Adverse Effects: Contraceptives

•  Introduction:contraceptives
  • low incidence of serious known toxicities
  • intermediary metabolism changes -- reversible
  • a number of minor adverse effects
  • remedies: change in formulation

return to main menu

   Mild Adverse Effects: contraceptives

• Nausea, mastalgia, edema, breakthrough bleeding
  • Remedy:
    • change preparation to one containing less estrogen
    • change preparation one containing progestins with greater androgenic action
• Changes in serum protein:
  • consider when evaluating thyroid function, pituitary function, adrenal function test results
  • increase sedimentation rates: secondary to increased fibrinogen levels
• Headache
  • typically mild/transient
  • migraine: often worsened by treatment
    • may be associated with increased incidence of stroke
    • if migraine onset occurs during treatment -- discontinue treatment
    • if cerebrovascular accident occurs during treatment -- discontinue treatment
• Withdrawal bleeding may fail to occur

return to main menu

  Moderate Adverse Effects:

(these effects may require discontinuation of oral contraceptive use)

• Breakthrough bleeding:
  • most common problem using progestational agent alone for contraception-- frequency = as many as 25%
  • more often seen in patients using low-dose agents compared to combination drugs with higher progestin/estrogen levels
• Weight gain:
  • more likely with combination drugs containing androgen-like progestins
  • Remedy: dieting/changing medication to one containing less progestin effect
• Increase Skin Pigmentation:
  • more common in dark-skinned women
  • incidence increases with time:
  • 5% -- end of first-year
  • 40% -- after eight years
  • worsened by vitamin D deficiency
  • usually slowly reversible upon drug discontinuation
• Acne:
  • worsened by androgen-like progestin containing contraceptives
  • improved by contraceptives containing large estrogen content
• Hirsuitism:
  • worsened by "19-nortestosterone" preparations/combinations
  • Remedy: use non-androgenic progestins
• Ureteral dilation:
  • similar to that observed in pregnancy
  • associated with bacteriuria
• Vaginal Infection:
  • more common
  • more difficult to managing patients taking oral contraceptives
• Amenorrhea:
  • some patients remain amenorrheic for years after termination of oral contraceptives use; galactorrhea also observed
  • prolactin levels: should be determined -- patient may have prolactinoma

return to main menu

   Severe Adverse Effects:

•  Venous Thromboembolic Disease
  • Frequency (superficial/deep thromboembolic or disease not taking oral contraceptives) = 1 per 1000 woman years
  • Frequency -- low-dose oral contraceptives = 3 per 1000 woman years
  • higher risk during first month of drug use then constant
    • additional risk ends with cessation of contraceptive use
  • Predisposing factors that increase risk include:
    • stasis, increased antithrombin III levels,injury, elevated homocysteinein
    • Genetic disorders that may increase venous thromboembolism include gene alterations influencing:
      • levels of protein C (factor V Leiden), protein S, hepatic cofactor II
      • family history: useful in identifying patients at risk
  • Venous thromboembolism incidence:
    • depended on estrogen (not progestin) component of oral contraceptives
    • unrelated to:
      • age
      • mild obesity
      • cigarette smoking
    •  Contributing factors:
      • reduced venous blood flow
      • arterial/venous endothelial proliferation
      • enhanced coagulation (reduced antithrombin III levels)

return to main menu

•    Myocardial Infarction:contraceptives
  • Slightly increased risk in patients using contraceptives if the following risk factors are also present:
    • obesity
    • hypertension/preeclampsia
    • hyperlipoproteinemia
    • diabetes
  • Significantly increased risk for smokers:
  • Risk: nonsmokers (women 30-40 years of age: 4 cases/100,000 users per year)
  • Risk: heavy-smokers (women 30-40 years of age:185 cases/1,000 uses per year)
  • Probable basis for increased risk:
    • acceleration atherosclerosis (atherogenesis)
      • decreased HDL
      • decreased glucose tolerance
      • increased LDL
      • increased platelet aggregation
      • possibly increased coronary vasospastic tendency
  • in combination oral contraceptives: progestational (i.e. progestin, androgenic) component decreases HDL levels; suggesting the particular risk may depend on the specific composition of the formulation used as well as individual patient's reaction

return to main menu

•   Cerebrovascular Disease:contraceptive
  • Stroke risk: women >35 years of age; current users -- not previous users
  • Subarachnoid hemorrhage: increased both among current and previous users
  • Risk Estimates: approximately 37 cases/ 100,000 users per year
    • Fatality incidence: 10%; most subarachnoid hemorrhages
  • Risk Factors: hypertension
    • 3-6-fold increase in hypertension in women using oral contraception
  • Summary:oral contraceptives increase risk of cardiovascular disorders at all ages, independent smoking status
    • highest risk group: women > 35 years of age who are heavy smokers

return to main menu

•   Gastrointestinal Disorders: contraceptive
  • probable increased risk of cholestatic jaundice with progestin-containing oral contraceptives
  • more commonly observed in patients with a history cholestatic jaundice during pregnancy
  • increase incidence of symptomatic gallbladder disease
    • cholecystitis
    • cholangitis
  • Possible increase risk of hepatic adenomas
  • possible increase risk of ischemic bowel disease (secondary to celiac and superior/inferior mesenteric arterial and venous thrombosis

return to main menu

•   Depression: contraceptive
  • Incidence: 6% with some contraceptive formulations; they be necessary to discontinue treatment.

return to main menu

•  Cancer:contraceptive
  • Risk Reduction: endometrial/ovarian cancer
  • Lifetime risk: breast cancer may not be affected by oral contraceptive use.
  • Increase risk: possibly in younger women
  • Cervical cancer risk: uncertain/controversy

return to main menu