ANDROPAUSE

Dr. Kamajaya, MSc,SpAnd. Dept. Biologi Fakultas Kedokteran - U.S.U. M e d a n.

TEORI PENUAAN.

I. Deoxyribonucleic acid (DNA) Damage Theory, a.l. : 1. DNA Damage and Repair Theory, 2. Free Radical and Oxydation Theory, 3. Mitochondrial DNA (Mt-DNA) Theory, 4. Radiation Theory. 2. Built-in Breakdown Theory, a.l.: 1. Disposable Soma Theory, 2. Genetics Theory, 3. Telomere Theory, 4. Immunological Theory, 5. Apoptosis Theory, 6. Hormonal Senescence Theory.

KELUHAN & FAKTOR MEMPERCEPAT ANDROPAUSE.

A.

KELUHAN. I. Mental / psikis. II. Sexual, III. Fisik. B. FAKTOR MEMPERCEPAT. I. Faktor Psikis, II. Faktor Lingkungan, III. Faktor genetik, IV. Faktor Organik (terutama Hormonal).

Androgen sintesis.
Cholesterol
Pregnenolone Progesterone Aldosterone

17OH-Pregnenolone
Adrenal androgen synthesis

17OH-Progesterone

Cortisol

DHEA

Androstenedione

Estrone

Androstenedione

Testosterone

Estradiol
Pheripheral aromatization

Dihydrotestosterone

17-ketosteroids

ANDROGEN

FETAL.
1. Diferensiasi Ductus Wolfii, 2. Maskulinasi genital externa.

PUBERTAS. 1. Retensi nitrogen,

ADULT. 1. Fungsi sexual normal.

2. Stimulasi pubertal growth spur,

3. Pertumbuhan phallus, 4. Pertumbuhan karakter sex sekunder.

2. Maintenance karakter sex sekunder,

3. Proses spermatogenesis normal, 4. Maintenance haematopoietik normal 5. Maitenance Otot dan Tulang.

Androgen target tissues.

Testosterone
Brain Bone

Dihydrotestosterone
Germinal epithelium Epididymis

Pituitary Kidney Muscle Submaxillary glands

Vas deferens Seminal vesicle Prostate Penis Hair follicles Sebaceous glands

Testosterone.
Produk

axis. Hasil sekresi Sel Leydig testis. Normal produksi : 3 10 mg/hari. Didarah 65% SHBG (sex hormone binding globulin). 35% terikat relatif dg albumin 1-2% free testosterone. Testosterone yg dipergunakan sel-sel adalah yang non-SHBG (bioavailable testosterone). Total Testosterone serum normal = 12-35 nmol/L, dan bioavailable testosterone = 2,5-4,2 nmol/L

akhir HPG (Hypothalamus-Pituitary-Gonad)

Dihydrotestosterone (DHT) & Estradiol.

Di

jaringan umumnya androgen aktif adalah testosterone, dan sebagian melalui DHT. Hanya 20% DHT disekresi oleh testis. Sebagian kecil testosterone diobah oleh enzim aromatase menjadi estradiol. Estradiol berfungsi maintain tulang dan mineral.

Andropause.

Pria usia lanjut yang sehat mirip dengan wanita lanjut usia, dimana terjadi perobahan hormonal terutama penurunan kadar androgen plasma menimbulkan sejumlah keluhan klinis seperti ; penurunan densitas tulang dan mineral, perobahan komposisi tubuh, dan penurunan interest dan aktivitas sexual. Terkadang mirip dengan keluhan penderita hipogonad. Beberapa terminologi diberikan utk andropause, a.l.: Age related hypogonadism, Partial androgen deficiency in aging men (PADAM), dan Low testosterone syndrome. Namun nama yang digunakan WHO adalah andropause.

Hormonal changes in healthy aging men.

Increase with aging
Luteinizing hormone (LH) Follicle stimulating hormone (FSH)

Unchanged with aging

Dihydrotestosterone (DHT) Estradiol (EZ)

Decrease with aging

Testosterone Dehydroepiandrosterone (DHEA)

Growth hormone (GH)

Insulin-like growth factor 1 (IGF-1)

Thyroid stimulating hormone (TSH)

Triiodothyronine (T3) Insulin

Gambaran klinik Andropause.

1.

Bone loss.

Di USA, pd pria usia 65 th., 4 5 % mengalami fraktur tulang pinggang per 1000 per tahun akibat osteoporosis. Reduksi densiti mineral tulang terutama pd bagian trabecular. Ada korelasi antara bioavailable testosterone dengan densiti mineral tulang.

Gambaran klinik Andropause.

2.

Otot dan komposisi tubuh.

Mengecil

a. Otot.
dan lemah, Penurunan sintesa protein otot, Degenerasi sistem syaraf.

b. Komposisi tubuh.
Lemak

menumpuk dibagian central dan atas tubuh. Obesitas. Peningkatan trigliserida plasma, penurunan densitas lipoprotein kholesterol, gangguan metabolisme insulin dan menurunnya sensitivitas insulin. Peningkatan resiko Diabetes tipe-2 dan peny. Cardiovaskuler dan kematian.

Gambaran klinik Andropause.

3.

Penurunan libido dan disfungsi ereksi.

Penyebabnya

a. Penurunan libido.
kurang diketahui, mungkin pengaruh biokimia, psikologis atau sosial secara subjektif. Di usia 50 th. Terjadi peningkatan problem libido; diperkirakan faktor penurunan kesehatan secara umum, gaya-hidup (rokok,alkohol,dll.) stress dan pengalaman sex kurang memuaskan dll. Kadar testosterone rendah tak berpengaruh terhadap penurunan libido, namun penurunan available testosterone menyebabkan penurunan sexual desire dan sexual arousal.

Gambaran klinik Andropause.

b. Disfungsi ereksi.
Umum

diketahui bahwa dengan peningkatan usia penurunan fungsi ereksi. Menurut Massachusetts male Aging Study, sekitar 12,4 kasus baru per 1000 pria di usia 40-49 th, meningkat menjadi 46,4 kasus baru per 1000 pria usia 60-69 th. Korelasi yg signifikan diantara rendahnya tingkat pendidikan, penyakit diabetes, peny.jantung, dan hipertensi dengan terjadinya disfungsi ereksi. Tidak jelas korelasi antara total testosterone serum dan bioavailable testosterone dengan disfungsi ereksi, kecuali pd penderita Hipogonad (7-15% kasus).

Gambaran klinik Andropause.

4.

Androgen endogen menstimulasi eritropoiesis, peningkatan jlh retikulosit, HB., dan bone-marrow. Testosteron stimulasi langsung eritropoietin renal eritropoietis stem cells.

Penurunan hematopoiesis.

5.

Rancho Bernardo Study Hubungan yg signifikan diantara penurunan bioavailable testosterone dengan peningkatan skor depressi; dan level bioavailable testosterone pd penderita depressi 17% lebih rendah dp pria sehat.

Depresi.

Gambaran klinik Andropause.

6.

Penurunan daya memori dan kognisi.

Hubungan diantara penurunan kadar testosterone plasma usia lanjut dengan memori dan kognisi (perhatian, persepsi visual, identifikasi objek, dan memori visual) menunjukkan relasi bentuk-U (level testosterone plasma subnormal dan suprafisiologis ber asosiasi dg rendahnya performans kognisi.

Skrining, Diagnosa, dan Monitoring.

1.

Skrining.

Defisiensi Testosterone di usia lanjut sering memberikan gejala yang tidak khas. Suatu tabel pertanyaan diperbuat untuk meng identifikasi adanya defisiensi testosterone di usia lanjut yg telah dicobakan pd 316 pria usia 40-62 tahun sensitivitas tinggi = 88%, adekwat spesifisitas = 60%.

Skrining, Diagnosa, dan Monitoring

The Saint Louis University Androgen deficiency in Aging Males (ADAM) Questionaire, positive answer to questions 1 or 7 or any three other questions suggest testosterone deficiency. All quuestions are answer yes or no.

Questioners
1. 2.

Yes

No

3.
4. 5. 6.

7.
8. 9.

10.

Do you have a decrease in libido (sex drive) ? Do you have a lack of energy ? Do you have a decrease in strength and/or endurance ? Have you lost height ? Have you noticed a decreased enjoyment of life ? Are you sad and/or grumpy ? Are your erections less strong ? Have you noticed a recent deterioration in your ability to play sports ? Are you falling asleep after dinner ? Has there been a recent deterioration in your work performance ?

Skrining, Diagnosa, dan Monitoring

2.

Diagnosa.

Diagnosa berdasarkan simptom dan kadar testosterone plasma. Untuk simptom : tentukan rating scale AMS the aging male symptom) questionair. The AMS questionair utk memonitor efek pengobatan testosterone.

Aging Males Symptom questionair.

Which of the following symptoms apply to you at this time ? Please mark the appropriate box for each symptom. For symptoms that do not apply, please mark none.
1.
none

mild

mod erate

seve re

Extr. sever e

Decline in your feeling of general well-being

(general state of health, subjective feeling)

2.

Joint pain and muscular ache

(lower back pain,joint pain in a limb, general back ache)

3.

Excessive sweeting Sleep problem.

(unexpected/sudden episodes of sweetin, hot flushes independent of strain)

4.

(difficulty in falling asleep, difficulty in sleeping through, working up early and feeling tired, poor sleep, sleeplessness). 5.

Increase need for sleep, often feeling tired. Irritability.

(feeling aggressive, easily upset about little things, moody).

6.

7.

Nervousness.
(inner tension, restlessness, feeling fidgety).

8.

Anxiety.
(feeling panicky)

9.

Physical exhaustion/lacking vitality.

(general decrease in performance, reduced activity, lacking interest in leisure activities, feeling of getting less done, of achieving less; of having to force self.

Which of the following symptoms apply to you at this time ? Please mark the appropriate box for each symptom. For symptoms that do not apply, please mark none.
10.

none

mild

mod erate

seve re

Extr. sever e

Decrease in muscular strength.

(feeling weakness)

11. Depressive mood. (feeling down, sad, on the verge of tears, lack of drive, mood swings, feeling nothing is of any use). 12.

Feeling that you have pass your peak. Feeling burnt out, having hit rock bottom. Decrease in beard growth.

13.

14.

15. Decrease

in ability/frquency to perform sexually.

in the number of morning erections. in sexual desire/libido. yes no

16. Decrease

17. Decrease

(lacking pleasure in sex, lacking desire for sexual intercourse).

Have you get any other major symptom ?

If yes please describe :

Severity of complaints : Score 17-26, no complaint; 27-36, few complaints; 37-49, moderate complaints; 50, severe complaints.

Practical and diagnostic algorithm for biochemical evaluation of men with suspected andropause.

Suspected or at risk of hypogonadism

Serum T determination

Low

Normal

Free T + SHBG +/- FSH,LH & Prl

Seek other causes

Abnormal

Normal

High gonadotropins

Normal/low gonadotropins

Seek other causes

T supplementation

Investigate pituitary

Monitoring

Treat accordingly

Skrining, Diagnosa, dan Monitoring

3.

Monitoring.
1.

Pengobatan dgn Testosterone, di monitor :

Testosterone level dlm batas normal. 2. Perbaikan thd simptom. 3. Meminimalkan efek samping dan resiko.

Kontra indikasi absolut terapi Testosterone :

Pre

existing : Prostate dan Breast carcinoma