weight gain
Ethinyl Estradiol; Levonorgestrel (Triphasil) Adverse Reactions
Emergency Contraceptive Regimens:
In postcoital emergency contraceptive regimens, nausea/vomiting are the most frequently reported side effects. Of women using emergency contraception via the Yuzpe methods, 50% will report nausea, and 20% will have vomiting. Menstrual irregularity, changes in heaviness of bleeding, or spotting are also common. Seventy-five percent of women experience normal cycles. A pregnancy test is indicated if menstrual bleeding does not occur within 21 days of taking the emergency regimen. Headaches and breast tenderness occur in 10 - 20% of women taking emergency contraception. Other reported side effects, like abdominal discomfort or dizziness, occur in less than 1% of patients taking postcoital contraceptive regimens. Serious side effects are not common.
Routine and Continuous Contraception:
The following adverse reactions often subside after the first few months of routine and continuous OC therapy and require medical attention only if prolonged or bothersome: abdominal discomfort or cramps, anorexia or appetite stimulation, mild nausea with rare vomiting, fluid retention or edema with weight gain, azotemia, breast enlargement, and fatigue. In some cases, switching to an oral contraceptive combination of a different dose strength or estrogen to progestin ratio or combination can resolve troublesome effects. Changes in vaginal bleeding often occur after initiation of hormonal contraceptive therapy. Breakthrough bleeding and spotting are common during the first 3 months of use and may be more frequent with continuous contraception regimens (e.g., Seasonale®). During continuous contraception, approximately 1 in 3 women have 20 or more days of unplanned bleeding or spotting during active hormone administration during the first cycle of continuous administration; the frequency of breakthrough bleeding tends to decrease in the following cycles with continued use. When breakthrough bleeding occurs cyclically after the first 3 months of routine contraception, the time the menstrual irregularity occurs in the cycle can indicate which component (i.e., estrogen or progestin) requires adjustment. Amenorrhea can occur during or after treatment with oral contraceptives, but is relatively rare.
Breast changes that can occur during therapy with hormonal contraceptive agents include breast discharge, breast pain or tenderness (mastalgia), and galactorrhea.
Vaginal discharge or vaginal irritation due to candidiasis or vaginitis can occur during therapy with hormonal contraceptive agents.
Oral contraceptive use has been associated with various thromboembolic disorders. The risk for the development of deep venous thrombosis and/or pulmonary embolism is approximately 3 - 6 times greater in OC users than in nonusers. In several studies, the risk was reported to be higher in smokers compared with nonsmokers. Both hormone amount and hormone type may be important factors regarding rates of thromboembolic disorders. Estrogens decrease levels of antithrombin-III and increase the production of blood clotting factors VII, VIII, IX and X; risks increase with ethinyl estradiol doses > 50 mcg/day. Women who took OCs containing certain types of progestin (e.g., desogestrel or gestodene) had an increased risk (adjusted RR = 1.9) for nonfatal venous thromboembolism compared with women who took OCs containing levonorgestrel. However, association of increases in thromboembolism risk with newer progestins cannot be proved due to limitations and inconsistencies in the results of several of these observational studies. No consistent differential effects on hemostasis with the newer progestins( e.g., desogestrel, gestodene) have been established versus older progestins.
Regarding stroke and OC use, risk may be related to the amount of estrogen as well as the type of progestin, although this issue is controversial. Early epidemiological studies showed an increased risk for stroke, as well as myocardial infarction and venous thromboembolism, however these studies assessed OCs containing more than 50 mcg of ethinyl estradiol. Use of OCs containing lower amounts of estrogen (i.e., <= 35 mcg ethinyl estradiol) has not been associated with an overall increased risk of stroke in more recent studies. Conflicting data exist, however, regarding the association of OC use and hemorrhagic stroke. In one study, norgestrel-type progestins (e.g., levonorgestrel) were associated with a higher risk of hemorrhagic stroke (odds ratio = 3.28) compared with non users of OCs. Another study, however, showed no increased risk of hemorrhagic stroke in users of levonorgestrel-containing OCs. Therefore, although the risk of stroke in users of OCs appears to be related to estrogen amount (i.e., increased risk has been demonstrated with products containing >= 50 mcg but not for products containing <= 35 mcg of ethinyl estradiol), further studies are needed to clarify the relationship of type of progestin to risk of stroke in users of OCs.
Cardiovascular adverse reactions are associated with hormonal contraceptive therapy. Hypertension can occur within a few months of initiating therapy and the prevalence increases with duration of use and patient age. There appears to be some correlation of hypertension with the progesterone concentration. Close monitoring of blood pressures is recommended for patients at risk for hypertension; blood pressures usually return to normal after discontinuation of therapy. Hormonal contraceptive therapy has been considered a risk factor for myocardial infarction (MI), especially with the use of products containing > 50 mcg of ethinyl estradiol. In a recent pooled-data analysis from 2 large United States sites, women between the ages of 18 - 44 years old who had no prior incidence of coronary heart disease (CHD) or cerebrovascular disease prior to their MI event were studied for relative risk related to low-dose oral contraceptives. After adjustment for ethnicity and major established risk factors for CHD, there was no evidence of increased risk of MI associated with OC use. Most other recent studies have concurred. One major exception was the WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. This international multicenter case-control study found a 5-fold increased risk of MI associated with current OC use. The authors, however, concluded that the increased risk may reflect more frequent use of OCs internationally in populations at higher risk, such as smokers and those with pre-existing cardiovascular risk factors. Of note is that no increased risk of MI was noted in the WHO study in women who were non-smokers and who had blood pressure screening prior to receiving OCs. Smoking is a well known additive risk to hormonal contraceptive therapy, increasing the relative risk of MI by five-fold. There is a 10 - 12 fold increase in risk of MI in patients who use hormonal contraceptive therapy and smoke compared to females who do not smoke or use OCs. Thus one would expect a higher incidence of MI in any woman taking oral contraceptives who has known risk factors. Other reactions include fluid retention and edema.
Ocular disorders can occur during therapy with hormonal contraceptive agents. These can include optic neuritis, diplopia, loss of vision, or retinal thrombosis. Estrogens can cause keratoconus. A conical cornea develops from steepening or increased curvature of the cornea, caused by thinning of the stroma. Patients with contact lenses may develop intolerance to their lenses. Any change in vision or visual acuity should be examined by an ophthalmologist. Hormonal contraceptive agents should be discontinued in patients developing any unexplained visual disturbance.
Mood or personality changes occur commonly in women taking hormonal contraceptive agents. These changes include mental depression, anxiety, libido decrease, frustration, anger, or other emotional outbursts.
The relationship of migraine headache and the administration of hormonal contraceptive agents is not clearly defined. A number of changes can occur when a woman initiates oral contraceptive therapy and include 1) migraines can appear for the first time, 2) a change in frequency, severity and duration of migraine headaches may be seen, or 3) an improvement or decrease in the occurrence of migraine headaches. When initiating therapy an individual’s migraine pattern should be observed; if migraines worsen consider discontinuing therapy.
Estrogens can cause a variety of dermatological reactions. Melasma, in the form of tan or brown patches, may develop on the forehead, cheeks, temples and upper lip. These patches may persist after the drug is discontinued. Photosensitivity can be experienced with oral contraceptive use and protective clothing and sunscreens should be employed when exposed to sunlight or UV light. Other dermatologic reactions are infrequent and include maculopapular rash, urticaria, erythema nodosum, alopecia, or hirsutism. Other erythematous eruptions may occur. Although oral contraceptives can be used to treat acne vulgaris, in some cases they may induce or aggravate an existing acne vulgaris. Oral contraceptives have not been shown to increase the incidence of skin cancer of any type, including melanoma.
Some women taking oral contraceptives notice tenderness, swelling, or minor bleeding of their gums, which may lead to gingivitis. Proper attention to oral care and regular dental visits are recommended.
Major adverse GI reactions are uncommon during therapy with hormonal contraceptive agents. Nevertheless, abdominal pain can indicate cholelithiasis or cholecystitis, cholestasis, hepatitis (and elevated hepatic enzymes), peliosis hepatis, or pancreatitis. Most case-control studies have shown a relationship between oral contraceptives and the incidence of benign hepatoma and hepatocellular carcinoma. Risk may increase with increasing duration of use. It must be noted that many studies of liver cancer and OCs have not controlled for the presence of the hepatitis B virus. Infection with hepatitis B has a strong correlation with the pathogenesis of hepatic cancer, and exclusion of this important variable in the OC studies makes it difficult to interpret true risk. Only one case of death related to liver cancer has been reported in the past 20 years of studies of OCs. Given the overall rarity of hepatocellular cancer in any population, the risk to women taking OCs is probably negligible. However, because liver tumors may spontaneously rupture and produce life-threatening hemorrhage, it is important to be aware of the possibility that tumors could occur. Hormonal contraceptive agents should be discontinued in any patient developing jaundice or severe abdominal pain.
The relationship between hormonal contraceptive use and certain types of secondary malignancy is controversial. The information from any study must be balanced with the knowledge that virtually all epidemiologic data on cancer risks and combined oral contraceptive use pertain to women younger than 60 years of age because oral contraceptives (OCs) were first available for general use in the early 1960’s. The World Health Organization (WHO), after a thorough review of published data, has classified combined estrogen-progestin oral contraceptives as carcinogenic in the development of breast, cervical, and hepatocellular cancer. However, there continues to be some controversy regarding the use of OCs and the risk of developing breast cancer as several large, well designed observational studies have provided conflicting data. It should be noted that the increased risk of breast cancer is small, and is only relevant in current or recent users (i.e., within the last 10 years).The breast cancer studies noted pertain to the use of OCs for the purpose of contraception, and may not apply to the use of OCs as hormone-replacement therapy alternatives in the perimenopausal woman (i.e., use of hormones later in life). The issue of prescribing hormonal contraceptives to women with a family history of breast cancer remains controversial. All women should be advised to report breast enlargement, lumps or unusual breast discharge (e.g., galactorrhea) to their health care professionals. If breast cancer is suspected in a woman who is taking hormonal contraceptives, the contraceptive should be discontinued. An association between oral contraceptive use and cervical cancer has been demonstrated. However, studies of cervical dysplasia and carcinoma in situ have been difficult to interpret due to the presence of confounding factors, such as difference in sexual practices and the presence of human papillomavirus (HPV). There has been suggestion that OCs may in some way act as a promoter for HPV-induced cancer, but this is speculative. In most studies, risks of cervical cancer begin to increase after 2 years of use and become clinically significant after 5 years of use. A meta-analysis of 14 studies in over 3800 women showed a summary relative risk of invasive cervical cancer of 1.37 after 4 years of use; relative risk increased to 1.6 after 8 years of use. Because a potential for cervical dysplasia may exist, it is prudent to regularly evaluate patients on OCs via cervical cytology screening on an annual basis.
A meta-analysis of 10 studies indicated significant trends in decreasing endometrial and ovarian carcinoma risks with increased duration of combined OC use. Risk of endometrial or ovarian cancers may be reduced by up to 60% with 4 or more years of use. Current evidence suggests OCs do not protect against hereditary forms of ovarian cancer (e.g., women who carry BRCA1 or BRCA2 gene alterations).
[ Last revised: 8/5/2005 11:14:00 PM ]
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