Page 748 - Basic _ Clinical Pharmacology ( PDFDrive )

734 SECTION VII Endocrine Drugs

7. Effects on the cardiovascular system—These agents cause to simple changes in pill formulation. Although it is not often
small increases in cardiac output associated with higher systolic necessary to discontinue medication for these reasons, as many as
and diastolic blood pressure and heart rate. The pressure returns one third of all patients started on oral contraception discontinue
to pretreatment levels when treatment is terminated. Although the use for reasons other than a desire to become pregnant.
magnitude of the pressure change is small in most patients, it is
marked in a few. It is important that blood pressure be followed A. Mild Adverse Effects
in each patient. An increase in blood pressure has been reported to 1. Nausea, mastalgia, breakthrough bleeding, and edema are
occur in a few postmenopausal women treated with estrogens alone. related to the amount of estrogen in the preparation. These

effects can often be alleviated by a shift to a preparation con-
8. Effects on the skin—The oral contraceptives have been noted taining smaller amounts of estrogen or to agents containing
to increase pigmentation of the skin (chloasma). This effect seems progestins with more androgenic effects.
to be enhanced in women with dark complexions and by exposure
to ultraviolet light. Some of the androgen-like progestins might 2. Changes in serum proteins and other effects on endocrine
increase the production of sebum, causing acne in some patients. function (see above) must be taken into account when thyroid,
However, since ovarian androgen is suppressed, many patients adrenal, or pituitary function is being evaluated. Increases in
note decreased sebum production, acne, and terminal hair growth. sedimentation rate are thought to be due to increased levels of
The sequential oral contraceptive preparations as well as estrogens fibrinogen.
alone often decrease sebum production. 3. Headache is mild and often transient. However, migraine is
often made worse and has been reported to be associated with
Clinical Uses an increased frequency of cerebrovascular accidents. When this
occurs or when migraine has its onset during therapy with these
The most important use of combined estrogens and progestins is agents, treatment should be discontinued.
for oral contraception. A large number of preparations are available 4. Withdrawal bleeding sometimes fails to occur—most often
for this specific purpose, some of which are listed in Table 40–3. with combination preparations—and may cause confusion
They are specially packaged for ease of administration. In general, with regard to pregnancy. If this is disturbing to the patient, a
they are very effective; when these agents are taken according to different preparation may be tried or other methods of contra-
directions, the risk of conception is extremely small. The pregnancy ception used.
rate with combination agents is estimated to be about 5–12 per
100 woman-years at risk. (Under conditions of perfect adherence, B. Moderate Adverse Effects
the pregnancy rate would be 0.5–1 per 100 woman-years.) Con- Any of the following may require discontinuance of oral
traceptive failure has been observed in some patients when one or contraceptives:
more doses are missed, if phenytoin is also being used (which may
increase catabolism of the compounds), or if antibiotics are taken 1. Breakthrough bleeding is the most common problem in using
that alter enterohepatic cycling of metabolites. progestational agents alone for contraception. It occurs in as
Progestins and estrogens are also useful in the treatment of many as 25% of patients. It is more frequently encountered in
endometriosis. When severe dysmenorrhea is the major symptom, patients taking low-dose preparations than in those taking
the suppression of ovulation with estrogen alone may be followed combination pills with higher levels of progestin and estrogen.
by painless periods. However, in most patients this approach is The biphasic and triphasic oral contraceptives (Table 40–3)
inadequate. The long-term administration of large doses of pro- decrease breakthrough bleeding without increasing the total
gestins or combinations of progestins and estrogens prevents the hormone content.
periodic breakdown of the endometrial tissue and in some cases 2. Weight gain is more common with the combination agents
will lead to endometrial fibrosis and prevent the reactivation of containing androgen-like progestins. It can usually be con-
implants for prolonged periods. trolled by shifting to preparations with less progestin effect or
As is true with most hormonal preparations, many of the by dieting.
undesired effects are physiologic or pharmacologic actions that 3. Increased skin pigmentation may occur, especially in dark-
are objectionable only because they are not pertinent to the skinned women. It tends to increase with time, the incidence
situation for which they are being used. Therefore, the product being about 5% at the end of the first year and about 40% after
containing the smallest effective amounts of hormones should 8 years. It is thought to be exacerbated by vitamin B deficiency.
be selected for use. It is often reversible upon discontinuance of medication but
may disappear very slowly.
Adverse Effects 4. Acne may be exacerbated by agents containing androgen-like
The incidence of serious known toxicities associated with the use progestins (Table 40–2), whereas agents containing large
of these drugs is low—far lower than the risks associated with amounts of estrogen usually cause marked improvement in acne.
pregnancy. There are a number of reversible changes in intermedi- 5. Hirsutism may also be aggravated by the “19-nortestosterone”
ary metabolism. Minor adverse effects are frequent, but most are derivatives, and combinations containing nonandrogenic
mild and many are transient. Continuing problems may respond progestins are preferred in these patients.