Men`s and Women`s Health Presentation Handout

9/27/15 TH
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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
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
• 
Identify appropriate treatment options for osteoporosis
• 
Compare and contrast health maintenance recommendations for both
Men and Women
DISCLOSURE
• 
I am on the Speaker Bureau
•  Merck, Inc.
• 
I am Advisory Board Member
•  Gilead Sciences
MEN’S HEALTH
HYPOGONADISM
“Low T” (decreased testosterone) OR Male Menopause
•  Definition – a condition in which the body no longer produces enough testosterone
•  Hypogonadism can be seen at birth or develop later on in life due to many factors but the major cause
is aging
•  Signs and Symptoms
•  Erectile dysfunction
•  Infertility
•  Decrease in body hair and beard growth
•  Decrease muscle mass
•  Development of breast tissue (gynecomastia)
•  Bone loss (osteoporosis)
•  Fatigue
•  Decease sex drive
•  Difficulty concentrating
•  Hot flashes
•  Mental and emotional changes
HYPOGONADISM
Testosterone Replacement
§  Dosage Forms
§  Buccal, Intramuscular, Subcutaneous, Topical, Transdermal
§  Available Products
§  Androderm
§  Androgel
§  Striant
§  Testim
§  Testro AQ
§  Testopel Pellets
§  Axiron
§  Fortesta
§  Adverse Effects – increased aggression, acne, blood dyscrasias, dyslipidemia, viralization (in
women)
§  Monitoring – Serum Testosterone, Liver Function Test, Lipid Concentrations, Hemoglobin and
Hematocrit, Prostate Cancer Risk (Increased)
1 9/27/15 ERECTILE DYSFUNCTION
ERECTILE DYSFUNCTION
Cause of erectile dysfunction (ED) is reduced blood flow to
the penis
Common drugs that cause ED
§ Antipsychotics – haloperidol, chlorpromazine, fluphenazine,
thioridazine
§ Antidepressants – SSRIs and SNRIs
§ Drugs that treated BPH (finasteride, dutasteride, silodosin)
§ Chemotherapy agents – leuprolide (Lupron®)
§ Cimetidine
§ Opioids – methadone
§ Nicotine – smokers
•  Types of ED
•  Low serum testosterone concentrations
•  Increased concentrations of serum prolactin
•  Includes one of the following designations
•  Persistent – at least 6 months of inability to achieve or maintain an
erection
•  Psychological
•  Organic
•  Mixed
ERECTILE DYSFUNCTION
Treatment of Erectile Dysfunction by controlling risk factors
§  Smoking cessation
§  Control diabetes mellitus
§  Control hyperlipideimia
§  Control hypertension
§  Decreased alcohol intake
§  Discontinue illicit drugs
§  Lose weight
§  Exercise
§  Check for medication causes
§  Stabilize cardiovascular disease
ED TREATMENT
Phosphodiesterase Type 5 Inhibitors (PDE5)
• 
First line agents for the treatment of ED in men without contraindications to use
Inhibits PDE-5 in the penile tissue, preventing the breakdown cGMP thus increasing
smooth muscle relaxation in the corpora cavernosa and enhances penile rigidity
§  Sidenafil (Viagra®) – given one hour prior to intercourse
§  Vardenafil (Levitra®) - given one hour prior to intercourse
§  Talalafil (Cialis®) - given one hour prior to intercourse, can also be used daily (lower
dose – 2.5 to 5 mg)
§  Side effects (For All) – headache, flushing, runny nose, stomach pain, priapism,
sudden vision loss, bluish haze (green blue), loss of hearing, ringing in the ears
§  Contraindications – those individuals using nitrates for angina , cardiovascular
disease, hypotension, uncontrolled HTN, MI/Stroke with 6 months, life-threatening
arrhythmias, penile deformities, renal/hepatic dysfunction, and degenerative retinal
disorders
• 
ED TREATMENT
Nonpharmacologic treatment
• 
Vacuum pump devices
•  May cause some adverse effects such as pain and bruising
• 
Venous constriction rings
•  May cause adverse effects such as pain and bruising
Testosterone Replacement
•  Oral testosterone should not be used due to potential for liver toxicity
•  Depot intramuscular injection of testosterone enanthate
•  Transdermal patch placed daily – Androderm and Testoderm TTS
•  Testosterone gel
•  Topical solution
•  Implanted (Testopel)
•  Striant buccal system
Adverse Effects – increase in BP, acne, enlarged prostate, liver toxicity , cholesterol changes,
polycythemia
ED TREATMENT
Alternative agents (Second-line therapy)
§  Caverject (injectable)
§  Alprostadil (Muse®) – inserted transurethral
§  Effects may last 30-90 minutes
§  Adverse Effects
§  Penile pain, cavernosal scarring, priapism, hypotension
§  Drug Interactions – DO NOT USE with PDE inhibitors
§  Yohimbine
§  Derivative of the African Yohimbe tree, alpha-2 antagonist
§  Efficacy is controversial, not recommended according to American Urological
Association Guidelines
§  Adverse Effects – headache, dizziness, insomnia, and anxiety
** Treating the underlying cause
2 9/27/15 BENIGN PROSTATIC HYPERPLASIA (BPH)
Etiology
•  Non-malignant growth of the prostate epithelial/glandular tissue, leading to physical obstruction
at the bladder neck, and agonism of alpha-receptor within the prostate, bladder neck, and
urethra. This leads to lower urinary symptoms and bladder outlet obstruction
Symptoms
§  Hesitant, interrupted, weak stream of urine, Urgency and leaking or dribbling, Frequent urination
at night
§  Normal to slightly elevated PSA values
§  Enlarged prostate
§  Digital rectal examination
§  Ultrasonograpy
Management
•  Goal – reduce urinary symptoms, delay progression, prevent complications, and need for surgery
BENIGN PROSTATIC HYPERPLASIA (BPH)
Treatment
§  Alpha Blockers
§ Terazosin (Hytrin®) and Doxazosin (Cardura®)
§ Side effects – orthostatic hypotension, worsening of ED, dizziness, HA
§  Selective alpha blockers
§ Tamsulosin (Flomax®), alfuzosin (Uroxatral®), silodosin (Rapaflo®)
§ Side effects and precautions – dizziness, fatigue, hypotension, HA, QT
prolongation, use in caution in patients with CrCl < 30 ml/min
§  5-α reductase inhibitors
§ Finasteride (Proscar®) and Dutasteride (Avodart®)
§ Side effects – pregnancy category X, sexual dysfunction (decrease libido,
ejeculation, impotence)
Adverse Effects (range depending on the agent used) – dizziness, hypotension,
syncope, asthenia, headache, edema, dyspnea, fatigue/somnolence, URI/nasal
congestion, abnormal ejaculation
URINARY INCONTINENCE
URINARY INCONTINENCE
Urinary incontinence physiology
•  Activation of the detrusor smooth muscle of the bladder causes the bladder to contract
•  Detrusor contraction increases pressure within the bladder and with the urethral sphincter
relaxation, bladder emptying occurs
Types of Incontinence
§  Functional Incontinence
§  Stress Incontinence
§  Overflow Incontinence
§  Urge Incontinence
§  Mixed Incontinence
Treatment and Management
•  Treat underlying cause
•  Goal – reduce or eliminate symptoms, increase quality of life, and prevent negative
consequences of having incontinence
•  Monitoring of treatment effectiveness should be related to goals of therapy
Non-pharmacologic Treatment
§  Behavior modification
§  Scheduled/timed voiding
§  Pelvic floor exercise (Kegel exercises)
§  Drugs (avoid those that can exacerbate incontinence
Pharmacologic Treatment
§  Based on type of incontinence being treated
§  Agents include – oxybutynin (Ditropan/Oxytrol), tolterodine (Detrol), fesoterodine (Toviaz),
tropium (Sanctura), solifenancin (VESIcare), darifenacin (Enablex),and mirabegron (Myrbetriq)
§  Adverse effects – dry mouth, constipation, dizziness, and vision changes
Reversible Causes (DIAPPERS)
•  Delirium, Infection, Atrophic urethritis, Psychiatric disorders, Pharmacologic agents, Excessive
urine output (diabetes, heart failure), restricted mobility (Parkinson’s Disease, Osteoarthritis,
Stroke, Alzheimer's disease), and Stool impaction
MENSTRUAL CYCLE
§  Average menstrual
cycle is 28 days
WOMEN'S HEALTH
§  Menstrual cycle is
under the control of
the following
hormones
Estrogen
Follicle stimulating
hormone (FSH)
Luteinizing hormone (LH)
Progesterone
Reference: embryology.med.unsw.edu.au
3 9/27/15 MENSTRUAL CYCLE
Types of Estrogen
§ Natural Estrogens
§ 17β-estradiol, estrone, and estriol
§ Synthetic estrogen (several exist)
§ Frequently used include
§ Ethinyl estradiol
§ Mestranol
§ Dienestrol
§ Estradiol valerate
Types of Progestin
§ Natural Progestin
§ Progesterone
§ Synthetic Progestin
§ Norethindrone
§ Norgestrel
§ Levonorgestrel
§ Dionegest
PRIMARY CONTRACEPTIVE METHODS AMONG WOMEN
AGE 15 TO 44 YEARS: UNITED STATES 1995, 2006-2010
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
CONTRACEPTIVE
OPTIONS
§  Intra-uterine Devices (IUD)
§  Diaphragm
§  Condoms (male and female)
§ Hormonal
§  Oral contraceptives
§  Long acting injectable or implantable progestin
§  Intra-uterine contraceptive (IUC)
§ Other
§  Spermicide
§  Withdrawal
§  Outer-course/Abstinence
Non-reversible methods (Male and Female) include:
§ Tubule ligation
§ Essure® procedure
§ Vasectomy
CHOOSING A METHOD
CHOOSING A METHOD
Top 10 Questions to Ask
•  Affordability
•  Convenience
•  Protection against
sexually transmitted
diseases
•  Duration of action
•  Reversibility and time to
•  Efficacy
return of fertility
•  Effect on uterine bleeding
1. 
What are your contraceptive goals? Do you ever plan to get pregnant? When?
2. 
Are you currently having sex with a male partner?
3. 
Have you tried any contraceptive methods? Which ones?
4. 
What did you like/dislike about that method(s)?
5. 
Do you take pills well?
6. 
How often do you forget to use the method(s)?
7. 
Are there any methods you have heard of and would like to try?
•  Frequency of side effects
and adverse events
8. 
How important is spontaneity of use?
9. 
Is protection from sexually transmitted infections an important consideration in your
current life situation?
10. 
Is cost an issue? Does your health insurance plan cover any contraceptive method(s)?
4 9/27/15 CONTRACEPTION
Types
§  Barrier Method
§  Condoms (Male/Female)
§  Diaphragm
§  Cervical Cap
§  Contraceptive Sponge
§  Intrauterine device (IUD’s) – contains copper
§  Hormonal Contraceptives
§  Oral Contraceptives – Loestrin Fe®, Yaz®, BeYaz®, Yasmin®
§  Transdermal Contraceptives - OrthoEvra® Patch
§  Injectable - Depo-Provera® (IM/SQ)
§  Intravaginal - NuvaRing®
§  Contraceptive Implant - Implanon® or Explanon®
§  Intrauterine Contraceptive - Mirena® and Skyla® - FDA approved Feb 2013
COMBINATION HORMONAL THERAPY
C O N T R A I N D I C AT I O N S
—  Breast Cancer
—  Current or history of Deep
Vein Thrombosis (DVT)
—  Current or history of
cerebovascular accident or
Coronary Artery Disease
(CAD)
—  Diabetes with nephropathy,
neuropathy, retinopathy, or
other vascular disease
—  Migraine Headache
—  Hypertension (>160/100mm
Hg) or with vascular disease
C O N T R A I N D I C AT I O N S
Liver disease
Pregnancy
Age >35 years of age (Precaution)
Smoker(15 or more cigarettes a
day) < 35 years of age (Precaution)
—  Smoker >35 years of age (15 or
more cigarettes a day)
—  Surgery with prolonged
immobilization or any surgery on
the legs
—  Structural heart disease
complicated by afib, pulmonary
hypertension, or history of acute
bacterial endocarditis
— 
— 
— 
— 
OTHER METHODS
OTHER METHODS
OTHER METHODS
Withdrawal “coitus interruptus”
Sterilization
§  Requires the man to withdraw from the vagina before ejaculation
§  Failure occurs if timing is not accurate or pre-ejaculation fluid contains sperm
§  Failure rate – 18-20%
§ Can be reversible but should be considered permanent (product/
procedure dependent)
§ Includes: Tubal Obstruction/Ligation or Vasectomy
Lactation Amenorrhea Method (LAM)
§  Women who breastfeed have delayed postpartum ovulation
§  Due to prolactin-induced inhibition of gonadotropin-releasing hormones
§  Dependent on the following factors
§  Less than 6 months postpartum
§  Exclusively breastfeeding
§  Amenorrehic
Sterilization
§  Requires no other contraceptive action after the procedure
Tubal Ligation (Women)
§ Prevention of tubal patency
§ Pregnancy after the procedure is uncommon
§ If it does occur it will most likely by a ectopic pregnancy (return of
fertility is unlikely if reversed)
Essure® procedure (Women)***
§ 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
5 9/27/15 INITIATION OF THERAPY
INITIATION OF THERAPY
OC’s can be started at anytime during the menstrual cycle
There are several possible methods
§ Quick Start Method, Sunday Start, and First Day Start
1.  Quick Start Method
§ If pregnancy is excluded
§ Backup method is required for the first 7 days
§ Full contraceptive effects are not immediate
2.  Sunday Start
§ OC’s are started on the first Sunday after period begins
§ Most pill packets are arranged for a Sunday start (avoid
withdrawal bleeding on the weekend)
2.  Sunday Start
§ Backup method is required for the first 7 days
§ Full contraceptive effects are not immediate
3.  First Day Start
§  OC’s is started on the first day of menses
§  Provides the maximum contraceptive effect in the first cycle
§  No back up method is required
Disadvantages of the Sunday and First Day Start
§  Can be confusing to patients
§  Pt’s will not fill the prescription right away
§  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
menopause (50-55 years of age)
§  In healthy non-smoking women
***Exception
§  Natazia®
§  Minimum of 9 days is required for back up method
(regardless of method used)
Efficacy 99.8 – 99.9%
§ With perfect use
§ 94 -97% with typical use
§ Non-adherence is likely (16-47%)
COC’s do not interfere with intercourse and have few side effects
§ NO STD PROTECTION!!!!
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
Estrogenic Effects
§ Nausea
§ Increased breast size
§ Weight gain/fluid retention
§ Hypertension
§ Thromboembolic risk
§ Increase growth of breast
neoplasia
Estrogen/Progesterone Effects
§ Breast tenderness
§ Headache
§ Hypertension
§ Myocardial infarction
Androgenic Effects
§ Increase appetite/weight gain
§ Depression, fatigue, tiredness
§ Decreased libido
§ Acne, oily skin
§ Increased breast size and
tenderness
§ Decreased carbohydrate
tolerance
§ Increased insulin resistance
§ Lipid abnormalities
§ Pruritus
EFFECTS OF HORMONAL
IMBALANCE WITH COC’S
Estrogen Excess
Common - nausea, dizziness, edema, bloating, cyclic weight gain,
uterine cramps, heavy menses, fibroid growth, irritability, depression, fat
deposition, hypertension, breast tenderness, increased breast size,
suppressed lactation
Serious – stroke, thrombophlebitis, myocardial infarction
Estrogen Deficiency
Irritability, nervousness, vasomotor symptoms (menopause), early-midcycle breakthrough bleeding/spotting, light menses, decreased libido,
headaches, depression, dry vaginal mucosa, atrophic vaginitis,
dyspareunia, uterine prolapse
Progestin Excess
Moodiness, non-cyclic weight gain, fatigue, depression, decreased sex
drive, hirsutism, acne, hair loss, decreased menstrual bleeding (may
result in amenorrhea), insulin resistance, hypertension, breast
tenderness, decreased breast size (breast regression), swelling of
arms/legs
Progestin Deficiency
Late breakthrough bleeding/spotting, delayed onset of menstrual
bleeding, hypermenorrhea
6 9/27/15 PRECAUTIONS
The following conditions should be considered for benefit before
initiation of hormonal contraceptive therapy
§ Anemia's
§ Sickle Cell
§ Iron Deficient – use precaution with IUDs (may cause
increased bleeding)
§ High risk for HIV
§ HIV infection (positive status)
§ AIDS diagnosis
§ Use IUD with caution (risk may out weight the noncontraceptive benefits)
§ Increased risk of abnormal cervical cells that could lead to
cancer
COMBO THERAPY: SIDE EFFECTS
Irregular bleeding or Spotting (breakthrough bleeding)
§ More common with low-dose or triphasic/quadrphasic CHCs
§ Increase Estrogen
§ If occurring in the beginning of the cycle
§ Increase Progestin
§ If occurring at the end of the cycle
Nausea/Vomiting, weight gain, moodiness, breast tenderness
§ Most common within first 3 months (after starting a new pack)
§ Usually due to estrogen excess (High-Dose)
§ Risk of weight can is generally low
§ Most women will not take combo CHC’s b/c of this reason (~40%)
COMBO THERAPY: SIDE EFFECTS
Factors that increase the risks Serious SE Include
§ Smoking
§ Hypertension
§ Age > 35 years
§ Not seen as frequently with Progestin-ONLY products
Note: new reports linking Yaz®/BeYaz®/Yasmin® to
increased risk of gallbladder disease
§ Specifically the drosperinone containing products
DRUG INTERACTIONS
CYP-450
§ Hepatic enzyme inducers decrease efficacy of oral contraceptives
Other drugs decrease CHC efficacy (different MOA)
§ Causing spotting, breakthrough bleeding, or pregnancy
Drugs that
decrease CHC’s
efficacy
Barbiturates, carbamazepine,
oxcarbazepine, phenobarbital, phenytoin,
modafinil, pioglitazone, rifamycins
(including Rifampin), and Antiretroviral protease inhibitors ( liponivir, ritonovir)
All patients should be notified of low potential
interactions with other anti-infectives
**ACOG states that PCN, ampicillin, doxycyline,
fluconazole, miconazole, metronidazole, FQs,
and tetracycline DO NOT interact with hormone
levels
Drugs that
Increase Effects of
CHC’s
Atorvastatin,
Atazanavir, Indinavir (Antiretroviral)
More adverse effects associated with
concomitant use
Herbals that
decrease the
effect of CHC’s
St. John’s wort
Avoid using herbal products if possible
Drosperinone
ONLY
Potassium-sparing diuretics, potassium
supplements, ACE-I, ARBs
Increased risk of hyperkalemia
Metabolism or
Clearance Altered
by CHC’s
Acetaminophen, antidepressants
(tricyclic), aspirin, benzodiazepines, beta
blockers, caffeine, corticosteroids,
cyclosporine, lamotrigine, theophylline
Interaction not clearly understood but known
possibility increased effects of noncontraceptive agent with long term
concomitant use
COMBO THERAPY: SIDE EFFECTS
Serious side effects (Rare)
§ V TE including DVT and/or PE (dose related- high dose
estrogen)
§ Myocardial infarction (MI)
§ High-dose estrogen
§ Migraine
§ Stroke (very low risk)
§ Hypertension
§ Premenopausal breast cancer
§ Highest risk in women who use for a duration of ≥ 4 years
before first full-term pregnancy
FDA ALERT AND LABELING CHANGE
Food and Drug Administration (FDA)
April 10, 2012
Conducted a observational (epidemiologic) study regarding risk of blood clots in women receiving
drospirenone-containing birth control pills
§  Based on this review the FDA concluded that drospirenone-containing birth control pills may be
associated with an increased risk of blood clots than other progestin-containing pills
Recommendation
§  Women should discuss the risks and benefits of drospirenone containing birth control pills
before starting on this method
§  Request that manufactures change the labeling of these products to account for the increased
risk seen in observation study
7 9/27/15 EMERGENCY CONTRACEPTIVE
AKA: postcoital contraception and the morning after pill
EMERGENCY
CONTRACEPTION
EMERGENCY CONTRACEPTION
Definition: the use of a drug or device as an emergency measure
to prevent pregnancy due to:
§ Recent unprotected sex
§ Failure of a contraceptive method
Intended for occasional or back-up use
§ NOT as primary contraceptive
EMERGENCY CONTRACEPTION
Mechanism of Action (can very among agents used)
1.  Levonorgestrel
§ Progestin ONLY (Plan B One-Step ®, Next Choice®)
2.  Ulipristal (Ella®)
3.  Ethinyl estradiol plus levonorgestrel (Yuzpe regimen)
§ No longer commercially packaged in the US
4.  Copper intrauterine contraception (*Skyla FDA approved EC)
Up to the minute information about emergency contraception:
§  www.not-2-late.com
§  By Princeton University faculty
Educate patients/health care providers to prevent barriers to receiving EC
when needed
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
contraceptives
§  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
Plan B®, Plan B OneStep®, Next Choice™
Levonorgestrel
0.75 mg given twice, 12 hours apart
1.5 mg single dose (Plan B One-Step®)
89% of pregnancies
prevented
Selective Progestin
Receptor Modulator
Ella® (Ulipristal)
30mg x 1 dose (with in 120 hours of
contraceptive failure)
~ 90% of pregnancies
prevented
Intrauterine Device
Copper Intrauterine
device (Paraguard®)
*Skyla (levonorgestrol
containing q3 years)
Inserted with in 120 hours after intercourse 99%
(Combination Estrogen/
progesterone)
Yuzpe Regimen
100 microgram ethinyl estradiol plus 0.5mg 75% -80% pregnancies
levonorgestrel, each given twice, 12 hours
prevented
apart
PREGNANCY
AND
LACTATION
8 9/27/15 PREGNANCY TESTING
PREGNANCY TESTING
Designed to detect the presence of human chorionic gonadotripin (hCG) in urine
§ Using monoclonal or polyclonal antibodies (enzyme immunoassay)
Pregnancy cannot be detected before implantation has occurred
§ Implantation will usually occur before the expected menstrual period (can be
later)
Highest sensitivity
§ First day of missed menses is 90%
§ One week after missed menses, accuracy is 97%
§ Accuracy may be as low as 50 – 75%
§  If directions are not followed
PREGNANCY CATEGORIES
•  Problems with FDA system
•  FDA is recommending more detail in the product labeling
regarding risk in pregnancy
•  Within category C especially
•  Manufacturers must describe the types of studies that have
been conducted and the study results
•  Current pregnancy categories have been replaced by the RULE
on pregnancy and lactation
Patient Counseling Points
§ Check the expiration date of the
test
§ Choose a simple test if possible
§ Some boxes contain more than one test
§ Most tests include a control
§ 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
•  Problems with FDA system
•  Drugs available prior to 1979 were “grandfathered” into the
system
•  Assumptions are made that drugs within the same class
have equal risk (typically inaccurate)
•  As of 2001, only 40% of all drugs carried a classification
designation
§  Category A - 0.7%
§  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
TERATOGENIC AGENTS
PREGNANCY CATEGORIES
Classification
and Category
Description
Medication Examples
A
Adequate, well-controlled studies in pregnant women have
not shown an increased risk of fetal abnormalities to the
fetus in any trimester of pregnancy
Levothyroxine
Prednisone
B
Animal studies have revealed no evidence of harm to the
fetus, however, there are no adequate and well-controlled
studies in pregnant women
Claritin, Keflex
Tylenol (APAP)
Metformin
C
Animal studies have shown an adverse effect and there
are no adequate and well-controlled studies in pregnant
women
Keppra (Anticonvulsant)
Cyclosporine
Clonidine
**Tylenol (APAP) – IV
formulation
D
Adequate well-controlled or observational studies in
pregnant women have demonstrated a risk to the fetus
Lisinopril (in 2nd and 3rd
Trimester)
X
Adequate well-controlled or observational studies in
animals or pregnant women have demonstrated positive
evidence of fetal abnormalities or risks.
The use of the product is contraindicated in women who
are or may become pregnant
Methotrexate
Accutane
Thalidomide
•  Retinoid
derivatives
• 
• 
• 
• 
• 
• 
Anticonvulsants
Coumadin
Anti-cancer
medications
Diethylstibestrol
(DES)
Thalidomide
Androgens
• 
• 
• 
• 
• 
• 
Lithium
“Statins” cholesterol
lowering agents
ACE inhibitors
Tetracyclines
Misoprostol,
mifepristone
(RU-486)
Anti-thyroid
medications
9 9/27/15 TERATOGENIC AGENTS
COMPLICATIONS DURING PREGNANCY
Retinoid Derivatives (iPLEDGE)
Requirements of patients
§ Go to laboratory for monthly pregnancy test
§ Answer monthly “quiz” questions on iPLEDGE web site
§ Provides the two birth control methods being used
Requirements of pharmacies
§ The pharmacy must interface with the iPLEDGE clearninghouse database to
determine patient eligibility
§ The pharmacy must fill prescription within 7 days of pregnancy testing (this
may or may not correspond with the date the prescription was written).
§ If > 7 days, patient must restart the process
§ The patient can get the prescription only once every 30 days
COMPLICATIONS DURING PREGNANCY
Smoking
§  Once pregnancy has occurred adverse outcomes to the mother and fetus are likely
§  Damage can lead to damage of the fetal brain, heart, and nervous system
§  Also associated with decrease fetal birth weight (average decrease of 200g)
§  Long-term consequences
§  Mental disabilities
§  Possible nicotine addiction
§  Exposure to second hand smoke
§  Associated with adverse effects such as low birth weight and intrauterine growth
retardation
§  Quitting smoking any time during the pregnancy is beneficial
§  Cessation prior to conception is key or shortly after conception
§  FDA approved smoking cessation products have not been study for safety and efficacy
in pregnant women
§  Counseling and behavior modification is required
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
10 9/27/15 COMPLICATIONS DURING PREGNANCY
Substance Abuse (Illicit Drugs)
§  Cocaine
§  Causes fetal vasoconstriction once it crosses into the placenta
§  Also associated with preterm labor, placental abruption, uterine rupture, cardiac
dysrhythmias, hepatic rupture, cerebral ischemia/infarction, and death
§  Marijuana
§  Associated with depressive symptoms and impaired cognitive function
§  Amphetamines
§  Associated with cardiac anomalies, cleft lip and palate, biliary atresia, intrauterine
growth retardation, intrauterine fetal demise, and cerebral hemorrhage
§  Opioids
§  Directly affect the fetus leading to intrauterine growth restriction
§  Also associated with symptoms of neonatal opioid withdrawal
IMMUNIZATIONS DURING PREGNANCY
Vaccine
Before pregnancy
During pregnancy After pregnancy
Type of vaccine
Hepatitis A
If at high risk for disease
If at high risk for disease
If at high risk for disease
Inactivated (IM)
Hepatitis B
Yes, if at risk
Yes, if at risk
Yes, if at risk
Inactivated (IM)
Human Papillomavirus
(HPV)
Yes, if ≤ 26 y/o
No, under study
Yes, if ≤ 26 y/o
Inactivated (IM)
Influenza (TIV)
Yes
Yes
Yes
Inactivated (IM)
Influenza (LAIV)
Yes, if < 49 y/o and
healthy
No, under study
Yes, if < 49 y/o and
healthy
Live (Nasal Spray)
MMR
Yes, avoid conception for
at least 28 days if
unvaccinated
No
Yes, avoid conception for
at least 28 days
Live (SC)
Meningococcal
• Polysaccharide
• Conjugate
If indicated
If indicated
If indicated
Pneumococcal
Conjugate/
Polysaccharide
If indicated
If indicated
If indicated
Inactivated (IM or SC)
Tdap (one dose for each
pregnancy)
Yes, preferred
Indicated at end of 2nd
trimester
Yes, if not during
pregnancy
Toxoid (IM)
Varicella
Yes, avoid conception for
at least 28 days
No
Yes, avoid conception for
at least 28 days
Live (SC)
Inactivated (SC)
Inactivated (IM)
DRUG USE AND LACTATION
DRUGS AND
BREASTFEEDING
DRUG USE AND LACTATION
Breastfeeding is the BEST method of infant feeding
§  The method at which all other types of feeding should be measured
Numerous benefits include
§  Decrease risk of
§ Gastroenteritis
§ Severe lower respiratory tract infections
§ Acute otitis media
§ Necrotizing enterocolitis
§ Sudden infant death syndrome (with in the first year of life)
§ Type 1 or 2 diabetes mellitus
§ Childhood leukemia
§ Obesity
•  Drugs taken orally by mother undergo multiple metabolic conversions
§ Before affecting infant circulation
•  Drugs diffuse passively across the mammary epithelium down a concentration
gradient
§ 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
Mother’s who breastfeed also have been benefits
§ Rapid uterine involution, decreased postpartum blood loss, fertility reduction
(while nursing and amenorrheic), and decreased risk of breast and ovarian
cancer, type 1 and 2 diabetes, and possibly osteoporosis and hip fracture later
in life
Drugs of Concern
§ Antidepressants
§ Narcotics
§ Long-Acting Sedatives
§ Water-Soluble β-blockers
§ Lithium
§ Iodine-Containing Drugs
§ Hemolytic Agents
11 9/27/15 DRUG USE AND LACTATION
Drug Effects on Lactation
§ Agents that decrease milk supply
§ Alcohol
§ Anti-cholinergics
§ Diuretics
§ Dopaminergic agents
§ Estrogens
§ Cigarette smoking
§ Sympathomimetic vasocontrictors
DRUGS OF ABUSE AND BREASTFEEDING
•  Amphetamine – irritability, poor sleeping
•  Cocaine – intoxication
•  Heroin – tremors, restlessness, vomiting, poor feeding
•  Marijuana – effects unknown
•  Nicotine – vomiting, diarrhea, tachycardia, restlessness,
decreased milk production
DRUG USE AND LACTATION
Galactagogues
§  Are defined as any agents or substance that can increase milk supply
§  Raises baseline prolactin concentration
§  Via dopamine antagonist activity
§  Agents include (clinically used for this purpose)
§  Metoclopramide (FDA approved)
§  Doperidone
§  Sulpiride
§  Fenugreek (herbal product)
§  Used as a galactogogue
§  If used in large amounts can cause hypoglycemia and have interact with warfarin
§  Also associated with allergy and asthma
§  Milk thistle (traditional herbal product)
§  Also used to increase breast milk production
§  No clinical data to support use
AVAILABLE REFERENCE
(LACTATION)
Online
§  LactMed – Drug and Lactation Database
§  A peer-reviewed and fully referenced database of drugs to which breastfeeding mothers may be
exposed
§  Data included are maternal and infant levels of drugs, possible effects on breastfed infants and
on lactation, and alternate drugs to consider
§  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
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.
MENOPAUSE
12 9/27/15 STAGES OF MENOPAUSE
STAGES OF MENOPAUSE
•  Menopausal Transition/Climacteric is the period of time when the
endocrinologic, biologic, and clinical features of the approaching menopause
commence
§ Early menopausal transition
§ Persistent difference of ≥ 7 days in the length of consecutive cycles
§ Variable FSH levels
§ Late menopausal transition
§ > 60 days of amenorrhea or 2 skipped menstrual periods
§ FSH criteria, random blood draw > 25 units/L
Perimenopause is the period immediately (2-8 years) prior to menopause and the first year after
menopause
§ Begins with irregularity in length of consecutive cycles
§ Overlaps with menopausal transition and postmenopause
§ FSH elevating (variable) and estradiol declining
Postmenopause is the period following final menstrual period (FMP)
§ FSH elevated, estradiol decreased
§ Early postmenopause = 3 years following FMP
§ Late postmenopause = 4+ years following FMP
73
74
Treatment
Algorithm
STAGES OF MENOPAUSE
Menopause
75
76
Reassess each step at least once every 6–12 months (assuming
patient's continued preference for HT).
who have vaginal dryness without moderate to severe
vasomotor symptoms may be candidates for vaginal estrogen.
c Traditional contraindications: unexplained vaginal bleeding;
active liver disease; history of venous thromboembolism due to
pregnancy, oral contraceptive use, or unknown etiology; blood
clotting disorder; history of breast or endometrial cancer; history
of CHD, stroke, transient ischemic attack, or diabetes. For
other contraindications, including high triglycerides (>400 mg/
dL); active gallbladder disease; and history of venous
thromboembolism due to past immobility, surgery, or bone
fracture; oral HT should be avoided but transdermal HT may be an
option.
e Women >10 years past menopause are not good candidates for
starting (first use of) HT.
g Consider selective serotonin or serotonin-norepinephrine reuptake
inhibitor, gabapentin, clonidine, soy, or alternative.
h HT should be continued only if moderate to severe menopausal
symptoms persist. The recommended cutpoints for duration are based
on results of the Women's Health Initiative estrogen-progestin and
estrogen-alone trials, which lasted 5.6 and 7.1 years, respectively. For
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
with breast cancer; susceptibility genes such as BRCA1 or BRCA2; or
a personal history of breast biopsy demonstrating atypia.
jWomen with premature surgical menopause may take HT until
average age at menopause (age 51 in the United States) and then
follow flowchart for subsequent decision making.
k If progestogen 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.
n Increased risk of osteoporotic fracture: documented osteopenia,
78
personal or family history of nontraumatic fracture, current smoking, or
weight <125 lbs.
a
VASOMOTOR SYMPTOM TREATMENT
TREATMENT
HRT/MHT= mainstay of therapy
§ Moderate - severe vasomotor symptoms
§  Lowest possible effective dose & shortest duration
§  Vasomotor symptoms may require treatment despite the presence of menstrual
bleeding
Other therapies for vasomotor symptoms
§ SSRI (e.g. fluoxetine, paroxetine, sertraline)
§ SNRI (e.g. venlafaxine)
§ Clonidine
§ Gabapentin
§ Phytoestrogens (e.g. soy products)
§ Herbal extracts (e.g. black cohosh)
77
bWomen
13 9/27/15 ESTROGEN TREATMENT CYCLES
Oral estrogen
(tablets) Conjugated estrogens
With intact uterus
§ Estrogen and Progestin daily without a break
§ Cyclic-sequential administration
Transdermal estradiol § Estrogen daily for 21-28 days of a 28-day cycle
§ Progestin added during the last 10-12 days
§ Estrogen is administered continuously over a 3-month cycle
§ Progestin is only added every third month
Without a uterus
§ Continuous unopposed Estrogen therapy
79
Micronized estrogen
Estradiol
Esterified estrogens
Patch
Gel
Vaginal
estrogen § Long-cycle regimen
Estropipate
Emulsion
Spray
Estradiol
Conjugated estrogens
BRAND CENESTIN
ENJUVIA
PREMARIN
OGEN
ORTHO-EST
ESTRACE
FEMTRACE
MENEST
ALORA
CLIMARA
ESCLIM
ESTRADERM
MENOSTAR
VIVELLE
VIVELLE-DOT
DIVIGEL
ELESTRIN
ESTROGEL
ESTRASORB
EVAMIST
ESTRACE (cream)
ESTRING (ring)
FEMRING (ring)
VAGIFEM (tabs)
PREMARIN (cream)
DOSE (mg) FREQUENCY 0.3, 0.45, 0.625, 0.9, 1.25
0.625, 1.25, 1.5
Once daily
0.75, 1.5
0.5, 1, 2
0.45, 0.9, 1.8
0.3, 0.625, 1.25, 2.5
0.025, 0.05, 0.075, 0.1
Twice weekly
0.025, 0.0375, 0.05, 0.06, 0.075, 0.1
Once weekly
0.025, 0.0375, 0.05, 0.075, 0.1
Twice weekly
0.05, 0.1
Twice weekly
0.014
Once weekly
0.05, 0.1
Twice weekly
0.025, 0.0375, 0.05, 0.075, 0.1
Twice weekly
0.25, 0.5, 1 g/packet
0.87 g/pump
Once daily
1.25 g/pump
1.74 g/pouch
Twice daily
1.53 mg/spray
1-3 sprays daily
0.1 mg/g
Once daily, then 1-3/week
7.5 g/24 hr
Once every 90 days
0.05, 0.1 mg/day
Once every 90 days
25 g
1/day for 2 weeks, then 80
2/week
0.625 mg/g
Once daily
ADVERSE DRUG REACTIONS
FROM MHT
CONTRAINDICATIONS TO MHT
Per AACE
§  Current, past, or suspected breast cancer
§  Known or suspected estrogen-sensitive malignant conditions
§  Undiagnosed genital bleeding
§  Untreated endometrial hyperplasia
§  Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary
embolism)
§  Active or recent arterial thromboembolic disease (angina, myocardial infarction)
§  Untreated hypertension
§  Active liver disease
§  Known hypersensitivity to the active substances of MHT or to any of the exceipients
§  Porphyria cutanea tarda (ABSOLUTE CONTRAINDICATION)
Minor
Major
§ Nausea, Vomiting
§ Dizziness
§ Weight gain
§ Breast tenderness
§ Breast enlargement
§ Possible uterine bleeding
§ Endometrial, breast, or
ovarian cancer
§ Venous thromboembolic
event
§ Stroke
§ Gallbladder disease
81
SEXUAL DYSFUNCTION
82
WOMEN’S HEALTH INITIATIVE
Estrogen & Testosterone levels may be unpredictable
§ Decreased libido/sexual desire
§ Methyltestosterone (Methitest®) 1.25 – 2.5 mg orally daily
§ Topical estrogens
§ Sildenafil
§ “Female Viagra” FDA approved Aug 2015 flibanserin (Addyi)
§ Orgasm disorder
§ Review medications (common with SSRIs)
§ Dyspareunia
§ Water based lubricants
§ Topical estrogen (in presence of vaginal atrophy)
§ Osphena (ospemifene)**
Important concepts
• HT for treatment of menopausal symptoms and HT for prevention
of chronic diseases
Five major points of agreement
1.  Younger women
o HT is an acceptable option for treating moderate to severe menopausal symptoms in
relatively young (up to age 59 or within 10 years of menopause) and healthy women
§  Individualization is key in the decision
to use HT
2.  Women with vaginal symptoms ONLY
§  Preferred treatments are low doses of vaginal estrogen
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
83
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14 9/27/15 WOMEN’S HEALTH INITIATIVE
Five major points of agreement
4.  Risk of blood clots and stroke
OSTEOPOROSIS
§  Both estrogen therapy and estrogen with progestogen therapy increase the risk of
blood clots in the legs and lungs
§  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
85
OSTEOPOROSIS
OSTEOPOROSIS
Causes
§  Menopause or Medication induced
National Health and Nutrition Examination Survey III
§ 8.9 million Americans have osteoporosis
§ 42.5 million have low bone density of the hip
Bone Mineral Density
§  T-score < -2.5
Treatment
§  Bisphosphonates (ex. Fosamax)
§  Selective Estrogen Receptor Modifiers (SERMs)
§  Hormone replacement therapy
§  Calcium and Vitamin D supplementation
National Osteoporosis Foundation (NOF)
§ Higher risk in women (4:1) versus men
§ 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
system
§ 2.5 million medical office visits
§ 432,000 hospital admissions
§ 180,000 long-term care admissions
§ 20% of hip fracture patients require long term care
•  60% will not regain pre-fracture function
•  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
Over 2 million fractures each year in men and
women over the age of 50
§ 300,000 hip fractures
§ 550,000 vertebral fractures
§ 400,000 wrist fractures
§  810,000 fractures at other sites
Image from http://biomed.brown.edu/Courses/BI108/BI108_2008_Groups/group01/
BIOL1080_2008_-_Kyphoplasty_Group_Webpage_Project/Pathophysiology_files/Osteoporosis.png
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15 9/27/15 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.
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Bone Health and Osteoporosis: A Report of the Surgeon General October 14, 2004
FACTORS AFFECTING PEAK BONE MASS
BONE REMODELING
93
Image from: http://pubs.niaaa.nih.gov/publications/arh26-4/images/sampson2.gif
94
Image from http://www.ns.umich.edu/Releases/2005/Feb05/img/bone.jpg
PATHOGENESIS OF OSTEOPOROSIS
Osteopenia
Osteoporosis
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Bone Health and Osteoporosis: A Report of the Surgeon General October 14, 2004
16 9/27/15 TYPES OF OSTEOPOROSIS
AGE-RELATED BONE LOSS
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
97
OSTEOPOROSIS & OSTEOPOROTIC FRACTURE
98
OSTEOPOROSIS & OSTEOPOROTIC FRACTURE
Risk Factors
§ Low BMD
§ Cigarette smoking
§ Low BMI (<19 kg/m2) or < IBW
§ Advanced age (>65 ♀, >70♂)
§ Gender (female > male)
§ Systemic glucocorticoid therapy
§ 10 Family history (hip fracture)
§ Low trauma fracture as an adult
§ Alcohol >1-2 drinks per day
Risk Factors
§ Secondary osteoporosis (RA)
§ Low calcium intake
§ Low physical activity
§ Poor nutrition, health, or frailty
§ Minimal sun exposure
§ Recent falls
§ Cognitive impairment
§ Estrogen deficiency before 45 years of age
§ Impaired vision
99
SECONDARY CAUSES – PHARMACOTHERAPY
100
TYPES OF SCREENING
Mechanism
§ Glucocorticoids
§ Decrease osteoblast activity
§ Increased osteoclast activity
§ Increased calcium excretion
§ Decreased calcium absorption
§ Suppressed sex steroid production
•  Physical assessment
•  Laboratory testing
§ Anticonvulsants (phenytoin, carbemazepine, barbituates)
§ Increase Vitamin D metabolism
•  On the horizon
§ Bone quality & density testing
•  Peripheral BMD testing
•  Central DXA BMD testing
•  Causes of secondary osteoporosis
§ Loop Diuretics (furosemide)
§ Inhibit the resorption of calcium in the thick ascending loop
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17 9/27/15 SCREENING
SCREENING RECOMMENDATIONS
Peripheral BMD devices
§ X-ray or ultrasonometry
§ T-score varies by device
§ Younger post-menopausal women without major risk factors
All patients aged ≥50 years should be evaluated for risk factors
for osteoporosis
Central DXA
§ Dual-Energy X-ray Absorptiometry
§ Actual BMD: measured in g/cm2
§ T-score: standard deviation(s) from the reference mean of healthy, young,
gender matched Caucasian population
§ Z-score: standard deviation(s) from the reference mean of healthy, gender
and age matched Caucasian population
BMD testing
§ All women ≥ 65 years of age
§ Younger postmenopausal women with at least 1 major or 2
minor risk factors
§ All men ≥ 70 years of age
§ Men aged 50–69 years with at least 1 major or 2 minor risk
factors
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BONE MINERAL DENSITY TESTING
104
DIAGNOSIS
USPSTF
NOF/AACE/NAMS
Women ≥ 65 years
Yes
Yes
Postmenopausal women
with fracture
Yes
Yes
Normal BMD
Yes
Osteopenia
Adults taking steroids
Postmenopausal women <
65 years with major risk
factors
At 60 years if:
-Wt < 70kg
-Estrogen deficiency
•  Based on Central-DXA scores and fracture history
< 65 years if:
-Weight < 57.6 kg
-Family history of fracture
-Smoking
-Early menopausal
-Medical issues
**Medicare reimburses for BMD testing every two years
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PREVENTION ALONE OF TREATMENT – BASED ON
DIAGNOSIS
T-score ≥ -1
-1 > T-score > -2.5
Osteoporosis
T-score ≤ -2.5
OR low trauma fracture
Secondary
Osteoporosis
Z-score < -2
consider secondary causes
*Each SD ~10 – 12% decrease in bone mass
*Each SD ~1.5 – 2.6 fold increased risk for fracture
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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
4.  Falls prevention
Osteoporosis
§ Treatment
107
108
18 9/27/15 PHARMACOLOGIC INTERVENTIONS
•  Bisphosphonates (1st line agents)
HEALTH MAINTENANCE
•  Selective Estrogen Receptor Modulators
• Menopause is the primary cause
•  Hormone Therapy
•  Menopause is the primary cause
•  Monoclonal Antibody (RANKL-binder)
•  Anabolic Therapy
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HEALTH SCREENINGS
Cardiovascular Disease
§  Includes heart disease and stroke
§  Heart health ABCS
§  A = take aspirin as directed by healthcare provider
§  B = control your blood pressure
§  C = manage your cholesterol
§  S = don’t smoke
Kidney Disease
§  Chronic Kidney Disease (CKD)
§  Risk factors – diabetes and high blood pressure
§  1 in 3 adults with diabetes and 1 in 5 adults with high blood pressure have CKD
§  Recommendations include screening those who are at high risk to prevent End Stage Renal
Disease (ESRD)
§  Screen those with history of diabetes, hypertension, or cardiovascular disease; and/or family
history of CKD
ADULT VACCINATIONS – BY AGE
HEALTH SCREENINGS
Colorectal Cancer
§  Screening recommended in those 50 years and older
§  Colonoscopy recommended every 10 years
Prostate Cancer
§  Recommended in adult males of all ages
§  Does not apply to those men already diagnosed or treated for prostate cancer
§  Prostate cancer is very common, in many cases, the cancer does not grow or cause symptoms. If it
does grow, it often
§  grows so slowly that it isn’t likely to cause health problems during a man’s lifetime
§  Those at risk include – Older men, African American men, those with a family history of prostate
cancer
§  Two screening tests – Prostate Specific Antigen (PSA) and digital rectal exam
§  PSA screening benefits do not out weight risk based on the US Preventative Task Force findings (due
to risk for serious harm)
ADULT VACCINATIONS – BY INDICATION
19 9/27/15 HEALTH MAINTENANCE
PAP SMEAR
HEALTH MAINTENANCE - PAP SMEAR
•  Developed in 1940s, this technique is used to identify abnormal
cervical cytology (cells)
§ PAP (Papanicolaou) Smear – names after who developed the
exam George Papanicolaou
§ Incidence of cervical cancer has been reduced by 70% in
countries that use the PAP test
•  Long delay between HPV infection and the development of
invasive cervical cancer
§  Disease is easy to prevent when screenings are done regularly
§ Cervical cancer cases are more common in women untested or
infrequently tested
CERVICAL CANCER SCREENING RECOMMENDATIONS
Age
USPSTF Recommendations
ACS/ASCCP/ASCP
Younger than
21 years
Recommends against screening
Women should not be screened regardless of age of
sexual initiation or other risk factors
21 – 29 years
Recommends screening with
cytology every 3 years
Screening with cytology alone every 3 years is
recommended
30 – 65
years
Recommends screening with
cytology every 3 years OR screening
with a combination of cytology and
HPV testing every 5 years
Screening with cytology and HPV testing (co-testing)
every 5 years (preferred) or cytology alone every 3 years
(acceptable) is recommended
Older than
65 years
Recommends against screening
who have had adequate prior
screening and not at high risk for
cervical cancer
Women with evidence of adequate negative prior
screening and no history of CIN2+ with in the last 20
years should not be screened
Screening should not be resumed even if the women
reports a new sexual partner
After
hysterectomy
Recommends against screening
who have had removal of cervix and
who do not have history of high
grade precancerous lesion or
cervical cancer
Women with history of removal of cervix with no history
of CIN2+ should not be screened for vaginal cancer.
Evidence of adequate negative prior screening not
required. Screening should not be resumed even if the
women reports a new sexual partner.
HPV
vaccinated
Women who have been vaccinated
should continue screening as
outlined above
Recommended screening practices should not change
on the basis of HPV vaccination status
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.
Stuenkel CA, Gass ML, Manson JE. A decade after the Womens Health Initiative the experts do
agree. Menopause. 2012;19(8):1-2.
•  Recommendations for screening were revised in March 2012
•  Information regarding these recommendations were published in Annals of
Internal Medicine, A Cancer Journal For Clinicians, Journal of Lower Genital
Tract Disease, and the American Journal of Clinical Pathology
•  Consensus statement published by the following agencies
§  U.S. Preventive Services Task Force (USPSTF)
§  American Cancer Society (ACS)
§  American Society of Colposcopy and Cervical Pathology (ASCCP)
§  American Society of Clinical Pathology (ASCP)
•  Guidelines developed to address cervical cancer screening in the general
population
§  Does not address special, high-risk populations that may need more
intensive or alternative screening (hx of cervical cancer, HIV +, DES baby)
REFERENCES
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey M, editors. Pharmacotherapy: a
pathophysiologic approach[internet]. 8th ed. New York: McGraw Hill; c2011. Section 9;
[cited 2013 April 9]. Available from: http://www.accesspharmacy.com
Micromedex® Healthcare Series [Internet database]. Greenwood Village, CO: Thomson
Reuters (Healthcare). Updated periodically.
National Survey of Family Growth (Centers for Disease Control and Prevention)
§  www.cdc.gov
New Cervical Cancer Screening Recommendations from the U.S. Preventative Tasks Force
and the American Cancer Society/American Society for Colposcopy and Cervical
Pathology/American Society for Clinical Pathology (released March 14th, 2012)
§  http://www.acog.org
Treatment Guidelines from The Medical Letter, Volume 8, Dec 2010
§  www.medicalletter.org
Briggs, GG, Nagoeotte, M. Diseases, Complications, and Drug Therapy in Obstetrics: A
Guide for Clinicians. American Society of Health System Pharmacists, 2009
Borgelt, LM, O’Connell, MB, Smith, JA, Calis, KA. Women’s Health Across the Lifespan: A
Pharmacotherapeutic Approach. American Society of Health System Pharmacist, 2010
Ung KD, McNulty J, “Chapter 46. Obstetric Drug Therapy” (Chapter). Koda-Kimble A, Young
LY, Kradjan WA, et al.: Applied Therapeutics: The Clinical Use of Drugs, 9e:
http://pt.wkhealth.com/pt/re/9780781765558/bookcontent.
01337318-9th_Edition-6.htm;jsessionid=LzpSPNb4nB1N2FZTn5q1GNCyRyly7Y6lJmh
GszSNjdzqGpVN2jlb
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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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