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Hormonal

Contraception
Oral, Parenteral and Implanted Contraceptives
Two types of preparation for oral
contraceptives
(1) combinations of estrogens and progestins
The combination agents are further divided into monophasic
forms (constant dosage of both components during the cycle) and
biphasic or triphasic forms (dosage of one or both components
is
changed once or twice during the cycle)
(2) continuous progestin therapy without concomitant
administration of estrogens.
Mechanism of Action
The combinations of estrogens and progestins exert their
contraceptive effect largely through selective inhibition
of pituitary function that results in inhibition of
ovulation
change in the cervical mucus, in the uterine
endometrium, and in motility and secretion in the
uterine tubes, all of which decrease the likelihood of
conception and implantation.
Effects on the Ovary
Chronic use of combination agents
depresses ovarian function.
Follicular development is minimal, and
corpora lutea, larger follicles, stromal
edema, and other morphologic features
normally seen in ovulating women are
absent. The ovaries usually become
smaller even when enlarged before
therapy
75% will ovulate in the first posttreatment
cycle and 97% by the third posttreatment
cycle. About 2% of patients remain
amenorrheic for periods
of up to several years
Effects on Uterus
After prolonged use, the cervix may show some
hypertrophy and polyp formation. There are also
important effects on the cervical mucus, making
it more like postovulation mucus, ie, thicker and
less copious
morphologic and biochemical changes of the
endometrial stroma under the influence of the
progestin, which also stimulates glandular
secretion throughout the luteal phase, more
glandular atrophy and usually less bleeding. (19
nor)
Effects on the Breast
Stimulation of the breasts
occurs in most patients receiving
estrogen-containing agents.
Some enlargement is generally
noted.
The administration of estrogens
and combinations of estrogens
and progestins tends to suppress
lactation
Other effects of Oral
Contraceptives
Effects on CNS - Estrogens tend to increase excitability in the brain, whereas
progesterone tends to decrease it. (in animal study not well known for human)
Endocrine function - inhibition of pituitary gonadotropin secretion. Estrogens also
alter adrenal structure and function. Estrogens given orally or at high doses increase
the plasma concentration of the 2 globulin that binds cortisol
(corticosteroid-binding globulin). alterations in the renin
angiotensinaldosterone system; increase in aldosterone secretion. Thyroxine-
binding globulin is increased. (inc. T4). Dec. androgen by gonadotropin suppression
Effects on blood - There is an increase in factors VII, VIII, IX, and X and a decrease in
antithrombin III. Increased amounts of coumarin anticoagulants may be required to
prolong prothrombin time in patients taking oral contraceptives.
There is an increase in serum iron and total iron-binding capacity similar to that
reported in patients with hepatitis.
Other effects
Liver - Important alterations in hepatic drug excretion and metabolism. Reduce
flow of bile. Inc. in Cholelithiasis.
Lipid Metabolism estrogens increase serum triglycerides and free and
esterified cholesterol. Phospholipids are also increased, as are HDL; levels of
LDL usually decrease
Carbohydrate Metabolism - reduction in the rate of absorption of carbohydrates
from the
gastrointestinal tract. Progesterone increases the basal insulin level and the rise in
insulin induced by carbohydrate ingestion.
Cardiovascular system cause small increases in cardiac output associated with
higher systolic and diastolic blood pressure and heart rate
Skin - increase pigmentation of the skin (chloasma). Some of the androgen-like
progestins might increase the production of sebum, causing acne in some patients
Clinical Use
Contraceptive failure has been observed in some patients when one or more
doses are missed, if phenytoin is also being used (which may
increase catabolism of the compounds), or if antibiotics are taken that alter
enterohepatic cycling of metabolites
Progestins and estrogens are also useful in the treatment of
endometriosis. When severe dysmenorrhea is the major symptom, the
suppression of ovulation with estrogen alone may be followed by painless
periods.
Mild Adverse Effects

Nausea, mastalgia, breakthrough bleeding, and edema are related


to the amount of estrogen in the preparation
Changes in serum proteins and other effects on endocrine function
Headache is mild and often transient. However, migraine is often
made worse and has been reported to be associated with an
increased frequency of cerebrovascular accidents. (DISCONTINUE
NOW)
Withdrawal bleeding
Moderate Adverse Effects
Breakthrough bleeding is the most common problem in using progestational
agents alone for contraception
Weight gain is more common with the combination agents containing
androgen-like progestins
Increased skin pigmentation may occur, especially in darkskinned women
Acne may be exacerbated by agents containing androgen-like progestins
Hirsutism
Ureteral dilation and Bacteriuria is frequent
Vaginal infections are more common and more difficult to treat
Amenorrhea occurs in some patients. Possible galactorrhea and prolactinomas
Severe Adverse Effects
Vascular disorders Thromboembolism (earliest)
Venous thrombosis
MI - slightly higher risk of myocardial infarction in women who are
obese, have a history of preeclampsia or hypertension, or have
hyperlipoproteinemia or diabetes and smoker
Cerebrovascular disease - risk of stroke is concentrated in women
over age 35
Gastrointestinal Disorders Cholestatic jaundice
Depression
Cancer
Contraindication and caution
patients with thrombophlebitis, thromboembolic phenomena, and cardiovascular and
cerebrovascular disorders or a past history of these conditions
patients with thrombophlebitis, thromboembolic phenomena, and cardiovascular and
cerebrovascular disorders or a past history of these conditions
avoided or used with caution in patients with liver disease, asthma, eczema, migraine,
diabetes, hypertension, optic neuritis, retrobulbar neuritis, or convulsive disorders.
oral contraceptives may produce edema, and for that reason they should be used with
great caution in patients in heart failure or in whom edema is otherwise undesirable or
dangerous.
agents are contraindicated in adolescents in whom epiphysial closure has not yet been
completed
Beneficial Use of Oral
Contraceptives
reduced risk of ovarian cysts, ovarian and endometrial
cancer, and benign
breast disease.
There is a lower incidence of ectopic pregnancy.
Iron deficiency and rheumatoid arthritis are less common,
and premenstrual symptoms, dysmenorrhea,
endometriosis, acne, and hirsutism may be ameliorated
with their use

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