Page 756 - Basic _ Clinical Pharmacology ( PDFDrive )

742 SECTION VII Endocrine Drugs

TABLE 40–6 Androgen preparations for replacement cell anemia, myelofibrosis, and hemolytic anemias. Recombinant
therapy. erythropoietin has largely replaced androgens for this purpose.
Route of E. Osteoporosis
Drug Administration Dosage
Androgens and anabolic agents have been used in the treatment of
Methyltestosterone Oral 25–50 mg/d osteoporosis, either alone or in conjunction with estrogens. With
Sublingual (buccal) 5–10 mg/d the exception of substitution therapy in hypogonadism, bisphos-
phonates have largely replaced androgen use for this purpose.
Fluoxymesterone Oral 2–10 mg/d
Testosterone enanthate Intramuscular See text
F. Use as Growth Stimulators
Testosterone cypionate Intramuscular See text
These agents have been used to stimulate growth in boys with
Testosterone Transdermal 2.5–10 mg/d delayed puberty. If the drugs are used carefully, these children will
Topical gel (1%) 5–10 g/d probably achieve their expected adult height. If treatment is too
vigorous, the patient may grow rapidly at first but will not achieve
full predicted final stature because epiphyseal closure is acceler-
be started with long-acting agents such as testosterone enanthate or ated. It is difficult to control this type of therapy adequately even
cypionate in doses of 50 mg intramuscularly, initially every 4, then with frequent x-ray examination of the epiphyses, since the action
every 3, and finally every 2 weeks, with each change taking place of the hormones on epiphyseal centers may continue for many
at 3-month intervals. The dose is then doubled to 100 mg every months after therapy is discontinued.
2 weeks until maturation is complete. Finally, it is changed to the
adult replacement dose of 200 mg at 2-week intervals. G. Anabolic Steroid and Androgen Abuse in Sports
Testosterone propionate, though potent, has a short duration The use of anabolic steroids by athletes has received worldwide
of action and is not practical for long-term use. Testosterone attention. Many athletes and their coaches believe that anabolic
undecanoate can be given orally, administering large amounts steroids—in doses 10–200 times larger than the daily normal
of the steroid twice daily (eg, 40 mg/d); however, this is not physiologic production—increase strength and aggressiveness,
recommended because oral testosterone administration has been thereby improving competitive performance. Such effects have
associated with liver tumors. Testosterone can also be administered been unequivocally demonstrated only in women. Furthermore,
transdermally; skin patches or gels are available for scrotal or other the adverse effects of these drugs clearly make their use inad-
skin area application. Two applications daily are usually required visable. As a result, most sports organizations have developed
for replacement therapy. Implanted pellets and other longer-acting extremely sensitive assays, conduct random testing, and apply
preparations are under study. The development of polycythemia strong penalties if drugs are detected.
or hypertension may require some reduction in dose.
H. Aging
B. Gynecologic Disorders Androgen production falls with age in men and may contribute to
Androgens are used occasionally in the treatment of certain the decline in muscle mass, strength, and libido. Preliminary studies
gynecologic disorders, but the undesirable effects in women are of androgen replacement in aging males with low androgen levels
such that they must be used with great caution. Androgens have show an increase in lean body mass and hematocrit and a decrease
been used to reduce breast engorgement during the postpartum in bone turnover. However, many factors other than deficient
period, usually in conjunction with estrogens. The weak androgen androgen production contribute to these effects of aging. Longer
danazol is used in the treatment of endometriosis (see above). studies will be required to assess the usefulness of this therapy.
Androgens are sometimes given in combination with estro-
gens for replacement therapy in the postmenopausal period in an Adverse Effects
attempt to eliminate the endometrial bleeding that may occur when
only estrogens are used and to enhance libido. They have been used The adverse effects of these compounds are due largely to their
for chemotherapy of breast tumors in premenopausal women. masculinizing actions and are most noticeable in women and
prepubertal children. In women, the administration of more than
C. Use as Protein Anabolic Agents 200–300 mg of testosterone per month is usually associated with
Androgens and anabolic steroids have been used in conjunction hirsutism, acne, amenorrhea, clitoral enlargement, and deepening
with dietary measures and exercises in an attempt to reverse pro- of the voice. These effects may occur with even smaller doses in
tein loss after trauma, surgery, or prolonged immobilization and some women. Some of the androgenic steroids exert progestational
in patients with debilitating diseases. Evidence to support this use activity, leading to endometrial bleeding upon discontinuation.
of androgens is poor except when hypogonadism is also present. These hormones also alter serum lipids and could conceivably
increase susceptibility to atherosclerotic disease in women.
D. Anemia Except under the most unusual circumstances, androgens
In the past, large doses of androgens were employed in the treatment should not be used in infants. Recent studies in animals suggest
of refractory anemias such as aplastic anemia, Fanconi’s anemia, sickle that administration of androgens in early life may have profound