Gonadal Hormones and

Inhibitors

Gonadal Hormones
• Ovary
(estrogen and progestins)
• Testis
(testosterone)
Ovarian Hormones
ovary – primary source of sex hormones in women
during the childbirth years
-when properly regulated by the follicle-
stimuli zing hormone and luteinizing hormone
from the pituitary, menstrual cycle occurs and
following the events:
• Follicle in the ovary matures and secrets
increasing amount of estrogen
• Release an ovum
• Transformed into a progesterone-secreting
corpus luteum
• The mechanism or action of both estrogen
and progesterone involves the entry into
the cells, binding to cytosolic receptors,
and translocation of the receptor-hormone
complex into the nucleus, where it
modulates gene expression
Estrogen
• Estradiol, estrone, and estriol

• Estradiol – low bioavailability, it is also

administered via transdermal patch, vaginal
cream, or intramuscular injection.

• Estradiol cypionate – long acing esters of

estradiol that is converted in the body to
estradiol. Administered via IM.

• Premarin – mixtures of conjugated estrogens

from biologic source. It is used orally for
hormone replacement therapy.
Effects of estrogen:
• Essential for female sexual development. The
growth of genital structure during childhood and
appearance of secondary sexual characteristics.
• For it’s metabolic effect: modifies serum protein
levels, reduces bone resorption, enhances
coagulability of the blood and increases plasma
triglyceride levels while reduce LDL cholesterol.
Uses of estrogen:
• Tx for hypogonadism in young females
• Hormone replacement therapy in women
• Prevents bone loss and osteoporosis.
Toxicity:
• Endometrial cancer for HRT
• Breast cancer and stoke for postmenopausal
women
• For dose dependent-nausea, migraine
headache, hypertension, gallbladder disease.
Progestins:
• Progesterone
-micronized form used orally for HRT
-vaginal creams are also availble
L-norgestrel and norethindrone are more
androgenic than norgestimate and desogestrel.
Effects of progesterone:
• Induces secretory changes in the endometrium
and required for the maintenance of pregnancy
Uses of progesterone:
• In combination with estrogen in HRT to prevent
estrogen-induced endometrial cancer.
• Assisted reproductive technology programs to
promote and maintain pregnancy.
Toxicity of progesterone:
• Increase blood pressure and decrease HDLs
Clinical uses and beneficial effects of hormonal
contraceptives:
• For young women with primary hypogonadism
• Combination of hormonal contraceptives and
progestins are used to treat acne, hirsutism,
dysmenorrhea and endometriosis.
• Reduce of ovarian cyst, ovarian and endometrial
cancer, benign breast disease.
Toxic effects of hormonal contraceptives:
• Thromboembolism
• Breast cancer
• Nausea
• Headache
• Skin pigmentation
Selective estrogen receptor modulator
• Mixed estrogen agonist that have estrogen
agonist effect in some tissues and acts as partial
agonist of estrogen in other tissues.
Tamoxifen (toremifene)
-tx for hormone responsive breast cancer.
-acts as an agonist at endometrial receptors,
causing hyperplasia and increase risk of
endometrial cancer.
Raloxifene
-prevention of osteoporosis
-no estrogenic effects on endometrial tissue
Drugs induce ovulation:
• Clomiphene
- Nonsteroidal compound with tissue selecive
action
- Selectively blocks estrogen receptors in the
pituitary.
Androgens:
• Testosterone – produces in the testis, adrenal,
and even the ovary.
• Synthesized from progesterone and
hydroepiandrosterone.
Oxandrolone and stanozolol
-increaed ratio of anabolic androgenic action
Mechanism of action of androgens:
enters the cell and binds to cytosolic receptors.
The hormone-receptor complex enters the
nucleus and modulates the expression of target
genes.
Effects of androgens:
• normal development of male fetus and infant.
And it is responsible for the major changes in
puberty
• Acts on the hair cells to cause male-pattern
baldness.
• Increase red blood cell production
• Maintain normal bone density
• Uses of androgen:
• Replacement therapy in hypogonadism
• Stimulate red blood cell production
Toxocity of androgens:
-by females, virilization and menstrual
irregularity.
-excessive dose in men can cause feminization
-behavioral defects
-cholestatic jaundice
-elevation of liver enzyme levels
-
Androgens:
natural: testosterone
synthetic: methyltestosterone,
fluoxymesterone
anabolic steroid: oxandrolone, stanozolol
Antiandrogens:
Treatment of benign and malignant prostate
disease, hair loss, hirsutism.
• Receptor inhibitors:
-flutamide, bicalutamide
• 5alpha reductase inhibitors
finasteride
does not interefere with the action of
testosterone, less likely than other
antiandrogens to cause impotence, infertility and
loss of libido.
• Synthesis inhibitors
ketoconazole
inhibits gonadal and adrenal steroid
synthesis
use to suppress adrenal steroid synthesis