Drugs used in reproductive system

Outline of this lecture

Introduction to steroid biosynthesis
Estrogen, progesterone, and their
modulators (SERM)
Contraceptives
Testosterone, dihydrotestosterone (DHT)
and androgen antagonists
Drugs used in erectile dysfunction ()
Quiz


 Pharmacological properties of estrogen (1)

Receptor mechanisms
A. Genomic effects through ER and
1 ERexpressed in reproductive tract and breast
1.ERexpressed
2.ERexpressed in ovary and brain
B. Rapid estrogen-induced effects

Estrogen mediates the

development of secondary
sex characteristics
Steroid receptor
as a nuclear
receptor
 Effects of estrogen/progesterone on
physiological function

1. Female maturation
2. Endometrial effects
3.
3 Metabolic and cardiovascular effects
Metabolic alterations in the liver are especially important, so that there is
a higher circulating level of proteins such as transcortin (corticosteroid-
binding globulin [CBG]), thyroxine-binding globulin (TBG), SHBG,
transferrin, renin substrate, and fibrinogen. This leads to increased
circulating levels of thyroxine, estrogen, testosterone, iron, copper, and
other substances.
4. Effects on blood coagulation
Goodman & Gilman's The Pharmacological
Basis of Therapeutics, 12th Edition
 (Premarin)

Cenestin
Pharmacokinetics
1. Well absorbed in the GI tracts
2. Rapidly metabolized in the liver
3.
3 Can be given topically
4. Excreted in urine
 Th
Therapeutic
ti uses off estrogens
t

Postmenopause: hormone
replacement
l t therapy
th (HRT)
Osteoporosis
Primary hypogonadism
Contraception
Pharmacology and the Nursing Process, 7th Edition
HRT and postmenopause
1. Uterine bleeding
2. Cancer
 Pharmacology and the Nursing Process, 7th Edition

From dermnetnz.org
Selective estrogen
g receptor
p
modulators (1)

Clomiphene
A partial estrogen agonist
Interferes with the negative feedback of
estrogen on the hypothalamus and pituitary Gn-
RH and Gonadotropin for the treatment of
infertility
Not
N effective
ff i iin women whose
h ..
g
Adverse effects: ovarian enlargement, hot
flashes, headache..
The gonadotropins
A. FSH and LH: menotropins
B. FSH:
S u urofollitropin,
o o t op , follitropin
o t op a alfa
a
and beta
C. LH: lutropin alfa
D HCG: choriogonadotropin alfa
D.
Selective estrogen receptor
modulators (2)

Tamoxifen and raloxifen

Pharmacological properties of progestins
 Therapeutic uses of progestins
Postmenopausal
P t l hormone
h therapy
th
Contraception
p
Endometriosis

Treatment of functional uterine
bleeding
Prevent miscarriage and alleviate the
symptoms of premenstual syndrome
Adverse effects of progestins
Major classes of contraceptives

Progestin pills
Progestin implants
Combination pills
Postcoital contraception

Possible mechanisms and adverse effects
Possible mechanisms:
Inhibits ovulation
Thickening of cervical mucus
Adverse effects
Most are due to the estrogen component
breast fullness, nausea, vomiting
Metabolic and serum lipids
Cardiovascular
C di l effects
ff t
Carcinogenicity
Contraindications:
C t i di ti ptt with
ith cerebrovascular
b l and
d
thromboembolic disease, estrogen-dependent neoplasm,
liver disease and migraine headache
headache.
Postcoital contraception

Morning-after pill

Adverse effects: nausea and vomiting

combined with antiemetic drugs
Mifepristone (RU-486)

A competitive
titi progesterone
t receptor
t antagonist
t i t (also
( l
with anti-glucocorticoid and antiandrogenic activity)
Blockade of progesterone action
1. Decay and death of decidua causes blastocyst to die
and detach from the uterus
2. The blastocyst is not secreting hCG the corpus
luteum involutes progesterone synthesis and
secretion
Adverse effect:
Vaginal bleeding

Androgens
Pharmacological properties of
androgens

Testosterone
T t t and
d dihydrotestosterone
dih d t t t

Functions:
1. Normal maturation
2. Sperm production
3. Decrease bone resorption
4. Anabolic effect on muscle proteins
 Therapeutic
p uses
As growth stimulators: inadequate androgen secretion
(hypogonadism).
(hypogonadism)
Androgen replacement therapy in men
Impotence (for men with serum androgen below normal
level)
Senile osteoporosis and anemia
As protein anabolic agents: severe burns or protein loss
after trauma..
Endometriosis: Danazol, a mild androgen with weak
progestational, androgenic and glucocorticoid activities,
is used in the treatment of endometriosis.
Unapproved use
 Antiandrogens
t a d oge s ((1))
Flutamide, Bicalutamide,
Flutamide Bicalutamide and Nilutamide
1. Not a steroid
2. For prostatic carcinoma
3. Adverse effect: mild gynecomastia,
and mild reversibe hepatic toxicity

Cyprotenone and cyproterone acetate

Antiandrogenic
The acetate
Th t t form
f has
h a marked
k d progestational
t ti l effect
ff t ->
>
feedback enhance antiandrogenic effect
Clinical uses:
1. (hirsutism)
2.
Adverse effects
In females: cause masculinization with acne ..
In males: cause priapism, impotence,
decreased spermatogenesis, and
gynecomastia.
In children: cause growth disturbance and
sexual maturation
General effects: increase the LDL/HDL ratio
In athletes: e.g.
g nandrolone hepatic
p
abnormalities, increased aggression (roid
rage), and psychotic episodes
Antiandrogens (2): Finasteride and
Dutasteride
A competitive inhibitor of
5-reductase
Reduces prostate DHT
content by 80%
Less effective in improving
urine flow than 1-
adrenergic antagonists
Clinical use: For benign
prostatic hypertrophy (BPH)
Adverse effect: impotence

Antiandrogens
Spironolactone
1. An aldosterone antagonist.
2. Interacts with androgen receptor.
3. Reduces the conc. cytochrome P-450s in testicular
microsomes testosterone synthesis .
Clinical use: hirsute women
Adverse effect: gynecomastia, irregular menses
Ketoconazole
Drugs used in erectile dysfunction
Phosphodiesterase 5 (PDE
Phosphodiesterase-5 (PDE-5)
5) inhibitors
Sildenafil,, Vardenafil,, and Tardalafil
Selective for cGMP PDE type V
 The drug most commonly used in patients who do not
respond to sildenafil is alprostadil , a PGE 1 analog that can
be injected directly into the cavernosa or placed in the urethra
as a minisuppository, from which it diffuses into the
cavernosal tissue. Phentolamine can be used by injection into
1 the cavernosa. These drugs will cause erection in most men
who do not respond to sildenafil.








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