A common side effect of oral combined hormonal contraceptives (CHCs) is breakthrough bleeding and spotting, especially during the first 3 months of CHC use. Menstrual irregularity is reported infrequently with CHCs. Oligomenorrhea and amenorrhea (defined as at least 1 of 6 cycles with a missed withdrawal bleed) are also reported. Menstrual cramps or dysmenorrhea, changes in menstrual flow, and premenstrual syndrome have also been reported during CHC use. If the patient has not adhered to the prescribed dosing schedule, consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses 2 consecutive periods, rule out pregnancy. A change to another CHC formulation may resolve irregularities that continue to occur during use.[43312] [50744] [62071]

Breast tenderness or mastalgia, breast enlargement, and breast discharge or secretion have been reported in patients receiving oral combined hormonal contraceptives (CHCs) and are believed to be drug-related. Possible lactation suppression may occur when CHCs are given in the immediate postpartum period.[43312] [50744] [62071]

Combined hormonal contraceptive (CHC) recipients have reported the following adverse vaginal and cervical reactions that are believed to be drug-related: vaginal candidiasis, bacterial vaginitis, and change in cervical ectropion and secretion. Vaginal discharge may be noted if vaginal candidiasis or vaginitis occurs. Urogenital adverse events such as cystitis-like syndrome have also been reported.[43312] [50744] [62071]

Headache is a relatively common adverse reaction reported with use of oral combined hormonal contraceptives (CHCs). Discontinue the CHC if new migraines are recurrent, persistent, or severe or if there is an increased frequency or severity of migraines during CHC use (which may be prodromal of a cerebrovascular event). A migraine with aura can increase the risk for cerebrovascular accidents.[43312] [50744] [62071]

Desogestrel; ethinyl estradiol combined hormonal contraceptives (CHCs) may cause edema (fluid retention) and weight gain. Postmarketing, both increased and decreased weight have been reported, as well as peripheral edema and changes in appetite (increase or decrease). There is an increased risk of hypertension in CHC users. Studies suggest that approximately 41.5 cases of hypertension per 10,000 person-years in the U.S. can be attributed to CHC use. Increased blood pressure is more likely in older people with an extended duration of CHC use. Discontinue the CHC if significant elevation of blood pressure occurs. Blood pressures usually return to normal after discontinuation of therapy, and no difference in the occurrence of hypertension exists among ever- and never-users.[43312] [50744] [62071] 

Combined hormonal contraceptives (CHCs) such as desogestrel; ethinyl estradiol are associated with an increased risk of thromboembolic and thrombotic disease. The risk for the development of VTE, such as deep venous thrombosis and/or pulmonary embolism is approximately 3 to 6 times greater in CHC users than in nonusers. In several studies, the risk was reported to be substantially higher in smokers compared with nonsmokers, and especially if the smoker was over 35 years of age. The relative risk of venous thromboembolism (VTE) in people who have predisposing conditions is twice that of those without such medical conditions. The risk of VTE due to CHC use gradually disappears after the CHC is discontinued. VTE risk is highest in the first year of use and when a CHC is started or re-started after a break in use of 4 weeks or more. 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 of more than 50 mcg/day. Serious thromboembolic events, such as heart attack or cerebrovascular accidents, are reported rarely in users of CHCs who do not smoke.[48201] Thrombosis/thromboembolism (coronary artery, pulmonary, cerebral, deep vein, mesenteric), thrombophlebitis and myocardial infarction have also been reported with postmarketing CHC use.[43312] [50744] [62071]

An increase in both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes with intracranial bleeding) has been shown in users of CHCs such as desogestrel; ethinyl estradiol. The risk is greater among people over 40 years of age, smokers, and in individuals with hypertension, dyslipidemia, diabetes, or obesity. In smokers, the risk for stroke increases with age, particularly in those 35 years of age and older, and with the number of cigarettes smoked.[48201] [43312] [50744] [62071]

During postmarketing use of desogestrel; ethinyl estradiol and other combined hormonal contraceptives (CHCs), the following ocular adverse effects have been reported: corneal thinning (keratoconus), and a change in corneal curvature (steepening). Contact lens intolerance may occur in some patients. Rarely, retinal thrombosis may occur, but may cause vision loss. Stop the CHC regimen if there is unexplained loss of vision or visual impairment, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately. While optic neuritis and cataracts have been reported in some CHC users, the association with CHC use has been neither confirmed nor refuted.[43312] [50744] [62071]

Desogestrel; ethinyl estradiol and other combined hormonal contraceptives (CHCs) have been reported to cause hypersensitivity and dermatologic adverse events. Acne vulgaris is infrequently reported; alopecia, rash (allergic), pruritus, hirsutism, erythema multiforme, erythema nodosum, and hemorrhagic eruption have also been reported. Anaphylactoid reactions, urticaria, angioedema, and severe reactions with respiratory (dyspnea) and circulatory symptoms have also been reported. Melasma, a brown patchy skin discoloration, may occur and persist after the CHC is discontinued.[43312] [50744] [62071] Photosensitivity has also been reported rarely with CHC use.[57603]

Nausea (mild and infrequent), vomiting, abdominal pain or cramps, bloating, and pancreatitis have been reported during use of combined hormonal contraceptives (CHCs), including desogestrel; ethinyl estradiol. Gallbladder disease (e.g., cholestasis, cholelithiasis, cholecystitis), hepatic adenoma, colitis, and hemangioma of the liver have been reported during postmarketing experience.[43312] [50744] [62071] Withhold or permanently discontinue the CHC if there are persistent or significant elevated hepatic enzymes or if jaundice occurs. Rare but serious GI system events which may occur with CHC use include cholestatic jaundice, peliosis hepatis, Budd-Chiari syndrome, or hepatic vein obstruction. Peliosis hepatis, a very rare consequence of taking estrogens and CHCs, is characterized by the presence of blood-filled spaces.[51257] In rare cases, CHCs can cause benign but dangerous liver tumors. Indirect calculations have estimated the attributable risk of hepatoma to be in the range of 3.3 cases per 100,000 users, a risk that increases after 4 or more years of use. These benign liver tumors can rupture and cause fatal internal bleeding.[43312] [50744] [62071]

Psychiatric system disorders reported with desogestrel; ethinyl estradiol or other combined hormonal contraceptive (CHC) regimens include mood swings or emotional lability (infrequent per other CHC studies), depression, anxiety or nervousness, and changes in libido (libido increase or libido decrease). Discontinue the CHC regimen if depression occurs to a significant degree.[43312] [50744] [62071]

Dizziness has been reported as a nervous system adverse effect with desogestrel; ethinyl estradiol and other combined hormonal contraceptive (CHC) regimens.[43312] [50744] [62071]

Combined hormonal contraceptives (CHCs) can alter certain laboratory tests. Estrogens may increase the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. Endocrine, metabolic or nutritional system effects that have been reported with desogestrel; ethinyl estradiol CHCs include reduced tolerance to carbohydrates resulting in impaired glucose tolerance or hyperglycemia. Those with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using CHCs which may increase the risk of pancreatitis. A decrease in serum folate levels has also been reported.[43312] [50744] [62071]

Porphyria has been reported with use of oral combined hormonal contraceptives (CHCs) such as desogestrel; ethinyl estradiol.[43312] [50744] [62071] Aggravations of varicose veins, exacerbation of systemic lupus erythematosus (SLE), and exacerbation of chorea have been reported and may be drug-related.[62071]

Renal effects reported with combined hormonal contraceptives (CHCs) have included impaired renal function and hemolytic-uremic syndrome; however, the association of CHCs to these effects has been neither confirmed nor refuted.[43312] [50744] [62071]

Some people taking combined hormonal 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 during desogestrel; ethinyl estradiol use.

The issue of hormonal influences on the development of cancers (new primary malignancy) has been widely researched for many decades. Most studies have been performed with oral combined hormonal contraceptives (CHCs), and the risks related to CHCs, regardless of route of administration, are thought to be similar. In general, the data suggest an increased risk of cervical cancer among CHC users, with a decreased risk for endometrial and ovarian cancers.[43312] [50744] [62071] Epidemiology studies have not found a consistent association between use of CHCs and breast cancer risk. Studies do not show an association between ever (current or past) use of CHCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (less than 6 months since last use) and current users with longer duration of COC use.[62904] Several large, well-designed observational studies have provided data regarding the risk of breast cancer with CHC use.[27233] [24750] [27234] Breast cancers diagnosed in current or previous CHC users tend to be less advanced clinically than in never-users. The risk of breast cancer is only slightly increased in current and recent CHC users (i.e., within 10 years); however, 10 years after CHC cessation, the risk of breast cancer appears to be similar to that in those patients that have never used CHCs.[62647] From one large study published in 2017, the risk of breast cancer was higher among women who currently or recently used contemporary CHCs than among women who had never used CHCs, and this risk increased with longer durations of use; however, absolute increases in risk were small. The absolute risk of breast cancer associated with any CHC use was 13 per 100,000 women-years, which corresponds to 1 extra case of breast cancer for every 7,690 CHC users in 1 year.[62904] Moreover, the same study data suggest that any increased risk of breast cancer usually disappears rapidly after an interruption in the use of CHCs.[62904] There continues to be controversy regarding the risk of CHC use in women with a family history of breast cancer (e.g., BRCA mutations). However, evidence does not suggest that the increased risk for breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes is modified by the use of CHCs.[48201] Patients should be instructed to perform monthly self-breast examination and report any breast changes, lumps, or discharge to their health care professional. If breast cancer is suspected, CHCs should be discontinued.[43312] [50744] [62071] Some studies suggest that CHC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia; however, such findings may be due to differences in sexual behavior, presence of the human papillomavirus (HPV) and other factors. HPV is thought to be the cause of more than 90% of all cervical cancers, although hormonal factors may influence risk. The relative risk of invasive cervical cancer is 1.37 after 4 years of use; relative risk increased to 1.6 after 8 years of CHC use. Because a potential for cervical dysplasia may exist, regularly evaluate patients taking CHCs via cervical cytology screening as recommended per standards of care.[62647] A meta-analysis of 10 studies indicated significant trends for a reduced risk for endometrial and ovarian cancer with increased duration of CHC use. Risk of endometrial or ovarian cancers may be reduced by up to 60% with 4 or more years of use.[25198] Data suggest CHCs do not protect against hereditary forms of ovarian cancer (e.g., women who carry BRCA1 or BRCA2 gene alterations).[25199] Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (more than 8 years) CHC users. However, these cancers are rare in the U.S., and the attributable risk (the excess incidence) of liver cancers in CHC users approaches less than 1 per million users.[62647][43312] [50744] [62071]

Combined hormonal contraceptives (CHCs), such as desogestrel; ethinyl estradiol, do not protect against human immunodeficiency virus (HIV) infection or other sexually transmitted disease. Patients infected with HIV or with known acquired immunodeficiency syndrome (AIDS) should be aware that the use of a CHC will not prevent the transmission of HIV or other sexually transmitted diseases to their partner(s).[43312] [50744] [62071]

Combined hormonal contraceptive agents are contraindicated in patients with a current or past history of stroke, cerebrovascular disease, coronary artery disease, coronary thrombosis, myocardial infarction, thrombophlebitis, thromboembolism or thromboembolic disease, or valvular heart disease with complications. Hormonal combined oral contraceptives (COCs) have been associated with thromboembolic disease such as deep venous thrombosis (DVT) and pulmonary embolism (PE). COCs are also generally contraindicated in women who have thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., subacute bacterial endocarditis with valvular disease, or atrial fibrillation), or known inherited or acquired hypercoagulopathies (e.g., protein S deficiency, protein C deficiency, Factor V Leiden, prothrombin G20210A mutation, antithrombin deficiency, antiphospholipid antibodies). Because tobacco smoking increases the risk of thromboembolism, DVT, myocardial infarction, stroke and other thromboembolic disease, patients receiving COCs are strongly advised not to smoke. Risk is especially high for female smokers over the age of 35 years or those who smoke 15 or more cigarettes per day. Therefore, COCs are generally considered contraindicated in women over the age of 35 years who are tobacco smokers. A positive relationship between estrogen dosage and thromboembolic disease has been demonstrated, and oral products containing 50-mcg ethinyl estradiol should not be used unless medically indicated. In addition, certain progestins may increase thromboembolic risk. The overall risk of venous thromboembolism in women using COCs has been estimated to be 3 to 9 per 10,000 woman-years. Preliminary data from a large, prospective cohort safety study suggests that the risk is greatest during the first 6 months after initially starting COC therapy or restarting (following a break from therapy 4 weeks or more) with the same or different combination product. The risk of arterial thromboses, such as stroke and myocardial infarction, is especially increased in women with other risk factors for these events. Pre-existing high blood pressure, kidney disease, hypercholesterolemia, hyperlipidemia, diabetes with vascular disease, and morbidly obese patients may also increase risk. After a COC is discontinued, the risk of thromboembolic disease due to oral contraceptives gradually disappears. Because of their association with elevations in blood pressure, COCs should be used cautiously in patients with mild to moderate hypertension or kidney disease; use is contraindicated in patients with uncontrolled or severe hypertension or hypertension with vascular disease. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use. The incidence of hypertension increases with increasing concentration of progestin. Blood pressure should be monitored closely in individuals with high blood pressure; discontinue desogestrel; ethinyl estradiol if blood pressure rises significantly. COCs may also cause fluid retention, and patients predisposed to complications from edema, such as those with renal disease or cardiac disease, should be closely monitored.[43312] [50744] [62071] [48201]

Surgery can increase the risk for thromboembolism from combined hormonal contraceptives (CHCs). If feasible, discontinue desogestrel; ethinyl estradiol products at least 4 weeks before and through 2 weeks after major surgery or other procedures known to have an elevated risk of thromboembolism, and during and following any prolonged immobilization.[43312] [50744] [62071]

Because of the increased potential for embolic risk, combined hormonal contraceptives (CHCs) containing desogestrel; ethinyl estradiol are contraindicated in people who currently have diabetes mellitus and are more than 35 years of age, diabetes mellitus with hypertension or with vascular disease or end-organ damage, or diabetes mellitus of greater than 20 years duration. People with diabetes mellitus should be observed for changes in glucose tolerance when initiating or discontinuing CHCs, since estrogens may exacerbate diabetes. Altered glucose tolerance secondary to decreased insulin sensitivity has been reported.[30858] [43312] [50744] [62071]

People who are being treated for dyslipidemia should be followed closely if they elect to use combined hormonal contraceptives (CHCs). Some progestogens may elevate LDL levels and may render the control of hyperlipidemia more difficult. Those with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using CHCs.[43312] [50744] [62071]

Desogestrel; ethinyl estradiol combined hormonal contraceptive (CHC) products are contraindicated in people with migraine or other headache that is accompanied by focal neurological symptoms, such as aura, or those more than 35 years of age with any migraine headaches. The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of CHCs and evaluation of the cause. A migraine with focal neurologic visual changes should be medically evaluated, as such changes may indicate cerebrovascular events.[30858] [43312] [50744] [62071]

There have been clinical case reports of retinal thrombosis associated with the use of combined hormonal contraceptives (CHCs); people with a history of retinal thrombosis should not receive CHCs. A CHC should be discontinued if there is unexplained visual disturbance, such as partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. Estrogens can increase the curvature of the cornea; patients using contact lenses wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.[30858] [43312] [50744] [62071]

Exogenous estrogens may induce or exacerbate symptoms of angioedema in individuals with hereditary angioedema.[43312]

Combined hormonal contraceptives (CHCs) are contraindicated for use in people with acute or chronic hepatic disease with abnormal liver function, such as acute hepatitis or decompensated cirrhosis. In general, CHCs are also contraindicated in those with history of cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use. Discontinue the CHC if jaundice or cholestasis develops during CHC use. Acute or chronic disturbances of liver function may necessitate CHC discontinuation until markers of liver function return to normal and CHC causation has been excluded. Liver conditions for which estrogen-containing birth control is inappropriate include acute hepatitis, Budd-Chiari syndrome, decompensated cirrhosis (cirrhosis with hepatic decompensation or complications, such as ascites or confusion), a liver transplant that is not working well, or benign or cancerous liver tumors. Patients with hepatitis C infection who are being treated with ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, are also contraindicated to receive CHCs due to a risk for elevated hepatic enzymes and hepatotoxicity. During clinical trials with the hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir (with or without dasabuvir), ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in those using ethinyl estradiol-containing medications. Discontinue CHCs prior to starting hepatitis C therapy with ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; CHCs can be restarted approximately 2 weeks following completion of treatment with these hepatitis C combination drug regimens.[43312] [50744] [62071] [48201] [70437]

Use of combined hormonal contraceptives (CHCs) is contraindicated in patients with benign or malignant liver tumors, such as hepatic adenoma or hepatocellular cancer. Benign hepatic adenomas are associated with CHC use, although the incidence of these benign tumors is rare. The attributable risk (the excess incidence) is 3.3 cases/100,000 CHC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Rupture of rare, benign hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (more than 8 years) CHC users. However, these cancers are extremely rare in the U.S. and the attributable risk of liver cancers in CHC users is less than 1 per million CHC users.[43312] [50744] [62071] [48201] [70437]

Studies suggest a small increased relative risk of developing gallbladder disease among combined hormonal contraceptive (CHC) users.[48201] [62071]

Given the increased prevalence of hypercoagulable states in people with systemic lupus erythematosus (SLE) (in particular antiphospholipid antibodies and lupus anticoagulant) and the risk factors for thromboembolism, consider risks vs. benefit of combined hormonal contraceptive (CHC) use. Avoid CHCs in SLE patients with a history of venous or arterial thrombosis or the presence of a hypercoagulable state. If CHCs are initiated in SLE patients without hypercoagulable states, choose a low-dose estrogen contraceptive (e.g., ethinyl estradiol 35 mcg per day or less); consider use of a progestin-only contraceptive. CHCs have also been reported to induce, unmask, or exacerbate SLE; more data are needed.[31435] [48201]

Mood disorders, like depression, may be aggravated in women taking combined hormonal contraceptives (CHCs). Data regarding the association of CHCs with onset of depression or exacerbation of existing depression are limited. If significant depression occurs, desogestrel; ethinyl estradiol should be discontinued.[43312] [50744] [62071]

Discontinue desogestrel; ethinyl estradiol if pregnancy is detected as there is no reason to continue combined hormonal contraceptives (CHCs) during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. The administration of CHCs to induce withdrawal bleeding should not be used as a test for pregnancy. CHCs should not be used during pregnancy to treat threatened or habitual abortion. For any CHC user who has missed 2 consecutive periods, pregnancy should be ruled out before continuing CHC use. If the CHC user has not adhered to the prescribed schedule, consider the possibility of pregnancy at the first missed period; discontinue the CHC until pregnancy is ruled out.[30858] [43312] [50744] [62071]

Manufacturers recommend avoidance of combined hormonal contraceptives (CHCs) during breast-feeding until the lactating individual has completely weaned their child. Small amounts of hormonal contraceptive steroids (estrogens and progestins) have been identified in human milk and a few reports of effects on the infant exist, including jaundice and breast enlargement.[43312] [50744] [62071] The U.S. Medical Eligibility Criteria state that postpartum breast-feeding individuals should not use CHCs during the first 3 weeks after obstetric delivery because of the increased risk for venous thromboembolism, and generally should not use CHCs through the fourth week postpartum because of concerns about potential effects of estrogen on breast-feeding performance during the establishment of lactation. Postpartum individuals with other risk factors for venous thromboembolism generally should not use CHCs until 4 to 6 weeks after delivery. CHCs may be used after 6 weeks postpartum without restriction as thromboembolism risk returns to baseline; if breast-feeding and taking a CHC, general monitoring of the breastfed infant for appetite changes, breast changes, and proper weight gain/growth should occur.[48201] One study found that low-dose CHCs (e.g., 10 mcg per day ethinyl estradiol) may not adversely affect lactation.[48200] However, a systematic review concluded that the available evidence, even from randomized controlled trials, is limited and of low quality; proper trials are needed.[48202] The World Health Organization (WHO) has published contraceptive criteria recommendations that are more restrictive than U.S. recommendations; the WHO criteria state CHCs should not be used in an individual who is breast-feeding before 42 days postpartum and that the disadvantages of using CHCs generally outweigh the advantages between 6 weeks and 6 months postpartum in this group.[48204] Alternate contraceptive agents to consider for the breast-feeding individual include non-hormonal contraceptive methods (e.g., copper IUD, barrier methods) and progestin-only contraceptives (e.g., medroxyprogesterone contraceptive injections, norgestrel oral contraceptive, levonorgestrel IUDs).[48201]

Combined hormonal contraceptives (CHCs) are contraindicated in people with a history of, or known or suspected breast cancer, which may be hormonally-sensitive. Individuals taking CHCs should receive clinical breast examinations and perform monthly self-examinations as recommended by their health care professional based on patient age, known risk factors, and current standards of care. Epidemiology studies have not found a consistent association between use of CHCs and breast cancer risk. Studies do not show an association between ever (current or past) use of CHCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (less than 6 months since last use) and current users with longer duration of CHC use.[43312] [50744] [62071] [48201] If breast cancer is suspected during CHC use, the contraceptive should be discontinued.[48201] Several large, well-designed observational studies have provided data regarding the risk of breast cancer with CHC use.[27233] [24750] [27234] [62647] From one large study published in 2017, the risk of breast cancer was higher among women who currently or recently used contemporary CHCs than among those who had never used CHCs, and this risk increased with longer durations of use; however, absolute increases in risk were small. The absolute risk of breast cancer associated with any hormonal contraceptive use was 13 per 100,000 women-years, which corresponds to 1 extra case of breast cancer for every 7,690 CHC users in 1 year. The same study data suggest that any increased risk of breast cancer usually disappears rapidly after an interruption in the use of CHCs.[62904] There continues to be controversy regarding the risk of CHC use by individuals with a family history of breast cancer (e.g., BRCA mutations). However, evidence does not suggest that the increased risk for breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes is modified by the use of CHCs.[48201]

Combined hormonal contraceptives (CHCs) are contraindicated in the presence of cervical cancer or other estrogen-responsive tumors. Most cervical cancers are related to the presence of the human papillomavirus (HPV), but hormonal factors influence risk. In women taking CHCs, studies have found an increased risk of cervical cancer compared with never-users. The risk appears to increase with duration of use and appears to decline when CHCs are discontinued. Clinical surveillance of all individuals using CHCs is important; perform pelvic examination and other diagnostic or screening tests, such as cervical cytology, as clinically indicated or as generally recommended based on age, risk factors, and other individual needs.[48201] [43312] [50744] [62071]

The estrogen component of combined oral hormonal contraceptives may raise the serum concentrations of thyroid-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. Doses of thyroid hormone replacement for hypothyroidism may need to be increased, as indicated by clinical and laboratory monitoring for the individual. Cortisol replacement therapy (e.g., corticosteroid therapy) may also need adjusted for some patients.[43312] [50744] [62071] 

Combined hormonal contraceptives (CHCs) are contraindicated in people with known endometrial cancer or other estrogen-dependent tumors (e.g., vaginal cancer, uterine cancer, ovarian cancer), as such tumors are hormonally-sensitive. CHCs are also contraindicated in people with undiagnosed vaginal bleeding; evaluate such patients before use to determine if a contraindication to use exists.[48201] [43312] [50744] [62071] The use of CHCs appears to have a protective effect against some cancers. A meta-analysis of 10 studies indicates a significant trend in decreasing endometrial and ovarian cancer risk with increasing duration of CHC use. The beneficial effects of CHCs in this regard may persist for 15 years or more after CHC use ceases.[25198] [48201] [62647]

Avoid combined hormonal contraceptives (CHCs) in persons with a history of chloasma gravidarum or increased sensitivity to sun and/or ultraviolet radiation exposure. Chloasma (melasma) may occur with CHC use, especially in people with a history of chloasma gravidarum.[43312] [50744] [62071]

Preexisting morbid obesity is one factor that may increase cardiovascular or thromboembolic risks associated with combination hormonal contraceptives (CHCs). Consider the presence of obesity and other underlying risk factors that may increase the risk of cardiovascular disease or thromboembolism, particularly for people more than 35 years of age.[43312] [50744] [62071] Limited literature suggests that the effectiveness of some hormonal contraceptive formulations might decrease with increasing body mass index (BMI). However, the evidence is conflicting; there are also data to suggest that the efficacy of most CHC products (with a few known exceptions) does not seem to be compromised in those who are overweight.[48201] [66895]