DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1834
SECTION IX
Table 66–1
One-Year Failure Rate with Various Forms of Contraception
FAILURE RATE
FAILURE RATE
BIRTH CONTROL METHOD (Perfect Use) (Typical Use)
Combination oral contraceptive pills 0.3% 8%
Progestin-only minipill 0.5% 8%
DEPO-PROVERA 0.3% 3%
Copper intrauterine device 0.6% 0.8%
Progestin intrauterine device 0.2% 0.2%
IMPLANON 0.05% 0.05%
ORTHO EVRA 0.3% 8%
NUVARING 0.3% 8%
Condoms/diaphragms 2% 15%
Spermicides 18% 29%
Tubal ligation 0.5% 0.5%
Vasectomy 0.1% 0.15%
None 85% 85%
SPECIAL SYSTEMS PHARMACOLOGY
LOESTRIN 24). Two products are packaged as 91-day packets, with
84 estrogen/progestin tablets and 7 placebo tablets (SEASONALE) or
7 tablets containing a lower dose of ethinyl estradiol alone (SEASONIQUE).
Finally, LYBREL is provided in 28-day packets that contain only hormone
pills and no placebo. All of these extended-cycle formulations appear to
be comparable to the traditional products as contraceptives, and, aside
from an increased frequency of breakthrough bleeding initially, no unexpected
adverse effects have been observed (Kiley and Hammond, 2007).
A weekly transdermal contraceptive patch (ORTHO EVRA)
releases ethinyl estradiol (20 μg/day) and norelgestromin (which is
metabolized to norgestimate; 150 μg/day). In response to pharmacokinetic
data suggesting that this patch provides higher estrogen
exposure (AUC) than the low-dose oral contraceptive pills, the FDA
added a black box advisory that notes this pharmacokinetic difference
and warns of a potential increased risk of venous thromboembolism.
Local reactions to the patch occur in ~5-15% of users and may be
decreased by pre-application of a topical glucocorticoid. A vaginal ring
(NUVARING) also is available that releases ethinyl estradiol (15 μg daily)
and etonogestrel (an active metabolite of desogestrel; 120 μg daily).
Each ring is used for 3 weeks, followed by a 1-week interval without
the ring.
Besides providing highly effective (~99%) contraception
when used properly, the combination estrogen/progestin formulations
have a number of noncontraceptive benefits, including protection
against certain cancers (e.g., ovarian, endometrial, colorectal),
decreased iron-deficiency anemia secondary to menstrual blood loss,
and decreased risk of fractures due to osteoporosis. Combination
oral contraceptives also are widely used for conditions such as
endometriosis, dysmenorrhea, menorrhagia, irregular menstrual
cycles, premenstrual dysphoric disorder, acne, and hirsutism (see
“Endometriosis” and “Drug Therapy in Gynecology”).
Serious adverse effects of the combination estrogen/
progestin contraceptive agents are relatively rare.
Thromboembolic disease, largely due to the estrogenic
component, is the most common serious side effect
associated with oral contraceptive use. Estrogen concentration,
the patient’s age, smoking, and inherited thrombophilias
all influence the risk of developing
thromboembolic disease in oral contraceptive users. The
impact of combination oral contraceptives on breast cancer
has been highly debated; although a meta-analysis
that combined the results of published epidemiological
studies concluded that the combination oral contraceptives
did increase the risk of breast cancer (relative risk
of 1.24; Collaborative Group on Hormonal Factors in
Breast Cancer, 1996), studies conducted with the lower
doses of hormones included in current formulations suggest
that the risk of breast cancer is not increased
(Marchbanks et al., 2002).
Other adverse effects include hypertension, edema, gallbladder
disease, and elevations in serum triglycerides. These are discussed
further in Chapter 40. With pills containing drospirenone,
which antagonizes the mineralocorticoid receptor, serum K + should
be monitored in women at risk for hyperkalemia (e.g., those on K + -
sparing diuretics or drugs that inhibit the renin–angiotensin system).
The combination oral contraceptives are contraindicated in women
with a history of underlying conditions such as thromboembolic disease,
cerebrovascular disease, migraine headaches with aura, estrogendependent
cancer, impaired hepatic function or active liver disease,
undiagnosed uterine bleeding, and suspected pregnancy. In addition,
patients with a history of gestational diabetes should be monitored
closely, and drug cessation should be strongly considered in anticipation
of events associated with an increased risk of venous thromboembolism
(e.g., elective surgery).