HORMON SEKS PADA

SISTEM REPRODUKSI
 HORMON SEKS

Hormon yang berpengaruh terhadap :

-perkembangan dan pemeliharaan sifat seks sekunder
-sistem reproduksi
Hormon -di produksi tbh
-diberikan dari luar, misal : - breast cancer
- hipogonadisme
- defisiensi
- gejala menopause
 HORMON SEX PRIA

Androgens & Anabolic steroids

 Regulation of secretion
Testosterone is the principle androgen
secreted by the testes (Leydig cells).
Testosterone and other androgens are also
secreted by the adrenal cortex and in small
amounts by the ovaries.
Once secreted, testosterone is 99% bound to
plasma proteins, mostly to sex hormone-
binding globulin.
 Regulation of secretion
Secretion of testosterone is regulated by the
hypothalamic-pituitary system.
LH stimulates the Leydig cells to synthesize
and secrete testosterone.
Testosterone and FSH act to increase
spermatogenesis.
Testosterone provides negative feedback to
the pituitary.
 Mechanism of action
Similar to other steroid hormones.
Binds to cytosolic receptors, which are
translocated to the nucleus where they
regulate gene expression.
In some organs (e.g., prostate), testosterone
is converted to dihydrotestosterone (via
5alpha-reductase activity), a more potent
receptor agonist.
 Physiologic effects
Necessary for the development of
secondary male sex characteristics and male
sexual behavior.
Required for spermatogenesis.
Promotes protein anabolism and growth.
Enhances linear bone growth and muscular
development.
 Physiologic effects
Causes an increase in the size of the larynx
and deepens the voice.
Increases sebaceous gland activity, which
may result in acne, and stimulates
erythropoiesis.
 Indications for Use
Used in replacement therapy for
hypogonadism and hypopituitarism.
Used to accelerate growth and to promote
anabolism.
In breast cancer, androgens are used as
palliatives.
Also used in the treatment of angioneurotic
edema and endometriosis (danazol).
 Specific agents
Compounds with androgenic and anabolic activity
include testosterone and methyltestosterone.
Synthetic analogs with greater anabolic than
androgenic properties include fluoxymesterone,
nandrolone, and oxandrolone.
These "anabolic steroids" were first produced for
treatment of patients with debilitating diseases or
prolonged immobilization to prevent negative
nitrogen balance.
 Side Effects
Include masculinization in women.
Prostatic hypertrophy, priapism, and
feminization in men.
Testicular atrophy and gynecomastia are
problems in chronic users.
The most common adverse reactions are
edema, jaundice, local irritation, urinary
obstruction, and steroid fever.
 Side Effects
Other adverse effects include:
Premature epiphyseal closure in children.
Liver dysfunction.
Hypercalcemia.
Alteration of serum lipids.
 Androgen Antagonist

Have been synthesized for the treatment of

prostate cancer and benign prostatic
hyperplasia.
 Androgen Antagonist
GnRH analogs (e.g., leuprolide).
Long-term therapy reduces the secretion of
FSH and LH, thus reducing testosterone
production.
Used for advanced prostate cancer.
 Androgen Antagonist
Flutamide
Nonsteroid competitive antagonist at
androgen receptors.
Used in metastatic prostate cancer to block
testosterone.
 Androgen Antagonist
Cyproterone acetate.
An androgen receptor antagonist with
progestin-like activity.
It is being tested for the treatment of
hirsutism in women.
 Androgen Antagonist
Finasteride.
Inhibitor of 5a-reductase and, thus, inhibits
the production of dihydrotestosterone.
It is used in the treatment of benign
prostatic hypertrophy and male pattern
baldness.
 Androgen Antagonist
Ketoconazole.
Imidazole type antifungal agent.
Inhibits steroid synthesis.
Used in androgen receptor-positive cancer
therapy.
 Other Drugs
Anastrozole.
An aromatase inhibitor used in breast cancer.

Danazol.
Inhibits ovarian steroid synthesis.
Used in endometriosis and breast fibrocystic
disease.
 Figure 4. Control of androgen
secretion and activity and some sites of
action of antiandrogens. (1)
competitive inhibition of GnRH
receptors; (2) stimulation (+) or
inhibition (-) by GnRH agonists; (3)
inhibition of testosterone synthesis by
ketoconazole; (4) inhibition of
dihydrotestosterone production by
finasteride; (5) inhibition of androgen
binding at its receptor by flutamide and
other drugs.
HORMON PRIA

Androgen testosteron, diproduksi di sel interstitial,

dipengruhi LH. FSH tub. Seminifersperma

Androgen hormone inhibitor

Mekanisme kerja :

Androgen
-potensi reproduksi pd pria dewasa
-pubertas sifat seks sekunder
rambut muka dan badan, suara, lemak
tubuh, otot perumbuhan ukuran organ
seks (penis, testis, vas deferens, prostat)
-proses pembentukan jaringan (anabolik)
-proses pelepasan jaringan (katabolik)
Contoh : metiltestosteron, testosteron
Androgen inhibitor sintetik
Menghambat konversi testosteron 5 alfa
dihydrotestosteron (DHT)menurunkan efek pd
prostat

Anabolic steroid aktivitas androgenik dan anabolik

proses pembentukan jaringan
efek minimal pd organ seks
Penggunaan :
Androgen laki-laki
defisiensi testosteron :
-hipogonadisme
- pubertas terlambat
Androgen wanita : - Ca mamma metastase
Anabolic steroid : anemia, insuf.renal, kontrol Ca
mamma metastase, pemacu pertumbh yg
terlambat
Anabolic steroid massa otot
Androgen inhibitor BPH
EFEK SAMPING :
Androgen :
Laki-laki ginekomasti, atropi testis, menghbt fs
testis, impotensi, pembesaran penis,
nausea, sakit kepala, kuning, cemas,
botak, jerawat, depresi, imbalans
cairan dan elekrolit.
Wanita Virilisasi
Anabolic steroid (cth : durabolin)
Virilisasi pada dosis tinggi, acne, nausea, vomiting,
diare, imbalans cairan dan elektrolit, atropi testis,
jaundice, anoreksia, kram otot.
Orang sehat penggunaan lama efek samping
Androgen inhibitor penurunan libido dan vol. ejaku
lasi, impoten.
Kontraindikasidan interaksi
Androgen : K/I hipersensitif obat, ggn hati,
peny.jtg serius, ggn prostat, hamil, laktasi
Interaksi meningkatkan efek antikoagulan
metiltestosteron dg imipramin
risiko respon paranoid
Anabolic steroid : K/I sama dg androgen
Orang tua meningkatkan risiko pembesaran
prostat dan kanker prostat, bersama sulfonilurea
meningkatkan efek hipoglikemi
HORMON
HORMON SEX
SEX WANITA
WANITA
ESTROGEN
ESTROGEN &
& PROGESTIN
PROGESTIN
ESTROGEN

Sintesa ovarium, korteks adrenal, testis

kead. khusus plasenta, Ca mamma
precursor androstenedion

sintesa & sekresi estrogen (& progestin) :

- pada pre pubertas langsung oleh ovarium
- pada masa reproduktif dikontrol oleh
EFEK FARMAKOLOGI ESTROGEN

1. Efek pertumbuhan
pra pubertas pubertas

sex primer : vagina, uterus, tuba falopii
sex sekunder : mammae, bentuk tubuh, kulit, rambut,
pigmentasi, tulang panjang

2. Kontrol neuroendokrin siklus menstruasi

(lihat gambar)
 REGULASI HORMONAL
PADA SIKLUS
MENSTRUASI

Sekresi estrogen secara siklis

pd fase folikular dipengaruhi
oleh FSH.
Sekresi progesteron scr siklis
pd fase luteal dipengaruhi
oleh LH
 Efek estrogen selain pada siklus menstruasi

*proliferasi dan diferensiasi organ reproduktif

*kontraksi tuba
*mukus cervix lebih encer shg memfasilitasi
sperma penetrasi cervix
*kontraksi ritmis pada myometrium
* Vasodilatasi pembuluh darah
3. Efek metabolik
Efek estrogen pada organ/ jaringan non reproduktif
melalui reseptor estrogen di organ tsb.
- Tulang : menghambat resorpsi tulang
gadis pertumbuhan tulang, epifise
menopause mempertahankan bone mass
- Metab. mineral : Ca balance, retensi Na
- Metab. lipid : lipoprotein total kolesterol , TG
HDL , LDL
- komposisi cairan empedu batu empedu
- gula drh
- serum protein protein binding
- faktor koagulasi ?
 MEKANISME KERJA
Estrogen hormon lipofilik menembus membran
reseptor estrogen yang terletak di dalam sel.
interaksi dg reseptor transkripsi gen

sintesa mRNA
sintesa protein
FARMAKOKINETIK
Efek

Absorpsi : p.o, im, topikal, transdermal

Metabolisme : hepar dg konyugasi resirkulasi
enterohepatik
Eksresi : ginjal
 EFEK SAMPING
Kontrasepsi (lama) Ca, tromboemboli, hipertensi,
perub. metab. lipid/ karbohidrat,
batu empedu, nausea, migren dll.
estrogen / progestin ?? terkait dg dosis

PENGGUNAAN KLINIK
* oral kontrasepsi
* hormon replacement therapy (terapi sulih hormon)
 ANTI ESTROGEN
- TAMOXIFEN Tx. Ca mamma,
- CLOMIPHENE Tx. infertility

MEKANISME KERJA
- kompetitif antagonis pada reseptor estrogen

aktivitas farmakologik dpt sebagai antagonis, agonis
atau parsial agonis tgt pada sel-sel spesifik.
- CLOMIPHENE antagonis reseptor estrogen
menghambat feed back (-)estrogen
LH, FSH ovulasi
- TAMOXIFEN menghambat proliferasi sel mamma
 PROGESTIN
Sintesa & sekresi ovarium (dipengh. LH)
adrenal, testis, plasenta

EFEK FARMAKOLOGI PROGESTIN

1 . Neuroendokrin diproduksi sesuai siklus pada
fase luteal

2. Reproduktif - siklus
sekresihaid
kel.cervix > kental
pada fase luteal
berfungsi sbg spermatisid
- mempertahankan kehamilan
- supresi menstruasi
 3. Kelenjar mammae pada kehamilan proliferasi
asini kel.mamma
4. Efek CNS - temperatur tubuh naik 100F
- efek depresan/ hipnotik
5. Efek metabolik - level insulin basal ?
- fat deposition
6. Efek androgenik
FARMAKOKINETIK
Absorpsi : oral, im (lar. minyak), implant
Metab. : hepar, di plasma berikatan dg albumin &
steroid binding globulin.
Ekskresi : urin.
PENGGUNAAN KLINIK PROGESTIN

-kontrasepsi suntikan (medroksi progesteron asetat)

-kontrasepsi oral (kombinasi), implant
-mengatasi perdarahan rahim disfungsional
-endometriosis
-penundaan haid
-abortus imminens, abortus habitualis
 KONTRASEPSI HORMONAL
* Kontrasepsi oral kombinasi -monopahsic
-biphasic
-triphasic
Kontrasepsi sekuensial
* Kontrasepsi progestin oral, implant, intramusk
* Kontrasepsi postcoital
MEKANISME KERJA
1. Kontrasepsi oral kombinasi menghambat ovulasi
mel. FSH, LH
2. Kontrasepsi progestin *hambatan GnRH LH

ovulasi (-)
 KEUNTUNGAN & KERUGIAN
KONTRASEPSI ORAL
KEUNTUNGAN :
* Siklus menstruasi teratur, premenstrual tension , dysmenorrhoe,
* Perbaikan endometriosis
* Insidens Ca ovarium & endometrium
* Lemak darah LDL , HDL

KERUGIAN :
* Ca mamma
* Efek metab. glukosa
* Efek androgenik
* Progestin jangka lama atropi endometrium