Goals and Objectives

• to review the currently available methods of contraception
• to understand each method's mechanism of action, effectiveness, health advantages, indications, health risks, problems, and cost
• to be able to choose appropriate methods of contraception for different patients

I. Background

Two thirds of American women are at risk for unintended pregnancy. Unintended pregnancies represent more than 80% of teen pregnancies, 42% of pregnancies in women aged 30-34, and 77% of pregnancies in women aged 40-44. In all, approximately 40% of live births to women aged 15-44 are unintended. Also, teenage sexual activity is increasing, with 32% of 9^th grade girls, 44% of 9^th grade boys, and more than two thirds of all high school seniors reporting having sexual intercourse in a 1993 survey. The rate of teenage pregnancy and teenage birth are higher in the United States than most other Western countries.

II. Current use

Accurate statistics on contraception use in the United States are avialable from the National Center for Health Statistics, which conducts periodic surveys of women ages 15-44. The 1988 survey revealed that 35 million (or 60% of reproductive-age women) use some form of contraception. The most popular contraceptive methods are oral contraceptive pills (10.7 million), female sterilization (9.6 million), condoms (5.1 million), and male sterilization (4.1 million). Figure 1 shows the methods of contraception used by women at risk for unintended pregnancy.

III. Efficacy

The only certain form of contraception is complete abstinence. With no contraception, it is estimated that 85% of average couples who engage in regular intercourse will conceive within one year. The effectiveness of different contraceptive methods is usually described in terms of "perfect use" (annual rates of pregnancy among couples who use the method correctly at every act of intercourse) and "typical use" (pregnancy rates among average users in retrospective trials or clinical studies). Figure 2 shows the failure rates of different contraceptive methods.

Oral Contraceptive Pills

• first licensed by the FDA in 1960
• The failure rate of OCPs is typically 3% per year. Perfect use failure rates differ among types of pills, with progestin-only pills having a 0.5% failure rate and combination pills having an estimated 0.1% failure rate per year.

Figure 2.

Method	Typical Use	Perfect Use
No method	85.0%	85.0%
Progestin-only pill	3.0	0.5
Combination pill	3.0	0.1
Progesterone T IUD	2.0	1.5
Copper T 380A IUD	0.8	0.6
Norplant	0.2	0.2
Female sterilization	0.4	0.2
Male sterilization	0.15	0.10
Depo-Provera	0.3	0.3
Spermicides	21.0	3.0
Periodic abstinence	20.0	-
Calendar Ovulation method	- -	9.0 3.0
Sympto-thermal	-	2.0
Post-ovulation	-	1.0
Withdrawal	19.0	4.0
Cap Parous	36.0	26.0
Nulliparous	18.0	9.0
Sponge Parous	36	20
Nulliparous	18	9
Diaphragm	18	6
Condom Female	21	5
Male	12	3

I. Combination Oral Contraceptives

A. Mechanism of action

The combined effects of estrogen and progesterone prevent ovulation by inhibiting gonadotropin secretion centrally. Estrogen prevents FSH secretion (inhibiting selection and development of a dominant follicle), and progesterone prevents LH surge (inhibiting ovulation).

Other effects of estrogen include:

1. Endometrial stabilization, leading to less breakthrough bleeding.
2. Potentiation of progestational activity by increasing intracellular progestational receptors.

Other progestational effects include:

1. Decidualized endometrium, which is hostile to implantation.
2. Thickened cervical mucus impervious to sperm.
3. Ovum transport may be slowed and/or fallopian secretions altered.

B. Types of estrogen

There are only two types of estrogen currently in use in the United States today: ethynyl estradiol and mestranol. Ethynyl estradiol is an active compound, whereas mestranol has to be converted in the liver to an active compound. Oral contraceptives contain ethynyl estradiol in doses ranging from 20 mcg to 100 mcg. Mestranol is available only in 50 mcg doses.

C. Types of progestin

There are several types of progestin available in the U.S.: norethindrone, norethindrone acetate, ethynodiol diacetate, norgestrel, levonorgestrel, norethynodrone, desogestrel, and norgestimate.

The newer progestins desogestrel, norgestimate, and gestodene (not available in the U.S.) seem to have some potential benefits:

1. Increased HDL and decreased LDL. This effect would be expected to have beneficial effects over time, but this has not yet been proven.
2. Lower free testosterone levels, higher sex hormone binding globulin, and greater affinity to progesterone binding sites (as opposed to androgen binding sites).
3. Less amenorrhea. Few women will go more than 2 months without withdrawal bleeding.

However, some observational data suggest that desogen- and gestodene-containing OCPs double the risk of venous thrombosis compared to norgestrel containing OCPs. Product labeling has been changed to reflect this new information.

D. Effectiveness

When combination OCPs are used perfectly, the estimated failure rate is 0.1% (i.e., one in 1000 women will become pregnant during the first year of use). The typical failure rate is about 3% in the United States. Most failures are caused by a delay in starting the next cycle of pills.

E. Advantages and indications

The pill is very effective when taken consistently and correctly

1. OCPs are very safe for most women. In the United States, unless a women is a heavy smoker (>35 cigarettes per day) and is over 35 years of age, taking the pill is safer than delivering a baby.
2. A choice throughout the reproductive years, OCPs can be used for a number of consecutive or cumulative years without a rest period.
3. Reversible. Fertility is not affected by the pill, though women trying to conceive may take longer to become pregnant after getting off the pill (the average is 2 to 3 months longer).
4. Menstrual effects
   1. Reduction in menstrual cramps and pain
   2. Elimination of mittleschmerz
   3. Decrease in number of bleeding days and amount of blood loss. Menstrual flow decreased 60% in normal uteri.
   4. Control of menstrual timing
   5. If menstruation is very undesirable (such as in severely retarded women in whom it is a hygienic problem) it can be decreased to once every 90 days by taking 4 packages of 21 pills in a row followed by 6 days off.
   6. Premenstrual symptoms improve in most women. Monophasic pills may be better than triphasic pills.

5. Protection against severe PID. Theories include:

1. Decreased menstrual blood flow
2. Thickened cervical mucous making sperm penetration difficult. It has been shown that bacteria gain access into the upper genital tract by attaching to sperm.
3. Cervical canal less dilated secondary to decreased cervical secretions and decreased menstrual blood flow.
4. Decreased uterine contractions during cycle which decreases chance of spreading infection from inside uterine cavity to fallopian tubes

1. Prevention of ovarian and endometrial cancer.
2. Decreased benign breast disease.
3. Fewer ectopic pregnancies.
4. Less acne due to lower serum testosterone.
5. Prevention of osteoporosis.
6. Prevention and treatment of endometriosis.
7. Less rheumatoid arthritis.
8. Fewer ovarian cysts.

F. Disadvantages

1. No protection from sexually transmitted diseases, including HIV.
2. Must be taken daily.
3. Menstrual changes such as missed periods, spotting, scanty bleeding, or breakthrough bleeding.
4. Nausea or vomiting, especially during first cycle.
5. Headaches.
6. Depression (sometimes severe).
7. Decreased libido, possibly due to decreased levels of free testosterone.
8. Chlamydia infection. Pill use causes cervical ectopia, which predisposes to Chlamydia trachomatis infection.

G. Other effects

1. Cardiovascular disease.

Serious cardiovascular side-effects are most likely to occur in women who are smokers, sedentary, overweight, over 50 years of age, hypertensive, diabetic, or have an elevated cholesterol or high LDL/HDL ratio. However, serious side effects are rare with today's low dose pills. Fig 3. Shows the incidence of selected cardiovascular conditions in pill users.

1. Hypertension has been documented as a side effect of OCPs. Usually the blood pressure elevation is mild and reversible with discontinuation of the pill. Both estrogens and progestins can affect blood pressure, but consideration should be given to switching to a progestin-only pill in a women who has become hypertensive on the pill, because the dosage of progestin in progestin-only pills is less than in combination OCPs.
2. Hypercoagulability is associated with estrogen. The low-dose pills appear to have fewer coagulation effects than did the older higher dose pills. Traditionally, it has been recommended that women discontinue the pill one month prior to surgery, or switch to a progestin-only pill or Depo-Provera. Women with polycythemia vera should not be given OCs. Women who are anticoagulated or who have bleeding disorders are good candidates for the pill.
3. Increased HDL and decreased LDL are effects of estrogens, while the opposite is true of some progestins. The newer progestins have a more positive effect on the lipid profile.

Condition	Incidence per 100,000 Women on Pills
Myocardial infarction:	1
stroke:	3
venous thrombosis/embolism:	11

2. Glucose tolerance.

Glucose tolerance is not affected to a significant degree in most women using most of the current low-dose pills. However, some studies have shown a worsening of glucose tolerance with combination OCPs. The major effect seems to be from the progestin component, with norgestrel being the most diabetogenic.

3. Gallbladder disease.

OCPs were associated with gallbladder disease in earlier studies, but more recent studies have not shown such an association. They may, however, cause an acceleration in the development of gallstones in patients who are already predisposed to gallbladder disease.

4. Hepatocellular adenomas.

Benign liver tumors have been associated with combined oral contraceptives, but the incidence is very small for the newer low-dose pills.

5. Cancer.

1. Breast cancer. Numerous studies have looked at the risk of developing breast cancer, and their findings are not consistent. Use of OCPs does not significantly increase the risk of breast cancer after age 45. It may slightly increase the risk of diagnosis of breast cancer in women under age 35, while slightly decreasing the risk of breast cancer in women age 45-54. It should be noted that most of the information on breast cancer is from studies of women on higher dose pills.
2. Ovarian cancer. The risk of ovarian cancer in oral contraceptive users is 40% less than non-users. The protective effect increases with duration of use, reaching an 80% reduction in risk with more than 10 years of use. The effect continues for at least 10-15 years after stopping the medicine.
3. Endometrial cancer. The risk of endometrial cancer is reduced by 50% with 12 months of oral contraception use, and the protective effect persists for at least 15 years. The risk decreases by 60% with 4 or more years of use.
4. Cervical cancer. Findings of epidemiological studies are not consistent. Confounding variables may include more frequent Pap screening in pill users and the fact that pill users tend to have more sexual partners.
5. Melanoma. No increase in pill users.
6. Hepatocellular carcinoma. A link between hepatocellular carcinoma has not been established, but an association may exist. The incidence of liver cancer in young women in developed countries is so low that the number of cases of liver cancer caused by oral contraceptives would be small even if there is an increased risk.

1. Cautions

Contraindications for oral contraceptive use include:

1. Thrombophlebitis or thromboembolic disorder.
2. Coronary artery disease.
3. Known or strongly suspected breast cancer or history of breast cancer.
4. Known or strongly suspected estrogen-dependent neoplasia.
5. Cerebrovascular accident.
6. Pregnancy.
7. Benign hepatic adenoma or liver cancer or history thereof.
8. Markedly impaired liver function.
9. Smokers over the age of 35.
10. Undiagnosed vaginal bleeding.

The following conditions are not contraindications, but if oral contraceptives are used, caution should be exercised and adverse effects carefully monitored:

1. Migraine headaches.
2. Hypertension.
3. Diabetes mellitus.
4. History of gestational diabetes.
5. Elective major surgery planned in next 4 weeks.
6. Sickle cell or sickle C disease.
7. Lactation.
8. Active gallbladder disease.
9. Obstructive jaundice in pregnancy.
10. Gilbert's disease.
11. Over 50 years old.
12. Completion of term pregnancy within the past 10-14 days.
13. Cardiac or renal disease.
14. Family history of premature death due to myocardial infarction.

I. Choosing a combination pill

There are many pills to choose from in the United States, and choosing a pill can be confusing. Any of the sub-50 mcg pills can be used by most women. Most of the currently available pills contain 30 or 35 mcg of estrogen, with one pill containing 20 mcg of estrogen and two of the triphasic pills containing a 30/40/30 mcg combination of estrogen. A good approach is to choose one of the lowest dose pills first for new patients and for those who are predisposed to estrogen-related complications or side effects. For women who are predisposed to androgenic side-effects or who need an improvement in their lipid profile, the new progestin-containing pills would be a good choice. Potency is no longer an issue with modern pills.

Even if a women is happy with her 80 mcg or 100 mcg pill, she should be switched to a lower dose pill. However, there are situations where a 50 mcg pill might be indicated:

1. Spotting that is resistant to therapy or absence of withdrawal bleeding.
2. Acne, DUB, ovarian cysts, and endometriosis.
3. Contraceptive failure during perfect use of a 30-35 mcg pill.
4. Rifampin and Dilantin both accelerate the breakdown of estrogens, and women on these drugs should be on 50 mcg pills.

J. Dealing with problems

1. Acne or oily skin. Try new progestin pill or increase the estrogen component of the pill.
2. Amenorrhea is usually due to inadequate endometrial buildup. Warn patient ahead of time that bleeding will be decreased on OCPs. An easy way for patient to test for pregnancy is to assess the basal body temperature during days 5-7 of the pill-free week. A temperature of less than 98^o F is inconsistent with pregnancy. If she misses two or more periods, a sensitive pregnancy test needs to be performed. If the problem continues, try switching to one of the new progestin pills.
3. Breakthrough bleeding is more common in the first few months and usually disappears by third cycle. Reassurance is usually sufficient management. Bleeding that occurs after months on the pill is caused by endometrial decidualization. If this bleeding occurs just before the end of the pill cycle, have the patient stop the pills and wait 7 days before starting a new cycle. If bleeding is prolonged or distressing to patient, regardless of point in cycle, it can be controlled with a short course of estrogen. Conjugated estrogens, 1.25 mg, or 2 mg of estradiol administered daily for 7 days is effective. Prostaglandin inhibitors may also be tried.
4. Mastalgia. After ruling out other causes, try switching to a low-estrogen pill or to a progestin-only pill, or try decreasing the amount of progestin. Effective therapies include danazol (200 mg/day), vitamin E (600 mg/day), bromocriptine (2.5 mg/day), or tamoxifen (20 mg/day).
5. Chloasma (facial hyperpigmentation). May be permanent.
6. Depression. Difficult to assess. If temporally related to OCPs, then discontinue for 3-6 cycles and observe. May be due to pill-induced pyridoxine deficiency, so supplementation with 20 mg of vitamin B6 may be beneficial. Lowering the estrogen and/or progestin may be of benefit (most likely to be due to the progestin).
7. Eye problems. Pills may cause inflammation of the optic nerve and predispose women to retinal vein and artery thrombosis. If patients have transient, total, or partial loss of vision, or visual symptoms accompanying migraine headaches, discontinue pills.
8. Galactorrhea. Consider pregnancy. Draw prolactin level (not after breast stimulation). Determine if galactorrhea is due to breast stimulation. If due to OCPs, will be most evident during pill-free week
9. Headaches. Evaluate as any other headache. If symptoms increasing or temporally related to initiation of pills, discontinue or change to a preparation with lower estrogen or progestin.
10. Decreased libido. Perhaps due to decreased androgen production by the ovary. Some women actually have symptoms of decreased estrogen such as vaginal dryness, which may affect sexual enjoyment. Free testosterone levels drop dramatically in women on the new progestins, but the clinical effect of this .is not known.
11. Pregnancy. Though rare, it may occur even with perfect use. The risk of fetal birth defects is small to none.
12. Weight change. Usually minimal and unrelated to pill use, but some women do gain 10-20 lb. or more. May be due to fluid retention (estrogen or progestin effect), increased fat deposition (estrogen effect), or increased appetite (androgenic effect).
13. Drug interactions. Numerous and sometimes unpredictable. The following drugs may cause decreased contraceptive efficacy by inducing liver metabolism: rifampin, phenobarbital, phenytoin, primidone, carbamazepine, and possibly ethosuximide and griseofulvin. Also of interest is vitamin C, which when taken in dosages of 1 gram or higher within 4 hours of taking an OCP, causes up to 50% higher concentration of serum hormones.
14. Switching from OCPs to hormone replacement therapy. Measure FSH during days 5-7 of the pill free week. If FSH is over 30mIU/ml, consider woman to be postmenopausal.

K. Instructions for patients

Missed pills

1. If a women misses one pill, she should take that pill as soon as she remembers and take the next pill as scheduled.
2. If 2 pills are missed in the first two weeks, she should take two pills a day for the next two days. Back-up is probably not needed, but is officially recommended for the next 7 days.
3. If 2 pills are missed in the third week, or if more than 2 pills are missed at any time in the cycle, a back-up method should be started and used for 7 days. The woman should continue taking pills daily until Sunday and if a Sunday starter, she should begin a new pack on Sunday. If she is a non-Sunday starter, she should begin a new pack the same day.

Timing of menstruation

If a woman wishes to postpone a menstrual period, she may begin a new package of pills after day 21 of her pack, skipping the 7-day hormone-free interval.

L. Cost: Ranges from $130 to $270 per year.

II. Progestin-Only Pills

Progestin-only pills, or mini-pills as they are sometimes called, were introduced about 10 years after combination OCPs. Progestin-only pills, have to be taken every day without a pill-free interval. There are a number of progestins available as mini-pills: norethindrone, norgestrel, levonorgestrel, ethynodiol diacetate, and lynestrenol.

A. Mechanism of action

1. Thickening and decreasing the amount of cervical mucus (inhibiting sperm penetration).
2. Inhibition of implantation by causing the development of thin, atrophic endometrium.
3. Inhibition of ovulation.
4. Possible premature luteolysis.

B. Effectiveness

Less effective than combined oral contraceptives. The perfect use failure rate is 0.5%, whereas the typical use failure rate ranges from 1.1% to 13.2%. Pills must be taken at 24-hour intervals. Studies of sperm penetration into cervical mucus show increased penetration distances if interval between pills is more than 24 hours. Nearly 100% effective in lactating women and no adverse effect on milk production.

C. Advantages

1. No estrogen, so no serious estrogen-related side-effects such as thrombophlebitis or pulmonary embolism.
2. Reversibility. Contraceptive effect stops within hours of missing a pill or discontinuing pills.
3. Decreased bleeding or no menses.
4. Decreased anemia.
5. Decreased menstrual cramps and pain.
6. Suppression of ovulatory pain (mittelschmerz) .
7. Decreased risk of endometrial cancer, ovarian cancer, and pelvic inflammatory disease.
8. Easier for some women to remember since the same pill is taken every single day.

1. Indications
   1. Older women. Progestin-only pills are more effective in older women. Older women also tend to have more risk of estrogen-related side-effects.
   2. Breastfeeding women. No adverse effects on lactation or infant growth have been documented. May be started in the first week postpartum.
   3. Women who cannot take estrogens.
2. Disadvantages
   1. Changes in the menstrual cycle. Usually increased number of days of light bleeding.
   2. Weight gain. Usually a small amount and less than that of women on combined OCPs. Weight gain is probably due to increased appetite.
   3. Interactions with anticonvulsants (except valproic acid). Known to cause unacceptable increases in pregnancy rates with Norplant, probably true for progestin-only pills also.
   4. Decreased bone density. Reported in one retrospective study of Depo-Provera users. The study had some design flaws but raises the concern that there may be long-term deleterious effects of a low-estrogen state.
   5. Effectiveness is sensitive to patient's regularity and timing of pill-taking. Women who have ovulatory cycles and whose cycles are least disturbed have a greater risk of pregnancy.
   6. Progestin-only pills are less available in some pharmacies.
   7. Ovarian cysts. Functional ovarian cysts are more common.
   8. Ectopic pregnancy is more common among pregnancy failures during progestin-only pill use.
3. Cautions
   1. Unexplained abnormal vaginal bleeding during the past 3 months. Diagnose before starting mini-pills.
   2. Functional ovarian cysts. If symptomatic, discontinuation of the pill is recommended.
   3. Concomitant rifampin or most anti-seizure medicines reduces effectiveness of the mini-pill.
   4. Pregnancy. Higher incidence of ectopics among pill failures.
4. Instructions for progestin-only pill users
   1. Begin the pill on the first day of menses
   2. Have a back-up contraceptive method available.
   3. Use a back-up contraceptive method during the first 7-28 days on progestin-only pills.
   4. Take your pills every single day, at the same time of the day if possible; minipills are very low-dose contraceptives. In fact, some women use their back-up method at all times while taking minipills just to increase the effectiveness of this type of birth control method.
   5. If you miss one pill, take the missed pill as soon as you remember it. Also take that day's pill on schedule, even if that means taking 2 pills in one day. If you are more than 3 hours late taking a pill, use a back-up method for the next 48 hours.
   6. If you miss 2 or more pills in a row, immediately start your back-up method. Restart your minipills and double up for 2 days. If your period doesn't start within 4-6 weeks, see your doctor for an exam and a pregnancy test.
   7. If you go more than 45 days without a period, you may need a pregnancy test.
   8. If you have breakthrough bleeding or spotting, continue taking your pills. If the bleeding is very heavy or if you have cramps, pain, or fever, see your doctor. Bleeding is more common during the first few months of taking the pill.
   9. If you become ill with vomiting and/or severe diarrhea, take your pills but use a back-up method while ill and until 48 hours after your illness is over.

H. Cost: Any where from $100 to$300 per year.

Norplant

Research began in 1966. The first clinical experience with a progestin released from a Silastic capsule was reported in Santiago, Chili in 1968. In 1974 the levonorgestrel / Silastic drug delivery system was developed with initial clinical studies in Chile. The system was approved in the United States in 1990. Worldwide experience was estimated at 1.8 million by 1992.

A Mechanism of action

Levonorgestrel diffuses slowly through six small flexible capsules made of Silastic (silicone polymer). The capsules are 34mm long and 2.4mm in diameter, and each one contains 36 mg of crystalline levonorgestrel. Constant blood levels of levonorgestrel prevent pregnancy by a number of different mechanisms:

1. Inhibiting ovulation.
2. Thickening and decreasing the amount of cervical mucus (making sperm penetration difficult).
3. Creating a thin and atrophic endometrium.
4. Causing premature luteolysis.
5. Interruption of early pregnancy is apparently not part of the mechanism of action.

B. Effectiveness

More effective than other reversible methods. Failure rates quoted are variable. The most recent study conducted in 11 countries with over 12,000 women showed a pregnancy rate of 0.2 pregnancies per 100 women-years of use. All but one of the failures were pregnancies that were present at the time of implant insertion. If the luteal phase pregnancies are excluded, the failure rate drops to 0.01 per 100 women-years in the first year of use. There are no weight restrictions for Norplant use, but heavier women experience slightly higher pregnancy rates in the 4^th and 5^th years than do lighter women. Original studies lumped all women over 70 kg in one category, but subsequent studies indicate that the 70 kg weight limit is an arbitrary one, with the risk of pregnancy being highest with only the heaviest of women. These failure rates are still better than with oral contraceptives, however. Norplant capsules should be replaced at the end of the fifth year. To avoid inserting Norplant into a patient who is already pregnant, insertion should be done within 7 days of onset of menstruation or within 3 weeks postpartum. A negative sensitive UPT also is beneficial.

Norplant continuation rates are reported ranging from 87%-95% after one year.

C. Advantages and Indications

1. No estrogen side-effects.
2. Rapidly reversible .
3. Patient compliance not an issue.
4. Low risk of ectopic pregnancy. The incidence of ectopic among Norplant users is less than that among women using no contraception at all (0.28 per 1000 women-years vs. 1.5 per 1000 women-years).
5. Amenorrhea, considered by most women to be an advantage. Amenorrhea decreases over time.
6. Decreased risk of endometrial cancer, ovarian cancer, and pelvic inflammatory disease.
7. Suppression of mittelschmerz pain.
8. Decreased menstrual cramps and pain.
9. Decreased anemia.
10. Long-term contraception.
11. Cost effective with long-term use.
12. No interference with breastfeeding.
13. No negative effect on serum lipid concentrations.
14. Fertility rapidly recovers after discontinuation.

D. Disadvantages

1. Menstrual irregularities in up to 80% of users, especially in the first year.
2. Not cost effective for short-term use.
3. No protection from STDs.
4. Decreased effectiveness with anti-seizure medicines.
5. Surgical insertion and removal required.
6. Weight gain, usually less than five pounds over five years.
7. Local skin irritation.
8. Headaches.
9. Breast tenderness.
10. Hair loss.
11. Acne.

E. Absolute contraindications

1. Active thrombophlebitis or thromboembolic disease (per package insert, but not a recognized risk).
2. Undiagnosed vaginal bleeding.
3. Acute liver disease.
4. Benign or malignant liver tumors.
5. Known or suspected breast cancer.

F. Cautions

1. History of ectopic pregnancy.
2. Diabetes mellitus. No apparent impact on carbohydrate metabolism.
3. Hypercholesterolemia.
4. Severe acne.
5. Hypertension.
6. History of cardiovascular disease.
7. Gallbladder disease.
8. Severe migraine headaches.
9. Severe depression.
10. Immunocompromised patients.
11. Concomitant use of medications that induce microsomal liver enzymes is not recommended.

G. Managing problems and follow-up

1. Most minor side-effects can be tolerated by women if they are given assurance that they do not represent a health threat. Some complaints respond to assurance, and others respond to simple therapies. Headache is the most common side-effect other than menstrual changes.
2. Menstrual disturbances can be managed with a short course of oral estrogen such as 1.25 mg of conjugated estrogen or 2 mg of estradiol daily for 7 days. Prostaglandin inhibitors are also useful, but they take 2-3 months.
3. Though pregnancy is rare, it must be ruled out in patients who have regular menses while using Norplant, but then cease menstruating.
4. Mastalgia. Rule out pregnancy. Symptoms decrease with time. Treatments include danazol (200 mg/day), vitamin E (600 mg/day), bromocriptine (2.5 mg/day), or tamoxifen (20 mg/day).
5. Galactorrhea. Rule out pregnancy or breast disease. Instruct patients to decrease breast and nipple stimulation during sexual relations. Check prolactin level if galactorrhea persists and is accompanied by amenorrhea.
6. Acne. Caused by androgenic activity of levonorgestrel and decreased sex hormone binding globulin. Usually can be controlled with topical antibiotics.
7. Ovarian cysts are 8 times more frequent in Norplant users than in normally cycling women. These cysts are simple cysts and need only be followed clinically since most regress spontaneously within one month of detection.

H. Choosing patients

History of the following side-effects while taking birth control pills may be a reason to use a levonorgestrel minipill on a trial basis:

1. Acne.
2. Weight gain.
3. Severe headaches.
4. Depression.
5. Allergy.

Menstrual cycle changes cannot be anticipated

I. Cost: $500 to $700

Depo-Provera

Depo-Provera is an injectable progestin that was approved in the U.S. in 1992. It has been used by millions of women in many different countries. It must be given every 3 months by deep intramuscular injection.

A. Mechanism of action

Depo-medroxyprogesterone acetate (DMPA) is delivered as microcrystals suspended in an aqueous solution, which dissolve slowly. The contraceptive dose is 150 mg by deep intramuscular injection every 3 months. The contraceptive effect lasts 14 weeks, so there is a safety margin for patents who cannot have the next injection at the scheduled time. Mechanisms of action include:

1. Suppression of ovulation.
2. Thickening of cervical mucus.
3. Atrophic endometrium.

B. Effectiveness

First year failure rate 0.3%.

C. Advantages

1. No estrogen.
2. Long acting.
3. Decreased risk of ectopic pregnancy.
4. Amenorrhea: 30-50% of women by the end of the first year, 70% by the end of the second, and 80% by the end of the fifth.
5. Decreased blood loss.
6. Decreased anemia.
7. Decreased dysmenorrhea.
8. Compliance is less of a problem.
9. Reduced risk of endometrial cancer and possibly ovarian cancer. Probably does not increase risk of cervical cancer.
10. No significant drug interactions.
11. Better seizure control in seizure patients.
12. May inhibit intravascular sickling and increase red cell survival in sickle cell patients.
13. Increases the quantity and protein content of breast milk.

1. Disadvantages and cautions
   1. Irregular menstrual bleeding 30% in first year, 10% thereafter.
   2. Breast tenderness.
   3. Weight gain.
   4. Depression ( < 5%).
   5. Impact on lipoprotein profile not certain. Monitoring is recommended.
   6. Some concern over low estrogen state. Possible increased risk of osteoporosis.
   7. Injections needed every 3 months.
   8. Not rapidly reversible. Average time to conception 9 months after last shot. Pregnancy rate however, is normal.
   9. Increased neonatal and infant mortality rates when accidental pregnancy occurs at time of initial injection. Give injection within first 5 days of menstrual cycle, or use a back-up method for first 2 weeks.
   10. Breast cancer risk essentially disproven.

E. Cost: $140 per year

Intrauterine Device (IUD)

A. History

According to legend, the first IUDs were used by caravan drivers who utilized intrauterine stones to prevent pregnancies in camels during long journeys. An IUD consisting of a silkworm catgut ring with a nickel and bronze wire was used during WWI in Germany, but was plagued with a high infection rate. Numerous other models followed with various amounts of success until the 1960s and 1970s, during which time IUDs proliferated in the U.S., with Lippies Loop being the most popular one. The Dalkon shield was introduced in 1970 and within 3 years a high incidence of pelvic infections was recognized, most certainly caused by the multifilament tail. Sales were discontinued in 1975, but a call for removal was not issued until the early 1980s. A large number of women with pelvic infections led to a large number of law suits, which eventually bankrupted the company. This problem tainted all IUDs in the public eye, and eventually manufacturers stopped marketing IUDs in the U.S. The IUD caught on, however, in the rest of the world, being the most popular form of reversible contraception in the world today.

B. Types of IUDs

1. Unmedicated IUDs

The Lippies Loop, made of polyethylene impregnated with barium sulfate, is used all over the world except in the U.S.. Flexible stainless steel rings are used in China.

2. Copper IUDs

The only copper IUD available in the U.S. is the ParaGard (Tcu-380A). The ParaGard is a T-shaped device with a polyethylene frame and 380 mm2 exposed copper surface. A polyethylene monofialment is tied to a ball on the stem for detection and removal. The frame contains barium sulfate to make it radiopaque. It is approved in the U.S. for 8 years of use. Also available in the rest of the world are the Tcu-220C, the Nova T, and the Multiload-375.

3. Hormone-releasing IUDs

The only hormone-releasing device available in the U.S. is the Progestasert. It is a T-shaped device made of an ethylene / vinyl acetate copolymer with titanium dioxide. The vertical stem contains 38 mg of progesterone mixed with barium sulfate in a silicone solution. Two blue-black monofilament strings are attached to the base of the stem. The progesterone is released at a rate of 65 ug /day. It must be replaced yearly. The LNG-20, marketed in Europe, contains levonorgestrel and is effective for 7 years.

4. Future IUDs

A frameless IUD, the Flexigard (Cu-Fix), is undergoing worldwide testing. It consists of six copper sleeves on a nylon thread that is knotted at one end. The knot is pushed into the myometrium with a miniature harpoon-like needle during insertion. It is expected to have a low rate of expulsion, bleeding, and pain because of its frameless construction.

C. Mechanism of action

General

1. Works mainly in the uterine cavity.
2. Ovulation not affected.
3. Apparently not an abortifacient.
4. Creates a spermicidal intrauterine environment.
5. Since IUDs protect against ectopics, there may be a cytotoxic effect against ova or a disruption of tubal function.

Copper IUDs create a foreign body inflammatory reaction in the uterus that is spermicidal. They release copper salts and free copper, the action of which are not completely understood.

Progestin-releasing IUDs combine the actions of progestin with the foreign body inflammatory reaction. The endometrium becomes decidualized with glandular atrophy. Progestin inhibits implantation as well as sperm capacitation and survival. The levonorgestrel IUD partially inhibits follicular development and ovulation. Cervical mucus is thickened, creating a barrier to sperm penetration.

D. Efficacy

The following chart demonstrates the failure rate of selected IUDs in the first year of use in parous women. Failure rates and removal rates for pain and bleeding decrease with increasing duration of use.

Device	Pregnancy Rate	Expulsion Rate	Removal Rate
Lippies Loop	3%	12-20%	12-15%
Tcu-380A	0.5-0.8	5	14
Progesterone IUD	1.3-1.6	2.7	9.3
Levonorgestrel IUD	0.2	6	17

E. Ectopic Pregnancy

IUDs (except for the progesterone-releasing IUD) offer some protection against ectopic pregnancy, though not as great as oral contraceptives.

Ectopic Pregnancy Rates per 1,000 Women-Years
All U.S. women	1.5
Non-contraceptive users	3.0
Copper T-380A IUD	0.2
Progesterone IUD	6.8
Levonorgestrel IUD	0.2

F. Disadvantages

1. Increased bleeding and dysmenorrhea. Less of a problem with the newer copper IUDs and with the progestin-containing ones. Usually worse in the first few months after insertion.
2. Infections. IUD-related infections are due to contamination of the endometrial cavity at the time of insertion. Acquired STDs are responsible for infections that occur 3-4 months after insertion. Careful patient selection is very important to decrease the risk of PID. Patients whose cervical cultures show evidence of chlamydia or gonorrhea infection should be treated with standard recommended antimicrobial regimens without removal of their IUD. Bacterial vaginosis should be treated also, but the IUD need not be removed unless pelvic inflammation is present. If, however, there is evidence of upper genital tract infection, the IUD must be removed promptly and therapy initiated.

Actinomycosis infection. Less common with copper IUDs.

1. Pregnancies that occur with an IUD in place have a 50% spontaneous abortion rate. The risk of septic abortion is very high, so an IUD should always be removed after pregnancy is diagnosed. If the IUD cannot easily be removed, the patient should be offered therapeutic abortion, because the risk of life-threatening septic abortion is increased 20-fold in pregnancies that continue with IUD in place.

G. Choosing patients

Close attention to STD risk factors will minimize problems. Parous patients in mutually monogamous relationships have very good success with IUDs (85%-95% continuing that method after one year). Uterine abnormalities may preclude IUD use. Not recommended for immunocompromised patients or patients with increased risk for endocarditis.

H. Timing of insertion

May be inserted at any time after delivery or during the menstrual cycle. Waiting until 4-8 weeks postpartum does not increase pregnancy rates, expulsions, or removals for bleeding or pain. Prophylaxis with oral doxycycline (200 mg ) one hour prior to insertion provides protection against insertion-related pelvic infections.

I. Removal

May be accomplished by grasping the string with ring forceps and exerting gentle traction. If strings cannot be located, the IUD may be located with a light plastic sound and then retrieved with alligator forceps after a paracervical block has been administered. If this is not successful, direct visualization may be accomplished with hysteroscopy or sonography.

J. Cost: $200 to $300

Barrier Methods

A. History

The use of vaginal contraceptives dates back to ancient civilization, some being described in Egyptian writings on papyrus from 1850 BC. Substances used with barrier or spermicidal properties have included honey, alum, spices, alum, tannic acids, lemon juice, and even crocodile dung. The earliest form of condom was described in 1564 as a linen covering for protection against syphilis, not for contraception. Animal skin and intestinal coverings for the penis followed but were not used for contraception until the 1700s. After vulcanization of rubber was perfected in the 1840s, rubber condoms became widespread and affordable. In the late 1800s, the diaphragm and cervical cap were invented, and experimentation with chemical inhibitors of sperm began.

B. Efficacy

The following chart shows the pregnancy rates for different barrier methods.

Percent of Failures per 100 Women Years in the First Year of Use

Method	Perfect Use	Typical Use
No method	85.0%	85.0%
Diaphragm and spermicides	6.0	18.0
Cervical cap	6.0	18.0
Sponge Parous women	9.0	28.0
Nulliparous women	6.0	18.0
Spermicides	3.0	21.0
Condom	2.0	12.0

C. Advantages

Barrier and spermicide methods provide about a 50% reduction in STDs and PID. Also, women who have never used a barrier method are almost twice as likely to develop cervical cancer.

D. Types available

The diaphragm. About 3% of American couples use the diaphragm for contraception (as of 1988). The failure rate for the method varies from 2% per year to as high as 23%. Older, married women with longer duration of use have the lowest failure rates. Some disadvantages include occasional vaginal irritation from latex or spermicides, and increased incidence of UTIs.

The cervical cap. The efficacy of the cervical cap is about the same as the diaphragm. An advantage is that it may be left in place for up to 36 hours. Disadvantages include increased incidence of foul-smelling discharge if left in for a long period of time, difficulty in fitting some women (only comes in 4 sizes), and difficulty for some women to insert the cap properly.

The sponge. The contraceptive sponge is a sustained-release system for Nonoxynol-9. It also absorbs semen and blocks the cervical canal. Advantages include less mess and continuous 24-hour protection. Disadvantages include less effective contraception than condoms or diaphragms, allergic reactions, and vaginal dryness, soreness, and itching. It is no longer available in the United States.

Spermicides. A wide variety are available. Efficacy of spermicides varies widely. Advantages include low cost and availability. There are occasional allergic reactions.

Condoms. Available in latex or "natural skin" (lamb's intestine). The lamb's intestine condom does not protect against STDs. Inconsistent use, incorrect use, and breakage account for most condom failures. Breakage rates range from 1-12 per 100 episodes of vaginal intercourse.

Female condoms. Made of polyurethane or latex. They should be as effective as male condoms, but acceptability and high cost are problems.

Future of Contraception

Male oral contraceptive . Human trials are underway, but widespread use is years away. A combination of oral testosterone and the progestin/antiandrogen cyproterone administered twice per day was shown to suppresses sperm counts after weeks of use.

A Norplant with only two silastic rods is undergoing trials in Europe.