Side effects of oral contraceptives

Posted On April 26, 2018

Oral contraceptives are widely used world over, but it’s use in India is comparitively less, due to fear of side effects. Following is a brief account of side effects of oral contraceptives.

Major side effects Minor side effects
Increased incidence of CVS diseases, viz venous thromboembolism, heart attack including ischaemic heart disease, cerebrovascular disease or stroke and hypertension. Break through bleeding, amenorrhoea
Weak association between long term use of OC and breast cancer diagnosed before the age of 36. Breast tenderness or fullness
Reduced glucose tolerance Nausea
Cholestasis Weight gain
Clotting disorders, Pulmonary embolism.  


Abnormal thyroid and adrenal function Decreased libido
Changes in lipid and lipoprotein metabolism Less commonly, dermatologic effects, like acne, gum inflammation, increased viral infections, cervical ectropion (which may increase the risk of chlamydia),



Oral contraceptives are least used in India, China and Japan.  However, with increasing urbanization and change in life style, there is an increased demand for the pill in India also.  With newer molecules being marketed to avoid the side effects produced by older preparations, it is necessary to remain appraised of the side effects caused by “pill” as well as the effects it may have on various medical conditions.

To enumerate in short, the side effects caused by oral contraceptive pils(OC’s) could be major or minor, and they are listed in the table below.

  Women may not accept OC as a method of contraception as they are afraid of side effects, but seldom abandon the use of OC’s due to side effects per se.  Lacks of accessibility, failure to take the drug regularly, etc are more common reasons for discontinuation. The most common treatment-related adverse effects are headache, nausea, breast tenderness, and weight gain.

Nausea,bloating : Found occasionally in a few patients, it is usually not very bothersome.  Low fat,low residue, spaced meals, reduce functional nausea.  In addition, changing the OC to a high progesterone, low estrogen combination could be tried.  The symptoms of bloating or swelling begins in the active week before the hormone-free interval and is most prevalent during that time3.

Break through bleeding:  Breakthrough bleeding is greatest in the first 3 months and it’s frequency decreases after that. Low dose oestrogen pills containing 20 microgram of estrogen are more likely to produce disorders in cycle control.  It is even more frequent in women taking COC 15-μg Ethinyle Estradiol (EE) than in those using 20-μg EE. Pills containing norethisterone produce more irregularities than those containing levonorgestrel.

If the woman could be reassured that bleeding will not reduce contraceptive efficacy and that it is only the result of the endometrium trying to adjust it’s thickness to the new hormone levels, no treatment need be given.  However, if it is distressing, to continue to let the woman enjoy the benefits of low dose oestrogen pills, these women could beneficially be given 1.25mg conjugated estrogen or 2 mg estradiol daily for 7 days when bleeding is present.  If 1 course of oestrogen is not enough, another 7 days of estrogen use is effective.

Amenorrhoea:   Amenorroea is an uncommon side effect found in some women, caused by endometrial atrophy.  It is distressing to some women, as it may be a sign of unwanted pregnancy.  Addition of extra oestrogen for 1 month (1.25mg conjugated oestrogen or 2mg estradiol) daily throughout the 21 days of that cycle will rejuvenate the endometrium and withdrawal bleeding resumes, persisting for many months. This could be resorted to in patients who prefer not to remain amenorrhoeic.

Headache: Headache, specially, migrainous headache is more prevalent in OC users.  Migrainous headaches frequently occur in the hormone free period, when oestrogen levels are falling. Use of estrogen replacement in this hormone free period could reduce this symptom.  However, women with migraine accompanied by aura are best advised to avoid OC’s.  Evidence from six case-control studies suggested that COC users with a history of migraine are four times as likely to have an ischemic stroke as nonusers with a history of migraine.

Weight gain: Weight gain due to water logging caused by progestin content was a common complaint in the past. The current low-dose OC containing 20 μg ethinyl estradiol EE and 100 μg LevononorgestrelLNG did not cause weight gain and was safe and well tolerated in a double blinded placebo controlled trial.  In another trial, among users of two 20mcg oestrogen-containing pills, in a one-year trial, 13% lost >2kg, 74% stayed at the same weight+2 Kg, and 13% did gain >2kg.  In fact, studies have shown that women often begin taking the pill during a time of life that typically coincides with weight changes, giving the pill an undeserved reputation for adding weight.

Breast tenderness: Incidence of this complaint is less with use of low dose estrogen pills. In a study comparing 3 types of contraceptives, participants in the Levonogestrel containing OC pill group experienced nausea, breast tenderness and irritability more frequently than did those in the other groups, using gestodene and etonogestrel as progestins.    Shortening the hormone-free interval from 7 to 4 or 5 days might increase the contraceptive safety margin and decrease the prevalence of symptoms such as breast tenderness and headaches.

Major side effects:

Combined oral contraceptives are by and large very safe.  However, in the rare special cases, it may cause serious side effects and awareness of these side effects could prevent major complications in these special category patients.

Cardiovascular side effects:

A WHO study found no increased risk of heart attack among healthy pill users.

Less than 5% of women using hormonal contraception develop hypertension, which may increase their risk for heart attack and stroke1.  Blood pressure checking should be an important part of clinical evaluation of pill users.

Thrombotic events: Oral contraceptives (OC) have been implicated in causing increased blood coagulation.  The hormone changes during pill ingestion are akin to those occurring in pregnancy and similarly, the risk of thrombotic events is also present only in the rare individual prone to it.  The risk posed is actually less than that incurred by pregnancy.  Women with an inherited resistance to activated protein C, the factor V Leiden mutation, congenital deficiencies in antithrombin III, protein C, or protein S, are prone to thrombotic events.

Acute maculo-neuroretinopathy, macular haemorrhage, central retinal vein occlusion, central retinal artery occlusion, and perivasculitis have been reported, mostly in patients on oral pills for a long time. Although long term use is unlikely in India, a rare case of central retinal artery occlusion following OC pills has been reported from India after 4 months of use of Mala-D2.

The risk of development of deep vein thrombosis was also found to be 2 to 5 times greater with a low-estrogen, desogestrel-containing oral contraceptive than with second-generation monophasic and triphasic preparations(containing progestin of the norgestrel type). Because desogestrel may have benefit for some patients, specially women with excessive androgen activity, one may restrict its use only for selected users prone to such thrombotic events.

Risk of cancer: Oral contraceptive use is associated with a very slight increase in breast cancer risk (relative risk=1.2) for current users vs. never-users.  However, breast cancer risk associated with the use of oral contraceptives disappears with time when use is discontinued.  1-4 years after discontinuation the relative risk is 1.16, at 5 to 9 years after use the risk is 1.07, and by 10 years from last use, breast cancer risk of ever-users is not different from never-users.  It has been found that even in women with familial cancer syndrome, incidence of breast cancer is not higher among oral contraceptive users compared to non-users.

There is an increased incidence of cervical cancer in HPV positive women on prolonged use of oral contraceptives (>5 years).  Till HPV screening becomes cheap and routine, yearly pap smear should be recommended for all women on oral contraceptive pills.

Incidence of ovarian cancer is reduced in OC users and incidence of colorectal cancer is reduced in current users of OCs.   There is no increased incidence of hepatocellular cancer and effect on lung cancer is known with use of OC’s.

Glucose intolerance: increased insulin resistance in pill users is generally met by  increasing insulin secretion, and there is just a slight elevation of 1 hour glucose levels. Low dose pills may be used by diabetic women.  However, high, pharmacologic dose of estrogen should be avoided by women with diabetes and vascular disease or major cardiovascular risk factors.

Oral contraceptives and medical problems:

Women who should avoid combined oral contraceptive pills:

  • Women known to have stones or a positive history for gallbladder disease
  • Women with triglyceride levels >20mgm/dl and women with existing vascular disease.
  • Mitral valve prolapse complicated with atrial fibrillation, migraine headaches, or clotting factor abnormalities .
  • Women with congenital heart disease or valvular heart disease if there is marginal cardiac reserve or a condition that predisposes to thrombosis.
  • Smokers over 35 years of age
  • Women with systemic lupus erythematosus.

Conditions where combined oral contraceptives are safe:

  • Women younger than 35 years who have hypertension well controlled by medication and who are otherwise healthy and do not smoke.
  • Women with pregnancy induced hypertension after the Blood pressure is normal
  • Women with history of gestational diabetes.
  • Women with fibroids, if low dose pills are used.
  • Benign breast disease.
  • Women with seizure disorders.  However, some antiepileptic drugs decrease efficacy of the pill, and this should be kept in mind.
  • Women with depression.
  • Women with sickle cell trait.
  • Women with hemorrhagic disorders and women taking anticoagulants.
  • Infectious mononucleosis provided liver function tests are normal.
  • Ulcerative colitis
  • Regional enteritis (Crohn’s disease).
  • Elective surgery if prolonged immobilization is not anticipated and if low dose preparations are used.  COC should be used till the last day before sterilization operation is performed if the woman is using it as a contraceptive measure.
  • Women with varicose veins, provided it is not very extensive.



The newer low oestrogen contraceptives and the use of newer progestins accompanying it have reduced side effects of combined oral contraceptives to a great extent.  Most of the studies which showed side-effects of oral contraceptives were done on the earlier preparations with high oestrogen content.  However, while using oral contraceptives for dysfunctional uterine bleeding, higher oestrogen doses may have to be employed and in these patients, the practitioner should be aware of all side effects, to take effective steps.