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| Diagram showing
complications of oral contraceptives: Vascular:
1. Retinal artery thrombosis 2.Stroke 3.
Pulmonary embolism 4. Myocardial infarction 5. Hepatic vein thrombosis
(Budd-Chiari syndrome) 6. Mesenteric thrombosis 7. Thrombophlebitis.
Hepatobiliary: 8. Cholestatic jaundice 9. Hepatic adenoma
10. Gallstones. |
Iatrogenic Drug Injury: click here
The most important contemporary drugs with important
gynecologic effects are the oral contraceptives.
These hormonal
preparations, are now the most commonly
used method of contraception in industrialized countries.
Almost all
current formulations are combinations of synthetic estrogens and steroids
with progesterone-like activity.
The oral contraceptives act by either
inhibiting the surge of gonadotropins in midcycle, thereby preventing
ovulation, or inhibiting implantation by altering the phase
of the endometrium.
Most of the complications are produced by the estrogenic component, but
some may be related to the progestin component or to a combination of the
two.
The current preparations contain only one-fifth as much estrogen as
earlier ones, and the incidence of side effects have progressively
decreased as the amount of hormone in the oral contraceptives has been
decreased.
Ethinyl estradiol, the synthetic estrogen in many
oral contraceptives, augments the liver's synthesis of several globulins
of the coagulation system, and may thereby cause a hypercoagulable state
and thrombosis.
An increased production of angiotensinogen may lead to an
increase in the level of angiotensin II, thereby raising blood pressure.
Estrogen's stimulation of tryptophan metabolism in the liver may lead to a
decrease in the level of tryptophan in the blood.
It may also lead to low
levels of serotonin, the end product of tryptophan metabolism.
Presumably
this can produce depression and behavioral changes.
The progestational agents, or gestagens, are
related structurally to androgenic steroids and therefore exert certain
virilizing effects, including weight gain, acne, and amenorrhea.
The
weight gain is presumed to be an anabolic effect of the progestin
component.
The progestins decrease the number of estrogen receptors
on the
endometrium.
The endometrial growth is therefore decreased, leading to
amenorrhea.
For reasons unknown oral contraceptives may induce
an increased pigmentation of the malar eminences, called chloasma,
which is accentuated by sunlight and persists for a long time after the
contraceptives are discontinued.
The incidence of cholelithiasis is
increased twofold in women who have used oral contraceptives for 4 years
or less, but decreases to lower than normal after that period of time.
Thus, oral contraceptives accelerated the process of cholelithiasis but do
not increase its overall incidence.
The risk of deep vein
thrombophlebitis is increased three to four times by oral
contraceptive use, as is the risk of thromboembolism.
The incidence
of stroke is increased in women who use oral contraceptives, but the
epidemiological data are conflicting.
It is probable that the incidence is
limited to women with preexisting hypertension and older women who smoke.
The risk of stroke
may be three times higher than normal.
Of particular
concern is the fact that women over 35 who smoke or have another
associated risk factor, such as hypertension or hypercholesterolemia, have
an increased risk of developing myocardial infarction when using
oral contraceptives.
The cause of myocardial infarction or stroke in users of oral
contraceptives is usually arterial thrombosis, and not atherosclerosis.
A few women develop high blood pressure, but this reverses upon
discontinuation of the oral contraceptives.
Benign liver adenomas occur
in a number of patients. The incidence is higher in women who have used oral
contraceptives for more than 5 years.
Despite earlier reports to the contrary, all of
the large prospective studies have shown that the use of the oral
contraceptives does not increase the risk of any type of cancer.
Data that appeared to implicate oral contraceptives in an increased
incidence of cervical cancer, breast cancer and melanoma are all filled
with confounding factors and have not been confirmed in other studies.
Contraindications to oral contraceptive
use in patients in the following conditions:
- a past history of vascular disease (thromboembolism,
thrombophlebitis, atherosclerosis, and stroke),
- a history of systemic
vascular disease (lupus erythematosus, sickle cell disease), hypertension,
diabetes mellitus with vascular disease and hyperlipidemia.
- Patients who suffer
from an estrogen-dependent tumor, such as cancer of the breast or endometrium, should probably not take oral contraceptives, although there
are no data showing an ill effect.
- Pregnancy is a contraindication because
of the masculinizing effect of the gestagens on the external genitalia of
the female fetus.
- Patients with heart disease may develop congestive heart
failure because of fluid retention.
- Women with active liver disease should
not receive oral steroids because they are metabolized in the liver.
- Those
over the age of 45 should not receive oral contraceptives except in
unusual circumstances.
The use of oral contraceptives is also beneficial for some conditions.
Protective effects have been shown against pelvic inflammatory disease,
ovarian and endometrial carcinoma, and fibrocystic disease of the breast.
Acne has been reported to be improved, and there is a decreased incidence
of rheumatoid arthritis.
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