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

Contraception and
Pharmacotherapy of Obstetrical
and Gynecological Disorders
Bernard P. Schimmer and
Keith L. Parker
Drugs used to control fertility and treat disorders of the
female reproductive organs collectively are among the
most frequently prescribed agents in clinical practice. This
chapter discusses a number of common clinical issues and
their drug therapies that are central to women’s health. The
focus is on reproductive disorders and aspects of therapy
rather than comprehensive coverage of the drugs themselves,
which are described in more detail elsewhere
(e.g., Chapter 33 for prostaglandins; Chapter 38 for the
gonadotropins, gonadotropin-releasing hormone [GnRH]
agonists and antagonists, and oxytocin; Chapter 40 for
estrogens and progestins; Section VII for antibiotics).
CONTRACEPTION
Contraception can either be administered as planned
prophylaxis (e.g., oral contraceptive pills, patches,
implants, vaginal or intrauterine devices, barrier foams,
spermicides, tubal ligation, vasectomy) or postcoitally
for emergency contraception (i.e., high-dose estrogencontaining
oral contraceptive pills, high-dose progestin
pills, a progesterone antagonist, intrauterine devices).
The progesterone antagonist also can be used to terminate
an established pregnancy.
Planned Contraception
Combination Oral Contraceptives. Of the various contraceptive
methods, pills containing an estrogen and
progestin in combination are the most widely used and
are among the most effective of the nonsurgical modalities
(Table 66–1); they act primarily by suppressing the
luteinizing hormone (LH) surge and thereby preventing
ovulation. A wide variety of preparations are available
for oral, transdermal, and vaginal administration
(Erkkola, 2007). (See Table 66–2 for a list of branded
formulations. Many of the same formulations also are
available as generics.) Almost all contain ethinyl estradiol
as the estrogen and a 17α-alkyl-19-nortestosterone
derivative as the progestin and are administered for the
first 21-24 days of a 28-day cycle. The major functions
of the estrogen are to sensitize the hypothalamus and
pituitary gonadotropes to the feedback inhibitory
effects of the progestin and to minimize breakthrough
bleeding. The progestin exerts negative feedback,
which suppresses the LH surge and thereby prevents
ovulation, and protects against uterine cancer by opposing
the proliferative effects of the estrogen on the uterine
endometrium. Newer formulations offer effective
contraception with improved activity profiles. They
contain lower amounts of hormones to minimize
adverse effects; some incorporate progestins with less
androgenic activity (e.g., gestodene, desogestrel) or that
antagonize the mineralocorticoid receptor and thereby
reduce the tendency toward edema (e.g., drospirenone).
Due to diminished endometrial proliferation, patients
taking these newer formulations may not experience a
menstrual bleed at the end of each cycle; if this occurs,
a pregnancy test generally is performed after the first
missed cycle to rule out contraceptive failure.
Traditionally, combination oral contraceptives were packaged
with 21 pills containing active hormone and 7 placebo tablets; each
active pill contained a constant amount of the estrogen and progestin
(i.e., a monophasic formulation). In an effort to maximize the antiovulatory
effects and prevent breakthrough bleeding while minimizing
total exposure to the hormones, some formulations provide active
pills with two (biphasic) or three (triphasic) different amounts of one
or both hormones to be used sequentially during each cycle.
Formulations called “extended-cycle” contraceptives extend the
number of active pills per cycle and thus decrease the duration of menstrual
bleeding. Two products contain 24 active pills with only 4 placebo
tablets (e.g., YAZ [which contains drospirenone as the progestin] and