###  A. General Precautions. 

  1. A complete medical and family history should be taken prior to the initiation of any estrogen therapy. The pretreatment and periodic physical examinations should include special reference to blood pressure, breasts, abdomen, and pelvic organs, and should include a Papanicolaou smear. As a general rule, estrogen should not be prescribed for longer than one year without another physical examination being performed.
  2. Fluid retention– Because estrogens may cause some degree of fluid retention, conditions which might be influenced by this factor such as asthma, epilepsy, migraine, and cardiac or renal dysfunction, require careful observation.
  3. Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding, mastodynia, etc.
  4. Oral contraceptives appear to be associated with an increased incidence of mental depression.24 Although it is not clear whether this is due to the estrogenic or progestogenic component of the contraceptive, patients with a history of depression should be carefully observed.
  5. Preexisting uterine leiomyomata may increase in size during estrogen use.
  6. The pathologist should be advised of estrogen therapy when relevant specimens are submitted.
  7. Patients with a past history of jaundice during pregnancy have an increased risk of recurrence of jaundice while receiving estrogen-containing oral contraceptive therapy. If jaundice develops in any patient receiving estrogen, the medication should be discontinued while the cause is investigated.
  8. Estrogens may be poorly metabolized in patients with impaired liver function and they should be administered with caution in such patients.
  9. Because estrogens influence the metabolism of calcium and phosphorus, they should be used with caution in patients with metabolic bone diseases that are associated with hypercalcemia or in patients with renal insufficiency.
  10. Because of the effects of estrogens on epiphyseal closure, they should be used judiciously in young patients in whom bone growth is not complete.
  11. Certain endocrine and liver function tests may be affected by estrogen-containing oral contraceptives. The following similar changes may be expected with larger doses of estrogen:
    1. Increased sulfobromophthalein retention.
    2. Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3: increased norepinephrine-induced platelet aggregability.
    3. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by PBI, T4 by column, or T4 by radioimmunassay. Free T3 resin uptakes is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.
    4. Impaired glucose tolerance.
    5. Decreased pregnanediol excretion.
    6. Reduced response to metyrapone test.
    7. Reduced serum folate concentration.
    8. Increased serum triglyceride and phospholipid concentration.



B. Information for the Patient. See text of PATIENT INFORMATION which appears after the REFERENCES.

C. Pregnancy Category X. See CONTRAINDICATIONS and BOXED WARNING.

D. Nursing Mothers. As a general principle, the administration of any drug to nursing mothers should be done only when clearly necessary since many drugs are excreted in human milk.