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 followinghormones?

(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 wasincreased 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 estrogen-

containingcontraceptive?

(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 second-

generation 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 drospirenone-containing 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 pelvicinflammatory 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 insertion3. IUDs should be removed before treating

patients for PID4. 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 intercourseor 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 cancers2. Genital warts are primarily associated with

types 16 and 283. The HPV vaccine is recommended for girls

11 to 12 yr of age4. 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 diagnosedcervical 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 travel3. 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 yr2. 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

• Hepititis B and C

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 ongoingsymptoms. 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), whichof 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 ofyoung 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 werescreened

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

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, S-adenosylmethionine,

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 (2-OHE1) 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 2-hydroxylation was increased, protection against tumors was achieved. Correspondingly, when 2-hydroxylation 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 100- and 200-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), depot-medroxyprogesterone 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 extended-cycle 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 low-dose 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• Switch to progestin product at older age

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 (AGC-neoplastic)

• 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), high-grade 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