Transcript Women’s Health Issues—From Womb to Tomb

Women’s Health Issues—
From Womb to Tomb
Barb Bancroft, RN, MSN
www.barbbancroft.com
Myth #1
• Diamond’s are a girl’s best friend.
• Bling.
• Wrong, estrogen is.
Think about it.
• Estrogen has over 300 functions.
• Where should I start? Brain? Heart? Bones?
Skin? Bladder? Vagina? Teeth?
• Since we lose our ovaries at 51.3 +/- 2.7 and will
be living another 30+ years, why would anyone
consider living without a hormone that has
OVER 300 functions? (a few exceptions, of
course)
• If men lost their testicles at 51.3 +/- 2.7 years,
would they be willing to live another 25.4 years
without testosterone?
Let’s start at the very beginning
with Myth #2…
• The sperm is the aggressor
• The egg is the “damsel in distress”
• WRONG. The egg is 1,000x bigger than
the sperm
“Which way do we go, George?”
• The sperm waits for a signal from the egg
to swim up the 5” Fallopian tube (Dr.
Gabriel Fallopius)
• calcium channel blockers
A major reproductive
difference…
• Women get all the eggs they are ever
going to have prior to birth
(not exactly, but almost--)
• However, our ovaries die at 51.3 +-2.7
years
HOW MANY EGGS/FOLLICLES
DO WE GET?
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At 6 months gestation ________________
At birth _____________
At age 30 ___________
At age 50 __
The age of an egg is YOUR age!
Could you possibly get pregnant at 50?
How do eggs meet their demise? Apoptosis and
primary ovarian failure—as the follicles drop out,
the FSH rises—trying to stimulate the ovary to
produce more eggs…rising FSH levels signal
impending doom of the ovary
Do guys get all the sperm they’re
going to get at birth?
• Nooooooooooo…
• Men produce sperm PRN until the day
they die
• Sperm is only 75-90 days old
• However, there are some interesting
differences…
• The sperm of a 20-year-old vs. the sperm of an
80-year-old
• Swimming prowess
• The germ cells that make the sperm and DNA
mutations
• Older fathers and mental illness
• Boys and ADHD, Tourette’s, Autistic spectrum
disorders
Multiple births are increasing—
why?
• Ovary has quantity control prior to age 35ish
• Only allows 1 egg to mature
• After 35-ish…
• Loss of quantity control—3 eggs, 5 eggs, 7
eggs
Gender advantage prenatally
• Male embryos outnumber female embryos
by 115 to 100
• Why? Faster swimmers…
• The sperm carrying the Y chromosome is
23% lighter than the sperm carrying the X
chromosome
• This is when..
What’s going on in the womb once
the sperm meets the egg?
• The embryo has female and male tissues until
the 8th week of gestation
• The Y chromosome kicks in (Sry region)
• Produces testosterone
• Maternal androgens cross the placenta and give
another “hit” in the male embryo—so boys get 2
“hits” of testosterone
• Female embryo receives one “hit” from maternal
androgens; her ovaries don’t “kick” in until
puberty
Testosterone and the Limbic
system
• Boys and the limbic system--Fight-Flight
response—aggression and assertiveness;
limbic area of sexual function is twice as
large in men as it is in women; Teenage
boys think about sex every 52 seconds
• Girls and the communication areas of the
brain—verbal areas are larger; women on
average, talk and listen a lot more than
men
Testosterone and the Limbic
system
• Testosterone and aromatase—the enzyme
located in the basal forebrain that converts
testosterone to estrogen; estrogen is
necessary for memory storage and
learning new tasks in the adult
• Is testosterone the forgotten hormone in
women?
Alzheimer’s disease and women
• Increased risk?
• Estrogen depletion?
• Testosterone depletion? Since men continue to
make testosterone throughout life does this
affect their AD risk?
• Drugs that antagonize estrogen may contribute
to temporary cognitive decline
• Tamoxifen (Nolvadex) and aromatase inhibitors
cognitive dysfunction (“chemo brain”)
Puberty—hormones from hell
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Migraines
Prior to puberty boys > girls
As adolescence approaches > females
15-18 3x greater in females
Adult prevalence is 2.1%-14.9% in males; 6.3%25.4% in females
• Family history
• Celiac disease? Gluten allergy?
• New study looking at memantine (Namenda) for migraines
Memantine (Namenda)
and migraines
• Females have a lower threshold for a
phenomenon called cortical spreading
depression (CSD)—bursts of intense electrical
activity across the cortex resulting in migraines
• Memantine (Namenda) blocks CSD
• Clinical trial reported in the September 2007
issue of the Journal of Headache Pain found the
more than 50% of the patients reported that their
headaches were half as frequent and of much
less severity (Charles A, Brennan K, et al.)
Estrogen and migraines
• During low estrogen states such as menses (the sudden
drop of estrogen triggers migraines)
• Or the placebo week of oral contraceptives, serotonin
levels decrease and the headaches occur
• (Lybrel (Wyeth)—first FDA-approved low-dose
combination oral contraceptive taken 365 days per year)
• How about using an estrogen patch 7 days prior to
menses, or OC without the placebo week?
• During high estrogen states, ie, pregnancy, serotonin
rises and headaches decrease
Depression
• Prior to puberty boys and girls have equal rates
of depression
• Increased incidence of classic depression
emerges between 15-18 in teenage girls
• Boys may present differently—eg, substance
abuse
• EATING TO TREAT OUR DEPRESSION…
Carbohydrates and chocolate boost
serotonin…
• In addition to increasing serotonin in the
brain, chocolates contain anandamide—a
substance that closely resembles
marijuana (“ananda” in Sanskrit means
“bliss”…
• Bliss is a 1 lb bag of M & M’s…
• Marijuana and the “munchies”
Low carb diets..ineffective in women;
dieters feel psychologically hungry
• Another problem w/ low carb diets—low
folate levels (higher risk of neural tube
defects) ( MMWR January 2007)
• Not to mention the halitosis, depression,
and constipation
Digression on depression
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Genetic influences
Nature vs. nurture?
Area of joy?
Mirror neurons
Treating depression during pregnancy and
postpartum
Depression in women of any age
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ASK ABOUT IT AND TREAT IT!
SALSA for diagnosis in young women
Say NO to St. John’s wort
SSRIs are the drugs of choice
SSRIs boost serotonin (makes you happy)
but can also decrease dopamine
• And libido takes a nosedive
What can you do?
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Change antidepressants
Bupropion (Wellbutrin)
Use a shorter acting SSRI
Add testosterone
Other hormonal changes during
adolescence increase the risk for:
• Autoimmune diseases
• Endometriosis (Endometriosis and autoimmune
disease (7x more likely to have Hashimoto’s;
higher risk for MS, RA, lupus, SS, CFS (100x),
Fibromyalgia (2x) (Human Reproduction 2002)
• Redheads and autoimmune disease and
endometriosis
• Hashimoto’s thyroiditis, celiac disease may also
accompany adolescents with Type 1 diabetes
Adolescents and polycystic ovary
disease (PCOS)
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Anovulation
Hirsutism
Metabolic syndrome
Many young women present to fertility
clinics
• Treatment? OCs, metformin
• Word to the wise about metformin—jump
starts ovulation, so if you’re NOT in the
mood to get pregnant, protect yourself!
STDs in teenagers
• March, 2008 National STD Prevention
Conference in Chicago
• 26% of teens (ages 14-19) tested positive
• Among teens who reported ever having sex
(oral, vaginal, anal); 40% tested + for at least 1
STD—HPV in 30%, Chlamydia in 7%
• AA—48%; Caucasian 20%; Mexican American
20%
• 20% with one lifetime partner
• 55% prevalence with 3 partners
The HPV vaccine in young women
• Gardasil to prevent cervical cancer (HPV 16, 18)
and genital warts (HPV-6 and11)
• By the way there are over 100 types of HPV, 30
of which invade mucus membranes
• Vaccinate girls between 9 and 26
• Is it 100% effective? HPV naïve, yes; already +
HPV with above types? Not effective…
Can Gardasil prevent other cancers
caused by HPV?
• Squamous cell carcinoma of the rectum
• Squamous cell carcinoma of the vagina
• Squamous cell carcinoma of the mouth
and throat
• When will boys get the HPV vaccine?
Before we leave the topic of
STDs…
• Forget teenagers for a moment…
• The fastest rising group for STDs in U.S. is
the over 60 crowd
• HPV, HSV, HIV, GC, Syphilis
• Why?
The Pfizer Riser
• Viagra, Levitra,Cialis
• Swingin’ singles, no pregnancy risks, who cares
what the neighbors think??
• Increased UTIs
• Increased STDs
• Increased marital bliss in some; marital
nighmares in others
• If you are “peri-menopausal, you might need…
Oral contraceptives
• Perimenopausal women and oral
contraceptives…can help smooth the ride
of the ovarian roller coaster during
perimenopause
• Teenagers and young adult
women…what’s old and what’s new in the
world of oral contraceptives?
Oral contraceptives…
• “It take many nail to build crib…only one
screw to fill it…”
• What is the best way to prevent
pregnancy?
OCs
• First oral contraceptive? 1960--Enovid
• Old OCs (80 to 100 mcg per pill) vs.
today’s OCs (20-35 mcg per pill)…
• Old days? SE were MIs and
Strokes…miss a pill? No big deal
• Today’s pills? Miss a pill AND…
The good news: extended-cycle
OCs
• Lybrel (Wyeth)—first FDA-approved low-dose
combination oral contraceptive taken 365 days
per year—no placebo, no pill-free
interval…yeah! Reduce the risk of a “mistake”…
• Contains 20 mcg of ethinyl estradiol/0.09 mg of
levonorgestrel
• Most oral contraceptives are packaged as a 21/7
cycle (21 days of active tablets and 7 days of
placebo) resulting in 13 withdrawal bleeding
episodes per year
Extended-Cycle Contraceptives
• Yaz—taken for 24 days followed by 4 days
of inert tablets (3 mg of drospirenone + 20
mcg ethinyl estradiol)—the drospirenone is
a testosterone blocker as well (acne)—use
for PCOS
• Loestrin 24—24 days on, 4 days inert; 1
mg norethindrone acetate + 20 mcg ethinyl
estradiol
Extended-length oral
contraceptives
• Seasonique—91 day cycle; 84 tablets of
0.15 mg levonorgestrel + 30 mcg ethinyl
estradiol; 7 tablets of 10 mcg ethinyl
estradiol – only 4 withdrawal bleeds per
year
• Seasonale—same as above with 7 inert
tablets
SJW and OCs
• Reduces the effectiveness of OCs…
• Adverse effect? Pregnancy and?
• Certain anticonvulsants can also reduce
the effectiveness of OCs
What are the benefits of OCs?
Besides the obvious?
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Reduce the risk of ovarian cancer
Treating dysmenorrhea
Treating endometriosis
Treating PCOS
Treating acne
Reducing estrogen deficiency symptoms in
perimenopausal females
• Continuous and extended cycle OCs may improve
mood, reduce headaches and increase quality of life…
• Long term effects of continuous regimens? Not
known…fertility? Thromboembolism?
Teenagers and smoking
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Weight maintenance
Anti-depressant?
Smoking and OCs—increased risk of clotting
Long-term problems?
Heart disease
PAD
Lung Cancer
Accelerated aging
Early onset of menopause
Let’s move into perimenopause…
• Transitional state from reproductive years to
postmenopausal years—length is variable--3 to 10 years
• Ovary is on a roller-coaster ride
• Variable menstrual cycles (greater than 7 days, different
from normal)
• FSH is rising
• Late perimenopause—greater than 2 skipped cycles and
an interval of amenorrhea (greater than 60 days)—
vasomotor symptoms begin
• Final menstrual period (hallelujah!)—no periods for a
year
• Welcome to your postmenopausal years
Postmenopause
• FSH continues to rise
• Early postmenopause lasts about 4 years and
vasomotor symptoms continue
• This is the time to consider hormone
replacement therapy
• So, let’s talk about one of the most controversial
subjects in the world of women’s health…
• The dreaded Women’s Health Initiative of 2002
The WHI
• Researchers followed nearly 17,000 women
taking specific combinations of hormones
(estrogen and progesterone in the form of
PREMPRO)
• Findings: small increase in BC, small increase in
strokes, pulmonary embolism and coronary
heart disease—absolute risks were small and
clinically INsignificant
• What didn’t they tell us? That this study only
applied to women who were at least 12 years
postmenopausal (mean age=63)
Panic ensued…
• Warning letters were sent to study subjects and
the trial was abruptly shut down
• MDs called their patients and told them to stop
their HT
• Women flushed their HT down the toilets
• By 2006 only six million prescriptions were
written for HT, vs. 16 million in 2001.
• Gloom and doom prevailed…
Summary of WHI—combination E
and P
• Per 10,000 women per year on E + P
Absolute risks: 7 more women with CHD, 8
with stroke, 8 with PE, 8 with BC
Benefits: 6 fewer with colorectal cancer, 5
fewer with hip fractures
Net effect: 19 to 20 extra adverse events;
no extra mortality per 10,000 women
Summary of WHI—estrogen only
• 10,000 women per year on estrogen (ET) alone
Benefit: Among the women 50 to 59: 16 ET
users developed CHD vs 29 in the placebo
group; 35 placebo users developed BC vs. 25 in
the ET group
Risk: small rise in stroke but this increase was
less in women less than 70
Bottom line: AGE strongly affects outcomes;
women in their 70s had similar rates of CHD on
ET compared with placebo
What is the latest???
• Does estrogen protect your bones?
• YES…YES…and YES…What is the prognosis for a hip
fracture vs. prognosis for breast cancer in the first year
after diagnosis
• Do women using estrogen look younger? YES…how
about Premarin vaginal cream on the face?
• Do women on estrogen have more teeth? YES…
• Do women have smaller waist sizes that use estrogen?
YES
• Do women on ET have a greater risk of breast cancer?
NO
• Do women on HT have a greater risk of breast cancer? ,
YES, slightly. Is it the P?
Newest study…hot off the press.
• WHI once again…
• Risk of breast cancer and HT (with 0.625 mg of CEE +
2.5 mg of MPA daily vs. placebo
• Results: fewer breast-cancer dx in the group receiving
HT in the initial 2 years of the study, but the number of dx
increased over the next 5.6 years
• After d/c use of HT, the incidence declined rapidly
• No differences in the frequency of mammography in the
groups
Chlebowski, RT et al. Breast cancer after use of estrogen
plus progestin in PMF women. N Engl J Med
2009;360;573-87.
Hormone therapy
• Vasomotor symptoms—hot flushes, night sweats, sleep
disturbances, and irritability begin late in the menopausal
transition stage (perimenopause) and early
postmenopause
• The most effective treatment for vasomotor symptoms is
estrogen—in patients suffering from moderate to severe
vasomotor symptoms (2 or 3 hot flushes daily with night
sweats and sleep disruption) hormone therapy is the
only treatment approved by the FDA
• Usually resolve with time—most resolve within 7 years
without treatment, but who wants to suffer through the
misery if you don’t have to?
• “Well, I don’t know if I have ever had a hot flush/flash…”
What if I still have a “ukerus”?
• Need to add the progesterone to prevent
the build-up of the uterine
lining…OR…agree to a yearly ultrasound
to determine uterine lining hyperplasia
• Why can’t our uterus have a
preprogrammed dropout, like the ovaries?
Hormone therapy
• Vaginal atrophy—vaginal dryness, vulvovaginal
irritation and itching and dyspareunia
• Worsen with time and not likely to resolve
without medical intervention
• 47% of women without treatment will have sx of
vaginal dryness 7 years after menopause vs
only 3% in early menopause
• Rx—oral hormone replacement (0.3 mg CEE/1.5
mg medroxyprogesterone (MPA)* and/or topical
hormone replacement
• *start with lowest effective dose
• Current thinking— “window of opportunity” is
early in menopause
• The KEEPS study—Kronos Early Estrogen
Prevention Study—women initiating HT within
three years of menopause
• The ELITE study—Early vs Late Intervention
Trial with Estradiol
• The LOBO study
• Start with the lowest dose that treats the
symptoms
Hormone Replacement Therapies
• Estrogen—Cenestine and Enjuvia are synthetic
conjugated estrogens
• Estrace is estradiol (micronized)
• Femtrace is estradiol
• Menest is an esterified estrogen
• Ogen and Ortho-Est are estropipates
• Premarin is conjugated equine estrogens (CEEs)
• Transdermal—Alora, Climara, Esclim, Estraderm,
Estrasorb, Estrogel, Menostar, Vivelle, Vivelle-dot
• Vaginal—Estrace, Estring, Femring, Vagifem, Premarin
• Progestogen (oral)—Aygestin (norethindrone acetate),
Prometrium (micronized progesterone), Provera
(medroxyprogesterone acetate)(MPA)
Coronary artery disease in women
• MYTH: Heart disease is a “man’s” disease.
• Truth: Heart disease is the number one killer of
women in the U.S. and a leading cause of
disability among women
• One in three American women dies of heart
disease
• Nearly 6,750,000 women have CHD (hx of an
MI, angina or both)
The evaluation of chest pain in
women
• The evaluation of chest pain is a critical step in the care
of women with heart disease. It is a point at which
women are likely to be treated differently from men,
especially when the diagnosis has not been established
• Chest pain—the differentiation between typical and
atypical chest pain is particularly important in women.
Atypical pain is more common in women than men,
because of the higher prevalence among women of less
common causes of ischemia, such as vasospastic and
microvascular angina, and syndromes of nonischemic
chest pain such as mitral valve prolapse
• ATYPICAL—chest pain at rest, with mental stress, or
during sleep
Most likely signs of a heart attack in
women
• Unusual fatigue or weakness (70% in the month
preceding the heart attack)
• Difficulty sleeping (50%)
• New, unusual shortness of breath during everyday
activities or at rest (40%)
• Dizziness or nausea
• Discomfort between shoulder blades
• Indigestion or mild heartburn (40%)
• Sense of doom or anxiety (30%)
• Palpitations or a feeling of extra heartbeats
• Flu-like symptoms, including chills and cold sweats
PEARL:
• A woman presenting with nausea,
abdominal pain and dizziness may be
having an acute coronary event!!
Microvascular heart disease
• Women’s Ischemia Syndrome Evaluation
(WISE) study--~1000 women
• Women with chest pain, all of whom had
undergone coronary angiography and other
testing
• Tracked for ~5 years
• Of 936 women with an average age of 58, only
1/3 (33 out of 100/ 33%) had obvious blockages
in their main coronary arteries on angiogram;
• In a similar number of men, it would have been
75 out of 100/75%
WISE study
• The remaining 2/3 (66 out of 100) were
considered to have “clear” arteries and labeled
low risk.
• This may have been false assurance
• The WISE researchers estimate that as many as
3 million out of 12 million American women with
heart disease may not have cholesterol plaque
that builds up into major blockages in the large
blood vessels
• And the point is?
Microvascular disease
• Many women (and some men) are prone to
more diffuse type of plaque in the smaller
branches of arteries. It can escape detection by
angiogram, which is the supposed “gold
standard” of heart tests
• In this hidden type of heart disease, called
coronary microvascular disease, plaque spreads
evenly along artery walls so they appear normal
instead of as clumps and visible blockages
• Women who have recurring chest pain and
abnormal stress testing but open arteries on
angiogram might still be at high risk
Risk factors for coronary artery
disease in women
• In general, risk factors for cardiovascular
disease are gender-blind—smoking,
hypercholesterolemia, diabetes mellitus,
hypertension, and the lack of exercise are the
major controllable risk factors for both sexes
• HOWEVER, when taking a closer look, four risk
factors affect women more than men
• And, what might those big 4 be?
4 risk factors higher in women
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Cigarette smoking
High triglycerides and low HDLs
Diabetes mellitus
Hypertension
Risk factors for coronary artery
disease in women--smoking
• Cigarette smoking—women who smoke have
their first heart attack 19 years earlier than
women who don’t smoke
• Women smokers are two to five times more
likely to have a heart attack than women who
don’t smoke
• When a woman quits smoking the risk of CHD
drops substantially in only 2-3 years, reaching
baseline after ten years
• Patients who cut down but continue to smoke 14 cigarettes per day continue to have an
elevated risk of CHD
LIPID ABNORMALITIES
• Elevated triglycerides (greater than 150 mg/dL)
and low HDL (less than 50 mg/dL) pose a
greater risk of CVD in women
• If you have high TGs and low HDLs check the
thyroid and fasting blood sugars—both
present with a similar lipid profile
• Elevated LDL cholesterol is a major risk factor
for both men and women
• Exercise, weight loss, eat right and SAY YES to
drugs—the STATINS (depending on the LDL
number)
PUMP up those HDLs the “E” way
• Eat right—reduces heart disease risk by 35%;
don’t forget portion control…it’s the calories!!
The Mediterranean diet is tops…
• Exercise—lack of exercise increases the risk by
20% … keep walking … it’s not how fast, it’s how
long!! 10,000 steps a day…
• Ethanol (aka ALCOHOL)
• Estrogen pumps up HDLs (oral estrogen, that is)
• Eliminate stress!! Yeah, RIGHT…
• HOW?
Ethanol!
• 5 oz of wine of any color FOR WOMEN
• Men can double the amount…
• This is a YES!!
Alcohol
• How much of the hard stuff?
1-2 ounces for women
2-3 ounces for men
• How much beer?
• 12 ounces for women
24 ounces for men
So, what’s my motto? The B rule…
• Bike a mile, eat a Bowl of Beans,, drink a
Beer…OR…
• Have a nice glass of white wine with a
salmon dinner with my Mom…
• OR…
Reduce blood pressure
• Increases risk for CHD and stroke and vascular
dementia…systolic pressure more important than
diastolic
• Eat right AGAIN…
• DASH diet—decrease sodium, increase potassium, and
increase calcium
• Weight loss; Stress reduction; Say YES to drugs…
• Are you a dipper or a non-dipper?
• Always add a thiazide diuretic—especially if you are
prone to osteoporosis…why? Thiazides SAVE your
bones…
Risk factors for coronary artery disease
in women—Diabetes mellitus
• Over 25 million type 2 diabetics in the U.S.
Among people over age 60, diabetes is more
common in women than men
• Women have a greater risk of heart disease than
men with diabetes
• A premenopausal woman with diabetes is NOT
protected against CAD. In the Nurses’ Health
Study, a premenopausal diabetic woman had a
sevenfold increase in CHD compared with
women who did not have diabetes
Risk factors for coronary artery disease
in women—Diabetes mellitus
• Although deaths from heart disease have
declined in the past few decades, this decline
was not observed in diabetic women. Diabetic
women actually had a 23% increase in deaths
compared with a 27% decrease for women
without diabetes.
• AGGRESSIVE control of LIPIDS and HTN—the
relative risk of death from CHD in patients with
Type 2 diabetes is 1.7 to 4 times higher in
women
Depression in women
• Depression is associated with an elevated
risk of fatal CHD in men and women, and
it is a stronger risk factor in women.
• Depression increases the risk of having a
heart attack by 400%--WHY?
• If untreated following an MI or bypass
surgery, the patient is less likely to survive
A digression on alcohol in women
• Women and GAD (gastric alcohol
dehydrogenase)—less enzyme in women, less
ability to metabolize alcohol before it is absorbed
by the stomach
• Cirrhosis – 10 years earlier in women
• Cardiomyopathy – 10 years earlier in women
• And one more HUGE problem with ETOH in
women of child-bearing years..
Fetal alcohol syndrome
• Alcohol has a direct hit on neurons; induces
neuronal apoptosis; inhibits migration of neurons
• 1 drink and one cigarette
• And how much alcohol consumption during
pregnancy?
• The amount consumed by the mom is directly
related to the development of FAS; 3 oz of pure
ETOH = 6 beers or 6 mixed drinks
Fetal alcohol syndrome
• Alcohol is the most prevalent teratogen in
Western society
• Microcephaly; short palpebral fissures,
hypoplastic maxilla and midface with a
short upturned nose, thin upper lip,
hypoplastic philtrum
• Average IQ of 68? Where will that get
you?
Other problems with drinking during
pregnancy
• Risk factor for early alcohol abuse and
dependence in the child
• Women who drank three or more glasses of
alcohol per day during pregnancy at least a few
times per month were twice as likely to bear a
child who developed alcohol abuse or
dependence by age 21
• Risk was three times as high if mom’s heavy
drinking occurred during the first trimester
• Alcohol before birth may affect the activation of
genes in the brain that make it more vulnerable
to alcohol addiction (Alati, et al.)
Breast cancer in women
• “But if I take estrogen, I’m going to get breast
cancer…”
• The myth—taking estrogen causes breast
cancer…
• The truth—being female increases your risk of
breast cancer
• The length of time of exposure to hormones—
when did you start your periods; when did you
end your periods?
• F = ~203,000 cases per year in 2007
• M = ~2030 new cases per year in 2007
The truth--aging increases the risk
of breast cancer
• 20 1/2044
• 30 1/249
• 40 1/67
• 50
1/36
• 60 1/29
• 70
1/24
• 80
1/9
• 90
1/8
(ACS, 2007)
Breast cancer risks— “relative
risks” as a comparison
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1st PG after age 30 = 1.48
BMI greater than 29.68 = 1.48
Waist size of greater than 35 inches = 3.3
College grad = 1.36
Smoking = 1.32
Alcohol greater than 5 g/d = 1.16
HRT (current low dose) = 1.12
ET (current low dose)=0.66
Women who develop BC while on HT have better
survival rates than women not on HT who develop BC
The truth…the lack of sleep increases the
risk of breast cancer
• Light at night is now clearly a risk for breast
cancer
• Hormone of sleep--melatonin
• What is the function of melatonin? The obvious?
Helps you to sleep…
• The not so obvious? Immune booster,
decreases circulating sex hormones (estrogen,
progesterone, and testosterone), decreases
endocrine-related cancers such as breast and
prostate
Sleep…and breast cancer risk
• Breast cancer is less common in women who sleep more
than 9 hours per night than in women who sleep less
• Women who consistently sleep more than 9 hours per
night have less than one-third the risk of developing a
breast tumor than women who sleep 7 or 8 hours per
night
• Women who work shifts have a 50% increase in breast
cancer (same with men and prostate cancer and
shiftwork)
• (Cancer Research, October 15, 2005)
• Other benefits of sleep?
New breast cancer risk…
• Childhood cancer survivors with radiation to the
chest (Hodgkin’s Lymphoma {HL} patients)
• Median time to breast cancer was 19 years after
dx of HL; 80% had primary invasive breast
cancer
• Recommend annual mammography and MRI of
breast beginning at age 25 or 8 years after
radiation (whichever comes first)
Breast cancer and prognosis
•
•
•
•
•
•
Estrogen receptors
Progesterone receptors
Lymph node involvement
HER-2/neu
BRCA genes
ER+ is a good prognostic indicator—the breast cancer is
more “mature” or well-differentiated
• HER-2/neu is an oncogene that amplifies the growth
potential of the tumor; high risk patient—treatment is
HERCEPTIN (trastuzumab) + chemo
• “Triple negative” breast cancer—high risk; E-, P-,
Her2/neu -
Tamoxifen (Nolvadex) for ER+
breast cancers
• Estrogen antagonist in the breast, agonist in the uterus,
agonist in the bone, antagonist in the hypothalamus
• SSRIs are commonly used in women with breast cancer
to treat both depression and to decrease hot flashes
• Tamoxifen must be metabolized by CYP2D6 to become
pharmacologically fully active
• Fluoxetine (Prozac) and paroxetine (Paxil) are strong
inhibitors of CYP2D6; use of these 2 antidepressants
may result in a higher 2-year recurrence rate (13.9% vs.
7.5%) (American Society of Clinical Oncology, 45th
annual meeting, May 29-June 2, 2009)
Aromatase inhibitors for ER+
breast cancer
•
•
•
•
Anastrazole (Arimidex)
Letrozole (Femara)
Exemestane (Aromasin)
The enzyme aromatase
converts antrostenedione
into estrone, and
testosterone to
estrogen—the primary
source of estrogen in the
PMF
• Major side effects—hot
flashes, arthralgias and
loss of bone density
Osteoporosis
• 2 million American men have osteoporosis and
another 12 million are at risk
• 8 million women and another 22 million at risk
• One in 2 women and one in four men over age
50 will have an osteoporosis-related fracture in
her/his remaining lifetime
• 300,000 hip fractures; 700,000 vertebral
fractures,250,000 risk fractures, 300,000
fractures at other sites (National Osteoporosis
Foundation, 2008)
Osteoporosis—interesting facts in
men
• More men than women die in the year after a hip
fracture with a mortality rate of up to 37.5%
• 40% occur in residential facilities; 20% will have
a 2nd hip fracture
• Often secondary causes—most frequent are
corticosteroid use, excessive alcohol use,
hypogonadism
• Vitamin D deficiency—levels of 25hydroxyvitamin D below 25 ng per milliliter are
associated with an increased risk of hip fracture
in men and women older than 65
Osteoporosis
• The role of Vitamin D in bone health
• Vitamin D and sunshine
• SPF #8 inhibits the activation of Vitamin D
in the skin by 97.5%
• How much vitamin D? What type of
vitamin D? D2 or D3?
• Vitamin D boosts the immune system
Ladies! Expose yourself! And your
kids!!!
• 10-15 minutes every day or every other day!
• Lighter skin? Less time. Darker skin? More time.
• Obviously if you have had skin cancer or are at
high risk for skin cancer, the prudent
recommendation is to take vitamin D orally.
• Other cancers that may be prevented by vitamin
D? Colon cancer, ovarian cancer, prostate
cancer
• Tell your husbands to get those prostates out in
the sun!
Don’t forget your calcium and
vitamin D
• The Coppertone girl
The “dronates” for osteoporosis
• The “dronates” for osteoporosis
• Alendronate [Fosavance] (Fosamax + D),
clodronate [Ostac,Bonefos), Risendronate
(Actonel), ibandronate (Boniva)
• zoledronic acid [Aclasta](Zometa)(Reclast) and
pamidronate (Aredia)--cancer
• Trigger apoptosis of osteoclasts
• Osteoblasts continue to build bone matrix but
without remodeling
• Any downside?
• Fractures? Osteonecrosis of jaw?
Other drugs for osteoporosis
• Evista (raloxifene)—antagonist in breast and uterus;
agonist in bone; increased risk of DVT
• What about tamoxifen?—antagonist in breast and brain;
agonist in uterus and bone; Not approved for
osteoporosis, however…
• Calcitonin (Miacalcin)—has some opiod-like properties
and is useful for the pain of vertebral fractures
• *Forteo (teriparatide)—use for steroid-induced
osteoporosis (boosts osteoblasts and blocks steroids
effects on the bone)(better results compared to
Fosamax)
• *Reclast (zoledronic acid)—15’ infusion x 1 per year
decreases vertebral fractures by 70%; hip by 41%
New drug for osteoporosis
• Monoclonal antibody
• Denosumab (twice a year)
• Cummings SR et al. Denosumab for
prevention of fractures in postmenopausal
females with osteoporosis. N Engl J Med
2009 Aug 20; 361:756.
One last note…get your thyroid
checked today if you’re over 35
•
•
•
•
•
•
•
•
Hyperlipidemia
Low or no energy
Depressed
Can’t find a word
Weight gain
Don’t blame it on menopause!!
Check the TSH!
1st TSH @ age 35
Check the thyroid!
• Signs and symptoms of thyroid dysfunction—
neurologic, hematologic (anemia and high
cholesterol) + the usual suspects of constipation,
dry skin, and brittle hair
• Thyroid replacement. The dose to initiate thyroid
replacement should be the patient’s weight in kilograms
(pounds divided by 2.2) x 1.6 = mcg dose. Then titer the
dose to keep the patient’s TSH less than 3. If the patient
says…“I am feeling fabulous…” check the TSH level
and keep it at that level. Brilliant. (Michigan NP group
discussion—2007, Lansing NP meeting)
Thyroid replacement
• Levothyroxine (T4) Preparations—1 hour before eating
Synthroid, Levoxyl, Thyro-Tab, Unithroid, Levothroid,
Levo-T, Novothyrox, L-thyroxine (no calcium
supplements, no iron supplements, no soy supplements,
no bulk laxatives, no Questran—4 hours apart)
Lots of conditions require an increased dose of T4—
pregnancy, ET, SERMS, diets high in soy protein or fiber,
drugs (sertraline/Zoloft, lovastatin/Mevacor),
anticonvulsants (carbamazepine, phenytoin)
• Liothyronine (T3) preparations—Cytomel
• Combination (T3, T4)—Thyrolar, dessicated thyroid
extract--Thyroid USP, Armour Thyroid
Oxytocin and female bonding
• Hang around with your friends
• Oxytocin is the “tend and befriend”
hormone
• Monogamy
• Oxytocin hormone nasal sprays for your
husbands. 
If you are going to talk to your reluctant MD
about HT, arm yourself with the facts…
• What was wrong with the WHI?
• The study population included older women with the
average participant being 12 years postmenopausal
• In actual clinical practice, most patients seek treatment
for menopausal symptoms within the first 2 years of
menopause
• The selection criteria excluded women more
characteristic of those seen in daily community
practices—these women are typically younger, less
obese, and healthier than the women recruited for this
study
WHI facts
• Also, the study did not evaluate the efficacy of hormonal
treatment in managing menopausal symptoms and
vaginal atrophy, symptoms which constitute the major
reason for choosing to remain on treatment
• In fact, women with severe vasomotor symptoms were
excluded from the study population
• The majority of MDs, (80%) found the WHI information to
be confusing and inconclusive
• Also, there was NO increase in cardiovascular or overall
mortality, and the increased absolute risk of cardiac
events (7/10,000/year), breast cancer 8/10,000 per year,
and strokes 8/10,000 per year noted in the EP arm were
small (statistically INsignificant)
Ammunition for all of the MDs of the world who
continue to use the WHI to deny HT to women
• Jacques Rossouw, who heads the WHI trials,
acknowledges that women younger than 60 who would
have been appropriate candidates for HT—were not
given hormones because of the WHI report. He states:
“With hindsight you could say, well maybe we should
have emphasized reasonable use even more.”
• Marcia Stefanick of Stanford University, another WHI
investigator states: “Maybe we didn’t need to do it that
way…it wasn’t an emergency—it wasn’t like people
were, you know, under serious threat of the adverse
outcomes.” She goes on to say, “I wished we could have
figured out a way to change prescribing practices but
have fewer people distressed about it.”
Continued…
• Wulf Utian, executive director of the North American
Menopause Society: “The WHI researchers have always
taken the glass-half-empty read on their data.” He goes
on to state that the declarations made in the press
releases or interview were much more negative than the
conclusions in published scientific papers. The data
seemed particularly alarming because the risks often
appeared in relative terms…such as a 29 percent
increase in heart attacks between hormone users and
non users—which actually translates into an actual
increased risk of just 0.07 percent, from 33 per year to
40 per 10,000 women per year.
Continued…
• The WHI ONLY applies to women who are
long past menopause…Women younger
than 60 should not be considered as part
of this recommendation.
• Age strongly affects outcomes…confirmed
by the SAME researchers that alarmed the
general public back in 2002.
• Last rule of thumb: Start with the lowest
dose of HT and titrate up as needed.
Bibliography
• Writing Group for the WHI Investigators.
JAMA 2002;288:321-333.
• The Women’s Health Initiative Steering
Committee. JAMA 2004;291:1701-1712.
• Interstate Postgraduate Medical
Association and MEV Healthcom, Inc.
Managing the Symptomatic Menopausal
Patient in Primary Care: A Case-Based
Approach. January 31, 2008.
Bibliography
• Mendelsohn ME and Karas RH. HRT and the
young at heart. N Engl J Med 2007 June
21;356:2639-41
• Manson JE et al. Estrogen therapy and
coronary-artery calcification. N Engl J Med 2007
Jun 21; 356:2591-602.
• Rossouw JE et al. Postmenopausal hormone
therapy and risk of cardiovascular disease by
age and years since menopause. JAMA 2007
Apr 4; 297:1465-77