Tube Thoracostomy: Complications and the Role of Prophylactic Antibiotics

Tube Thoracostomy: Complications and the Role of Prophylactic Antibiotics
By Ashley Laird

Indications for Tube Thoracostomy
* PTX (spontaneous, iatrogenic, traumatic)
* Hemothorax
* Chylothorax
* Decreased breath sounds in unstable patient after blunt or penetrating trauma
* Multiple rib fractures, sucking chest wound, subcutaneous air in intubated trauma patient
* Complicated pleural effusion, empyema, lung abscess
* Thoracotomy, decortication
* Pleural lavage for active rewarming for hypothermia

Complications
* Undrained PTX, hemothorax, or effusion despite TT clotted hemothorax, empyema, fibrothorax
* Improper placement +/- iatrogenic injuries (lung, diaphragm, subclavian, right atrium)
* Recurrent PTX after tube removal
* Intrapleural collections following tube removal
* Thoracic empyema

Factors Influencing Complications: Louisville study
* Prior studies report TT complication rates of 3-36%
* Etoch SW, Bar-Natan MF, Miller FB, Richardson JD. Tube Thoracostomy: Factors related to complications. Arch Surg. 1995; 130:521-525.
o Retrospective chart review (U of Louisville)
o 379 trauma pts, 599 tubes

Factors Influencing Complications: Louisville study
* Complications:
o Empyema
o Undrained PTX or effusion
o Improper tube placement (+/- iatrogenic injury)
o Post-tube PTX
o Other
* Measures:
o Rate of complications in association w/ TT setting, operator, patient characteristics, MOI, and severity of injury

Factors Influencing Complications: Louisville study
* Overall rate of complications: 21% per patient (16% per tube)
* 8.2% of complications required thoracotomy

Factors Influencing Complications: Setting
* 48% of tubes placed in ED, 23% in OR, 12% in ICU, 7% on floor, and 9% at OSH prior to transfer
* Significantly higher complication rate when TT performed in outside hospital prior to transfer (33%, p<.0001)
* No significant difference in complication rates between TT in ED (9%) vs. TT in other areas of study hospital (7%)

Factors influencing Complications: Operator
* 59% of tubes placed by surgeons, 26% by ED physicians, 8% by physicians prior to transfer
* Highest complication rate for tubes placed by physicians in outside hospitals, mostly nonsurgeon physicians (38%)
* Complication rates for TT’s in study hospital: 13% for ED physicians, 6% for surgeons (p<.0001)
* For TT’s in ED: 13% complication rate for ED physicians vs 5% complication rate for surgeons (p<.01)

Factors influencing Complications: Mechanism/Severity of Injury

* No difference in complication rate related to:
o Age and sex of patients
o Mechanism of injury (23% for blunt vs 18% for penetrating)
o ISS
* Significantly increased complication rate related to:
o ICU admission (29% vs 11%, p<.0001)
o Mechanical ventilation (29% vs 15%, p<.002)
o Presence of hypotension (SBP<90) on admission (31% vs 17%, p<.003)

Factors Influencing Complications: University Hospital study
* Deneuville M. Morbidity of percutaneous tube thoracostomy in trauma patients. Eur J CT Surg. 2002; 22:673-678.
o Prospective observational study (University Hospital, Guadeloupe)
o 128 trauma pts, 134 tubes
o ‘Non-thoracic’ operators vs. thoracic surgeons

Factors Influencing Complications: University Hospital study
* Overall complication rate 25% (29% per tube)
o 5 (12.8%) improper placement, no iatrogenic injury
o 4 (10.3%) improper placement w/ iatrogenic injury (lung x 2, diaphragm, subclavian artery)
o 4 (10.3%) undrained hemothorax/PTX
o 12 (30.8%) post-removal PTX
o 7 (18%) post-removal fluid collection
o 3 (2.3%) empyema
o 4 (10.3%) combined
* 18 (46.2%) of complications required surgery (thoracotomy or VATS)

Factors Influencing Complications: University Hospital study
* No difference in complication rate related to:
o Blunt trauma vs. penetrating wounds
o Indication for TT: hemothorax vs PTX
o Presence of pulmonary contusion, abdominal injury, or need for immediate abdominal surgery
* Significantly increased risk of complication related to:
o Polytrauma (RR 2.7, p<0.05)
o Need for assisted ventilation (RR 2.7, p<.003)
o TT by non-thoracic surgeons (RR 8.7, p<.0001 for blunt trauma and RR 12.5%, p<.0001 for penetrating trauma)

Thoracic Empyema
* Causes of post-traumatic empyema:
o Iatrogenic infection during TT
o Direct infection from penetrating injury
o Secondary infection from associated intra-abdominal injuries w/ diaphragmatic disruption or hematogenous or lymphatic spread to pleural space
o Secondary infection of undrained hemothoraces
o Parapneumonic empyema resulting from posttraumatic pneumonia, contusion, or ARDS

Thoracic Empyema
* Empyema occurred in 1.8% (Louisville study) and 2.3% (University Hospital study) of patients undergoing TT
* No difference in rate of empyema related to setting or operator
* No difference in rate of empyema related to administration of antibiotics within 24 hours of initial TT in Louisville study (2% vs 2%)


‘Prophylactic’ Antibiotics in TT: EAST Guidelines
* Does ‘prophylactic’ antibiotic use in injured patients requiring TT reduce the incidence of empyema and/or pneumonia?
* Paucity of literature, especially well-designed multi-institutional double-blinded trials that control for setting, operator, mechanism of injury, timing of antibiotic administration, choice and dose of antibiotic, and duration of prophylaxis

‘Prophylactic’ Antibiotics in TT: EAST Guidelines
* Luchette FA, Barrie PS, Oswanski MF, Spain DA, Mullins CD, Palumbo F, Pasquale MD. Practice Management Guidelines for Prophylactic Antibiotic Use in Tube Thoracostomy for Traumatic Hemopneumothorax: the EAST Practice Management Guidelines Work Group. J Trauma. 2000; 48(4):753-7.
o MEDLINE search (1977-1997) for references using query words: antibiotic prophylaxis, chest tubes, human, drainage, tube thoracostomy, infection, empyema, and bacterial infection-prevention and control.
o 11 articles reviewed: 9 prospective series, 2 meta-analyses

Prophylactic’ Antibiotics in TT: EAST Guidelines
* Articles classified by Agency for Health Care Policy and Research (AHCPR) methodology
o Class I: prospective, randomized, double-blinded, controlled trials
o Class II: prospective, randomized, non-blinded trial
o Class III: retrospective series of patients or meta-analysis
* Four class I articles, five class II, and two class III meta-analyses

Prophylactic’ Antibiotics in TT: Conclusions and Recommendations
* Incidence of empyema in placebo groups ranged from 0-18%, compared to 0-2.6% in antibiotic groups
* Two class I studies saw a reduced incidence of empyema w/ antibiotic Rx (Cant, 1993; Grover, 1977)
* Two class II studies saw no benefit w/ antibiotics (Mandal, 1985; Demetriades, 1991)
* Other studies didn’t control for MOI
* Insufficient evidence to support prophylactic antibiotics as a standard of care for reducing incidence of empyema or PNA in patients requiring TT

Prophylactic Antibiotics in TT: Conclusions and Recommendations
* Extreme variability in choice of antibiotic, dosing, and duration of therapy among studies
* One class I study reported no empyema in patients receiving cefazolin for 24hrs compared to 5% incidence in placebo group (Cant et al, 1993)
* Administration of antibiotics for >24hrs did not significantly reduce risk of empyema compared with shorter duration (Demetriades, 1991)

Prophylactic’ Antibiotics in TT: Conclusions and Recommendations

* Incidence of pneumonia in placebo groups ranged from 2.5-35.1%, compared to 0-12% in antibiotic groups
* In most reports, significant reduction in pneumonitis seen in patients receiving prolonged antibiotics (but also see increased cost and length of hospital stay)
* Presumptive, rather than prophylactic therapy, in setting of acute trauma

‘Prophylactic’ Antibiotics in TT: Conclusions and Recommendations

* Recommendations (for isolated chest trauma)
o Level I: insufficient data to support level I recommendation as standard of care
o Level II: insufficient data to suggest prophylactic antibiotics reduce incidence of empyema
o Level III: sufficient class I and II data to recommended prophylactic antibiotic use in patients receiving TT after chest trauma. A first generation cephalosporin should be used for no longer than 24hrs. There may be a reduction in incidence of PNA, but not empyema.


Recommendations
* Additional training of all trauma physicians
* Early thoracotomy or VATS in settings of persistent fluid collection or multiple chest tube placements as means to prevent against development of empyema
* First generation cephalosporin for no more than 24 hours
* Further research!

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Tools of Prenatal Diagnosis

Tools of Prenatal Diagnosis
By:Julie Moldenhauer, MD
Reproductive Genetics
Maternal Fetal Medicine
Obstetrics and Gynecology

Objectives:
* Discuss various prenatal screening and testing tools
* Discuss the timing of the various tools in gestation
* Discuss benefits and risks of various options
* Review the difference between screening and testing
Baseline Risk for Birth Defects in the General Population is 3-5%
What Can We Diagnose in the Prenatal Setting?
* Structural Abnormalities
o Congenital heart disease
o Spina bifida
o Gastroschisis
* Chromosomal Abnormalities
o Trisomy 21
o Triploidy
* Infections
o Parvovirus
o Cytomegalovirus
o Toxoplasmosis
* Growth Abnormalities
* Hematologic Abnormalities
o Anemia
o Thrombocytopenia
* Functional Defects
o Arthrogryposis
o Renal dysfunction
* Syndromes
o Skeletal Dysplasia
o Diabetic embryopathy

Prenatal Diagnosis Tools

* History
o Personal History
o Family History
* Population Screening
* Serum Screening
* Ultrasound
* Fetal MRI
* Invasive Diagnosis
o Chorionic villus sampling
o Amniocentesis

History is a Screening Tool!
o Maternal Age
+ > 35 years at delivery
o Obstetric History
+ Prior baby born with Down syndrome
+ Prior stillbirth
o Medical History
+ Is mom diabetic? How well controlled is her sugar?
+ Does she have PKU?
+ Is she hypertensive?
o Medication Exposures
+ What medications?
+ When was the exposure?
o Environmental Exposures
+ Does she work in a preschool and was exposed to parvovirus?
+ Is she exposed to high doses of radiation?
o Family History
+ Brother with hemophilia
+ Uncle with cystic fibrosis
+ Ethnic background
+ Consanguinity

As maternal age increases, the risk for aneuploidy increases. This is due to maternal meiotic nondisjunction.
Maternal age > 35 at the time of delivery is considered “Advanced Maternal Age” or AMA
The risk for recurrence of chromosome abnormalities is dependent upon the genetic mechanism involved.
Trisomy: 1% or maternal age-related risk
Translocation:
Maternal carrier: 10-15%
Paternal carrier: 2%

Down syndrome phenotype caused by trisomy 21
Down syndrome phenotype caused by 14;21 translocation

Maternal Diabetes: Reproductive Risks
* Fetal and Neonatal
o Congenital anomalies: 6-12%
o Intrauterine fetal demise
o Macrosomia – Shoulder dystocia
o Growth restriction
o Hyperbilirubinemia
o Hypoglycemia
o RDS
o Polycythemia
o Organomegaly
o Long term – obesity and carbohydrate intolerance
* Obstetric
o Spontaneous preterm labor
o Polyhydramnios
o Preeclampsia (15-20%)
o Intrauterine growth restriction
o Shoulder dystocia
o Cesarean delivery

Caudal Regression Syndrome
Teratogen Exposure
Fetal growth
Organogenesis complete
Eyes, heart, lower limbs
Axial skeleton, limb buds, musculature
CNS
None, “ALL or NONE”
* Examples:
* Accutane
* ACE inhibitors
* Lithium
* Antiepileptic drugs (AEDs)
* Anticoagulants: warfarin
* Antidepressants
* Methotrexate
* Thalidomide

Teratogen Exposure
* Fetal effects are timing and dose dependent

* Each medication is assigned a pregnancy category based on available data; A-D, X
* www.Reprotox.org
* www.otispregnancy.org

Ultrasound images of fetal hydrops – abnormal collection of fluid in multiple body compartments.
Mom works at a daycare where there was a Parvovirus B19 or Fifth Disease outbreak 4 weeks ago. Parvovirus causes fetal aplastic anemia that can be life-threatening.

Suspicion of diagnosis by altered maternal serum titers of Parvo IgG and IgM and confirmed by amniotic fluid PCR for Parvo.
Confirmed Parvo infection in a fetus with hydrops can be treated with intrauterine blood transfusions.

Fetal Ultrasound Showing Cardiac Rhabdomyoma
Fetal MRI Showing Tubers
Prenatal Findings Consistent with Tuberous Sclerosis Confirmed as Neonate
Screening for Genetic Disease
Ethnic Group Disease
African American Sickle Cell Disease: 1/12
Mediterranean Beta-Thalassemia: 1/30
Southeast Asian Alpha-Thalassemia: 1/20
Caucasian Cystic Fibrosis: 1/25

ASHKENAZI JEWISH ANCESTRY
GENETIC CARRIER TESTING
Gaucher’s disease
Bloom syndrome
Mucolipidosis IV
Niemann-Pick disease type A
Fanconi Anemia Group C
Familial Dysautonomia
Cystic Fibrosis
Canavan disease
Tay-Sachs disease
Detection rate
Carrier Frequency
Disease Incidence
Testing and screening options should be made available to all pregnant women
Prenatal Screening & Testing
When Screening
(risk estimate)
Definitive
(Invasive)
First Trimester
FIRST screen*
Ultrasound
CVS

Second Trimester
Maternal Serum Screen*
Ultrasound
Amnio
Cordo
*First and Second Trimester Integrated and Sequential Screening

Test Performance
* Detection rate – the percentage of affected that are test “positive”
o (the higher, the better)
* False positive rate – the percentage of unaffected that are test “positive”
o (the lower, the better)

Goals in Prenatal Screening:
* High sensitivity - low false positive rate
* Wide availability
* Reproducibility and accuracy
o Human error, testing conditions

First Trimester Screening
o 11-13 6/7 weeks (CRL 39-79 mm)
o Maternal serum sample for PAPP-A and Free b-HCG
o Ultrasound for Nuchal translucency
o Detection Rates:
+ 80% for Trisomy 21
+ 90% for Trisomy 18
+ Does not screen for NTDs

PAPP-A
b-HCG
T21
T18

Increased NT vs Cystic Hygroma
* Increased NT > 95th%
o With or without septations
* Structural defects
o Heart defects most common
* Syndromic associations
* Chromosomal defects
o Exponential increase with increased NT
o 50% Down syndrome
o 25% Trisomy 13 or 18
o 10% Turner Syndrome
o 5% Triploidy
o 10% other

NT > 3 mm is ABNORMAL
Second Trimester Serum Screening: Chromosome Abnormalities

* Maternal Serum Screening
o 15-20 weeks
o Triple screen: 60% for T21
o Quad screen: 70% for T21
o Gestational Age Dependent**
* Targeted Ultrasound
o 50% aneuploid fetuses will have ultrasound markers
AGE +AFP +hCG +uE3 +InhA
DR at 5% FPR
2nd trimester
single double triple quadruple
Serum Screening Test Performance at a fixed 5% False Positive Rate (Dating by Ultrasound)

Prediction
SURUSS
FASTER
Second Trimester Serum Screening: Neural Tube Defects
* Neural Tube Defects
o Spina Bifida
o Anencephaly
* AFP increased in “open” defects
* Sensitivity
o 90% anencephaly
o 80-85% open spina bifida
* False positive – 3-4%
Interpreting a Quadruple Screen

Bottom Line: AFP is increased with NTDs and decreased with chromosome abnormalities

Elevated MSAFP
* Incorrect Dates – most common reason
* Multiples
* Congenital Nephrosis
* Ventral Wall Defects
* IUFD
* Adverse Pregnancy Outcomes
o Stillbirth
o Placental abruption
o Preterm labor
o Oligohydramnios
o IUGR

Ultrasound detection of aneuploidy
Nuchal Fold
CPC
Duodenal atresia
Pyelectasis
Clinodactyly
Second trimester sonographic markers of Down syndrome
AV Canal
Trisomy 18
Edward Syndrome
* Close to 90% detected by prenatal scan
* US:
o Growth restriction
o Clenched fists
o >90% with cardiac defects
o Multiple malformations
* Grim prognosis
o 50% Stillbirth
o 50% die within the first week
o 5-10% survive the first year

Trisomy 13
Patau Syndrome
Fetal Anatomy by Ultrasound
Ventral Wall Defect
Gastroschisis
NTDs
Lemon Sign
Banana Sign
Meningomyelocele Sac
Meningomyelocele Sac on Newborn
PGD: Preimplantation Genetic Diagosis
Pearls for Invasive Testing
* Risk for Sensitization
o Mom Rh negative – Rhogam
o Other antibodies may increase risk
* Risk for Infection transmission
o Hepatitis B
o Hepatitis C
o HIV
o Need to know familial mutations prior to performing invasive testing

Chorionic Villus Sampling
* Performed 10-14 weeks
* Does not test for ONTD
* Technique – “Placental biopsy”
o Transabdominal
o Transcervical
* Risk for limb reduction defects if performed < 9 weeks
* Loss rate 1/100-1/200
* Risk for mosaicism (~1%)

Transcervical
CVS
Transabdominal
Performed at 10-14 weeks
Amniocentesis
* > 15 weeks
* Loss rate 1/200 (probably closer to 1/300-1/500)
* Tests for ONTD
* Technique
o Fine gauge needle
o Ultrasound guidance
o Aspiration of 20-30 cc of fluid

PERFORMED ROUTINELY 15-20 WEEKS
Ultrasound Guided Procedure
AMNIOCENTESIS
Cordocentesis
* Percutaneous Umbilical Blood Sampling
* Loss rate 1/100-1/200
* Typically done after 18 weeks
* Ability for:
o Rapid karyotype
o Blood/platelet counts
o Direct fetal injections/transfusions

Fetal Blood Sampling
“PUBS”
Conclusions

* Many options for screening and testing.
* Prenatal screening should provide the most effective test to the greatest number of women.
* The best method of screening is yet to be determined.
* Patient preference should be considered.
* Testing and screening should be available to all women.

Tools of Prenatal Diagnosis.ppt

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Menopause

Menopause
Division of Urogynecology and Reconstructive Pelvic Surgery
Department of OB/GYN

Epidemiology
* Average age is 51.4 years
* 95% confidence interval of Bell Curve gives a range of 45-55 years. Less than 2% occur before age 40.
* Factors associated with early menopause
o Cigarette smoking (1.5 yrs earlier)
o History of short intermenstrual interval
o Family history
o Chemo / Radiation / Genetic factors
* Unrelated to number of prior ovulations, pregnancies, use of OCPs, height, weight, age at menarche, race, class or education

Elderly Population
* In 2000, life expectancy:
o Women 79.7 years
o Men 72.9 years
* Once you reach 65:
o Women expect to live until 84.3 years old
o Men expect to live until 80.5 years old
* Therefore, more than 1/4 of a woman’s life is spent in menopause

Peri-menopause
* Peri-menopause
o Transitional period
+ Hallmark is menstrual irregularities
# Shortened cycle length
# Skipped cycles
# 10% of women will have abrupt cessation of menses
+ Median length of 4-5 years
o Median age of onset is 47.5 years

Physiology
General feature is depletion of follicles with loss of granulosa and thecal cell function
* 6-7 million oocytes at 20 weeks fetal age
* 1 million oocytes at birth drop to 400,000 at puberty
* 300-400 ovulatory events over lifetime
* Accelerated follicular loss 2-8 yrs before menopause

Physiology
* Granulosa cells produce less inhibin, which provides negative feedback for FSH secretion by the pituitary gland.
* Increase in FSH levels
* After menopause, LH levels are also elevated.
* Would you check a FSH or LH level to diagnose menopause?

Symptoms
* Menstrual irregularities is the primary reason women seek medical attention
* Cycles shorten as increased FSH triggers early ovulation
* Skipped cycles due to anovulation
* Long periods of anovulation can lead to excessive estrogen states and irregular, unexpected menses
* Do you think the perimenopausal women can get pregnant?
o YES
o Guinness World Record = 57 yrs & 120 days
o So, remember to recommend contraception. Low does oral contraceptives may be used in women without contraindications (i.e. smoking).
* Hot Flushes
o Subjective feeling of intense heat followed by skin flushing and diaphoresis.
o Sudden dilation of peripheral vasculature secondary to abrupt estrogen withdrawal. Skin temperature increases and core temperature drops.
o Usually, occurs for a few seconds to minutes.
o Duration is about 1-2 years. 25% for > 5 years.
* Genitourinary atrophy
o A variety of symptoms
o Atrophic vaginitis, urethritis, recurrent UTIs, dyspareunia
o Pelvic organ prolapse is NOT caused by estrogen deficiency
* Urinary Incontinence
o Atrophy of estrogen-dependant tissues such as the urethra may contribute to existing causes for urinary incontinence
o Typically addressed with local application of estrogen cream
* Sexual Disturbances
o Decreased interest in sexual activity
+ May be related to decreased testosterone levels
+ May be related to psychosocial stressors
o Anatomic changes secondary to estrogen deficiency
+ Atrophy of vaginal mucosa and lower urethra
+ Thinning of vaginal mucosa with decreased lubrication and elasticity, leading to dyspareunia
* Sleep Disturbances
o Estrogen appears related to producing restful, deep-stage sleep
o Hot flushes more common at night
+ Wakening or disruption of deep-stage sleep
+ Contributes to feeling of overall fatigue
* Mood Swings / Irritability / Depression
o NOT associated with menopausal hormone changes alone
o Stage of life associated with multiple changes (e.g., children leaving home, parents aging, retirement)
o Hot flushes and fatigue can lead to emotional lability
* Cognitive Function
o Some types of memory and brain function may be influenced by estrogen
o Some evidence suggests that Alzheimer’s disease is less frequent in estrogen users and the effect was greater with increasing dose and duration of use.

Adverse Health Effects
* Cardiovascular Disease
o Leading cause of death in US women (f/b malignancies, cerebrovascular disease and MVAs)
o Death rate for CV disease is 3X the rate for breast cancer and lung cancer.
o Changes in lipid profile in menopause
+ Increased LDL
+ Decreased HDL
+ ? Decrease in triglycerides
* Osteoporosis
o Spinal bone density peaks at 20 years, while cortical bone density peaks in late 20s
o Rate of loss of 0.5%/year prior to age 40, then anywhere from 2-9%/year for first 10-15 years after menopause
o Primary loss is trabecular bone, leading to compression fractures, loss of height, kyphosis
o Osteopenia = BMD between -1 and -2.5 SD of a young, white adult woman.
o Osteoporosis = BMD -2.5 or greater SD
o 25-50% of women will have spinal compression fractures by age 70
o 20% of Caucasian women age 80 will have hip fractures, with 15-20% mortality.
o Annual incidence is 1.3% after age 65
o High risk:
+ Caucasian, Asian
+ Thin, inactive, smokers
+ High caffeine/alcohol intake, low dietary calcium, high dietary protein and phosphates
+ H/o oligomenorrhea, excessive exercise, eating disorder
+ Medical conditions – hyperthyroid, cancer, myeloproliferative disorders
o Low Risk:
+ African American
+ Obese, active
o Protection:
+ Ca supplements (1200mg, 1500mg)
+ Weight-bearing exercise
+ HRT: estrogen increases
# Intestinal calcium absorption
# Renal conservation of calcium
# Increases 1,25-dihydroxyvitamin D (active form)
+ Vitamin D (400-800IU)

Hormone Replacement
* Types of hormone replacement
o Estrogen alone (for women without a uterus)
o Estrogen and progesterone
+ Sequential
+ Continuous
o Local estrogen
o SERM’s (Selective Estrogen Receptor Modulators)

HRT - Advantages
1. Relief of vasomotor symptoms
+ HRT is effective in reduces the number of hot flashes
+ 6-8 weeks to see maximal effect
+ Combination HRT (0.625mg estrogen/2.5mg MPA)
+ What about lower doses of HRT?
# For combination HRT, all doses resulted in similar relief of symptoms
# For estrogen alone, most relief with higher doses
2. Vaginal atrophy

# Menopause thins the vaginal epithelium and increases the vaginal pH (> 6.0).
# Estrogen decreases the vaginal pH, thickens the vaginal epithelium and reverses vaginal atrophy.
# Less atrophic changes with higher doses of HRT
3. Bone protection

+ Reduction of bone loss
+ Prevents OP-related hip fractures
+ Protects the spine and the small bones
+ WHI: 5 fewer hip fractures per 10,000 person-yrs
4. Colon cancer

o Some observational studies have suggested a reduced risk.
o WHI: 6 fewer cases / 10,000 person-yrs
1. Endometrial cancer
+ 8-10 fold increased risk with unopposed estrogen.
+ PEPI: unopposed estrogen x 3 yrs = 24% with atypical hyperplasia (vs 1% women on placebo)
+ Risk is increased with:
# Increased duration and dose
# Continuous versus cyclic therapy
# Absence of a progestin
2. Breast cancer

o Meta-analysis of 51 case-controlled & cohort studies showed no increased risk with short-term use.
o After 5 years of use, risk increased by 35%.
o WHI: 8 more invasive cases / 10,000 person-yrs
o Women diagnosed with breast cancer while using HRT have been shown to have better survival

HRT - Disadvantages

3. Thromboembolic disease

o Increases risk for DVT 2 – 3.5 fold
o Strokes: 8 more / 10,000 person-yrs
o PEs: 8 more / 10,000 person-yrs

HRT - Disadvantages

4. Cardiovascular disease:

o Traditionally, HRT was thought to provide protection against coronary heart disease (CHD)
o Observational studies found lower rates of CHD in postmenopausal women on HRT.
o The consensus was that CHD was about 35-50% lower in women using HRT.
o Many studies showed that HRT improved lipid profiles.

HRT - Disadvantages

4. Cardiovascular disease:

o What about secondary prevention? i.e. women who have a h/o coronary heart disease, does HRT help?
o Heart and Estrogen/Progestin Replacement Study (HERS) was a RCT, double-blinded study of 2,763 PM women with intact uteri and a h/o CHD
o 52% higher rate of major coronary events in the 1st year
o Then there was a reduction in the risk with longer use – i.e. 33% lower risk in the 4th and 5th years
o What about primary prevention? i.e. in healthy women, does HRT prevent CHD?
o Women’s Health Initiative (WHI)
o RCT of 16,608 postmenopausal women aged 50-79 years old with an intact uterus
o 40 different US centers
o Combination HRT – 0.625mg CEE and MPA 2.5mg vs placebo

Cardiovascular disease (WHI):
o 7 more CHD events
o 8 more strokes
o 8 more PEs
o 8 more invasive cancers
o Study stopped after 5.2 yrs (planned 8.5yrs) because of cases of breast cancer

SERMs
* Selective estrogen receptor modulators
* Work as agonists and antagonists depending on the tissue
* Raloxifene and tamoxifen

Estrogen Raloxifene Tamoxifen

Prevent OP
Risk Breast
Cancer
Hot Flashes
Endometrial
Cancer
Venous
Thrombosis
SERMs
* Overall, SERMs can help to prevent OP and breast cancer
* However, they aggravate hot flashes, the most common indication for estrogen therapy.
* Also, tamoxifen stimulates the endometrium.

Alternative Medicine
* Limited studies with relatively short duration of therapy and follow-up.
* Soy and isoflavones may be helpful in the short-term (< 2 yrs) for vasomotor sx and may protect against osteoporosis.
* 35-75mg qd isoflavones / day
* Black cohosh may be helpful in the short-term (< 6 mos) for vasomotor symptoms.

Summary
* Health Risks
o Osteoporosis
o Lipid abnormalities
o Cardiovascular disease
o Cancer
* Menopause is the natural course aging of the female reproductive system, driven by loss of oocytes
* Symptoms of menopause include:
o Menstrual irregularities
o Hot flushes
o Sleep disturbances
o Mood changes
o Sexual disturbances
o Urinary incontinence
o Cognitive function
o Hair growth

Hormone Replacement
Benefits
Detriments

* Vasomotor sx
* Vaginal atrophy
* Osteoporosis
* Colon cancer
* Endometrial ca
* Breast ca
* VTE
* CHD

Abnormal Bleeding
* A 44-year old woman presents for evaluation of abnormal menstrual bleeding. Her periods have been regular in the past but for the last 6 months she has had a period every 35-56 days, lasting 7-9 days. The bleeding is heavier than usual and she feels tired all the time. She has gained 15 lbs over the last 2 years, which she believes is due to lack of exercise and increased eating/sleeping. She complains that her skin is dry. Exam is unremarkable. What would your recommend next?
o Check pregnancy test
o Discuss exercise / eating patterns
o Check TSH, PRL
o Consider endometrial biopsy
o Expectant management versus hormonal management

Health Maintenance
* 58 year old postmenopausal woman referred to you by a friend. She has no known medical problems and is on no medications. Her social history is remarkable for an 80-pack/year history of tobacco use. Her physical exam is unremarkable. What are the important health maintenance aspects of the exam to focus on?
o Blood pressure
o Pelvic exam
o Breast exam / mammography
o Fecal occult blood
o Smoking cessation
o Flu shot
o Osteoporosis

Abnormal Bleeding
* A 47 year old woman, G2P2, presents with menstrual cycles varying in length from 20 to 40 days. Until 9 months ago she had regular 28 day cycles. She reports frequent hot flushes. She recently resumed sexual activity and uses no contraception, but she does not desire pregnancy. She does not smoke and has no other medical problems. Her physical exam is unremarkable. What are her options for cycle control?
o Low dose combination oral contraceptive
o Continuous low dose estrogen and progestin menopause regimen
o Cyclic progestin therapy for 12 days a month
o Continuous low dose estrogen (0.625mg conj EE)
o Estradiol vaginal ring

Osteoporosis

* A menopausal patient with osteoporosis has been reading information on the Internet about different treatment modalities for osteoporosis. She wishes to know more about what therapies are actually available and how they work?
o Estrogen: Reduces osteoclast activity
o SERMs: Reduces osteoclast activity
o Bisphosphonates: Reduces osteoclast activity
+ Take on empty stomach, first thing in AM with 8oz water and no food for 30 minutes
+ Take sitting up due to esophagitis risk
+ Calcium supplementation within 4 hours
o Calcium / Vitamin D supplements

Menopause.ppt

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