Introduction

Requests for effective and easy-to-use contraception are common and important reasons for patient visits to primary care and ob-gyn physicians. Speaking to a crowded room of primary care practitioners at Primary Medicine Today (East), Dr. Jane S. Sillman, Women's Health Center, Brigham and Women's Hospital, Boston, MA, said that a woman has an 85 percent chance of becoming pregnant within one year if she is sexually active and does not use contraception. "This underscores for all of us the tremendous importance of making sure that our patients have good and effective contraception and that we do everything we can to help them use these methods well and prevent unintended pregnancies," she told attendees.

Oral Contraceptives

The most widely used combination OCPs contain 20 to 35 mg of estrogen as ethinyl estradiol and several progestins, all of which differ in androgenicity and progestational activity. "A progestin that is high in androgenic activity (e.g. norethindrone acetate [various brands] or norgestrel [various brands]) would have more potential to cause side effects like acne and hirsutism and possibly weight gain, whereas OCPs with progestins low in androgenicity (e.g. desogestrel or norgestimate) have been shown to be helpful in the treatment of acne," Dr. Sillman noted. Those in the middle (e.g. norethindrone or levonorgestrel), she described as "nice, middle of the road, all purpose progestins, adequate for most patients."

OCPs also vary in their progestational activity. A progestin high in progestational activity (e.g. norethindrone acetate) will produce greater endometrial atrophy, an effect that is helpful in treating women with polycystic ovarian syndrome (OR), who have regular, heavy menses. Dr. Sillman noted that, "those progestins that are very low in androgenicity are also very high in progestational activity (e.g. desogestrel and ethinyl estradiol [various brands]) and are helpful for women with acne and heavy periods."

Health Benefits of Oral Contraceptives

The health benefits of OCPs are that they regulate the menstrual cycle and lead to periods that are lighter and associated with less dysmenorrhea. They are also associated with a significant decrease in ovarian cysts and cancer, with a benefit that persists up to 19 years after stopping the agents. This benefit is thought to be due to decreased ovarian stimulation. Interestingly, OCPs are associated with a decrease in pelvic inflammatory disease (PID), which is thought to be due to changes in the cervical mucus and uterine and tubal motility, making it more difficult for a lower genital tract infection to spread to the upper genital tract. "The progestin component causes the cervical mucus to become much thicker and viscous, making it difficult for bacteria as well as sperm to ascend into the upper tracts," Dr. Sillman explained.

OCPs are also associated with a decrease in endometrial cancer, with benefits lasting up to 12 years after stopping the pills. This benefit is most likely related to the endometrial atrophy caused by the agents, which are also associated with a decrease in the incidence of breast fibroadenomas and fibrocystic changes.

Health Risks of Contraceptives

As with any pharmacotherapy, there are health risks associated with OCPs. There is a risk for myocardial infarction (MI), primarily in women over 35 who smoke. The mechanism is thought to be acute thrombosis due to the estrogen in the pills. "Fortunately, the incidence of MI in women is rare now because of lower dose pills and carefully targeted prescribing," Dr. Sillman said.

Deep vein thromboses (DVTs) are another risk, again due to the estrogen component in the OCPs, which increases clotting factors II, VII, and X, and decreases antithrombin III and fibrinolysis. The baseline risk of DVT in women not on OCPs is five cases in 100,000, but the risk for women taking OCPs triples to 15 cases in 100,000.

"A huge international study was done by the World Health Organization in 1995, looking at this DVT question. The data showed that for patients who were on Desogen®, the incidence seemed to be significantly higher (30 cases in 100,000)," Dr. Sillman said. There was much controversy, however, surrounding this report. A re-analysis of the data revealed that this most likely represented a case selection bias, with desogestrel and ethinyl estradiol being given to older, more high-risk women. Additional data show that older women on this drug are significantly less likely than their peers on other OCPs to have an MI, suggesting that it is not inherently a more "thrombogenic" pill. Concerning the cardiovascular risks of OCPs, although the effect on lipids is negligible, five percent of normotensive women develop hypertension on the agents, and ten percent of women with hypertension will have an increase in blood pressure (BP) while taking the pills, so monitoring of BP is advised.

Regarding the risk of cancer, a 1996 re-analysis of 54 studies demonstrated only a tiny increase in the risk of breast cancer in women taking OCPs. Current users were found to have a 24 percent increase in risk, which decreased after stopping the agents. As for adenocarcinoma of the cervix, there is a two-fold increased risk with OCPs. There is also an increase in risk for benign liver ademonas and gallstones.

Absolute contraindications for OCPs include a history of coronary artery disease, stroke, or DVT, a history of breast or endometrial cancer, severe liver disease or known hepatic adenoma (with severe liver disease, there is a concern that estrogen will be inadequately metabolized, and circulating levels will become significantly higher than planned), undiagnosed genital bleeding, and uncontrolled hypertension. OCPs should not to be used in women over 35 who smoke. Further, "there is relative contraindication for women under 35 who are heavy smokers," Dr. Sillman warned.

Proper Use of Oral Contraceptives

"How should you choose an OCP?" Dr. Sillman queried. In general, she advised choosing one with a low dose of progestin that is also low in androgenicity. Some examples are low dose norethindrone (Ovcon®, Necon®, Modicon®), desogestrel (Desogen®, Ortho-Cept®, Mircette®), and norgestimate (Ortho-Cyclen®, Ortho-Tri-Cyclen®). For patients who are hirsute and anovulatory (possible signs of polycystic ovarian syndrome), it is helpful to use a progestin with low androgenicity and a strong progestational effect to maximize endometrial atrophy. An example is ethynodiol diacetate (Demulen®, Zovia®). The best time to start therapy with an OCP is on the first Sunday after the menstrual period begins or on the first day of the menstrual period, Dr. Sillman confirmed. "The reason that we tell people to start on a Sunday is really for social reasons," she explained. "If she starts her OCP on a Sunday, she is not going to have a period on a weekend, and this can be a very good thing for one's social life. We encourage people to take their pills at the same time every day-this is particularly important with progestin-only pills-and to use a back-up method for the first seven days." Follow-up should be done at three months to check blood pressure and for side effects.

Managing Side Effects Successfully

Concerning side effects, Dr Sillman said, "many women stop taking their OCPs because they don't like the side effects, and there are many things that you can easily do to diminish the importance and troubling nature of these problems."

The most common complaint is irregular bleeding, which is frequently observed in the first three cycles of OCP use. "You need to reassure your patient when you write the prescription that this is very common and not something to worry about. However, if she has irregular bleeding in the fourth cycle or later, then you need to proceed with an evaluation," Dr. Sillman cautioned.

Other problems with OCPs include amenorrhea, which is due to progressive atrophy of the endometrium. This is not medically harmful but often causes concern in patients, Dr. Sillman noted, adding that if patients want their menses to return, they should be treated with 0.625 to 1.25 mg conjugated equine estrogen (oral Premarin®).

Nausea due to estrogen can be managed by decreasing the estrogen in the pill or by having the patient take her pills with food or at bedtime. Increased appetite, caused by progestins with higher androgenicity, often leads to weight gain and can be managed by switching to an OCP with lower progestational/androgenic activity. Increased fluid retention can be resolved by switching to an OCP with lower estrogenic activity. In addition, mood changes, thought to be due to progestin, can be improved by switching to an OCP with a lower progestin dose.

Tension headaches are not caused by OCPs, but if migraine headaches begin to occur and increase in frequency or severity, combination OCPs should be stopped, Dr. Sillman cautioned. "Patients who have first onset of migraine while on combination OCPs have been noted to have an increased risk of thrombotic stroke in some studies," she said. "A progestin-only contraceptive can be tried."

Injectable Contraceptives

The only injectible contraceptive available in the US is Depo-Provera®-150 mg of sterile medroxyprogesterone acetate suspension, given as an IM injection every 12 weeks. "This preparation is appropriate for every woman except those who wish to become pregnant within one year," Dr. Sillman said. Sterile medroxyprogesterone acetate suspension acts by inhibiting ovulation, and the ideal time to give it is within five days of the onset of menses. After injection, ovulation does not occur for at least 14 weeks.

"Depo-Provera® does not have any estrogen and therefore doesn't have the estrogen-associated problems of thrombosis and hypercoagulability. So, it is a great choice for women with coronary disease, the older smoker, and the patient with a history of DVT," Dr. Sillman advised. Interestingly, patients with sickle cell anemia have been shown to have hematologic improvement with sterile medroxyprogesterone acetate suspension.

Problems associated with this treatment option include irregular bleeding, amenorrhea, modest weight gain, headache, bloating, fatigue, depression, and decreased libido. On the positive side, the agent can decrease premenstrual symptoms, risk of PID, and risks of endometrial and ovarian cancers, and is also associated with a decreased frequency of seizures in women with seizure disorders.

Implantable Contraception

Implanted under the forearm, Norplant® consists of six silastic capsules, each filled with 36 mg of levonorgestrel. This form of contraception is effective for five years, Dr. Sillman announced. This levonorgestrel pill prevents ovulation in 60 to 70 percent of women. In addition, progestin-induced changes in cervical mucus and endometrial atrophy interfere with sperm mobility and inhibit implantation. According to Dr. Sillman, side effects include menstrual changes (irregular bleeding, amenorrhea) and headaches, and there is potential difficulty associated with removing the implants. Further, "asymptomatic ovarian cysts can develop in some women," she stated, adding that that they usually resolve spontaneously. As with serile medroxyprogesterone acetate suspension, there are no estrogen-related side effects.

Intrauterine Devices

Whereas intrauterine devices (IUDs) were once condemned due to studies showing high rates of pelvic inflammation with the Dalkon Shield, modern IUDs offer safe, effective contraception, Dr. Sillman reassured the audience. "Currently available IUDs are the Copper T 380A (ParaGard®), approved for ten years of use, and the Progestasert®, a progesterone-releasing IUD approved for one year of use," she said. The levonorgestrel IUD (LNg 20-IUD®) is approved for five years of use in several European and Asian-Pacific countries and may be approved for use in the United States soon.

Emergency Contraception

Sometimes the need arises for emergency contraception if a woman has been exposed to sperm and is at risk for unwanted pregnancy. Some of the options recommended by Dr. Sillman include:

• Ovral® (50 mg EE and 0.5 NG per pill): two white pills per dose, repeated 12 hours later. • Four pills per dose, repeated 12 hours later of Lo/Ovral®, Levlen®, Levora®, Nordette®, Tri-Levlen®, or Triphasil®. • Five pills per dose, repeated 12 hours later of Alesse® or Levlite®. • Preven®, a new emergency contraception kit (50 mg EE and 0.25 mg LN per pill): 2 pills per dose, repeated 12 hours later. • Plan B® kit (0.75 mg LN per pill): 1 pill per dose, repeated 12 hours later. Causes much less nausea than the above options. Not widely available yet. • Mifepristone® (RU 486): single 600 mg dose, available in Europe. • Insertion of copper-releasing IUD.

Dr. Sillman said that emergency contraceptive pills should be started within 72 hours of intercourse. The failure rates are less than two percent, but if the menstrual period is delayed beyond seven days, a pregnancy test should be considered.

The main problems with emergency contraception are nausea (30 to 50 percent of women) and vomiting (15 to 25 percent of women). This can be reduced with the use of ten milligrams of prochloroperazine (Compazine®) one hour before taking the pills, but if the patients vomits within one hour of taking the contraception, the dose should be repeated, Dr. Sillman advised.

In closing, Dr. Sillman said to her primary care audience, "I want you to feel empowered and happy about your role in providing your patients with good contraceptive advice and to recognize that you have a very important and valuable role to play in helping your patients control their fertility."