Transcript (D) Oral contraceptives

Female Concerns
Which form of estrogen is
mainly produced
postmenopausally, or in
overweight women?
(A) Estrone
(B) Estradiol
(C) Estriol
Answer
• (A) Estrone
Depression, weight gain, and
fatigue can be associated with
excess amounts of which of the
following
hormones?
(A) Estrogen
(B) Testosterone
(C) Cortisol
(D) All the above
Answer
• (D) All the above
Choose the correct statement
about synthetic progesterone
(progestin).
(A) Balances estrogen
(B) Protects breast tissue from
cancer
(C) Can cause acne, hair loss, or
spasms of coronary arteries
(D) Derived from flax
Answer
• (C) Can cause acne, hair loss, or spasms of
coronary arteries
Testosterone replacement
therapy in women who are
estrogen-deficient may
increase risk for arterial
plaque.
(A) True
(B) False
Answer
• (A) True
Transdermal progesterone is most
accurately measured by:
(A) Blood testing
(B) Saliva testing
(C) Urine testing
(D) Hair follicle testing
Answer
• (C) Urine testing
The Heart and Estrogen/Progestin
Replacement Study (HERS)
concluded that hormone therapy
(HT) was not
useful in reducing cardiac risk in
women with established disease.
(A) True (B) False
Answer
• (A) True
The risk for cardiovascular
disease (CVD) in participants in
the Women’s Health Initiative
(WHI) study was
increased to a greater extent by
_____ than by ________.
(A) HT; obesity (B) Obesity; HT
Answer
• (B) Obesity; HT
Findings of the WHI study include which of
the following?
(A) Increased risk for colon cancer in the HT
group.
(B) Decreased risk for breast cancer in the HT
group.
(C) No difference between the HT and
placebo groups in risks for CVD, stroke, or
pulmonary embolism
(D) No adverse outcomes in >90% of
participants
Answer
• (D) No adverse outcomes in >90% of
participants
WHI Estrogen-Alone Trial
showed a possible reduction in
breast cancer risk
• A. True
• B. False
Answer
• A. True
Which of the following
interventions is necessary when
prescribing or refilling a
prescription for an estrogencontaining
contraceptive?
(A) Blood pressure check
(B) Papanicolaou (Pap) testing
(C) Bimanual pelvic examination
(D) A, B, and C
Answer
• (A) Blood pressure check
Choose the correct statements about combined
oral contraceptives (OCs).
1. Migraine headache without aura in women
<35 yr of age is not a contraindication to OCs
2. Data show compliance in taking OCs
increases with each cycle
3. Extended-cycle regimens are associated
with shorter withdrawal bleeding
4. Venous thromboembolic events (VTE) are
most closely associated with secondgeneration progestins
(A) 1,2,4 (B) 1,3 (C) 2,3,4 (D) 3,4
Answer
• 1. Migraine headache without aura in
women <35 yr of age is not a
contraindication to OCs
• 3. Extended-cycle regimens are associated
with shorter withdrawal bleeding
Data show drospirenonecontaining OCs are
superior to other OCs in
controlling acne.
(A) True
(B) False
Answer
• (B) False
The transdermal
contraceptive patch may be
less effective in:
(A) Women who weigh
>90 kg
(B) Teenage girls
(C) Nulliparous women
(D) A, B, and C
Answer
• (A) Women who weigh >90 kg
Depot medroxyprogesterone
acetate (DMPA; Depo Provera) is
associated with:
(A) Rapid return to fertility
(B) Increased fracture risk
(C) Permanent decrease in bone
mineral density (BMD)
(D) Irregular bleeding
Answer
• (D) Irregular bleeding
A study by the World
Health Organization
confirmed an association
between intrauterine
devices (IUDs) and pelvic
inflammatory disease
(PID).
(A) True (B) False
Answer
• (B) False
Choose the correct statement(s) about IUDs.
1. Data show no benefit in giving prophylactic
antibiotics at the time of insertion
2. Nulliparity is a contraindication to insertion
3. IUDs should be removed before treating
patients for PID
4. All patients, regardless of individual risk
factors, should be screened for gonorrhea and
chlamydia before insertion
(A) 1 (B) 2 (C) 2,3,4 (D) 1,2,3,4
Answer
• 1. Data show no benefit in giving
prophylactic antibiotics at the time of
insertion
The rationale behind the recommendation that
cervical cancer screening begin 3 yr after the
onset of sexual intercourse
or no later than 21 yr of age is that:
(A) Cancer lesions in adolescents and young
women often regress
(B) Women <21 yr of age are at low risk for
cancer
(C) Screening may lead to unnecessary and
harmful treatment
(D) A, B, and C
Answer
• or no later than 21 yr of age is that:
• (A) Cancer lesions in adolescents and
young women often regress
• (B) Women <21 yr of age are at low risk for
cancer
• (C) Screening may lead to unnecessary and
harmful treatment
• (D) A, B, and C
Choose the correct statement(s) about human
papillomavirus (HPV) and HPV vaccination.
1. HPV DNA sequences have been found in
>99% of all invasive cervical cancers
2. Genital warts are primarily associated with
types 16 and 28
3. The HPV vaccine is recommended for girls
11 to 12 yr of age
4. The HPV vaccine provides protection
against all anogenital HPV types
(A) 1 (B) 1,2,3 (C) 1,3,4 (D) 1,3
Answer
• 1. HPV DNA sequences have been found in
>99% of all invasive cervical cancers
• 3. The HPV vaccine is recommended for
girls 11 to 12 yr of age
• (D) 1,3
Which of the following
management interventions is
appropriate for a sexually active
adolescent with newly diagnosed
cervical intraepithelial neoplasia
1 (CIN 1)?
(A) Repeat cytology at 6-mo
intervals
(B) Colposcopy-directed biopsy
(C) Loop electrosurgical excision
Answer
• (A) Repeat cytology at 6-mo intervals
Which of the following methods of
contraception are considered highly
effective?
1. Copper intrauterine device (IUD)
2. Combination oral contraceptives
(COCs)
3. Single subdermal implant
4. Sterilization
(A) 1,2,4 (B) 1,3,4 (C) 2,3,4 (D)
1,2,4
Answer
•
•
•
•
1. Copper intrauterine device (IUD)
3. Single subdermal implant
4. Sterilization
(B) 1,3,4
Which of the following are risk
factors for venous
thromboembolism in women
taking COCs?
1. Older age
2. Long distance travel
3. Smoking
4. Varicose veins
(A) 1,2,3,4 (B) 1,2,3 (C) 1,2 (D)
3,4
Answer
• 1. Older age
• 2. Long distance travel
• (C) 1,2
Estrogen-containing products are
contraindicated for women with:
1. Diabetic vascular disease or
diabetes >20 yr
2. Migraine with aura
3. Asymptomatic mitral valve
prolapse
4. Uncontrolled hypertension
(A) 1,3,4 (B) 2,3,4 (C) 1,2,4 (D)
2,4
Answer
• 1. Diabetic vascular disease or diabetes >20
yr
• 2. Migraine with aura
• 4. Uncontrolled hypertension
• (C) 1,2,4
Estrogen-containing products
should not be prescribed for
patients with:
(A) Personal history of breast
cancer
(B) Family history of breast
cancer
(C) BRCA gene mutation
(D) A, B, or C
Answer
• (A) Personal history of breast cancer
All the following are
contraindications for COCs,
except:
(A) Family history of breast
cancer (C) Undiagnosed
abnormal genital bleeding
(B) Cholestatic jaundice of
pregnancy (D) Hepatic adenomas
or carcinomas
Answer
• (A) Family history of breast cancer
The efficacy of COCs is
compromised by which of the
following antibiotics used to treat
tuberculosis?
(A) Levofloxacin
(B) Streptomycin
(C) Rifapentine
(D) Rifampin
Answer
• (D) Rifampin
What is the recommended
Papanicolaou testing interval for
a woman infected with HIV?
(A) Every 3 mo
(B) Every 6 mo, regardless of
tests results
(C) Every 6 mo, then yearly after
2 normal tests
(D) Annually
Answer
• (C) Every 6 mo, then yearly after 2 normal
tests
Answer
• (C) Every 6 mo, then yearly after 2 normal
tests
Which of the following
contraceptive options is not
recommended for women
infected with HIV.
(A) Intrauterine device (IUD)
(B) Ultra low-dose oral
contraceptives
(C) Transdermal patch
(D) Vaginal ring
Answer
• (B) Ultra low-dose oral contraceptives
•
•
•
•
•
•
•
A patient wants you to test them
for STDs after unprotected sex.
You should screan them for
which of the following?
Trichomoniasis
Bacterial Vaginosis
Gonorrhea
Chlamydia
HIV
Syphilis
Consider HSV-2
Answer
•
•
•
•
•
Gonorrhea
Chlamydia
HIV
Syphilis
Consider HSV-2 serology if patient likely to
change behavior based on result
A woman diagnosed with trichomoniasis
is treated with a single dose (2 g) of
metronidazole, but reports ongoing
symptoms. The patient should be
prescribed:
(A) Tinidazole or metronidazole, 500 mg
bid for 1 wk
(B) Vaginal metronidazole for 1 wk
(C) High-dose tinidazole for 3 days
(D) High-dose metronidazole for 3 days
Answer
• (A) Tinidazole or metronidazole, 500 mg
bid for 1 wk
All the following statements about bacterial
vaginosis (BV) are correct, except:
(A) Due to loss of normal Lactobacillus and
overgrowth of anaerobic bacteria in vagina
(B) Treatment of male sex partners reduces
number of recurrences in women
(C) Horizontal transmission may occur
between women who have sex with women
(D) Risk for BV greater in women with
multiple sex partners
Answer
• (B) Treatment of male sex partners reduces
number of recurrences in women
Which of the following should trigger
screening for gonorrhea and chlamydia
in women greater than 26 yr of age?
(A) Positive history of gonorrhea,
chlamydia, or pelvic inflammatory
disease in last 2 yr
(B) >1 sex partner in last year
(C) New sex partner in last 90 days
(D) All the above
Answer
• (D) All the above
If a partner is negative, for Herpes the use of valacyclovir
over 1 yr results in ___fewer cases per 100 patients of
horizontal transmission per year (number needed to treat to
prevent 1 case, ____)
• A. 2 fewer cases of horizontal transmission per
year (number needed to treat to prevent 1 case, 59)
• B. 4 fewer cases of horizontal transmission per
year (number needed to treat to prevent 1 case, 39)
• C. 6 fewer cases of horizontal transmission per
year (number needed to treat to prevent 1 case, 10)
• D. 8 fewer cases of horizontal transmission per
year (number needed to treat to prevent 1 case, 14)
Answer
• A. 2 fewer cases of horizontal transmission
per year (number needed to treat to prevent
1 case, 59)
Which of the following should be
performed before starting a
woman on hormonal
contraception?
(A) Breast examination
(B) Papanicolaou testing
(C) Blood pressure evaluation
(D) Screening for gonorrhea and
chlamydia
Answer
• (C) Blood pressure evaluation
According to the World Health Organization’s
Medical Eligibility Criteria for Contraceptive
Use (WHO MEC), which
of the following methods of contraception is
safest for women with a history of thrombotic
stroke?
(A) Transdermal patch
(B) Medroxyprogesterone
(C) Copper intrauterine device
(eg, Depo-Provera)
(D) Oral contraceptives (OCs)
Answer
• (C) Copper intrauterine device
Which of the following methods
is acceptable for use by patients
with liver disease?
(A) OCs
(B) Progestin-only methods
(C) Transdermal patch
(D) Vaginal ring
Answer
• (B) Progestin-only methods
In women with breast
fibroadenomas, hormonal
contraceptives are classified as:
(A) WHO MEC category 1
(B) WHO MEC category 2
(C) WHO MEC category 3
(D) WHO MEC category 4
Answer
• (A) WHO MEC category 1
Which of the following may
increase blood glucose levels in
women with diabetes?
(A) OCs
(B) Transdermal patch
(C) Progestin-only methods
(D) All the above
Answer
• (D) All the above
Women with a positive history of
idiopathic or postpartum deep
venous thrombosis should never
use estrogen-containing
contraceptives.
(A) True (B) False
Answer
• (A) True
Which three diseases account for
90% of sexually transmitted diseases
(STDs) in the United States?
(A) HIV/AIDs, chlamydia, herpes
(B) Gonorrhea, human
papillomavirus (HPV), syphilis
(C) HPV, trichomoniasis, chlamydia
(D) Chlamydia, HPV, herpes
Answer
• (C) HPV, trichomoniasis, chlamydia
In women, Neisseria gonorrhoea
infects:
(A) Ectocervix
(B) Endocervix
(C) Vagina
(D) Any mucosal surface with a
break in the skin
Answer
• (B) Endocervix
The lesion (chancre) of primary
syphilis is:
(A) A watery blister
(B) Condyloma latum
(C) Painless and nontender, with
indurated borders
(D) Painful and tender, with
ragged borders
Answer
• (C) Painless and nontender, with indurated
borders
A pregnant woman with syphilis
who is allergic to penicillin
should be treated with:
(A) Erythromycin
(B) Ciprofloxacin
(C) Tetracycline
(D) Penicillin G benzathine
Answer
• (D) Penicillin G benzathine
Which of the following statements about screening
for chlamydia is correct?
(A) Studies have shown no improvement in rates of
pelvic inflammatory disease (PID) with routine
screening of
young women
(B) Screening for chlamydia is only advantageous in
symptomatic patients
(C) The United States Preventive Services Task
Force does not recommend screening of pregnant
women
(D) A 60% reduction was seen in the rate of PID
when both asymptomatic and symptomatic young
women were
screened
Answer
• (D) A 60% reduction was seen in the rate of
PID when both asymptomatic and
symptomatic young women were screened
Approximately _______ of adults
in the United States have been
infected with genital HPV.
(A) 25%
(B) 50%
(C) 80%
(D) 90%
Answer
• (C) 80%
Which of the following microorganisms
are implicated in the etiology of PID?
(A) Chlamydia trachomatis, N
gonorrhoeae, and Mycoplasma
genitalium
(B) C trachomatis and N gonorrhoeae
only
(C) Treponema pallidum, Escherichia
coli, and Haemophilus influenzae
(D) HPV, C trachomatis, and M
genitalium
Answer
• (A) Chlamydia trachomatis, N
gonorrhoeae, and Mycoplasma genitalium
PID can present as cervicitis
alone (without endometritis,
salpingitis, or peritoneal
inflammation).
(A) True (B) False
Answer
• (A) True
Which test provides the most
specific findings for diagnosing
PID?
(A) Bimanual examination
(B) Complete blood cell count
(C) DNA probes for gonorrhea
and chlamydia
(D) Vaginal ultrasound
Answer
• (D) Vaginal ultrasound
Which of the following was
recommended for outpatient
treatment of mild-to-moderate
PID?
(A) Azithromycin
(B) Ciprofloxacin
(C) Doxycycline plus
metronidazole
(D) Clindamycin
Answer
• (A) Azithromycin
All the following are associated
with increased risk for
endometrial hyperplasia or
cancer, except:
(A) Obesity
(B) Younger age at time of
menopause
(C) Low parity
(D) Diabetes
Answer
• (B) Younger age at time of menopause
A woman who is not on hormone
therapy presents with postmenopausal
bleeding. Her endometrial stripe
thickness on pelvic ultrasonography is
<5 mm. Which of the following
diagnoses is most likely?
(A) Hyperplasia
(B) Polyps
(C) Endometrial cancer
(D) Atrophy
Answer
• (D) Atrophy
Choose the correct statement about
atypical hyperplasia seen on endometrial
biopsy.
(A) Reversible lesion
(B) Progresses to invasive cancer if
untreated with hysterectomy
(C) Treated with low-dose estrogen for 2
wk
(D) Treated with high-dose progestin for
2 wk
Answer
• (B) Progresses to invasive cancer if
untreated with hysterectomy
Which of the following is not a
feature of tinea cruris?
(A) Itching
(B) Red rash
(C) Satellite lesions
(D) Circular lesions with raised,
scaly edges
Answer
• (C) Satellite lesions
Which of the following vulvar
dermatoses is best treated with
high-potency steroids?
(A) Lichen sclerosus
(B) Lichen simplex chronicus
(C) Vulvar candidiasis
(D) Tinea cruris
Answer
• (A) Lichen sclerosus
All the following are typically
seen in the differentiated type of
vulvar intraepithelial neoplasia,
except:
(A) Human papillomavirus
infection
(B) Papule formatio
(C) Pruritus
(D) Parakeratosis
Answer
• (A) Human papillomavirus infection
All the following risk factors are
more predictive of cardiovascular
(CV) disease in women than in
men,
except:
(A) Tobacco smoking
(B) Obesity
(C) Low-density lipoprotein
elevation
(D) Diabetes
Answer
• (C) Low-density lipoprotein elevation
There is sufficient evidence that
_______ reduces CV risk in
women.
(A) β-carotene
(B) Hormone replacement
therapy
(C) Selective estrogen receptor
modulators
(D) None of the above
Answer
• (D) None of the above
Depression is an
independent risk
factor for CV death.
(A) True (B)False
Answer
• (A) True
In older women at
highest risk for CV
disease, aspirin may
be beneficial for
primary prevention.
(A) True (B)False
Answer
• (A) True
Papanicolaou (Pap) testing
• can be stopped after age 65 to 70 yr if
woman had 3 normal and no abnormal Pap
test results in last 10 yr
• can be stopped in women who underwent
total hysterectomy for benign disease (Pap
testing still required in women who
underwent hysterectomy for highgrade
dysplasia or cervical or endometrial cancer)
• Women ≥30 yr of age should undergo Pap
testing every 3 yr
Differential diagnosis of postmenopausal bleeding (PMB)
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
hormonal—exogenous estrogens (eg, hormone therapy)
Endogenous estrogens (caused by, eg, acute stress [withdrawal bleeding occurs 4-5 days after
stressful event
Monitor women]) or estrogen-secreting ovarian tumor
anatomic— atrophic vaginitis
foreign body
endometrial atrophy (hypoplasia)
endometrial hyperplasia
endometrial cancer
Corpus sarcoma
cervical cancer
“cancer until proven otherwise’
endometrial cancer—red flags include PMB and advanced age (>60 yr of age
less concerning in women 50-60 yr of age)
months to years of exposure to endogenous or exogenous estrogen without progestin results in
endometrial hyperplasia
risk factors for endometrial hyperplasia or cancer—obesity
older age at time of menopause
low parity
estrogen-secreting ovarian tumor
diabetes (relative risk increased 3-fold)
Hypertension
positive personal or family history of breast or colon cancer
hereditary nonpolyposis colon cancer—accounts for ≈ 5% of endometrial cancers
25% to 50% lifetime risk for endometrial cancer
Work-up of PMB
•
•
•
•
•
•
•
•
•
•
•
•
women not on hormone therapy—
perform endometrial biopsy or pelvic ultrasonography to assess stripe
thickness of endometrium (if stripe <5 mm, hyperplasia or cancer highly
unlikely)
women on continuous combined (estrogen and progestin) hormone therapy—
spotting in first 2 mo common (should resolve by 3 mo)
women on continuous sequential estrogen and progestin therapy (ie, estrogen
used daily while progestin cycled on and off)—used less commonly
withdrawal bleeding occurs when cycling off progestin
evaluate unscheduled bleeding
single episode of light PMB lasting few days— may be due to stress
observation acceptable
perform endometrial biopsy or imaging study to assess endometrial stripe
thickness
often does not recur (bleeding recurs in hyperplasia or cancer)
endometrial stripe thickness—if <5 mm, atrophy most likely, rather than
hyperplasia, polyps, or cancer
stripe thickness ≥5 mm possibly normal, but pathologic condition more likely
•
•
•
•
•
•
•
•
•
•
•
•
Endometrial biopsy
start with bimanual examination to evaluate uterine axis and size
cleanse cervix with antiseptic
apply tenaculum slowly
choose sampling device based on appropriate rigidity
“crack” stylet to ensure easy movement and advance to fundus; note
depth of uterine sounding
pull stylet back to establish vacuum
push sampling device to fundus, and remove while rotating it
apply sample to fixative (avoid contaminating tip if making multiple
passes)
cervical stenosis or discomfort—consider paracervical or intracervical
block
freeze endometrial sampling device to increase rigidity
use sponge forceps to grab shaft of endometrial sampler 3 to 4 cm from
tip to pass through internal os; use “os finder” (tapered, small
disposable dilator) or small-sized Pratt or Hegar dilators
Consider softening cervix with 400 μg of sublingual or vaginal
misoprostol 2 to 4 hr before procedure (not evidence-based)
Results of endometrial biopsy
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
insufficient—tissue amount
insufficient for interpretation
most women do not have sufficient amount of tissue to sample
note depth of endometrial cavity, gritty sensation, and amount of tissue sampled
(if sample amount adequate, do not repeat biopsy)
if depth of uterine sounding <5 cm, further work-up necessary
chronic endometritis—uncertain whether associated with plasma cell infiltration of
endometrium
no evidence about efficacy of antibiotics
cystic hyperplasia—endometrial atrophy
no hyperplasia
observe patients
if bleeding recurs, use low-dose estrogen for few weeks to 1 mo
Endometrial hyperplasia—reversible lesion
treat with high-dose progestin for 3 to 4 mo
repeat endometrial biopsy
Atypical hyperplasia—irreversible lesion
progresses to invasive cancer if untreated
treat with hysterectomy
Endometrial cancer—treat with hysterectomy
need for radiation therapy based on staging
Symptoms of menopause
• many women have symptoms (eg, hot
flushes, mood swings, night sweats, vaginal
dryness, anxiety, irritability, insomnia,
digestive problems) 5 to 15 yr before
menopause
• bone loss can be associated with proton
pump inhibitor (PPI) use, stress, and
abnormal cortisol levels
• other—migraines; weight gain; memory
lapse most common symptom
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Functions of estrogen
among others— stimulates production of choline acetyltransferase
improves insulin sensitivity
helps prevent muscle damage
improves sleep
reduces risk for cataracts and macular degeneration
decreases platelet stickiness and arterial plaque
maintains collagen in skin
Decreases blood pressure (BP)
decreases low-density lipoprotein (LDL) and its oxidation
helps maintain memory and fine motor skills
enhances production of nerve growth factor
Raises high-density lipoprotein (HDL)
decreases lipoprotein (a)
maintains bone
improves sexual interest
reduces homocysteine
aids in formation of neurotransmitters
Excess estrogen (estrogen dominance)
• symptoms—eg, cervical dysplasia,
depression, agitation, weight gain,
headaches, poor sleep, swollen breasts,
heavy menstrual periods
• can be associated with increased risk for
uterine or breast cancer, autoimmune
disease, hypothyroidism, and fibroids
• causes—poor elimination of estrogen
• lack of exercise
• diet low in fiber
• environmental estrogens
Forms of estrogen
• conjugated estrogen (eg, Premarin)—most
common synthetic estrogen
• comprised of estrone (E1) and estradiol (E2)
• E1—main form produced postmenopausally
or in overweight
• believed to increase risk for breast cancer
• E2—many functions
• estriol (E3)—shown protective against
breast cancer
• 80 times weaker than E2 (therefore, less
bone, heart, and brain protection)
Pathways of estrogen metabolism
• 2-hydroxyestrone—does not stimulate cell growth and is protective
against cancer when methylated in methoxyestrone pathway
• 16-hydroxyestrone—small amount needed to maintain bone structure
• if 16-hydroxyestrone level high and 2-hydroxyestrone level low, Sadenosylmethionine, methionine, vitamin B6, vitamin B12, folate,
methylenetetrahydrofolate, or trimethylglycine may help
• high levels associated with obesity, hypothyroidism, pesticide toxicity,
excess omega-6 fatty acids, and inflammatory cytokines
• 4-hydroxyestrone—damages DNA: it is a breakdown product of
conjugated estrogen and is higher in women with methionine or folic
acid deficiency, or fibroids
• ways to increase 2-hydroxyestrone—exercise; diet (eg, cruciferous
vegetables, flax, soy, protein); indole-3-carbinol (I3C) or
diindolylmethane data show 200 to 300 mg of I3C may be protective
against breast cancer (500 mg in women already diagnosed);
sulforaphane; omega-6 fatty acids; vitamins B6, B12, and folate;
rosemary; turmeric; weight loss
• factors that affect metabolism—obesity; xenoestrogens; plastics;
cosmetics that contain hormones; alcohol use; antibiotics found in
foods
2-Hydroxyestrone: the 'good' estrogen
• H L Bradlow, N T Telang, D W Sepkovic and M P
OsborneThe issue of the role of 2-hydroxyestrone (2OHE1) in breast cancer has been the subject of
considerable controversy as to whether it is carcinogenic or
anticarcinogenic. The expanding data base outlined below
is most consistent with the conclusion that 2-OHE1 is
anticarcinogenic. In every experimental model in which 2hydroxylation was increased, protection against
tumors was achieved. Correspondingly, when 2hydroxylation was decreased, an increase in cancer risk
was observed. Even more dramatically, in the case of
laryngeal papillomas induction of 2-hydroxylation with
indole-3-carbinol (I3C) has resulted in inhibition of
tumorgrowth during the time that the patients continue to
take I3C or vegetables rich in this compound.
• Journal of Endocrinology (1996) 150, S259–S265
Oral
estrogen
• can increase BP, triglycerides, E1, and cause
•
•
•
•
•
•
•
gallstones
can increase liver enzymes and sex hormone–
binding globulin (SHBG), and decrease
testosterone
can interrupt tryptophan metabolism
can lower growth hormone (GH)
Prothrombotic effect
can increase C-reactive protein and cravings for
carbohydrates
use of transdermal estrogen preferred
Individualize care
Low progesterone
• symptoms—eg, anxiety, insomnia, mood
swings
• depression, bladder, and gut problems
• causes—high prolactin
• Stress
• antidepressants, eg, selective serotonin
reuptake inhibitors
• excessive arginine, sugar, or fat
consumption
• vitamin or zinc deficiency
• hypothyroidism
Synthetic progesterone (progestin)
• can cause, eg, weight gain, fluid retention,
irritability, breast tenderness, decreased
sexual interest, acne, hair loss
• interferes with progesterone production
• does not balance estrogen
• can cause spasms of coronary arteries and
raise LDL and total cholesterol
• protects uterus, but not breast from cancer
• counteracts positive effects of estrogen on
heart and serotonin
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Natural progesterone
can be derived from yams or soy
Helps balance estrogen
helps body use and eliminate fats
lowers BP and cholesterol
protects breast tissue
Diuretic
antidepressant
anti-inflammatory
stimulates production of new bone
Improves libido
promotes TH2 immunity
induces conversion of E1 to more inactive state
promotes myelination (useful in stroke)
progesterone-to-estrogen ratio—key
more progesterone than estrogen can increase total cholesterol, lower HDL, and increase
triglycerides
can also cause insulin resistance, elevate cortisol, and increase appetite and carbohydrate
cravings
can relax muscles of gut, leading to bloating and incontinence, lower GH, compromise
immune system
patients with anxiety and insomnia given oral progesterone experience calming effect
Treatment with
progesterone
• medroxyprogesterone (eg, Provera)
• available in 2.5, 5, and 10-mg doses
• oral progesterone recommended for patients
with anxiety and insomnia
Low testosterone
• symptoms—eg, muscle wasting, low self-esteem, low HDL, thinning
lips, anxiety
• associated with menopause, chemotherapy, and postpartum state
• causes—adrenal dysfunction
• Endometriosis
• psychologic trauma
• depression
• oral contraceptives
• statin drugs
• administration—oral
• Transdermal (easier on liver; rotate application sites to avoid hair
growth)
• for effective testosterone therapy, optimize estrogen
• to avoid arterial plaque, do not give testosterone in women with
estrogen deficiency
• ways to increase testosterone—decrease caloric intake; increase
protein in diet, exercise, and sleep; decrease stress; zinc
Excess testosterone
• can be caused by polycystic ovary syndrome and
menopause
• associated with anxiety, depression,
• fatigue, hypoglycemia, and hyperglycemia
• increases risk for heart disease
• causes acne, weight gain, and unwanted hair growth
• ways to lower testosterone—saw palmetto
• spironolactone, 100 mg bid
• Metformin
• important to measure SHBG (low SHBG may be marker
for hypothyroidism)
• high insulin and prolactin levels negatively modify SHBG
• oral estrogen raises SHBG by 50% (100% by conjugated
estrogens
• Slight increase with transdermal estrogen)
Low dehydroepiandrosterone (DHEA)
• associated with menopause, stress, aging,
and tobacco smoking
• women highly sensitive to DHEA (start
with 1 mg
• >20 mg in women rare)
• DHEA can elevate GH
• keto-DHEA cuts off testosterone pathway
Cortisol
• only hormone that increases with age
• effects of excess cortisol—eg, decreased immune function,
osteoporosis, fatigue, irritability, sugar cravings,
confusion, night sweats, elevated BP and cholesterol, easy
bruising, and impaired conversion of thyroxine to
triiodothyronine
• adrenal burnout or adrenal fatigue— due to long-term
stress
• cortisol and DHEA levels drop, corticotropin normal
(patients do not have Addison’s disease)
• Unresponsive hypothyroidism—do not treat
hypothyroidism without treating adrenal dysfunction first
• increased cortisol decreases progesterone production, and
increases binding of thyroid hormone
• pearl—low estradiol stresses body, compromises cortisol,
and decreases neurotransmitters
Treatment of adrenal fatigue
•
•
•
•
•
•
•
•
•
•
•
DHEA with cortisol support
adaptogenic herbs (eg, ginseng, ashwaganda)
adrenal extracts
licorice (contraindicated in hypertensive patients)
nutrients (eg, vitamins C and B, magnesium, selenium)
for high evening cortisol levels, phosphatidylserine, 300
mg may be effective
Eicosapentaenoic acid and docosahexaenoic acid
augmentation with hydrocortisone (eg, Cortef, Delcort,
Hycort)
use, eg, 7.5 mg in morning
lifestyle modifications
relaxation techniques
Measuring hormones
• blood testing may be accurate in
measuring some hormones initially
• saliva and urine testing measure
• free (vs bound) amounts in tissue
• urine testing accurately measures
transdermal progesterone
General considerations
•
•
•
•
•
•
•
•
•
•
•
pregnancy-related mortality ratio in United States 11.5
50% of deaths due to medical problems
50% of pregnancies unintended
pregnancy termination in United States highest of any developed
country
50% of women with unintended pregnancy used contraception in
month of conception
teenagers (women 15 to 19 yr of age) —pregnancy rate decreased in
2002 compared to 1994, but percentage of unintended pregnancies
increased
slight decrease in number of pregnancy terminations
percentage using no contraception decreased between 1994 and 2001
use of condoms, oral contraceptives (OCs), depotmedroxyprogesterone acetate (DMPA
eg, Depo-Provera and withdrawal increased
no contraceptive use, use of less effective methods, and inconsistent
use of effective methods reasons for high incidence of unintended
pregnancy
Provider barriers to contraception
• requiring physical examination before prescribing
contraceptive method
• obtain blood pressure to assess for undiagnosed
hypertension before prescribing estrogen-containing
methods
• Pelvic examination and Papanicolaou (Pap) testing not
necessary (same for refills)
• awareness about need for birth control—
• health care provider should be aware of medications
patient taking and patient’s need for contraception
• data show 50% of women prescribed category D or X
medications not counseled about contraception such ACE
inhibitors and ARBS
• knowledge about medical contraindications—data show
most methods safe in most conditions
Health screening for hormonal
contraceptive users
• Perform blood pressure evaluation before
starting method and at each visit
• Not recommended as a barrier to prevent
contraception
• breast or genital tract examination, Pap
testing, STI assessment, hemoglobin, or
other routine laboratory testing
Counseling issues
• efficacy—consider inherent efficacy (perfect use in ideal
world) of method as well as typical (real world) use
• efficacy of method correlates with frequency of
intervention
• safety—know where to find evidence about safety of
methods
• World Health Organization (WHO) medical eligibility
criteria tool to determine safety of method for patient
• other issues— convenience of use
• patient’s desires about childbearing
• Noncontraceptive benefits of method
• patient’s preference—after safety concerns, most important
consideration
Contraceptive methods
• highly effective—pregnancy rates <1% per
year
• Sterilization
• copper intrauterine devices (IUDs)
• levonorgestrel-releasing intrauterine
systems (LNG-IUS; eg, Mirena)
• DMPA (intramuscular and subcutaneous);
single subdural implant
Contraceptive methods
•
•
•
•
effective—combination OCs (COCs)
transdermal patch
vaginal ring
progestin-only OCs
Contraceptive methods
•
•
•
•
Less effective
barrier methods
natural family planning
withdrawal
IUD
• ParaGard Copper IUD: <2% cumulative pregnancy rate at
end of 10 yr
• can be used in teenagers
• LNG-IUS: 5-yr method Minerva
• 1% cumulative pregnancy rate
• Nulliparity and nulligravity not contraindications for IUDs
• Do not cause infection in women without Chlamydia or
gonorrhea at time of insertion
• no increased risk for infertility after use
• long-acting method
• requires only one visit to health care professional for 5 to
10 yr of easily reversible contraception
• 400 μg misoprostol sublingually 8 hr before inserting IUD
facilitates insertion and does not increase rates of
expulsion
Intrauterine Contraception
•
•
•
•
•
•
•
•
Intrauterine device (IUD): Copper T 380 (ParaGard)—
effective 10 yr
failure rate 0.8% at 1 yr and 1.2% at 7 yr
levonorgestrel-releasing system (Mirena)—releases
secondgeneration levonorgestrel in uterus, with small
amount absorbed by serum
side effects rare and few; failure rate 0.1% at 1 yr, 1.1% at
7 yr can be used until woman reaches menopause;
use in woman desiring long-acting effective method
pelvic inflammatory disease (PID)—IUD negatively
associated with PID
substantial data to support that current IUDs do not cause
PID
Mirena
• Mirena safe choice for woman >35 yr of
•
•
•
•
•
age who smokes
postpartum IUD insertion—safe within first
48 hr or at 6-mo visit
also safe after abortion
size of uterus—if uterus <6 cm by
ultrasonography, more caution required
when inserting IUD
aura—considered focal neurologic
symptom
patients with migraine with aura should not
use patch, ring, or OC with estrogen
PID and IUDs
•
•
•
•
•
•
•
•
•
•
•
•
•
data from worldwide WHO study show risk for PID within 3 wk after insertion
10 per 1000
after 3 wk postinsertion, risk at baseline level of PID in population (1.4 per
10,000)
interpretation that PID related to insertion process and sexual behaviors, not
IUD
recommended IUD not be removed if patient being treated for PID
data show no benefit in giving prophylactic antibiotics at time of insertion
Follow usual screening guidelines for sexually transmitted diseases (STDs),
but screening only for IUD placement not necessary
nulliparity and infertility not contraindications to IUD
no association between PID and previous use of copper IUD
Copper IUD associated with heavier menstrual periods and increased blood
loss
lighter periods with levonorgestrel IUD, and after 12 mo, 50% of these women
have amenorrhea
counsel women about increased cramping and spotting during first 6 mo after
insertion
IUD long-term ( 10 yr) highly effective option
do not insert in woman with active PID (treat first, then insert)
DMPA
•
•
•
•
reversible after delay of 6 to 9 mo
causes abnormal uterine bleeding
50% of patients amenorrheic at 1 yr
Associated with decrease in bone mineral
density (BMD)
• however, no evidence of increased fracture
rate
• Measurement of BMD or use of
bisphosphonates not recommended in
teenagers using DMPA
•
•
•
•
•
•
•
•
•
Depot medroxyprogesterone
acetate (Depo Provera)
one injection every 3 mo
highly effective
failure rate 3% with typical use
side effects—delayed return to fertility irregular bleeding
(50% of women have amenorrhea)
weight gain
subcutaneous low dose now available
bone mineral density (BMD)—1% to 2% decrease in BMD
per year; disagreement among organizations as to duration
of use
strong evidence showing no increased risk for fractures,
and decrease in BMD reverses after discontinuation
no indication for bone densitometry
Single subdermal implant
•
•
•
•
•
Implon single progestin-only rod
lasts 3 yr
causes irregular bleeding
estrogen can be added to eliminate bleeding
less synthesis of androgenic progestin with
newer formulations, thus fewer associated
side effects
• still associated with risk for venous
thromboembolism (VTE)
Implanon
• Implant Single-rod implant
• only one available in United States (Implanon)
• releases 60 μg of etonogestrel per day on average
over 3 yr
• highly effective
• insertion easy and well tolerated
• 1-yr continuation rate high
• bleeding most common reason for discontinuation
• counsel patient to expect irregularly irregular
bleeding pattern
• 2% to 3% of women reported weight gain
OCs
• no progestin-like substances
• current formulations decrease hormone-free
interval
• one formulation approved for daily
continuous use
Combined Oral Contraceptives (OCs)
• Efficacy: efficacy rates 97% to 98% with perfect use
• 92% to 93% with typical use
• study—followed college-aged women for 3 cycles to
evaluate compliance
• pill pack contained electronic monitoring device
• data show women missed, on average, 2.6 pills per cycle
• 33% of women missed no pills in first cycle, but only 20%
of women missed no pills by cycle 3
• traditional OC regimen—21 active pills followed by 7
placebo pills; flawed; 47% of women have follicle ready to
ovulate by day 7
• high risk for pregnancy if new pill pack delayed
Extended-cycle OC regimens
• shorten hormone-free week—23 or 24 days of
hormone followed by 4 to 5 days of placebo
• Decreased ovarian activity at end of placebo week,
compared to 7-day placebo pills
• shorter withdrawal bleeding
• no difference in breakthrough bleeding, despite
more exposure to hormones
• no increased risk with extra days of hormone
exposure
• Fewer hormone-free weeks—12 wk of hormones
with 1 wk off
• May have lower failure rate
Extended-cycle OC regimens
• Three month cycles
• 2 products available, both with levonorgestrel and ethinyl estradiol
(Seasonale; Seasonique)
• Seasonale® (levonorgestrel/ethinyl estradiol tablets) is an extendedcycle oral contraceptive consisting of 84 pink active tablets each
containing 0.15 mg oflevonorgestrel, a synthetic progestogen and 0.03
mg of ethinyl estradiol, and 7 white inert tablets (without hormones).
• Seasonique™ (levonorgestrel/ethinyl estradiol combination tablets and
ethinyl estradiol tablets) is an extended-cycle oral
contraceptive consisting of 84 light blue-green tablets each containing
0.15 mg of levonorgestrel, a synthetic progestogen and 0.03 mg of
ethinyl estradiol, and 7 yellow tablets containing 0.01 mg of ethinyl
estradiol.
• Seasonique adds small amount of ethinyl estradiol during placebo
week to reduce breakthrough bleeding (no improvement shown)
Extended-cycle OC regimens
• continuous use —levonorgestrel and ethinyl
estradiol (Lybrel)
• LYBREL® a blister pack of 28 (90 mcg
levonorgestrel and 20 mcg ethinyl estradiol)
Tablets
• high acceptability
• 72% of women have amenorrhea at 1 yr
• increased spotting and breakthrough bleeding
tapers off in second 6 mo
• median of 1.5 days of spotting by last 3 mo
• consider shortening placebo week or extending
hormone weeks
•
•
•
•
•
•
•
•
•
•
Things to consider
estrogen—most OCs low-dose pills (<50 μg of estrogen)
20 μg of estrogen in ultra low-dose pills
Progestin type—first, second, or third generation
different progestins developed for different degrees of androgenicity
Third generation progestins, particularly desogestrel (Desogen)
associated with increased risk for venous thromboembolic events
(VTE), compared to second-generation progestins
however, absolute risk for VTE much lower than in pregnancy, and all
considered safe to use
Consider initial approach— 30- or 35-μg monophasic OC with
second-generation progestin (eg, levonorgestrel)
side effects with ultra low-dose OC lower, but associated with
increased breakthrough bleeding that may lead to increased
discontinuation rates
biphasic or triphasic—different doses of hormone each week
no added benefit
Things to consider
• use OC with same dose of hormone throughout 3
active weeks
• drospirenone—spironolactone-like progestin
• drospirenone and ethinyl estradiol contained in 2
products (Yas and Yasmin)
• hoped that it would decrease symptoms of
premenstrual dysphoric disorder
• trial showed no difference at 2 yr
• also marketed as treatment for acne
• all Ocs improve acne
• data show drospirenone-containing OCs
equivalent to other OCs in controlling acne
Transdermal patch
• worn 1 wk and replaced weekly for 3 wk
• fourth week patch-free to allow for
withdrawal bleeding
• higher doses of estrogen cause concern
about increased risk for VTE (conflicting
studies)
• safe and effective
Transdermal Contraception
•
•
•
•
•
•
•
•
•
•
•
•
Patch: only one transdermal contraceptive patch available
Ortho Evra
20 μg ethinyl estradiol and 150 μg norelgestromin)
One patch each week for 3 wk, followed by 1 wk off
improved compliance, compared to Ocs
side effects similar to those of OCs
3% detachment rate in trials, but postmarketing studies found 50% of
women have 1 detachment in each cycle
Conflicting study results on risk for VTE
risk for clot may be increased, but absolute risk low
patch shown effective for teenaged girls and good option for this
population
patch and body weight— concern about efficacy, not side effects or
adverse events
Data show greatest proportion of failures in obese women (5 of 15
failures in women weighing >90 kg)
Vaginal ring
• worn 3 wk and removed 1 wk to allow for
withdrawal bleeding
• 15 μg of ethinyl estradiol per day
• Excellent bleeding pattern
• self-insertion and removal
Contraceptive Vaginal Ring
• Monthly option: releases ethinyl estradiol (EE) and desogestrel at
low, constant amount
• ring in vagina for 3 wk, removed for hormone-free week (evidence to
support shortening hormonefree interval)
• side effects few and comparable to those of Ocs
• spotting in 5% of women (less in first month, compared to women on
patch or OCs); increased vaginal discharge, but does not lead to
discontinuance
• data show 20% of women expelled ring at least once during 3-wk
period (efficacy not compromised as long as ring not out for >3 hr)
• extended-cycle ring—can be used continuously for 4, 8, or 12 wk; all
regimens well tolerated
• data show women in 8- and 12-wk continuous use group had overall
fewer bleeding days but more unpredictable spotting days
• potential for use on monthly basis (enough hormone in ring for 35
days)
• increased risk woman can ovulate after 7 days without hormone
• instruct patient to remove ring last 3 to 4 days of month
•
•
•
•
•
•
•
•
NuvaRing
NuvaRing is the trade name for a combined hormonal contraceptive vaginal
ring manufactured by Merck(formerly Schering-Plough, formerly Organon)
that is available by prescription. It is a flexible plastic (ethylene-vinyl
acetate copolymer) ring that releases a low dose of a progestin and
an estrogen over 3 weeks.
Insertion of the ring is comparable to insertion of other vaginal rings. The
muscles of the vagina keep NuvaRing securely in place, even during exercise
or sex. Women can check the contraceptive ring periodically with their finger.
In rare instances, NuvaRing may fall out during sexual intercourse, while
straining during a bowel movement, or while removing a tampon.
In the case of accidental expulsion, the manufacturer recommends rinsing the
ring with cool water before reinserting. Contraceptive efficacy is not reduced
if the ring is removed or accidentally expelled and is left outside of the vagina
for less than three hours.
The benefits of the ring include:
once-a-month self-administered use offering convenience, ease of use and
privacy (most users and most partners do not feel the ring, and of those who
do, most do not object to it)
lower estrogen exposure than with combined oral contraceptive pills or
the contraceptive patch Ortho Evra.
a low incidence of estrogenic side effects such as nausea and breast tenderness
a low incidence of irregular bleeding despite its lower estrogen dose
Nuvaring compressed
Emergency contraception (Plan B)
• contains levonorgestrel
• decreases risk for pregnancy by 89% after
unprotected intercourse
• no contraindication
• does not harm established pregnancy
• available over-the-counter for women >17 yr of
age
• instruct patient to take both pills at same time
• 150 μg levonorgestrel in Plan B One-Step
• no physical examination required;
• can be used up to 5 days after unprotected
intercourse, but most effective if taken within 24
hr
Categories of contraceptives
• estrogen plus progestin—
• thrombophilic; COCs, transdermal patch,
and vaginal ring
• progestin only—not thrombophilic;
• progestin-only Ocs DMPA injections;
steroid-releasing IUDs (LNG) and implants
• no steroids—copper IUD
Metabolic effects of steroids
• estrogen increases hepatic globulin
synthesis (including clotting factors and
angiotensinogen)
• progestin decreases sex hormone binding
globulin SHBG
• No effect on globulin synthesis
Thrombophilic effects of contraceptives
• do not appear to be dose-related between 20 and 35 μg of
estrogen
• estradiol used postmenopausally metabolized rapidly (not
thrombophilic)
• ethynyl estradiol in contraceptive patch metabolized
slowly (can cause thrombophilia)
• studies show no significant increase in VTE with
progestin-only OCs and DMPA
• risk for VTE with COCs—baseline incidence 4 per 10,000
womanyears (previously believed to be 1.0)
• approximately doubled with COCs and 5-fold higher with
pregnancy
Risk factors for VTE
• risk factors for VTE with COCs—obesity; older age;
surgery; presence of hereditary
• thrombophilia; postpartum period; long distance travel
• smoking and varicose veins do not increase risk for VTE
• factor V Leiden and COCs—increased risk for VTE
(synergistic, not additive)
• incidence 30 per 10,000 womanyears
• women with positive screen have small absolute risk of
developing VTE
• routine screening not cost-effective
• consider progestin-only contraceptive in women with
family history of VTE or IUD without screening
World Health Organization (WHO)
medical eligibility criteria
for contraceptive use
• category 1—no restriction
• Category 2—benefits outweigh
risks
• Category 3—risks outweigh
benefits
• Category 4—unacceptable health
risk
WHO MEC categories for women with history of
thrombotic stroke
• 4—OCs; patch; ring; any estrogen-containing methods
• 3—Depo-Provera; progestin-only pills; continuation of
implant method
• conservative, since progestins do not increase
hypercoagulability (in United States guidelines,
progestinonly methods graded as 1 or 2)
• 2—other lower-dose progestin methods
• 1—copper IUD; to avoid risk for repeat stroke,
• avoid estrogen
• management—determine whether patient candidate for
hormonal contraception; evaluate other cardiovascular risk
factors (eg, diabetes, hyperlipidemia, hypertension)
• Depo-Provera recommended for patients who had stroke,
then developed seizure disorder
• Consider IUCs
Deep venous thrombosis (DVT) and pulmonary
embolism (PE)
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
risk factors—age; pregnancy; obesity; immobilization with venous stasis
personal history of DVT or venous thromboembolic event
positive family history of factor V Leiden mutation or protein S or C deficiency
hypertension and tobacco smoking not considered risk factors for venous complications
estrogen increases risk for DVT and PE (dose response relationship)
controversial but important study saw similar risk for DVT with norelgestromin/ethinyl estradiol transdermal system
(Ortho Evra) and Ocs
risk declines with prolonged use
progestins have no effect on DVT and PE
Risk for DVT and PE greater in OC users, but likelihood of dying not greater
risk for DVT higher in pregnancy than with use of hormones
women with positive history of idiopathic or postpartum DVT or venous thromboembolism should never use
estrogen-containing contraceptives
estrogen-containing contraceptives can be considered in women with DVT related to, eg, immobilization or trauma, if
DVT has not recurred
Ocs in patients with factor V Leiden mutation shown to have 30- fold increased risk for DVT (OCs, patch, or ring
should not be used in women with this history)
personal or positive close
family history of inherited thrombophilia best predictors (screen for inherited coagulopathy)
activated protein C best low-cost screening test (if abnormal, follow with polymerase chain reaction test to look for
factor V Leiden mutation)
Superficial varicose veins—no effect on risk for DVT or PE
women should stop OC 30 days before undergoing major surgery (not for minor procedures)
OC, patch, or ring category 4 if woman has known thrombogenic mutation (eg, factor V Leiden) or past
thromboembolic disorder
all methods category 1 in women with varicose veins or superficial thrombophlebitis
WHO MEC categories for liver
disease
•
•
•
•
•
•
•
•
•
•
1 or 2—all methods safe for hepatitis carriers
3—in mild cirrhosis, OC, patch, and ring
4—any estrogen-containing methods (ie, OC, patch, or ring) in patients with
severe cirrhosis, active hepatitis (particularly with elevated transaminase
levels), benign liver adenomas, malignant hepatomas, or cholestatic jaundice
during pregnancy
management—no good studies about estrogen containing methods and liver
disease
if patient with history of hepatitis wants OC, patch, or ring, confirm specific
diagnosis of liver disease and evaluate recent liver function tests (LFTs)
if transaminase level less than 2 times normal, reasonable to start hormonal
method
repeat LFTs in 2 to 3 mo
transaminase level more than 2 times normal indicates active liver disease
(estrogen-containing contraception not recommended)
all progestin-only methods acceptable in patients with liver disease
IUCs safe
WHO MEC categories for breast disease
• 1 or 2—benign breast disease (ie, fibrocystic change); positive family
history
• of breast cancer (OCs do not increase risk in women with firstdegree
relative with breast cancer); undiagnosed breast mass (acceptable for
patient to remain on OC, patch, or pill during work-up)
• 3—positive history of breast cancer with no evidence of disease 5 yr
after treatment
• 4—positive history of breast cancer and treatment within past 5 yr
• extended regimen of OC, patch, or ring can be effective for cyclic
mastodynia (reduces likelihood of development of breast cysts by
70%)
• in women with breast fibroadenoma, hormonal contraceptives category
1
• for women with abnormal breast findings, continuation of OC, patch,
or ring recommended until diagnosis made (stopping method and
substituting with less effective method may result in pregnancy)
• if findings nonsuspicious, plan follow-up
• if findings suspicious, refer for evaluation and do not stop
contraceptive method
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
WHO MEC categories for diabetes
progestins increase insulin resistance, but usually do not significantly increase blood
glucose (BG) level
estrogen may cause hypercoagulability
In diabetics, estrogen-containing methods can be used in patients who do not have
clinically manifest diabetes-induced vascular disease, ie, retinopathy, nephropathy,
peripheral vascular disease, or heart disease
1 or 2—all methods in patients without vascular disease or gestational diabetes (GED)
3—OC, patch, or ring in patients with diabetes and vascular disease, or diabetes for >20
yr; Depo-Provera may increase BG level
management—be aware starting OC, patch, ring, or progestin- only method may
increase BG (adjust insulin or oral hypoglycemic agent)
when using OC, look at other cardiovascular risk factors
if patient not hypertensive or hyperlipidemic and does not smoke tobacco, consider lowdose OC
Progestin only methods marginally safer and easier to manage
IUCs safe
counsel patients about normalizing BG and reducing hemoglobin A1C to <7% before
becoming pregnant
GED— newer studies show OCs do not hasten development of insulin dependence
2-hr postglucose load test 6 wk postpartum and annually (>50% of women with GED
develop type 2 diabetes in next 10 yr)
progestin-only pills for women who are breastfeeding
Depo-Provera and implants not first choice, but not contraindicated
Obesity
• most recent studies show no decrease in effectiveness of
COCs with high body mass index (BMI)
• risk for VTE—in women not taking COCs, risk with BMI
>30 double that of women with BMI <25
• with COC use, risk increases 2- to 5- fold for obese
women, relative to women with BMI <25
• Use of COCs in obese women category 2 risk (benefits
outweigh risks)
• risk factors for arterial thrombosis with COC use—
smoking and age >35 yr; uncontrolled hypertension;
diabetes with vascular disease; atherosclerosis; other
arterial disease
• no increased risk in normotensive women >35 yr of age
who smoke
Medical conditions
• history of VTE or pulmonary embolism (PE)—COCs
category 4
• progestin category 2
• copper IUD category 1
• family history of VTE—COCs category 2
• obesity—COCs category 2
• ischemic heart disease—COCs category 4
• progestin category 3
• copper IUD recommended
• hypertension—COCs category 4 if uncontrolled and
category 3 if controlled
• progestin category 2
• copper IUD category 1
• smoking—if <35 yr of age, COCs category 2
Medical conditions
• hyperlipidemia—estrogen plus progestin category 2
• use progestin-only product or IUD in women with
hypertriglyceridemia
• headache—migraine headache with aura increases risk for
cerebrovascular accident (CVA) in women using COCs
• no contraindication for any hormonal contraceptive with
nonmigraine headache
• COCs can be used in woman <35 yr of age with migraine
without aura; >35 yr of age category 3
• valvular heart disease—COCs can be used in patient with
asymptomatic mitral valve prolapse unless patient has
classic migraine or history of other cerebral event, atrial
fibrillation or congestive heart failure, history of
thrombotic effect, or mechanical valves
Migraine headache and OCs
• synergistic effect of migraine headache and OCs causes
concern about increased relative risk for stroke
• data show odds ratio 8.7 to 13.9 times greater in women
with migraine using OCs, compared to healthy women not
using Ocs
• absolute risk for stroke low in young healthy women
• absolute risk for stroke in women with migraine with aura
taking OCs 30 per 100,000 women years (low absolute
risk, especially when compared to risk for stroke in
pregnancy)
• OCs safe to use in woman <35 yr of age with migraine
without aura
• focal neurologic symptoms with migraine contraindication
for OCs
Medical conditions
• diabetes—COCs category 1 with history of gestational diabetes
• can use estrogen-containing contraceptive, progestin, or IUD if
noninsulin-dependent or insulin-dependent without vascular disease
• estrogen contraindicated in women with vascular disease or diabetes
>20 yr
• no evidence COCs worsen type 1 or 2 diabetes or increase likelihood
of insulin-dependence in women with gestational diabetes
• epilepsy—progestin decreases seizure frequency and estrogen lowers
seizure threshold
• speaker recommends DMPA or progestin-only agent anticonvulsant
drugs interfere with estrogen metabolism
• more unscheduled bleeding and possibly less efficacy
• second generation anticonvulsants do not interact with contraceptive
steroids
• depressive disorders and thyroid disease—no contraindications with
any method
• Breast disease—estrogen-containing agent contraindicated
Medical conditions
• Breast disease—estrogen-containing agent contraindicated with
personal history of breast cancer
• data show no increased risk for breast cancer, including women with
BRCA gene mutation, and reduced risk for endometrial and ovarian
cancer associated with Ocs
• can be used if woman has first-degree relative with history of breast
cancer
• anemias—increased blood loss with copper IUD
• no increased blood loss with hormonal agents
• systemic lupus erythematosus—estrogen appropriate, unless vascular
disease present
• HIV/AIDS— IUD appropriate in immunocompromised women
• can be used with antiretrovirals (ARVs); efficacy of COCs not
compromised by concomitant antibiotic use, except rifampin
• may be compromised by concomitant prolonged use of oral antifungal
Medical conditions
• contraindications for COCs—cholestatic
jaundice of pregnancy or jaundice with
previous OC use
• current or past history of thrombophlebitis
• cerebrovascular or coronary artery disease
• cancer of breast, endometrium, or other
estrogen-dependent neoplasia
• undiagnosed abnormal genital bleeding
• hepatic adenomas or carcinomas
Healthy women with special conditions
• COCs appropriate for women with polycystic
ovarian syndrome, women with first-degree
relative with breast cancer, or women using
nonsteroidal anti-iflammatory drugs
• contraindicated in women with first degree
relative with history of VTE or asymptomatic
women with factor V Leiden mutation (even
without thrombosis)
• Don’t recommend estrogen- containing products
for women with BMI >40 (including
postmenopausally)
• consider long-acting reversible methods for
teenagers (eg, IUD, implant)
•
•
•
•
•
•
•
•
•
•
•
•
•
Recommendations for cervical cancer screening
American Cancer Society—begin 3 yr after onset of sexual intercourse, but no
later than 21 yr of age
once screening begins, annual Papanicolaou (Pap) testing recommended
Rationale for recommendation—little risk of missing important lesion within 3
to 5 yr after initial exposure to human papillomavirus (HPV)
National Cancer Institute Surveillance Epidemiology and End Results (SEER)
program indicates no cases of cervical cancer in females <20 yr of age
screening <3 yr after initiation of sexual activity may result in overdiagnosis of
lesions that often regress spontaneously
inappropriate interventions increase risk for premature labor, premature
rupture
of membranes, and other problems
American College of Obstetricians and Gynecologists (ACOG)
recommendations
decision to initiate screening should be based on age of first sexual intercourse,
behaviors that place patient at greater risk for HPV infection, and risk for
noncompliance with followup visits
clinicians must educate communities about appropriate
time for early education on sexual behavior and initiation of Pap screening
by 18 yr of age, two-thirds of women
have initiated sexual relations
National Cancer Institute
• Women should have a Pap test at least once
every 3 years, beginning about 3 years after
they begin to have sexual intercourse, but
no later than age 21
• If the Pap test shows abnormalities, further
tests and/or treatment may be necessary
• Human papillomavirus (HPV) infection is
the primary risk factor for cervical cancer
• Women who have been vaccinated against
HPVs still need to have Pap tests
Risk factors for HPV
•
•
•
•
•
•
•
•
•
•
•
•
•
multiple sexual partners
male partner with multiple sexual partners
history of other STDs
Early age of first intercourse
immunosuppression; noncompliance;
HPV DNA sequences found in >99% of all invasive cervical cancers
pharyngeal, anal, vaginal, vulvar, penile, and some nonmelanoma skin cancers,
particularly of lower genital tract, related to HPV
>200 types of HPV identified (40 anogenital types)
genital warts associated primarily with types 6 and 11 (low-risk types)
types 16 and 18 high risk and account for majority of cervical cancer
worldwide (type 16, 80%; type 18, 10%-20%)
6.2 million new HPV infections annually; >9 million adolescents and young
women infected
HPV infection in adolescent or young woman can be transient or persistent and
can progress to invasive carcinoma
adolescent with one sexual partner has >60% risk of HPV-associated disease
over 5-yr period
HPV vaccine
• contains no infectious component of HPV
• Capsid protein used for injection
• immunity from quadrivalent vaccine appears to last 4 to 5 yr (unclear
whether booster needed)
• approved for females 9 to 26 yr of age; recommended for girls 11 to 12
yr of age
• sexually active women can receive and benefit from vaccine
• vaccination not recommended for pregnant or breastfeeding women
• Patient counseling—vaccine administration does not cause HPV
• few major adverse events reported
• vaccine highly effective in preventing majority of cervical cancers
• appears safe in majority of population
• Pap testing and follow-up important because vaccine does not cover
every anogenital HPV type
• studies show vaccine 100% effective in preventing precancer and
cancer changes as well as condylomatous changes
The Bethesda System (TBS) is a system for
reporting cervical or vaginal cytologic diagnoses
• Abnormal results include:
• Atypical squamous cells
– Atypical squamous cells of undetermined significance (ASC-US)
– Atypical squamous cells - cannot exclude HSIL (ASC-H)
• Low grade squamous intraepithelial lesion (LGSIL or LSIL)
• High grade squamous intraepithelial lesion (HGSIL or HSIL)
• Squamous cell carcinoma
• Atypical Glandular Cells not otherwise specified (AGC-NOS)
• Atypical Glandular Cells, suspicious for AIS or cancer (AGCneoplastic)
• Adenocarcinoma in situ (AIS) or (CIS)
Abnormal test results.
Dysplasia is a term used to describe abnormal cells. Dysplasia is not cancer, although it may
develop into very early cancer of the cervix. The cells look abnormal under the
microscope, but they do not invade nearby healthy tissue. There are four degrees of
dysplasia, classified as mild, moderate, severe, or carcinoma in situ, depending on how
abnormal the cells appear under the microscope. Carcinoma in situ means that abnormal
cells are present only in the layer of cells on the surface of the cervix. However, these
abnormal cells may become cancer and spread into nearby healthy tissue.
• Squamous intraepithelial lesion (SIL) is another term that is used to describe
abnormal changes in the cells on the surface of the cervix. The word squamous
describes thin, flat cells that form the outer surface of the cervix. The word lesion refers
to abnormal tissue. An intraepithelial lesion means that the abnormal cells are present
only in the layer of cells on the surface of the cervix. A doctor may describe SIL as
being low-grade (early changes in the size, shape, and number of cells) or high-grade
(precancerous cells that look very different from normal cells).
• Cervical intraepithelial neoplasia (CIN) is another term that is sometimes used to
describe abnormal tissue findings. Neoplasia means an abnormal growth of cells.
Intraepithelial refers to the layer of cells that form the surface of the cervix. The term
CIN, along with a number (1 to 3), describes how much of the thickness of the lining of
the cervix contains abnormal cells.
• Atypical squamous cells are findings that are unclear, and not a definite abnormality.
• Cervical cancer, or invasive cervical cancer, occurs when abnormal cells spread deeper
into the cervix or to other tissues or organs.
Abnormal cervical cytology
•
•
•
•
•
•
•
•
•
•
average length of detectable HPV 13 mo in adolescents with newly acquired
HPV infection
HPV infection resolves within 2 yr in most adolescents with intact immune
system (reason guidelines for management of abnormal cervical cytology
different for adolescents)
Further evidence HPV infection can resolve without treatment comes from
high rates of resolution of cervical intraepithelial neoplasia (CIN) 1 and 2
atypical squamous cells of undetermined significance (ASC-US) or low-grade
squamous intraepithelial lesion (LSIL)—ASC-US identifies woman harboring
HPV
high prevalence of HPV in ASC-US in adolescents
3 yr after initiation of sexual intercourse, perform cytology twice at 6 mo
intervals or single HPV/DNA test in 12 mo; colposcopy if either positive
atypical squamous cells, cannot rule out highgrade lesion (ASC-H), highgrade squamous intraepithelial lesion (HSIL) and atypical glandular cells
(AGC)—risk for high-grade disease
immediate colposcopy
endocervical assessment (and possible endometrial evaluation) should be done
in patient with AGC
Biopsy-proven disease
•
•
•
•
•
•
•
•
•
•
•
•
CIN 1—resolution extremely high in adolescents
management without therapy preferred
Monitor with repeat cytology or HPV DNA testing at 12 mo
Colposcopy if either positive at 12 mo
follow guidelines for 24 mo before considering treatment
if treatment indicated, remove least amount of cervical tissue necessary
to eradicate lesion
CIN 2—considered to have higher rate of resolution in adolescent than
in adult woman
manage conservatively with either observation or treatment
if lesion remains stable or regressing, continue to follow
if lesion persists at 24 mo, excise or ablate
CIN 3—treatment recommended
likelihood of resolution has not been evaluated
Prevention and treatment of genital herpes
• evaluate partner of infected patient
• avoid intercourse and touching of herpetic lesions
• condoms not highly protective against vulvar
lesions but somewhat protective against herpetic
lesions on penile shaft
• If partner negative, use of valacyclovir over 1 yr
results in 2 fewer cases of horizontal transmission
per year (number needed to treat to prevent 1 case,
59)
• treatment of recurrent herpes—acyclovir, 800 mg
tid for 2 days; famciclovir, 1 g bid for 1 day (more
expensive)
• 1- or 2-day regimens as effective as 5-day
regimens
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Trichomoniasis
caused by Trichomonas vaginalis
Irritative vaginal discharge (usually profuse; green or cream color)
some women asymptomatic carriers
point-of-care tests— OSOM Trichomonas Rapid Test (Clinical Laboratory Improvement
Amendments-waived costs $8; takes 10 min)
Affirm VPIII Microbial Identification Test
both fairly sensitive and quite specific
treatment—metronidazole, 2 g (single dose; $1)
for those who fail metronidazole, tinidazole, 2 g (single dose $12
cure rate slightly higher with fewer side effects [eg, abdominal cramping, metallic taste,
tinnitus])
Patients should not drink alcohol within 24 hr of last dose
metronidazole-resistant T vaginalis—according to Centers for Disease Control and
Prevention (CDC), patients with ongoing symptoms should be treated with tinidazole or
metronidazole (500 mg bid for 1 wk)
if no response, use higher doses of metronidazole for 3 to 5 days
if still no response, use high-dose tinidazole and vaginal metronidazole, and report case
to CDC
management—treat partners
microscopy of saline suspensions (fresh solution) should be performed within 5 min
must see motility
metronidazole acceptable in pregnancy (category B)
Bacterial vaginosis (BV)
• loss of normal Lactobacillus in vagina (due to, eg,
antibiotic use, douching, adhesion to sperm during
intercourse) and overgrowth of anaerobic bacteria
• New developments—identification of BV-associated
bacteria (Atopobium, Mobiluncus)
• studies show high rates (60% chance) of concordance
between women who have sex with women (horizontal
transmission does not occur between men and women, but
may occur between women)
• risk for BV greater in women with multiple sex partners
• condoms decrease risk
• no identified carrier state in men
• treatment of male sex partners does not affect recurrence in
women
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Bacterial vaginosis (BV)
symptoms—noticed by 50% of women with BV
profuse watery vaginal discharge with ammonia-like fishy odor, notably worse after
intercourse
few irritative symptoms (eg, itching, burning)
classic widely distributed filmy white discharge
Amsel criteria—white discharge, amine odor with addition of potassium hydroxide
pH 4.5; clue cells on microscopy
point-of-care tests include OSOM BV Blue test and card testing based on pH or amines
no routine testing
candidates for treatment—symptomatic women
pregnant women with BV at risk for preterm delivery
women scheduled for pelvic surgery (eg, induced abortion, hysterectomy)
screen before insertion of intrauterine contraception (IUC)
start treatment same day as insertion (no evidence this reduces risk for pelvic
inflammatory disease [PID])
women with BV more likely to acquire HIV
treat asymptomatic BV if patient at high risk for PID (ie, adolescents and women with
multiple sex partners)
little or no additional value of treating asymptomatic women 30 to 50 yr of age with low
risk for PID and mutually monogamous relationships
treatment—1) metronidazole, 500 mg bid or 1 wk,
2) metronidazole gel for 5 days, clindamycin cream for 7 days, or clindamycin
sustained-release cream (single dose); cure rates similar
Routine screening for sexually
transmitted infections (STIs)
• based on population, rather than patients’ behaviors
• Women less than 26 yr of age should be screened for cervical
chlamydia annually
• if gonorrhea not commonly seen in practice (eg, less than1%), routine
screening not recommended for women <26 yr of age
• according to CDC, all people should undergo HIV testing once
between 13 to 64 yr of age (repeat testing based on individual
behaviors)
• pregnant women should be screened for syphilis, HIV, and chlamydia
(if <26 yr of age), and hepatitis B antigen
• prevalence of chlamydia high in teenagers and women 20 to 23 yr of
age
• women >26 yr of age without high risk sexual behaviors do not need
screening for chlamydia or gonorrhea