risk for disease Inactivated (IM) § Causes fetal vasoconstriction once it crosses into the placenta § Also associated with preterm labor, placental abruption, uterine rupture, cardiac Hepatitis B Yes, if at risk Yes, if at risk Yes, if at risk Inactivated (IM)

dysrhythmias, hepatic rupture, cerebral ischemia/infarction, and death Human Papillomavirus Yes, if ≤ 26 y/o No, under study Yes, if ≤ 26 y/o Inactivated (IM) § Marijuana (HPV) § Associated with depressive symptoms and impaired cognitive function Influenza (TIV) Yes Yes Yes Inactivated (IM) § Amphetamines Influenza (LAIV) Yes, if < 49 y/o and No, under study Yes, if < 49 y/o and Live (Nasal Spray) healthy healthy § Associated with cardiac anomalies, cleft lip and palate, biliary atresia, intrauterine MMR Yes, avoid conception for No Yes, avoid conception for Live (SC) growth retardation, intrauterine fetal demise, and cerebral hemorrhage at least 28 days if at least 28 days § Opioids unvaccinated Meningococcal If indicated If indicated If indicated § Directly affect the fetus leading to intrauterine growth restriction • Polysaccharide Inactivated (SC) § Also associated with symptoms of neonatal opioid withdrawal • Conjugate Inactivated (IM) Pneumococcal If indicated If indicated If indicated Inactivated (IM or SC) Conjugate/ Polysaccharide Tdap (one dose for each Yes, preferred Indicated at end of 2nd Yes, if not during Toxoid (IM) pregnancy) trimester pregnancy

Varicella Yes, avoid conception for No Yes, avoid conception for Live (SC) at least 28 days at least 28 days

DRUG USE AND LACTATION • Drugs taken orally by mother undergo multiple metabolic conversions DRUGS AND § Before affecting infant circulation • Drugs diffuse passively across the mammary epithelium down a concentration gradient BREASTFEEDING § Semi-permeable lipid barrier • Drugs with MW less than 200 pass unimpeded through pores • Larger molecules must dissolve in lipid membrane of epithelial cells, diffuse across an aqueous medium in cell interior, and pass through second cell membrane • No drugs enter breast milk through active transport processes

DRUG USE AND LACTATION DRUG USE AND LACTATION Breastfeeding is the BEST method of infant feeding Mother’s who breastfeed also have been benefits § The method at which all other types of feeding should be measured § Rapid uterine involution, decreased postpartum blood loss, fertility reduction Numerous benefits include (while nursing and amenorrheic), and decreased risk of breast and ovarian cancer, type 1 and 2 diabetes, and possibly osteoporosis and hip fracture later § Decrease risk of in life § Gastroenteritis Drugs of Concern § Severe lower respiratory tract infections § Antidepressants § Acute otitis media § Narcotics § Necrotizing enterocolitis § Long-Acting Sedatives § Sudden infant death syndrome (with in the first year of life) § Water-Soluble β-blockers § Type 1 or 2 diabetes mellitus § Lithium § Childhood leukemia § Iodine-Containing Drugs § Obesity § Hemolytic Agents

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DRUG USE AND LACTATION DRUG USE AND LACTATION Galactagogues Drug Effects on Lactation § Are defined as any agents or substance that can increase milk supply § Agents that decrease milk supply § Raises baseline prolactin concentration § Via dopamine antagonist activity § Alcohol § Agents include (clinically used for this purpose) § Anti-cholinergics § Metoclopramide (FDA approved) § Diuretics § Doperidone § Dopaminergic agents § Sulpiride § Estrogens § Fenugreek (herbal product) § Used as a galactogogue § Cigarette smoking § If used in large amounts can cause hypoglycemia and have interact with warfarin § Sympathomimetic vasocontrictors § Also associated with allergy and asthma § Milk thistle (traditional herbal product) § Also used to increase breast milk production § No clinical data to support use

DRUGS OF ABUSE AND BREASTFEEDING AVAILABLE REFERENCE

• Amphetamine – irritability, poor sleeping (LACTATION)

• Cocaine – intoxication Online • Heroin – tremors, restlessness, vomiting, poor feeding § LactMed – Drug and Lactation Database § A peer-reviewed and fully referenced database of drugs to which breastfeeding mothers may be • Marijuana – effects unknown exposed § Data included are maternal and infant levels of drugs, possible effects on breastfed infants and • Nicotine – vomiting, diarrhea, tachycardia, restlessness, on lactation, and alternate drugs to consider decreased milk production § http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT • PCP - hallucinations

AVAILABLE REFERENCES (PREGNANCY) Text § Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and MENOPAUSE Lactation: A Reference Guide Fetal and Neonatal Risk. 8th ed. Baltimore: Lippincoott, Williams & Wilkins, 2009 § Koren G. Medication Safety in Pregnancy and Breastfeeding. New York: McGraw-Hill, 2007 § Shepard TH, Lemire RJ. Catalog of Teratogenic Agents. 12th ed. Baltimore: The jOhns Hopkins University Press, 2007.

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STAGES OF MENOPAUSE STAGES OF MENOPAUSE

Perimenopause is the period immediately (2-8 years) prior to menopause and the first year after • Menopausal Transition/Climacteric is the period of time when the menopause endocrinologic, biologic, and clinical features of the approaching menopause § Begins with irregularity in length of consecutive cycles commence § Overlaps with menopausal transition and postmenopause § Early menopausal transition § FSH elevating (variable) and estradiol declining § Persistent difference of ≥ 7 days in the length of consecutive cycles § Variable FSH levels Postmenopause is the period following final menstrual period (FMP) § Late menopausal transition § FSH elevated, estradiol decreased § > 60 days of amenorrhea or 2 skipped menstrual periods § Early postmenopause = 3 years following FMP § FSH criteria, random blood draw > 25 units/L § Late postmenopause = 4+ years following FMP

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STAGES OF MENOPAUSE Treatment Menopause Algorithm

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a Reassess each step at least once every 6–12 months (assuming patient's continued preference for HT). bWomen who have vaginal dryness without moderate to severe vasomotor symptoms may be candidates for vaginal estrogen. VASOMOTOR SYMPTOM TREATMENT TREATMENT c Traditional contraindications: unexplained vaginal bleeding; active liver disease; history of venous thromboembolism due to HRT/MHT= mainstay of therapy pregnancy, oral contraceptive use, or unknown etiology; blood clotting disorder; history of breast or endometrial cancer; history § Moderate - severe vasomotor symptoms of CHD, stroke, transient ischemic attack, or diabetes. For other contraindications, including high triglycerides (>400 mg/ § Lowest possible effective dose & shortest duration dL); active gallbladder disease; and history of venous thromboembolism due to past immobility, surgery, or bone § Vasomotor symptoms may require treatment despite the presence of menstrual fracture; oral HT should be avoided but transdermal HT may be an bleeding option. e Women >10 years past menopause are not good candidates for starting (first use of) HT. Other therapies for vasomotor symptoms g Consider selective serotonin or serotonin-norepinephrine reuptake inhibitor, gabapentin, clonidine, soy, or alternative. § SSRI (e.g. fluoxetine, paroxetine, sertraline) h HT should be continued only if moderate to severe menopausal symptoms persist. The recommended cutpoints for duration are based § SNRI (e.g. venlafaxine) on results of the Women's Health Initiative estrogen-progestin and estrogen-alone trials, which lasted 5.6 and 7.1 years, respectively. For § Clonidine longer durations of HT use, balance of benefits and risks is not known. iAbove-average risk of breast cancer: one or more first-degree relatives § Gabapentin with breast cancer; susceptibility genes such as BRCA1 or BRCA2; or a personal history of breast biopsy demonstrating atypia. § Phytoestrogens (e.g. soy products) jWomen with premature surgical menopause may take HT until average age at menopause (age 51 in the United States) and then § Herbal extracts (e.g. black cohosh) follow flowchart for subsequent decision making. k If is taken daily, avoid extending duration. If progestogen is cyclical or infrequent, avoid extending duration more than 1–2 years. l If menopausal symptoms are severe, estrogen plus progestin can be taken for 2–3 years maximum and estrogen alone for 4–5 years maximum. mIf at high risk of osteoporotic fracture (see Q6), consider bisphosphonate, raloxifene, or alternative. 77 n Increased risk of osteoporotic fracture: documented osteopenia,78 personal or family history of nontraumatic fracture, current smoking, or weight <125 lbs.

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ESTROGEN BRAND DOSE (mg) FREQUENCY TREATMENT CYCLES Conjugated estrogens CENESTIN ENJUVIA 0.3, 0.45, 0.625, 0.9, 1.25

PREMARIN Estropipate OGEN 0.625, 1.25, 1.5 With intact uterus Once daily ORTHO-EST 0.75, 1.5

§ Estrogen and Progestin daily without a break (tablets) Micronized estrogen ESTRACE 0.5, 1, 2 § Cyclic-sequential administration estrogen Oral Estradiol FEMTRACE 0.45, 0.9, 1.8 Esterified estrogens MENEST 0.3, 0.625, 1.25, 2.5 § Estrogen daily for 21-28 days of a 28-day cycle Patch ALORA 0.025, 0.05, 0.075, 0.1 Twice weekly

§ Progestin added during the last 10-12 days CLIMARA 0.025, 0.0375, 0.05, 0.06, 0.075, 0.1 Once weekly ESCLIM 0.025, 0.0375, 0.05, 0.075, 0.1 Twice weekly § Long-cycle regimen ESTRADERM 0.05, 0.1 Twice weekly § Estrogen is administered continuously over a 3-month cycle MENOSTAR 0.014 Once weekly § Progestin is only added every third month VIVELLE 0.05, 0.1 Twice weekly VIVELLE-DOT 0.025, 0.0375, 0.05, 0.075, 0.1 Twice weekly Without a uterus Gel DIVIGEL 0.25, 0.5, 1 g/packet ELESTRIN 0.87 g/pump Once daily § Continuous unopposed Estrogen therapy ESTROGEL 1.25 g/pump Transdermal estradiol estradiol Transdermal Emulsion ESTRASORB 1.74 g/pouch Twice daily Spray EVAMIST 1.53 mg/spray 1-3 sprays daily

Estradiol ESTRACE (cream) 0.1 mg/g Once daily, then 1-3/week ESTRING (ring) 7.5 g/24 hr Once every 90 days FEMRING (ring) 0.05, 0.1 mg/day Once every 90 days

79 Vaginal VAGIFEM (tabs) 25 g 1/day for 2 weeks, then 802/week estrogen estrogen Conjugated estrogens PREMARIN (cream) 0.625 mg/g Once daily

CONTRAINDICATIONS TO MHT ADVERSE DRUG REACTIONS FROM MHT Per AACE § Current, past, or suspected breast cancer Minor Major § Known or suspected estrogen-sensitive malignant conditions § Nausea, Vomiting § Endometrial, breast, or § Undiagnosed genital bleeding ovarian cancer § Untreated endometrial hyperplasia § Dizziness § Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary § Weight gain § Venous thromboembolic embolism) § Breast tenderness event § Active or recent arterial thromboembolic disease (angina, myocardial infarction) § Breast enlargement § Stroke § Untreated hypertension § Gallbladder disease § Active liver disease § Possible uterine bleeding § Known hypersensitivity to the active substances of MHT or to any of the exceipients § Porphyria cutanea tarda (ABSOLUTE CONTRAINDICATION)

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SEXUAL DYSFUNCTION WOMEN’S HEALTH INITIATIVE Estrogen & Testosterone levels may be unpredictable Important concepts § Decreased libido/sexual desire • HT for treatment of menopausal symptoms and HT for prevention § Methyltestosterone (Methitest®) 1.25 – 2.5 mg orally daily of chronic diseases § Topical estrogens § Sildenafil Five major points of agreement § “Female Viagra” FDA approved Aug 2015 flibanserin (Addyi) 1. Younger women § Orgasm disorder o HT is an acceptable option for treating moderate to severe menopausal symptoms in § Review medications (common with SSRIs) relatively young (up to age 59 or within 10 years of menopause) and healthy women § Individualization is key in the decision § Dyspareunia to use HT § Water based lubricants 2. Women with vaginal symptoms ONLY § Topical estrogen (in presence of vaginal atrophy) § Preferred treatments are low doses of vaginal estrogen § Osphena (ospemifene)** 3. Women with a uterus § Women who still have a uterus need to take a progestogen (progesterone or a similar product) along with the estrogen to prevent cancer of the uterus § Women who have had their uterus removed can take estrogen alone

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WOMEN’S HEALTH INITIATIVE Five major points of agreement 4. Risk of blood clots and stroke § Both estrogen therapy and estrogen with progestogen therapy increase the risk of blood clots in the legs and lungs OSTEOPOROSIS § Although the risks of blood clots and strokes increases with HT, the risk is rare in the 50-59 year old age group 5. Risk of breast cancer § Increased risk in breast cancer is seen in 3-5 years of continuous estrogen/ progestogen therapy § Risk decreases after HT is stopped

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OSTEOPOROSIS OSTEOPOROSIS

Causes § Menopause or Medication induced National Health and Nutrition Examination Survey III Bone Mineral Density § 8.9 million Americans have osteoporosis § T-score < -2.5 § 42.5 million have low bone density of the hip Treatment § Bisphosphonates (ex. Fosamax) § Selective Estrogen Receptor Modifiers (SERMs) National Osteoporosis Foundation (NOF) § Hormone replacement therapy § Higher risk in women (4:1) versus men § Calcium and Vitamin D supplementation § NH White 20% § Asian American 20% § Latino/Hispanic 10% § NH Black 5%

§ Caucasians § 50% of women and 20% of men will experience an osteoporosis-related fracture in their lifetime 88

OSTEOPOROSIS OSTEOPOROSIS • Osteoporosis has a large economic burden on our health care Over 2 million fractures each year in men and system women over the age of 50 § 2.5 million medical office visits § 432,000 hospital admissions § 300,000 hip fractures § 180,000 long-term care admissions § 550,000 vertebral fractures § 20% of hip fracture patients require long term care § 400,000 wrist fractures • 60% will not regain pre-fracture function § 810,000 fractures at other sites • Decreased quality of life § Depression, low self-esteem, worry, chronic pain

• 8 – 36% mortality within 12 months of initial fracture • Increased risk of future fractures

Image from http://biomed.brown.edu/Courses/BI108/BI108_2008_Groups/group01/ 89 90 BIOL1080_2008_-_Kyphoplasty_Group_Webpage_Project/Pathophysiology_files/Osteoporosis.png

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OSTEOPOROSIS - GUIDELINES

• National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

• Watts NB, Adler RA, Bilezikian JP, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(6):1802-1822.

• The North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause. 2010;17(1):25-54.

• Watts NB, Bilezikian JP, Camacho PM, et al; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal ostroporosis. Endocr Pract. 2010;16(Suppl 3):1-37.

91 92 Bone Health and Osteoporosis: A Report of the Surgeon General October 14, 2004

FACTORS AFFECTING PEAK BONE MASS BONE REMODELING

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Image from: http://pubs.niaaa.nih.gov/publications/arh26-4/images/sampson2.gif Image from http://www.ns.umich.edu/Releases/2005/Feb05/img/bone.jpg

PATHOGENESIS OF OSTEOPOROSIS

Osteopenia

Osteoporosis

95 96 Bone Health and Osteoporosis: A Report of the Surgeon General October 14, 2004

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AGE-RELATED BONE LOSS TYPES OF OSTEOPOROSIS

Type 1: Post-menopausal (Female) § Estrogen deficiency increases osteoclast activation and prolongs survival of mature osteoclasts § Increased number of bone turn-over sites § Inadequate osteoblast activity § Trabecular bone is most susceptible Type 2: Age-Related § Calcium & vitamin D deficiencies Type 3: Secondary Osteoporosis

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OSTEOPOROSIS & OSTEOPOROTIC FRACTURE OSTEOPOROSIS & OSTEOPOROTIC FRACTURE

Risk Factors Risk Factors § Low BMD § Secondary osteoporosis (RA) § Cigarette smoking § Low calcium intake § Low BMI (<19 kg/m2) or < IBW § Low physical activity § Advanced age (>65 ♀, >70♂) § Poor nutrition, health, or frailty § Gender (female > male) § Minimal sun exposure § Systemic glucocorticoid therapy § Recent falls § 10 Family history (hip fracture) § Cognitive impairment § Low trauma fracture as an adult § Estrogen deficiency before 45 years of age § Alcohol >1-2 drinks per day § Impaired vision

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SECONDARY CAUSES – PHARMACOTHERAPY TYPES OF SCREENING

Mechanism • Physical assessment § Glucocorticoids • Laboratory testing § Decrease osteoblast activity § Increased osteoclast activity • Peripheral BMD testing § Increased calcium excretion • Central DXA BMD testing § Decreased calcium absorption • Causes of secondary osteoporosis § Suppressed sex steroid production

§ Anticonvulsants (phenytoin, carbemazepine, barbituates) • On the horizon § Increase Vitamin D metabolism § Bone quality & density testing

§ Loop Diuretics (furosemide) § Inhibit the resorption of calcium in the thick ascending loop

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SCREENING SCREENING RECOMMENDATIONS Peripheral BMD devices § X-ray or ultrasonometry All patients aged ≥50 years should be evaluated for risk factors § T-score varies by device for osteoporosis § Younger post-menopausal women without major risk factors BMD testing Central DXA § All women ≥ 65 years of age § Dual-Energy X-ray Absorptiometry § Younger postmenopausal women with at least 1 major or 2 2 § Actual BMD: measured in g/cm minor risk factors § T-score: standard deviation(s) from the reference mean of healthy, young, gender matched Caucasian population § All men ≥ 70 years of age § Z-score: standard deviation(s) from the reference mean of healthy, gender § Men aged 50–69 years with at least 1 major or 2 minor risk and age matched Caucasian population factors

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BONE MINERAL DENSITY TESTING DIAGNOSIS USPSTF NOF/AACE/NAMS Women ≥ 65 years Yes Yes • Based on Central-DXA scores and fracture history Postmenopausal women Yes Yes with fracture Normal BMD T-score ≥ -1

Adults taking steroids Yes Osteopenia -1 > T-score > -2.5 Postmenopausal women < At 60 years if: < 65 years if: 65 years with major risk -Wt < 70kg -Weight < 57.6 kg Osteoporosis T-score ≤ -2.5 factors -Estrogen deficiency -Family history of fracture -Smoking OR low trauma fracture -Early menopausal Secondary Z-score < -2 -Medical issues Osteoporosis consider secondary causes

**Medicare reimburses for BMD testing every two years *Each SD ~10 – 12% decrease in bone mass 105 *Each SD ~1.5 – 2.6 fold increased risk for fracture 106

PREVENTION ALONE OF TREATMENT – BASED ON DIAGNOSIS NON-PHARMACOLOGIC INTERVENTIONS Normal § Depends on age, gender, and risk factors 1. Healthy Diet 2. Smoking Cessation Osteopenia § Depends on gender and risk factors 3. Exercise

Osteoporosis 4. Falls prevention § Treatment

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PHARMACOLOGIC INTERVENTIONS

• Bisphosphonates (1st line agents) • Selective Estrogen Receptor Modulators • Menopause is the primary cause HEALTH MAINTENANCE • Hormone Therapy • Menopause is the primary cause • Monoclonal Antibody (RANKL-binder) • Anabolic Therapy

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HEALTH SCREENINGS HEALTH SCREENINGS

Cardiovascular Disease Colorectal Cancer § Includes heart disease and stroke § Screening recommended in those 50 years and older § Heart health ABCS § Colonoscopy recommended every 10 years § A = take aspirin as directed by healthcare provider Prostate Cancer § B = control your blood pressure § Recommended in adult males of all ages § C = manage your cholesterol § Does not apply to those men already diagnosed or treated for prostate cancer § S = don’t smoke § Prostate cancer is very common, in many cases, the cancer does not grow or cause symptoms. If it Kidney Disease does grow, it often § Chronic Kidney Disease (CKD) § grows so slowly that it isn’t likely to cause health problems during a man’s lifetime § Risk factors – diabetes and high blood pressure § Those at risk include – Older men, African American men, those with a family history of prostate § 1 in 3 adults with diabetes and 1 in 5 adults with high blood pressure have CKD cancer § Recommendations include screening those who are at high risk to prevent End Stage Renal § Two screening tests – Prostate Specific Antigen (PSA) and digital rectal exam Disease (ESRD) § PSA screening benefits do not out weight risk based on the US Preventative Task Force findings (due § Screen those with history of diabetes, hypertension, or cardiovascular disease; and/or family to risk for serious harm) history of CKD

ADULT VACCINATIONS – BY AGE ADULT VACCINATIONS – BY INDICATION

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HEALTH MAINTENANCE HEALTH MAINTENANCE - PAP SMEAR PAP SMEAR • Recommendations for screening were revised in March 2012 • Developed in 1940s, this technique is used to identify abnormal • Information regarding these recommendations were published in Annals of cervical cytology (cells) Internal Medicine, A Cancer Journal For Clinicians, Journal of Lower Genital § PAP (Papanicolaou) Smear – names after who developed the Tract Disease, and the American Journal of Clinical Pathology exam George Papanicolaou • Consensus statement published by the following agencies § Incidence of cervical cancer has been reduced by 70% in § U.S. Preventive Services Task Force (USPSTF) countries that use the PAP test § American Cancer Society (ACS) § American Society of Colposcopy and Cervical Pathology (ASCCP) • Long delay between HPV infection and the development of § American Society of Clinical Pathology (ASCP) invasive cervical cancer • Guidelines developed to address cervical cancer screening in the general § Disease is easy to prevent when screenings are done regularly population § Cervical cancer cases are more common in women untested or § Does not address special, high-risk populations that may need more infrequently tested intensive or alternative screening (hx of cervical cancer, HIV +, DES baby)

CERVICAL CANCER SCREENING RECOMMENDATIONS REFERENCES Age USPSTF Recommendations ACS/ASCCP/ASCP

Recommends against screening Women should not be screened regardless of age of DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey M, editors. Pharmacotherapy: a Younger than pathophysiologic approach[internet]. 8th ed. New York: McGraw Hill; c2011. Section 9; 21 years sexual initiation or other risk factors [cited 2013 April 9]. Available from: http://www.accesspharmacy.com Micromedex® Healthcare Series [Internet database]. Greenwood Village, CO: Thomson 21 – 29 years Recommends screening with Screening with cytology alone every 3 years is Reuters (Healthcare). Updated periodically. cytology every 3 years recommended National Survey of Family Growth (Centers for Disease Control and Prevention) § www.cdc.gov 30 – 65 Recommends screening with Screening with cytology and HPV testing (co-testing) years cytology every 3 years OR screening every 5 years (preferred) or cytology alone every 3 years New Cervical Cancer Screening Recommendations from the U.S. Preventative Tasks Force with a combination of cytology and (acceptable) is recommended and the American Cancer Society/American Society for Colposcopy and Cervical th HPV testing every 5 years Pathology/American Society for Clinical Pathology (released March 14 , 2012) § http://www.acog.org Recommends against screening Women with evidence of adequate negative prior Older than Treatment Guidelines from The Medical Letter, Volume 8, Dec 2010 65 years who have had adequate prior screening and no history of CIN2+ with in the last 20 screening and not at high risk for years should not be screened § www.medicalletter.org cervical cancer Screening should not be resumed even if the women Briggs, GG, Nagoeotte, M. Diseases, Complications, and Drug Therapy in Obstetrics: A reports a new sexual partner Guide for Clinicians. American Society of Health System Pharmacists, 2009 Recommends against screening Women with history of removal of cervix with no history Borgelt, LM, O’Connell, MB, Smith, JA, Calis, KA. Women’s Health Across the Lifespan: A After Pharmacotherapeutic Approach. American Society of Health System Pharmacist, 2010 hysterectomy who have had removal of cervix and of CIN2+ should not be screened for vaginal cancer. who do not have history of high Evidence of adequate negative prior screening not Ung KD, McNulty J, “Chapter 46. Obstetric Drug Therapy” (Chapter). Koda-Kimble A, Young grade precancerous lesion or required. Screening should not be resumed even if the LY, Kradjan WA, et al.: Applied Therapeutics: The Clinical Use of Drugs, 9e: cervical cancer women reports a new sexual partner. http://pt.wkhealth.com/pt/re/9780781765558/bookcontent. 01337318-9th_Edition-6.htm;jsessionid=LzpSPNb4nB1N2FZTn5q1GNCyRyly7Y6lJmh HPV Women who have been vaccinated Recommended screening practices should not change GszSNjdzqGpVN2jlb vaccinated should continue screening as on the basis of HPV vaccination status outlined above

REFERENCES

Update in Therapeutics 2015 Ambulatory Care Preparatory Review Course and Recertification Course Materials Kalantaridou SN, Dang DK, Davis SR. Hormone Therapy in Women. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011;Chap 91. Harrell TK, Low AK. Menopausal Hormone Therapy. In: Wofford MR, Posey LM, Linn WD, O'Keefe ME, eds. Pharmacotherapy in Primary Care. New York, NY: McGraw-Hill; 2009:Chap 29. Manson JE, Bassuk SS. The Menopause Transition and Postmenopausal Hormone Therapy. In: Fauci AS, Kasper DL, Jameson JL, Longo DL, Hauser SL, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012:Chap 348. The North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause. 2012;19(3):257-271. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2011;17(Suppl 6):1-25. UPDATE AND REVIEW OF Stuenkel CA, Gass ML, Manson JE. A decade after the Womens Health Initiative the experts do MEN’S AND WOMEN’S HEALTH agree. Menopause. 2012;19(8):1-2. Christina M. Madison, Pharm.D., BCACP, AAHIVP Associate Professor of Pharmacy Practice Roseman University of Health Sciences Clinical Assoicate Professor – Department of Internal Medicine University of Nevada School of Medicine September 27th, 2015

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