Case 44. Contraception

 A 25-year-old G2P2002 desires contraception for the next 3 years. She reports

that she had a deep venous thrombosis when she took the combination oral

contraceptive pill 2 years ago. She cannot remember to take the pill every day

and wants contraception that will allow her to be spontaneous. She does not

take any medications and has no known allergies to medications. Menarche

was age 13. Menstrual cycle is every 28 days, lasting for 7 days. She has quarter-size clots the first 3 days of her menstrual cycle. She has been married for

3 years and denies any sexually transmitted infections. Her blood pressure is

120/70 mm Hg, heart rate is 80 beats per minute (bpm), and temperature is

99°F (37.2°C). Heart and lung examinations are normal. The abdomen is nontender and without masses. Pelvic examination reveals a normal anteverted

uterus and no adnexal masses.

» What would be the best contraceptive agent for this patient?

» What would be contraindications to the proposed contraceptive agent?

CASE 44

www.myuptodate.com424 CASE FILES: OBSTETRICS AND GYNECOLOGY

ANSWERS TO CASE 44:

Contraception

Summary: A 25-year-old multiparous woman, in a stable monogamous relationship, desires long-term contraception. She has had a deep venous thrombosis

(DVT ) while taking a combination oral contraceptive pill, is forgetful about taking

pills every day, and wants contraception that will allow spontaneity. She reports

heavy menses. Physical examination is within normal limits.

 Best contraceptive agent for this patient: The levonorgestrel-releasing intrauterine device (LN G-IUD).

 Contraindications to the proposed contraceptive agent: Contraindications

include pregnancy, current or recent history of pelvic inflammatory disease,

current sexually transmitted disease, current or recent puerperal or postabortion sepsis, purulent cervicitis, undiagnosed abnormal vaginal bleeding,

malignancy of the genital tract, known uterine anomalies fibroids distorting

the uterine cavity in a way incompatible with IUD insertion, or allergy to any

component of the IUD.

ANALYSIS

Objectives

1. Know the various types of contraceptive agents including indications and contraindications, mechanisms of action, and efficacy.

2. Know benefits, risks, and contraindications for the combination oral contraceptive pill.

3. Know about intrauterine devices.

4. Know about emergency contraception.

Considerations

Each form of contraception has advantages and disadvantages, and the individual

patient situation should be evaluated to find the best contraceptive choice. Factors

that assist the physician in the counseling of the patient include agents requiring more patient action, such as remembering to take a pill each day, or putting

on a barrier device (diaphragm or condom), duration of contraception desired,

history of sexually transmitted infections, amount of vaginal bleeding, medical

conditions, and contraception side effects. Because of the history of DVT, estrogen-containing contraception agents would be contraindicated. The desire for

spontaneity would make barrier methods less desirable. Options for this patient

would include depot medroxyprogesterone acetate (DMPA), nexplanon (progestin subdermal implant in the arm), or the levonorgestrel IUD. Because of

the heavy menses, this 25-year-old would most benefit from a levonorgestrelreleasing intrauterine device or a progestin containing device (ie, Nexplanon),

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APPROACH TO:

Contraception

DEFINITIONS

INTRAUTERINE CONTRACEPTIVE DEVICES: Small T-shaped device, usually plastic with or without copper or a progestin, placed in the endometrial cavity

as a method of long-term contraception.

TYPICAL USE EFFECTIVENESS: Overall efficacy in actual use, when forgetfulness and improper use occur.

PERFECT USE EFFECTIVENESS: Efficacy of a method when always used

correctly, consistent, and reliably.

BARRIER CONTRACEPTIVE: Prevents sperm from entering upper female

reproductive tract.

STEROID HORMONE CONTRACEPTION:Synthetic estrogen and/ or progestin to provide contraception in various methods, including oral contraceptive pills,

contraceptive patch, contraceptive ring, contraceptive injection, and implant.

YUZPE REGIMEN: Use of specific oral contraceptive regimen first reported by

Dr Yuzpe, consisting of two tablets of 100 to 120 mcg of ethinyl estradiol, and

500-600 mcg of levonorgestrel at time zero and two tablets after 12 hours.

PLAN B (PROGESTIN ONLY): Levonorgestrel 0.75 mg taken orally at time zero

and the same dose after 12 hours within 72 hours of unprotected intercourse.

PLAN B ONE-STEP: Enteric-coated levonorgestrel 1.5 mg taken as one pill.

ULIPRISTAL (ELLA): Selective progesterone receptor modulator taken as one

dose.

CLINICAL APPROACH

Contraceptive agents have different effectiveness, which are characterized as theoretical (or perfect) and with typical use (see Table 44– 1). The various agents

since the progestin would cause the endometrial lining to be thinner and decrease

the amount of menstrual bleeding. LN G-IUD is a device placed inside the uterus

by a provider during an office visit and can be left in place for up to 5 years. The

progestin implant is inserted subdermally in the arm by a provider and can be left

in place for up to 3 years. Both methods do not rely on the patient’s memory for

effectiveness. The progestin in these devices is released slowly over time and can

decrease the amount and frequency of menses. The IUD does not protect against

sexually transmitted infections. Also, this patient has had a DVT, which is a contraindication to any form of contraception that contains a combination of estrogen

and progestin, like the combination oral contraceptive pill, patch, or ring. DMPA is

not as effective as the LARCs (long acting reversible contraceptive options).

www.myuptodate.com426 CASE FILES: OBSTETRICS AND GYNECOLOGY

each have particular advantages and disadvantages and unique factors that may

make one method better suited for a particular patient. Thus, the history and

physical examination should focus on a patient’s preference of method, factors

such as the ability to remember to take a pill every day, and other medical conditions (see Table 44– 2).

Barrier contraceptives prevent sperm from entering the upper female reproductive tract. Various forms include the male condom, female condom, vaginal diaphragm, cervical cap, and spermicides. The male condom is made of latex, polyurethane, or animal tissue. It is a sheath placed on an erect penis prior to intercourse

and ejaculation. The latex condom is the most effective method of contraception

to prevent transmission of sexually transmitted infections. It is the second most

commonly used method of reversible contraception in the United States. The

female condom is a sheath with two polyurethane rings. One ring is placed inside

the vagina at the closed end of the sheath and provides an insertion mechanism and

anchor. The second ring is at the outer edge of the device and is outside the vagina

providing coverage for the labia and the base of the penis. The vaginal diaphragm

must be fitted by a physician. It should be placed 1 to 2 hours before intercourse,

should be used with a spermicide, and should be left in place for at least 8 hours

after coitus. Drawbacks include higher rate of urinary tract infections and increased

risk of ulceration to the vaginal epithelium with prolonged usage.

The cervical cap is also fitted by a physician. Compared to a diaphragm, the cap

can be left in place for up to 48 hours and is more comfortable. It also carries a

risk of ulceration and infection of the cervix if left in place for too long. However,

the cap is only for use in women with normal cervical cytology due to concern of

Table 44–1 • CONTRACEPTIVE FAILURE RATES COMPARING TYPICAL USE

AND PERFECT USE

% Failure Within First Year of Use

Method Perfect Use Typical Use

No method 85 85

Periodic abstinence (calendar) 9 24

Diaphragm 6 12

Male condom 2 18

OC (combined and minipill) 0.3 9

Patch 0.3 9

Ring 0.3 9

Depo-Provera 0.3 6

Levonorgestrel implants (Nexplanon) 0.05 0.05

IUD (Levonorgestrel) 0.2 0.2

ParaGard (copper-T) 0.6 0.8

Female sterilization 0.5 0.5

Male sterilization 0.1 0.15

www.myuptodate.comTable 44–2 • CONTRACEPTION AGENTS COMPARED INCLUDING BEST-SUITED PATIENTS

Category Agents Mechanism Best Suited For Disadvantages and Contraindications

Barrier Diaphragm

Cervical caps

Condoms (male and

female)

Mechanical obstruction Breast Feeding

Not desiring hormones

Decrease sexually transmitted infections (male condom

provides the best protection

against STI)

Patient discomfort with placing devices on

genitals

Lack of spontaneity

Allergies to material

Diaphragm may be associated with more UTIs

and risk of toxic shock syndrome

Combined

hormonal

(estrogen and

progestin)

Combined oral contraceptives

Contraception patch

Vaginal ring

Inhibit ovulation

Thickens cervical mucous to

inhibit sperm penetration

Alters motility of uterus and

fallopian tubes

Thins endometrium

Iron-deficiency anemia

Dysmenorrhea

Ovarian cysts

Endometriosis

OCP—take pill each day

PATCH—less to remember

RING–less to remember, vaginal

irritation, and discharge

Known thrombogenic mutations

Prior thromboembolic event

Cerebrovascular or coronary artery disease

(current or remote)

Cigarette smoking (>15 cigarettes/day) at or

over the age of 35

Uncontrolled hypertension

Diabetic retinopathy, nephropathy, peripheral

vascular disease

Known or suspected breast or endometrial

cancer

Undiagnosed vaginal bleeding

Migraines with aura

Benign or malignant liver tumors, active liver

disease, liver failure

Known or suspected pregnancy

(Continued)

www.myuptodate.comTable 44–2 • CONTRACEPTION AGENTS COMPARED INCLUDING BEST-SUITED PATIENTS (CONTINUED)

Category Agents Mechanism Best Suited For Disadvantages and Contraindications

Progestin-only

pill

Minipill Thickens cervical mucous to

inhibit sperm penetration

Inhibit ovulation

Alters motility of uterus and

fallopian tubes

Thins the endometrium

Breastfeeding Very dependent on taking pill each day at

same time

Patient needs to remember to take pill

Injectables Depot medroxy

progesterone acetate

Inhibits ovulation

Thins endometrium

Alters cervical mucous to

inhibit sperm penetration

Breastfeeding

Iron-deficiency anemia

Sickle cell disease

Epilepsy

Dysmenorrhea

Ovarian cysts

Endometriosis

Depression

Osteopenia/osteoporosis

Weight gain

Implants

(subdermal in

arm)

Etonorgestrel Implant

(Nexplanon)

Inhibits ovulation

Thins endometrium

Thickens cervical mucous to

inhibit sperm penetration

Breastfeeding

Desires long-term contraception

(lasts for 3 years)

Iron-deficiency anemia

Dysmenorrhea

Ovarian cysts

Endometriosis

Hepatic tumors (benign or malignant), active

liver disease

Undiagnosed abnormal vaginal bleeding

Known or suspected carcinoma of the breast

or personal history of breast cancer

Hypersensitivity to any of the components of

etonogestrel implant

May lead to irregular vaginal bleeding

www.myuptodate.comIUD Levonorgestrel intrauterine device

Thickens cervical mucous to

inhibit sperm penetration

Thins endometrium

Breastfeeding

Desires long-term, reversible

contraception

Stable, mutually monogamous

relationship

Menorrhagia

Dysmenorrhea (NOTE: decreased

bleeding and dysmenorrhea)

Current STI or PID

Unexplained vaginal bleeding

Malignant gestational trophoblastic disease

Untreated cervical or endometrial cancer

Current breast cancer

Anatomical abnormalities distorting the

uterine cavity

Uterine fibroids distorting endometrial cavity

IUD Copper-T Inhibits sperm migration

and viability

Changes transport speed

of ovum

Damages ovum

Desires long-term reversible contraception (10 years)

Stable, mutually monogamous

relationship

Contraindication to hormonal

steroids

Current STI

Current or PID within the past 3 months

Unexplained vaginal bleeding

Malignant gestational trophoblastic disease

Untreated cervical or endometrial cancer

Anatomical abnormalities distorting the

uterine cavity

Uterine fibroids distorting endometrial cavity

Wilson disease

May cause more bleeding or dysmenorrhea

Permanent

sterilization

Bilateral tubal occlusion

(can be postpartum,

laparoscopic, or hysteroscopic)

Mechanical obstruction of

tubes

Does not desire future fertility Contraindications to surgery

Risk of regret

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traumatizing the cervix. Spermicides include gels, foams, suppositories, and jellies

placed in the vagina. The active agent is nonoxynol-9 which disrupts the sperm cell

membrane and provides a mechanical barrier. The contraceptive sponge is made

of polyurethane impregnated with 1 mg of nonoxynol-9 and does not have to be

inserted into the vagina before each act of intercourse. Because barrier methods

are used only at time of coitus, the advantages include low cost, decreased transmission of certain sexually transmitted infections with condoms (not cervical

cap or diaphragm), and no exposure to continuous hormones or ongoing IUD

use. Disadvantages include relatively high failure rate (approximately 20%) due to

required use with each act of intercourse.

Oral contraceptives were initially marketed in the United States in 1960. These

quickly became the most-used method of reversible contraception among women.

Oral steroid contraceptives come in combination pills at a fixed dose or a phased

dose, or a progestin-only pill (minipill). The main effect of the progestin is to inhibit

ovulation and cause cervical mucus thickening. The main effect of the estrogen is

to maintain the endometrium, prevent unscheduled bleeding, and inhibit follicular

development. The most common side effects are relatively mild and include nausea,

breast tenderness, and fluid retention.

The main risks of combined hormonal contraception are due to the estrogen component and include venous thromboembolism, strokes in patients with migraines

with aura, myocardial infarction in women who are heavy smokers (> 15 cigarettes

per day), and who are age 35 and older. There are many noncontraceptive benefits

of hormonal oral contraceptives including decreasing the risk of developing ovarian, colon or endometrial cancer, shortening the duration of menses, decreasing

blood loss during menses, improving pain from dysmenorrhea and endometriosis,

decreasing abnormal uterine bleeding, and improving acne.

The contraceptive patch delivers norelgestromin and ethinyl estradiol transdermally. It is worn on the buttocks, upper outer arm, lower abdomen, or upper torso

excluding the breast. It is changed weekly for 3 weeks followed by a week without a patch to allow for withdrawal bleed. In women weighing > 90 kg, efficacy

may be less. A recent FDA warning indicated the risk of DVT was twice that of

OCP, although the data is conflicting. The contraceptive ring allows steroids to be

absorbed through the vaginal epithelium into circulation. The ring is worn for 21

days and then removed for 7 days to allow for withdrawal bleed. The patch and ring

have similar efficacy and side effects to combination oral contraceptives.

Only oneinjectable contraceptiveis currently available in the United States, DMPA.

It is administered subcutaneously every 3 months. Women receiving the injection

have a relatively low pregnancy rate (but higher than that of LARCs). There is a significant disruption of the normal menstrual cycle that usually leads to amenorrhea.

A single subdermal implant, placed in a woman’s upper arm, releases a steady

amount of etonogestrel. The duration of action for this implant, named Nexplanon, is 3 years. Return to fertility is delayed about 2 weeks after cessation of pills,

patches, or rings, but can take up to 9 to 10 months stopping contraceptive injection. Postpill amenorrhea may persist for up to 6 months.

An intrauterine contraceptive device is a small device, usually plastic with or without copper or a progestin, placed in the endometrial cavity as a method of contraception. Four IUDs are currently available in the United States: the copper T380A

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and three levonorgestrel-releasing intrauterine devices; the 5-year version (Mirena)

and two 3-year versions, Skyla which is smaller and designed for younger women, and

Liletta which is marketed for affordability. The copper T380A is approved for use

for 10 years and has a 10-year cumulative pregnancy rate comparable to that of

sterilization. Many mechanisms of action have been described for the coppercontaining IUD, including inhibition of sperm migration and viability, change in

transport speed of the ovum, and damage to or destruction of the ovum.

The levonorgestrel-releasing intrauterine device (Mirena) releases 20 µg of levonorgestrel daily and is approved for use for 5 years; Skyla releases 14 µg/ day and is

approved for 3 years; and Liletta releases 18.6 µg/ day and is approved for 3 years.

The main effect of the progestin is to cause thickening of the cervical mucus and

decreasing fallopian tube motility, suppressing ovulation, and thinning the endometrium. The small amount of steroid causes minimal amounts of systemic side

effects, and it also decreases menstrual bleeding due to the local effect on the endometrium. The levonorgestrel-releasing IUD also has noncontraceptive benefits and

can be used to treat patients with menorrhagia, dysmenorrhea, and pain due to

endometriosis and adenomyosis.

All IUDs have the advantage of requiring a single act of motivation for long-term

use. The unintended pregnancy rate during the first year of use is 0.2% to 0.6%.

They also have rapid return to fertility after removal of the device. Insertion has an

infrequent association with uterine perforation (1:1000) and transiently increases

the risk of upper genital infection (1:1000) due to endometrial contamination.

WH O contraindications to IUD insertion include current pregnancy, current

sexually transmitted infection, current or pelvic inflammatory disease within the past

3 months, unexplained vaginal bleeding, malignant gestational trophoblastic disease,

untreated cervical cancer, untreated endometrial cancer, uterine fibroids distorting

the endometrial cavity, current breast cancer (for levonorgestrel-releasing IUD only),

anatomical abnormalities distorting the uterine cavity, known pelvic tuberculosis, and

allergy to component of IUD or Wilson disease (for copper-containing IUD).

Emergency contraception is the therapy for women who have had unprotected

sexual intercourse, including victims of sexual assault. It is also known as the “morning after pill.” The three most common regimens are progestin Plan B (two doses

12 hours apart), Plan B One-Step which is an enteric-coated levonorgestrel pill,

and Ulipristal (ella) which is a progesterone agonist/ antagonist. The copper IUD

is another option (see Table 44– 3). The combination oral contraceptive method,

known as the Yuzpe method, which consists of two tablets of 100 to 120 mcg (total

200-240 mcg) of ethinyl estradiol, and 500-600 mcg (total of 1000-1200 mcg) of

levonorgestrel in two doses, 12 hours apart, is only rarely used due to GI side

effects. The efficacy of the pharmacologic methods is accepted to be about a 75%

reduction in pregnancy rate, thus decreasing the risk of a midcycle coital pregnancy

from 8 per 100 to about 2 per 100.

The mechanisms of action may include inhibition of ovulation, decreased tubal

motility, and, possibly, interruption of implantation. There are no medical conditions where the risk of emergency contraception outweighs the benefits. Therefore,

women with cardiovascular disease, migraines, liver disease, or who are breast feeding may use emergency contraception.

The major side effect of emergency contraception is nausea and/ or emesis.

Emergency contraception should not be used in patients with a suspected or

www.myuptodate.comTable 44–3 • EMERGENCY CONTRACEPTION METHODS

Method Dosing Formulation Efficacy

Number of Days

after Intercourse Comments

Plan B Need 2 doses 12 hours

apart

Levonorgestrel 750 mcg taken orally ASAP and

also in 12 hours (available only by prescription

to women below 17 yo, and available over the

counter to women 17+ yo)

75% efficacy 72 hours Well tolerated

Plan B: One-step One dose Levonorgestrel (1.5 mg or 1500 mcg) entericcoated pill (available only by prescription to

women below 17 yo, and available over the

counter to women 17+ yo)

75% efficacy 72 hours Well tolerated

Ulipristal (Ella) One dose Selective progesterone modulator, 30 mg tablet 75% efficacy 5 days (120 hours) Frequent n&v

Copper IUD One insertion 99% efficacy Up to 5 days

Combination estrogen

and progestin (Preven)

Needs 2 doses 12 hours

apart

Ethinyl Estradiol 200 mcg and Levonorgestrel

1 mg ASAP and in 12 hours

75% efficacy 72 hours Rarely used;

frequent n&v

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known pregnancy, or those with abnormal vaginal bleeding. Those women who do

not have onset of menses within 21 days following the emergency contraception

should have a pregnancy test.

The copper IUD can be inserted up to 5 days after unprotected intercourse for

emergency contraception. Women who receive the copper IUD under emergency

conditions often choose to maintain the IUD for contraception. The levonorgestrel-releasing IUD is not effective for emergency contraception.

Emerging Concepts

At the time of this writing, postplacental IUD insertion was gaining interest in the

United States. The insertion of an IUD immediate after delivery (within 10 minutes of placental expulsion) or at the time of hysterotomy closure during cesarean

seems to be efficacious; however, there seems to be a higher expulsion rate.

CASE CORRELATION

 See also Case 31 (Sexual Assault).

COMPREHENSION QUESTIONS

44.1 A 17-year-old G0P0 woman desires a reversible form of contraception. After

reviewing the various options, she chooses depot medroxyprogesterone acetate.

Which of the following tests is most likely to be abnormal after 2 years of use?

A. Dual energy x-ray absorptiometry (DEXA) scan

B. Serum glucose level

C. Serum creatinine level

D. Ultrasound of the gallbladder

44.2 Which of the following patients can safely receive combination oral contraceptive pills?

A. 35-year-old woman with diabetes with peripheral circulatory problems

B. 37-year-old woman who smokes cigarettes, about 1 pack (20 cigarettes)

per day

C. 25-year-old woman with persistent tension headaches

D. 30-year-old whose blood pressure is 160/ 90 mm H g

44.3 A 28-year-old G1P1 woman has been prescribed an oral contraceptive agent.

She was counseled about some risks, but also some benefits. Which of the

following is a benefit of combination oral contraception?

A. Decreased risk of breast cancer

B. Decreased gallstone formation

C. Decreased deep venous thrombosis risk

D. Decreased benign breast masses

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44.4 A 28-year-old woman experienced an episode of unprotected intercourse.

Her last menstrual period was about 2 weeks previously. She receives a combination oral contraceptive agent for emergency contraception. Which of the

following is the most common side effect of the Yuzpe regimen (combination

OC)?

A. Vaginal spotting

B. Nausea and/ or vomiting

C. Elevation of liver function enzymes

D. Glucose intolerance

E. Renal insufficiency

44.5 A 25-year-old nulliparous woman is being evaluated for possible IUD insertion. Which of the following characteristics is most acceptable for IUD use?

A. Current sexually transmitted disease

B. Nulliparity

C. Recent pelvic inflammatory disease

D. Enlarged uterus with an irregular cavity

44.6 A 29-year-old G1P1 woman requests emergency contraception for unprotected intercourse. She is given choices between the progestin-only (Plan B)

regimen versus the Yuzpe (combination OC) regimen. Which of the following is the main effect of the progestin-only regimen as compared with the

Yuzpe regimen in EC?

A. H igher ectopic pregnancy rate

B. Less effective prevention of pregnancy

C. Less nausea

D. More liver dysfunction

ANSWERS

44.1 A. Depot medroxyprogesterone acetate is associated with loss of bone mineral density particularly in adolescents. If it is the best type of contraception

for the patient, then the loss in bone mineral density should not discourage

the use of the agent, but it should be considered in the choice of the contraception agent.

44.2 C. Tension headaches are not a contraindication for oral contraceptive agents.

Migraines with aura increase the risk of strokes in patient who take combination hormonal contraception. Other contraindications to combination

hormonal contraception include diabetes with vascular disease, heavy smoker

over the age of 35, and uncontrolled hypertension.

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44.3 D. Oral contraceptives have many beneficial effects including decreasing the

risk of endometrial and ovarian cancer, and decreasing the risk of benign

breast disease; there may be a slight increase in risk of breast cancer and incidence of gallstones.

44.4 B. Because of the high dose of estrogens, nausea and vomiting are the most

common side effects.

44.5 B. Nulliparity is not a contraindication to IUD insertion. Contraindications

include pregnancy, current or recent history of pelvic inflammatory disease,

current sexually transmitted disease, current or recent puerperal or postabortion sepsis, purulent cervicitis, undiagnosed abnormal vaginal bleeding,

malignancy of the genital tract, known uterine anomalies or fibroids distorting the uterine cavity in a way incompatible with IUD insertion (Note: Small

fibroid [3-4 cm] not impinging on the uterine cavity is not a contraindication), or allergy to any component of the IUD or Wilson disease.

44.6 C. As compared to the combination OC regimen, the progestin-only method

has better efficacy and fewer side effects (nausea). Thus, it is the preferred

method. Patients who are given the combination OC agents usually require

an antiemetic agent.

CLINICAL PEARLS

» Emergency contraception is effective when initiated within 72 hours of

intercourse.

» Emergency contraception consists of high-dose combination hormones,

high-dose progestin, or insertion of an a copper IUD.

» The main side effects of combination hormonal emergency contraception therapy are nausea and vomiting.

» An advantage of copper IUD insertion for emergency contraception is

that it can be retained for continuous long-term contraception.

» The levonorgestrel-releasing IUD can be used to improve bleeding

profiles in patients with abnormal uterine bleeding.

» Nonuser-dependent methods (long acting reversible contraception) like

the IUD and the subdermal implant, have the lowest failure rates.

» Oral contraceptives decrease the risk of ovarian and endometrial cancer;

there may be a slightly increased risk of breast cancer.

» It decreases the duration of menses and the amount of blood loss per cycle.

» Smoking >15 cigarettes per day over the age of 35 years is an absolute

contraindication for combination hormonal contraceptives.

» Sickle cell crisis and epilepsy occur less often with DMPA.

» The contraceptive patch may be associated with a greater risk of DVT.

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