Relative Contraindications

Smoking (less than 15 cigarettes per day) at any age

History of migraine headache disorder

Hypertension

Fibroid tumors of the uterus

Breast-feeding

Diabetes

Women stop their oral contraceptives owing to side effects such as headaches, nausea, vomiting, or weight gain that occur during oral contraceptive use. Package labeling reports a higher incidence of these side effects, although it cannot be determined if they occurred because of the pill or just happened when the women were on the pill.1 One double-blind trial compared women taking oral contraceptives with women taking placebo for 6 months. A similar percentage of patients in each group experienced headaches, nausea, vomiting, mastalgia, and weight gain, and there were

no significant differences in the traditional "hormone-related" side effects. Given that oral contraceptives often are discontinued owing to side effects, proper counseling before initiation of COCs is necessary.

Between 30% and 50% of women complain of breakthrough bleeding or spotting when oral contraceptives are initiated. These side effects tend to resolve by the third or fourth cycle.1 Before changing formulations, other more serious causes of bleeding or spotting, such as pregnancy, infection, poor absorption of the oral contraceptive owing to drug interaction, or GI problems should be ruled out. Once these causes have been ruled out, the timing of the spotting must be determined in order to adjust the formulation appropriately.

Women who have spotting or bleeding before they finish their active pills need a higher progestin content to increase endometrial support. Either a monophasic formulation with a higher progestin or a triphasic formulation with an increasing dose of progestin would be appropriate. Women with continued bleeding after menses need more estrogen support. Either increasing the estrogen component or having a lower early progestin component (in triphasic pills) should be sufficient. If midcycle bleeding occurs, it is more difficult to determine the cause. It may be best to increase both the estrogen and progestin component for such women.1

Hormonal methods of contraception usually decrease the amount of withdrawal bleeding quite significantly, and patients need to be made aware of this. Lower-dose estrogen formulations may increase the risk of breakthrough bleeding. Switching to a higher estrogen formulation or to a triphasic formulation will help to minimize breakthrough bleeding and will increase the amount of withdrawal bleeding.

Acne, oily skin, and hirsutism are all side effects from progestins with increased androgenicity. Older progestins such as norgestrel and levonorgestrel have more an-drogenic effects, whereas agents containing norgestimate or desogestrel are less likely to have such side effects. If patients are complaining of such side effects, switching to a product with a lower risk of androgenic effects is appropriate.

GI complaints are seen often with oral contraceptives. Estrogen can induce nausea and vomiting via the CNS, whereas progesterone slows peristalsis, causing constipation and feelings of bloating and distention.1 Most women will adjust to the symptoms, and the symptoms often will resolve within 1 to 3 months. Taking the pill at bedtime or with food may be a good strategy to help cope with nausea. If women are unable to tolerate the GI side effects, then either a decrease in ethinyl estradiol to a low-dose 20 mcg formulation may minimize nausea or a decrease in progestin may minimize bloating and constipation. Progestin-only products may be considered if even low-dose ethinyl estradiol causes nausea.

Headaches are a common occurrence for women, and they must be evaluated because they can be a major warning sign for stroke. If headaches begin or become worse after initiation of COCs, all differential diagnoses must be considered. Blood pressure should be evaluated to rule out hypertension. If any neurologic symptoms or blurred vision occur with the headache, the oral contraceptive should be stopped immediately. Migraine headaches with aura showed a significant increase in the risk for ischemic stroke in one WHO study.17 If the headaches are not serious but still are troublesome to the patient, the following changes are suggested: (a) discontinue the oral contraceptive, (b) lower the dose of estrogen, (c) lower the dose of progestin, or (d) eliminate the pill-free interval for two to three consecutive cycles (for women with headaches during the pill-free interval only).1

Although rare, some women may complain of a decrease in libido. This often is found to coincide with feelings of depression. Alterations to vaginal lubrication and free testosterone levels may occur with some COCs, and both can relate to decreased

libido. Low levels of estrogen can decrease vaginal lubrication as well and make intercourse painful. Use of the vaginal hormonal ring (NuvaRing) may help with lubrication problems.1

Dyslipidemias can occur from hormone therapy. Estrogen is known to cause an increase in high-density lipoprotein cholesterol (HDL-C), triglycerides, and total cholesterol levels and to decrease low-density lipoprotein cholesterol (LDL-C). Androgenic progestins are more likely to decrease HDL-C and triglycerides and increase LDL-C. Depending on the ratio of estrogen to progestin content, the HDL-C, LDL-C, and triglyceride levels may fluctuate up or down. In women with no risk factors for dyslipidemias (e.g., women who do not smoke, have hypertension, or have a family history of heart disease), it is not necessary to obtain a baseline lipid panel. However, if the lipid panel is monitored, and if dyslipidemia occurs, then it is recommended to replace an androgenic progestin with a more estrogenic progestin. In women with triglyceride levels greater than 350 mg/dL (3.96 mmol/L) at baseline, estrogen-containing formulations should be used only with caution, and low doses of 20 to 25 mcg ethinyl estradiol or a progestin-only formulation might be preferred.1

Mastalgia can occur in up to 30% of women taking oral contraceptives and is most likely due to the estrogen component. The average woman has a 20% increase in breast volume in the luteal phase owing to venous and lymphatic engorgement. Estro gen also causes adipose cell hypertrophy in the breast.1 Lower-dose pills (20 mcg) produce less mastalgia than those with 35 mcg of ethinyl estradiol.2 If tenderness occurs prior to menses, switching to a contraceptive that offers extended cycle length (see Unique Oral Contraceptives below) may minimize problems as well.

Women often are concerned about using oral contraceptives for fear of gaining weight. It has been proven that oral contraceptives containing less than or equal to

35 mcg ethinyl estradiol do not increase the risk of weight gain in women compared 24

with placebo. Estrogen can cause hypertrophy of adipose cells, and therefore, women see an increase in measurement of their breasts, hips, and thighs.1 Decreasing the estrogen content of the COCs will minimize this effect. Weight gain associated with premenstrual fluid retention may occur with the combination of estrogen and a higher androgenic progestin. Switching to a lower-dose estrogen and a progestin with less androgenic activity may be beneficial in this situation.1

Additional side effects have been noted in some women. Women wearing contact lenses may have visual changes and more disturbances with lenses. If normal saline eye drops do not help, referral to an ophthalmologist is recommended. Melasma and chloasma can occur secondary to estrogen stimulation of melanocyte production. Women with darker pigmentation are more susceptible to hyperpigmentation effects. The melasma may not be completely reversible on discontinuation. Progestin-only products may be preferable, and sunscreen use is highly recommended.1

As described earlier, many of the side effects of COCs may be minimized by adjusting the estrogen or progestin content of the preparation. However, while low- and ultra-low-dose COCs may cause fewer side effects, it is important to note that in the event that doses are missed, such COCs may be more likely to result in contraceptive failure.

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