Dwi Indria Anggraini

Faculty of Medicine Lampung University

 Estrogen
Hormon replacement therapy
Post menoupousal hormon therapy
Indication : menopausal symptoms ( for
examples hot flashesor hot flushes and
vaginal atrophy
Combining with progesteron would reduces
the risk of endometrial carcinoma for woman
who have intact uterus
For women who have undergo histerektomi
estrogen is more recommended than progestin
in beneficial effect of lipid parameter

 Stimulated

development of
secondary sex characteristics in
young women ( 11-13 years of age
with primary hipogonadism ,usually
in combination with a progesteron.
Used for women who have
premature menoupouse or
premature ovarian failure

 Farmakokinetik
Naturally occuring estrogens: Readily absorbed

through the gastrointestinal tract , skin, and

mucous membranes. Estradiol metabolized
by the microsomal enzyme of the liver , but it
is not sufficient to lessen the effectiveness
when taken oraly
Synthetic estrogen analogs, such as ethinil
estradiol and mestranol are well absorb after
oral administration, metabolized more slowly,
being fat soluble , they are stored in adipose
tissue , from which they are slowly released.

 Metabolism:
transported in the blood by binding to

serum albumin or sex hormon-binding

globulin,
bio availability of estrogen taken orally is
low due to first past metabolism in the liver.
metabolites undergo excretion into bile and
are then reabsorbed through the
enterohepatik circulation.
Inactive product are excreted in urine

 Adverse

effects

Nausea & breast tenderness

Post menopausal uterine bleeding
Thromboembolic event, Myocardial

infarktion
Breast & endometrial cancer ( the
incraesed risk of endometrial cancer can
be offset by including a progesteron
along with estrogen therapy)

 Selective

estrogen- receptor
madulators(SERMs)
Agonism
Antagonism
According to the tissue type
Include : tamoxifen, raloxifene(orphan

drug), and clomiphene

 Mechanism

of action
tamoxifen >< estrogen

Estrogen receptor (breast tissue)

Some

breast tumor regress following

treatment with tamoxifene
Raloxifene is a second generation SERM
, in addition raloxifene decrease bone
resorption and overal bone turn over

 Raloxifene

apparently has little to no

effect on the endometrium .
Raloxifene lowers total cholesterol and
LDL in serum, but it has no effect on
HDL or TG levels
Clomiphene act as a partial estrogen
agonist and interferes with the negative
feedback of estrogens on
hypothalamus . GnRH
,
stimulating ovulation

 Therapeutic

uses

Tamoxifene is currently use in the

paliative treatment of metastatic breast

cancer in postmenopausal women.
Adjuvant therapy following mastectomy
or radiation in breast cancer
Prophylactic therapy to reduce the risk
of breast cancer in high risk patients

 Raloxifene is approved for prophylaxis

of breast cancer in high risk women

Prevention and treatment of
osteoporosis in postmenopausal women
Clomiphene has been used successfully
to treat infertility associated with
anovulatory cycles. But it is not effective
in women with ovulatory dysfunction
due to pituitary or ovarian failure.

 Pharmacokinetik
The SERMs are rapidly absorbed after oral

administration.
Tamoxifen is extensively metabolized by
cytochrome P 450 enzymes
Raloxifene is rapidly converted to glucuronide
conjugates through first-pass metabolism.
More 95% of raloxifene is bound to plasma protein.
All three agent undergo enterohepatic cycling and
the primary route of excretion is through the bile
into feces.

 Advers

event

tamoxifene

raloxifene

clomiphene

Hot flash , nausea

Hot flash , leg

cramps

Headache , nausea,
vasomotor flushes,
visual disturbance

Menstrual
irregularities,
vaginal bleeding

Deep vein
trombosis
Pulmonary
embolism, retinal
vein trombosis

Ovarian enlargment

Hyperplasia ,
malignancy
endometrium
Drug interaction:
amiodarone,
haloperidol,

Drug interaction :
colestiramin
60% adminitration
of raloxifene

risk of multiple
birds

 Progestogens
Mechanism

of action

1. An increase in hepatic glycogen , probably

2.

3.
4.
5.

through an insulin- mediated mechanism;

A decrease In Na reabsorption in the
kidney due to competition with aldosterone
at the mineralocorticoid receptor
An increase in the body temperature
through an unknown mechanism
A decrease in some plasma amino acids
An increase in excretion of urinary
nitrogen.

 Hormonal defisiensy & contraception

Postmenopousal hormone terapy
Control of dysfungtional uterine

bleeding
Tretment of dismenore
Management of endometriosis and
infertility

micronized preparation of
progesterone is rapidly absorbed
after oral administration
It has a short half-life in plasma
Almost completely metabolized by
the liver.

 Headache

, depresion, weight gain, and

change in libido
Some progestine , such as the 19nortestosterone derivatives, have
androbenik activity and can increase
the ratio of LDL to HDL cholesterol and
cause acne and hirsutism
Medroxy progesterone acetate has been
associated with an increased risk of
osteoporosis

 Mifepristone

is a progesterone
antagonist with partial agonist activity
Administration of this drug to females
early in pregnancy usually result in
abortion of the fetus
Mifepristone is often combine with
prostaglandin analog misoprostol
( administered orally or intravginally),
to induce uterine contraction

 Significant uterine bleeding

Possibility of an incomplete abortion.
Mifepriston has also been

invetigated as an oral contraceptive

and an emergency contraceptive
agent.