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

1190 is discontinued. These agents also decrease the incidence
of ovarian cysts and benign fibrocystic breast
disease.
Oral contraceptives have major benefits related to
menstruation in many women. These include more
regular menstruation, reduced menstrual blood loss and
less iron-deficiency anemia, and decreased frequency
of dysmenorrhea. There also is a decreased incidence of
pelvic inflammatory disease and ectopic pregnancies,
and endometriosis may be ameliorated. Some women
also may obtain these benefits with progestin-only contraceptives.
There are suggestions that MPA may
improve hematological parameters in women with
sickle-cell disease (Cullins, 1996).
From a purely statistical perspective, fertility regulation
by oral contraceptives is substantially safer
than pregnancy or childbirth for most women, even
without considering the additional health benefits of
these agents.
for reduction of risk of breast cancer in high-risk
patients. Raloxifene does not increase the risk of uterine
cancer but does increase the incidence of thromboembolic
events and hot flashes.
The pure estrogen antagonist fulvestrant is also
used to treat breast cancer, especially in patients who
become refractory to tamoxifen. Another estrogen
antagonist, clomiphene, is used to treat infertility in
anovulatory women. Both compounds may cause hot
flashes.
Aromatase inhibitors, including letrozole, anastrozole,
and exemestane, are highly effective for both
adjuvant and metastatic treatment of breast cancer in
postmenopausal subjects, and their prophylactic use is
being explored. Untoward effects include hot flashes;
potential long-term effects of these agents on osteoporosis
and bone fractures remain to be established.
Mifepristone is used therapeutically as an antiprogestin
for medical abortion, and it is administered
with a prostaglandin for this purpose.
Estrogens and progestins are widely used as
CLINICAL SUMMARY
“combination” contraceptives and are 99% effective in
Estrogens are most commonly used to treat vasomotor
disturbances (“hot flashes”) in postmenopausal women.
Other important benefits are amelioration of the effects
of urogenital atrophy, a decreased incidence of colon
cancer, and prevention of bone loss. A variety of
preparations, including oral, transdermal, and vaginal,
are available. Regardless of the specific drug(s) selected,
treatment should use the minimum dose and duration
for the desired therapeutic end point.
In postmenopausal women with an intact uterus,
a progestin is included to prevent endometrial cancer.
Medroxyprogesterone acetate is used in the U.S., but
micronized progesterone is preferred; norethindrone
and norgestrel/levonorgestrel are also commonly used.
Women without a uterus are administered estrogen
alone. Postmenopausal hormone therapy and contraception
are the most frequent uses of progestins.
Tamoxifen, a selective estrogen receptor modulator
or SERM, is widely used for the adjuvant treatment
of breast cancer and for prophylaxis of the
disease in high-risk women, but treatment should
be limited to 5 years. The drug is most effective in
the treatment of estrogen-receptor positive disease,
and untoward effects include hot flashes as well as an
increase in blood clots and uterine cancer. Another
SERM, raloxifene, is used to prevent osteoporosis
and decreases the incidence of vertebral fractures in
postmenopausal women. Raloxifene is also licensed
preventing ovulation. These combinations are most
often used orally, although transdermal preparations,
once-monthly injections, and vaginal rings are available.
Ethinyl estradiol (or mestranol) and 19-nor
steroids such as norgestrel/levonorgestrel, norethindrone,
or another synthetic progestin are commonly
used. The greatest concern with these agents is the risk
of stroke or other thromboembolic events; consequently,
they should not be used in older women (>35 years of
age) who smoke or have other risk factors (e.g., hypertension)
for cardiovascular disease.
Several progestin-only contraceptives are available,
including low-dose pills, long-lasting (e.g., 3-
month) depot injections, and subdermal implants.
These agents are also highly efficacious and exert a
number of actions, including decreased frequency of
ovulation and effects on cervical mucus, ovum transport,
and implantation. They may be used in nursing
mothers and in some women with contraindications for
combined estrogen-progestin combinations. The most
common untoward effect is unpredictable vaginal
bleeding.
A levonorgestrel-only pill and high-dose estrogenprogestin
oral contraceptives are available and effective
for postcoital or emergency contraception within 72
hours of unprotected intercourse. These preparations
are ineffective in cases of established pregnancy and
should not be used to terminate pregnancy.
SECTION V
HORMONES AND HORMONE ANTAGONISTS