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HORMONES and
INHIBITORS
Drugs for Reproductive Endocrinology
Leonila A. Estole-Casanova, MD
Department of Pharmacology and Toxicology
University of the Philippines – College of Medicine
September 9, 2008
↓ + GnRh
+/- Pituitary
↓ + LH and FSH
ovary
progesterone
estrogen
Follicular growth and ovulation
O
CH3
CH3 OH
CH3 OH
H
H H OH
H H
H H H H
HO
HO HO
ESTRONE
ESTRADIOL ESTRIOL
The Induce
Gonadal the synthesis of progesterone
Hormones and Inhibitors : Drugs for Reproductive
The Estrogens:
Pharmacokinetics
Estradiol (E2) binds STRONGLY to α globulin
(SHBG)
LOWER affinity to albumin
19
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
Combination Oral
Contraceptives (COCs) –
ESTROGEN component
20
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
The Pharmacology of the
Estrogen Component of COCs
E2 is the most potent natural estrogen ---
inactive orally
E2 + ethinyl group at the 17 position =
Ethinyl Estradiol
--- orally active
23
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
The Pharmacology of the
Progestin Component of COCs
2 major types of synthetic progestins
q Derivatives of 19 nortestosterone
q Derivatives of 17α acetoxyprogesterone
“ Current formulations of
COCs are made from
SYNTHETIC steroids and
contain no natural
estrogens or progestins.”
49
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
COCs: Incidental Benefits
LESS ENDOMETRIAL CANCER
Use for 12 months reduces the risk by
50%
Greatest protective effect if use for >3
years
Compliance is improved by a
fixed schedule that is habit
forming
63
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
COCs: Clinical problems
BREAKTHROUGH BLEEDING
2. Irregular bleeding in the first few months
after starting oral contraception
3. Unexpected bleeding after many months of
use
77
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
POPs: Mechanisms of Action
Suppress ovulation
(not consistently suppressed)
81
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
POPs: Noncontraceptive
Benefits
82
The Gonadal Hormones and Inhibitors : Drugs for Reproductive
POPs: Problems
Irregular menstrual bleeding – major reason
why women discontinue POPs
More functional ovarian cysts
Levonorgestrel associated with acne
Clomiphene
Tamoxifen
Raloxifene
↓ + GnRh
Pituitary
↓ + LH and FSH
testes
Androgens T DHT
Adverse reactions
Virilization (in females, prepubertal boys)
Feminization (males)
Suppression of HPG axis
Edema, jaundice, hepatic carcinoma