Page 759 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 40 The Gonadal Hormones & Inhibitors 745

Spironolactone, a competitive inhibitor of aldosterone (see PREP AR A TIONS
Chapter 15), also competes with dihydrotestosterone for the andro- A V AIL ABLE *
gen receptors in target tissues. It also reduces 17α-hydroxylase
activity, lowering plasma levels of testosterone and androstene-
dione. It is used in dosages of 50–200 mg/d in the treatment of GENERIC NAME AVAILABLE AS
hirsutism in women and appears to be as effective as finasteride, ESTROGENS
flutamide, or cyproterone in this condition. Conjugated estrogens (equine) Premarin
†
Diethylstilbestrol Generic, DES, Stilphostrol
Esterified estrogens Cenestin, Enjuvia, Menest
CHEMICAL CONTRACEPTION Estradiol Generic, Estrace, others
IN MEN Estradiol cypionate in oil Depo-Estradiol, others
Generic, Estraderm, Estrasorb,
Estradiol transdermal
Estrogel, others
Although many studies have been conducted, an effective and Estradiol valerate in oil Generic, Delestrogen
nontoxic oral contraceptive for men has not yet been found. For Estropipate Generic, Ogen
example, various androgens, including testosterone and testos- PROGESTINS
terone enanthate, in a dosage of 400 mg per month, produced Levonorgestrel Generic, Plan B, others
azoospermia in less than half the men treated. Minor adverse Medroxyprogesterone acetate Generic, Provera
reactions, including gynecomastia and acne, were encountered. Megestrol acetate Generic, Megace
Testosterone in combination with danazol was well tolerated but Norethindrone acetate Generic, Aygestin
no more effective than testosterone alone. Androgens in combina- Progesterone Generic, Prometrium, others
tion with a progestin such as medroxyprogesterone acetate were ANDROGENS & ANABOLIC STEROIDS
no more effective. However, preliminary studies indicate that the Fluoxymesterone Androxy
intramuscular administration of 100 mg of testosterone enanthate Methyltestosterone Android, others
weekly together with 500 mg of levonorgestrel daily orally can Nandrolone decanoate Generic, Deca Durabolin, others
produce azoospermia in 94% of men. Retinoic acid is important Oxandrolone Generic, Oxandrin
in the maturation of sperm and the testis contains a unique iso- Oxymetholone Androl-50
form of the alcohol dehydrogenase enzyme that converts retinol Testosterone Generic
to retinoic acid but no nontoxic inhibitor of this enzyme has been Testosterone cypionate in oil Generic, Depo-testosterone
found to date. Testosterone enanthate in oil Generic, Delatestryl
Cyproterone acetate, a very potent progestin and antian- Testosterone transdermal system Androderm, AndroGel
drogen, also produces oligospermia; however, it does not cause Testosterone pellets Testopel
reliable contraception. ANTAGONISTS & INHIBITORS
At present, pituitary hormones—and potent antagonist analogs (See also Chapter 37)
of GnRH—are receiving increased attention. A GnRH antagonist Abiraterone Zytiga
in combination with testosterone has been shown to produce Anastrozole Generic, Arimidex
reversible azoospermia in nonhuman primates. Bazedoxifene (in combination with Duavee
conjugated equine estrogens)
Bicalutamide Generic, Casodex
GOSSYPOL Clomiphene Generic, Clomid, Serophene,
Milophene
Extensive trials of this cottonseed derivative have been conducted Danazol Generic, Danocrine
in China. This compound destroys elements of the seminiferous Dutasteride Avodart
epithelium but does not significantly alter the endocrine function Enzalutamide Xtandi
of the testis. Exemestane Generic, Aromasin
In Chinese studies, large numbers of men were treated with Finasteride Generic, Propecia, Proscar
20 mg/d of gossypol or gossypol acetic acid for 2 months, Flutamide Generic, Eulexin
followed by a maintenance dosage of 60 mg/week. On Fulvestrant Faslodex
this regimen, 99% of men developed sperm counts below Letrozole Generic, Femara
4 million/mL. Preliminary data indicate that recovery (return Mifepristone Mifeprex, Korlym
of normal sperm count) following discontinuance of gossypol Nilutamide Nilandron
administration is more apt to occur in men whose counts do not Raloxifene Evista
fall to extremely low levels and when administration is not con- Tamoxifen Generic, Nolvadex
tinued for more than 2 years. Hypokalemia is the major adverse Toremifene Fareston
effect and may lead to transient paralysis. Because of low effi- *
cacy and significant toxicity, gossypol has been abandoned as a † Oral contraceptives are listed in Table 40–3.
Withdrawn in the United States.
candidate male contraceptive.