ANDROGEN &

ANTIANDROGEN

Dr. Wening Sari, dr., M.Kes

A.N.D.R.O.G.E.N
 Biosintesis (1)
 Sintesis: testis, ovarium, korteks adrenal laki-laki &
perempuan
 Proandrogen : androstenedion, dihidroepiandrosteron
 Testosteron merupakan androgen utama
 Kadar tinggi pada laki-laki:
 Embrio diferensiasi fenotif
 Neonatus

 Dewasa

 Kadar dalam testis 100x kadar dalam sirkulasi

sistemik  spermatogenesis
Biosintesis (2)

 GnRH (hipotalamus)
+
 LH & FSH (hipofisis anterior) (-)
+ (-)
 Testosteron ++(testis)
 Testoteron estradiol ++
aromaterase
Faal & Farmakodinamik (1)
 Fungsi sesuai periode pertumbuhan :
 Embrional : fenotif laki-laki
 Neonatus : organisasi & penandaan SSP dalam behavior
dan fungsi seksual laki-laki
 Sex :
 Mempertahankan fungsi testis, vesikula seminalis, prostat,
epididimis, kemampuan seksual
 Tanda kelamin sekunder
 Rambut di ketiak, pubis, tubuh & ekstremitas
 Kulit tebal & proliferasi glandula sebasea
 Pertumbuhan laring & pita suara
Faal & Farmakodinamik (2)
 Anabolik
 Pertumbuhan otot rangka
tulang & massa otot
 Penambahan massa otot
pada atlet ??
 Eritropoesis
 Hematokrit & Hb laki-laki >
perempuan
 Effect Testosterone Men Women
Male sexual Testosterone and DHT Hyperandrogenism in
characteristics: are important for women causes hirsutism,
sexual development which is the excessive
Promotes the as well as secondary growth of body hair in
development of the sexual characteristics areas associated with
male sexual organs such as thick skin and male-pattern growth
as well as male-pattern hair such as the chin and
secondary sexual growth. upper lip.
characteristics
Mood, sexual drive In men, increased In women with adrenal
and desire: testosterone is insufficiency and
associated with an consequent low
Testosterone has a increase in sexual androgen levels,
stimulatory effect on drive and the drop in replacement with DHEA
libido in both testosterone with age has been found to
women and men. is associated with a increase energy and
decreasing libido. improve libido and
sexual thoughts.
Bone formation: The effect of Testosterone increased
testosterone on bone, bone mineral density in
Increase bone via aromatisation to women with
thickness and estrogen, is thought hypopituitarism but this
periosteal bone to account for may have been due to
formation. increased bone the effects of
strength in men over aromatization to
women. estrogen.
 Effect Men Women
Metabolism: Testosterone In women with
increases basal hypopituitarism,
Has an important metabolic rate and testosterone
role in metabolism muscle mass. supplementation
and muscle increased fat-free mass
deposition. and muscle.
Erythropoiesis: Replacing Low levels of
testosterone in males testosterone in older
Promotes red blood with hypogonadism women may increase the
cell formation and results in increases in risk of anemia.
protects against red blood cell mass.
anemia.
Estrogen precursor: In men, peripheral In postmenopausal
aromatization of women, aromatization
Testosterone and testosterone plays an of circulating androgens
androstenedione important role in is an important source
can be aromatized estrogen production of estrogens and may
to form estrogens. in bones and the help to ameliorate some
reproductive tract, of the consequences of
where it plays an menopause.
important role in
normal physiology.
 Mekanisme Kerja

 Testosteron – reseptor
 Testosteron 
dihidrotestosteron (DHT) –
reseptor
 Testosteron  estrogen-
reseptor estrogen
 Afinitas DHT >>> testosteron
Farmakokinetika (1)
 Oral : absorbsi cepat, hampir seluruhnya
dimetabolisme efek lemah <<
 Pelarut minyak absorbsi cepat, metabolisme
segera, ekskresi cepat  efek lemah
 Transdermal  hindari 1st pass metab, jumlah yg
absorbsi mll kulit dpt diatur  kadar serum stabil
 Testosteron ester kurang polar  IM: absorbsi lebih
lambat, masa kerja lebih panjang
Farmakokinetika (1)
 Metabolisme di hepar  inaktivasi menjadi
androstenedion, androsteron, etiokolanolon
 Alkilasi testosteron pada gugus 17 
memperlambat metabolisme  memungkinkan
pemberian per oral
 Alkilasi testosteron  hepatotoksik (!!)
 Waktu paruh 10-20 menit, 98% terikat protein
plasma, ekskresi melalui urin
sediaan
 Testosteron
 Testosteron propionat ester
 Testosteron sipionat ester
 Testosteron enantat ester
 Metiltestosteron
 Fluoksimesteron
 Danazol
 Steroid anabolik : metiltestoteron, etilestrenol,
metandrostenolon, oksandrolon, oksimetolon
Sediaan Androgen Rute Indikasi
Testosteron propionat IM Karsinoma payudara
ester

Testosteron sipionat ester IM Hipoganadisme prepubertas &

dewasa, karsinoma payudara
Testosteron enantat ester IM Stimulus
pubertas/pertumbuhan
Metiltestosteron Oral,
bukal Hipogonadisme dewasa,
Fluoksimesteron Oral anabolik, karsinoma payudara

Danazol Oral Endometriosis, fibrosistik

payudara, edema
angioneurotik herediter
Sediaan Steroid anabolik Rute Indikasi selain anabolik
Metandrostenolon Oral osteoporosis

Oksandrolon Oral

Oksimetolon Oral Anemia

Nandrolon fenpropionat Injeksi Karsinoma payudara

Metandriol Injeksi

fluoksimesteron Oral Anemia

Metiltestosteron Oral

Testolakton Oral Karsinoma payudara

 Indikasi
 Terapi subtitusi : defisiensi androgen  hipogonadisme &
hipopituitarisme
 Efek anabolik :
 muscle wasting pd ODHA
 doping pada olahraga  drug abuse
 Anemia refrakter  anemia aplastik, anemi pd gagal ginjal
 Testosteron  Sekresi erythropoietin ↑↑, aktivitas sumsum tulang
↑↑ , Fe mudah masuk dalam eritrosit.
 Edema angioneurotik herediter
 Karsinoma payudara
 Osteoporosis  jika krn defisiensi androgen
 Infertilitas
 Endometriosis  danazol
Efek samping (1)
 Maskulinisasi
 Tanda kelamin sekunder
 Perempuan : hambat menstruasi

 Feminisasi
 Laki-laki dg gangguan fs hati  metabolisme androgen
diperifer >>  aromatisasi  estrogen
 Penghambatan spermatogenesis
 Mekanisme umpan balik negatif
 Hiperplasia prostat
 Gangguan pertumbuhan
 Prapubertas : mempercepat penutupan epifisis
Efek samping (2)
 Edema  dosis besar  retensi cairan
 Ikterus  metiltestosteron  hepatitis kolestatik
(reversibel)
 Kulit : acne, hirsutisme
 Behavior: iratabilitas, agresif
 Testosteron dan kardivaskular :
 Hipertrofi miokardium
 Hipertensi (ringan, sementara)
 Protrombotik
 LDL ↑↑, HDL ↓↓  risiko penyakit arteri koroner
Interaksi Obat
 17-α-alkil androgen meningkatkan efek
antikoagulan kumarin & indandion
 Metandrostenolon:
 menurunkan metabolisme oksifenbutason
 Meningkatkan efektivitas & efek toksik kortikosteroid
 A.N.T.I
A.N.D.R.O.G.E.N
 Antiandrogen (1)
 Hambat sintesis, sekresi, atau kerja androgen
 Estrogen :
 antiandrogenalami, efek berlawanan pd jaringan target
 penghambat kuat sekresi GnRH  efek sekunder:
androgen<<
 Progesteron
 Antiandrogenlemah, kecuali siproteron asetat
 Hambat sekresi GnRH, hambat kompetitif androgen
Antiandrogen (2)
 Agonis & antagonis GnRH
 Produksi LH <<  testosteron <<
 Agonis GnRH: leuprolid, buserelin
 Abareliks  antagonis GnRH untuk kanker prostat

 Flutamid, bicalutamid, nilutamid

 Antiandrogen nonsteroid, tidak punya aktivitas hormon
 regresi organ yg dipengaruhi testosteron (vesikula seminalis,
prostat)
 LH ↑↑  testosteron plasma ↑↑  flutamid dosis dibatasi
 Keamanan : Bicalutamid > flutamid > nilutamid
 Anti 5- reductase : finasterid, dutasterid
Antiandrogen (3)
 Indikasi
 BPH , kanker prostat
 keadaan yang berhubungan dengan kadar testosteron
yang berlebihan, baik pada laki-laki / perempuan
 Kontrasepsi pria (??)

 Efek samping:
 Ginekomastia, Feminisasi
 Penghambatan spermatogenesis

 Penurunan libido
Terima kasih