This document discusses androgens and the male reproductive system. It describes the structure and function of the male reproductive system and the role of testosterone as the main hormone. Testosterone is produced in the testes and regulates sperm production and male characteristics. It binds to receptors in target tissues like muscle and bone. The effects, production, regulation, and clinical uses of testosterone are summarized along with descriptions of anti-androgen drugs that block testosterone's actions.

1. ANDROGEN: THE
MALE REPRODUCTIVE
SYSTEM
BY : PUNEET VASHISTHA

2. MALE REPRODUCTIVE SYSTEM
• The male reproductive system consist of external genitalia ( penis and scrotum),
a pair of testis, associated duct system, the accessory glands and ducts(seminal
vesicles, prostate gland and vas deferens and ejaculatory duct)
• It is located in pelvic region of male.

3. STRUCTURE OF MALE REPRODUCTIVE SYSTEM

4. FUNCTION OF MALE REPRODUCTIVE SYSTEM
1. Gametogenesis(Sperm production)
2. Regulation of male reproductive functions by various
hormone secretion.

5. BIOSYNTHESIS OF TESTOSTERONE

6. SYNTHESIS OF HORMONE AND THEIR
REGULATION

7.  Main hormone: Testosterone
 Secreted by Leydig cell into the blood stream
 High concentration in Sertoli cells maintained by direct diffusion and by androgen
binding protein (ABP)
Secretion rate is 8 mg/day in normal adult males.
 The serum level of testosterone in adult males ranges from 300 to 800 ng/ dl and in
women approximately 30 to 50 ng/dl.

8. Follicular stimulating hormone (FSH)
 Trophic to Sertoli cells
 Stimulates secretion of androgen binding protein (ABP)
Stimulates secreation of inhibin
Luteinizing hormone (LH) :
Trophic to Leydig cells
 Stimulates secreation of testosterone
Inhibin’s:
 Inhibit FSH release

9. CROSS SECTION OF TESTIS

10. MECHANISM OF ACTION
Testosterone binds to an intracellular receptor Receptor steroid
complex binds to DNA in the nucleus, facilitating transcription of
genes
In addition, testosterone is converted to dihydrotestosterone (DHT)
BY 5alpha reductase in some target cells such as prostate, seminal
vesicles and epididymis.

11. DHT binds to intracellular receptor as testosterone
 DHT also circulates, plasma level about 10% of the testosterone level
Testosterone receptor complex are less stable then dihydrotestosterone receptor complex
in target cells
DHT formation is way of amplifying the action of testosterone in target tissues.

12. ACTION OF TESTOSTERONE

13. PHYSIOLOGIC EFFECTS
• In the normal male, testosterone or its active metabolite (DHT) is responsible for
many changes that occur in puberty include:
• Growth of penis and scrotum in boys.
• Increase the growth of pubic, axillary, and beard hair.
• The larynx grows and the vocal cord become thicker, leading to a lower pitched
voice.
• Androgen play an important role in stimulating and maintaining sexual function
in men

14. PHYSIOLOGIC EFFECTS
• Androgens increase lean body mass and stimulate body hair growth and
sebum secretion.
• Metabolic effects include reduction of hormone binding and increase liver
synthesis of clotting factors, triglyceride lipase and haptoglobin.
• Other effects include growth of prostate and stimulate erythropoietin
production.

15. ANDROGENS PREPARATIONS
Testosterone Preparations: Dose:
Testosterone (free) 25 mg daily to twice weekly
• Easter form:
Testosterone propionate 25-50mg/3 times a week
Testosterone enanthate 250 mg /2-4weeks
Testosterone cypionate 100-200mg/2 weeks
• Orally active preparations:
Methyltestosterone
Flouxymesterone
• Transdermal patches patches/day(Back/Abdomen/Thigh

16. PHARMACOKINETICS
Testosterone when administered orally, is rapidly convert to inactive metabolite and only
about one sixth of the dose administered is available in active form.
 Testosterone can be administered through parenteral route, but it has a prolonged
absorption time and a greater activity in the propionate, undecanoate or cypionate Easter
form. These derivatives are hydrolysed to release free testosterone at the site of injection.
 17- alkyl substituted derivative of testosterone such as methyltestosterone and
fluoxymestrane are orally active. Because of resistance to first pass metabolism

17.  65% of circulating testosterone is bound to sex hormone binding- globulin(SHBG) and remaining
testosterone is bound to albumin. Approximately 2% remaining free and available to enter into the cells
and bind to intracellular receptor.
 The major metabolic products of testosterone are androsterone and etiocholanolone which are
excreted in urine, mostly as conjugates with glucuronic acid and sulphate.

18. METABOLITES OF TESTOSTERONE

19. ADVERSE EFFECTS OF TESTOSTERONE
• Excess body hair and menstrual irregularities in women.
• Acne in both male and female
• Cholestatic jaundice: most commonly occur with methyltestosterone
and other 17 alkyl substituted derivative
• Hepatic carcinoma: incidence is higher in patients who have received
long-term methyltestosterone or other oral androgens.
• Salt retention and edema: especially when large doses are used in
patients with heart or kidney disease

20. ADVERSE EFFECTS OF TESTOSTERONE
• Replacement therapy in men can cause acne, sleep apnea, erythrocytosis
and gynecomastia.
• Increase LDL level and decrease HDL level
• Increase aggressiveness and psychotic symptom

21. CONTRAINDICATION
• Androgens are contraindicated in carcinoma of breast and prostate.
• The use of androgenic steroid is contraindicated in pregnant women
• Androgen should not given to patient with acute coronary syndrome and
CHF.

22. CLINICAL USE OF ANDROGENS
• Androgen replacement therapy in Men: Androgens are used to replace or
augment endogenous androgen secretion in hypogonadal men
• Protein anabolic agents: Androgens and anabolic steroids have been used in
conjunction with dietary measures and exercises in an attempt to reverse protein
loss after trauma, surgery.
• Anemia: In the past, large doses of androgens were employed in the treatment of
refractory anemias such as aplastic anemia, Fanconi’s anemia, sickle cell anemia,
myelofibrosis, and hemolytic anemias. Recombinant erythropoietin has largely
replaced androgens for this purpose.

23. CLINICAL USES OF TESTOSTERONE
• Use as growth stimulator: Androgens are used to stimulate growth in boys with
delayed puberty.
• Osteoporosis: Androgens and anabolic agents have been used in the treatment
of osteoporosis, either alone or in conjunction with estrogens.

24. ANTI-ANDROGENS
• some effects of androgens are undesirable, at least under certain circumstances,
agents have been developed specifically to inhibit androgen synthesis or effects.

25. ACTION OF ANTI ANDROGEN DRUGS

26. ANDROGEN RECEPTOR INHIBITOR
Flutamide
• Competitive inhibitor of androgen receptor.
• Rapidly metabolize in human.
• Side effect: Frequently cause gynaecomastia and occasionally cause reversible
hepatotoxicity.
• Uses:
• Cancer of prostate along with GNRH
• Female hirsutism
• Dose: 50mg tds.

27. ANDROGEN RECEPTOR INHIBITOR
• Bicalutamide, nilutamide and enzalutamide are potent orally active
antiandrogens that can be administered as a single daily dose.
• Use in treatment of metastatic carcinoma of prostate.

28. CYPROTERONE ACETATE
• Block androgen receptor
• Secretion of gonadotropins
USES: Side effects:
 Acne Hepatotoxicity
 Male pattern baldness
 Hirsutism
 Virilizing syndrome
 Precocious puberty

29. 5-ALPHA REDUCTASE INHIBITOR
Finasteride
• Orally active Prostate volume
• Decrease DHT level Symptom
• Benign prostatic hyperplasia DHT level in prostate
Dose: 5MG/DAY
Also used for Prevention of hair loss
Side effects: loss of libido and impotence in 5% patients

30. 5 -ALPHA REDUCTASE INHIBITOR
Finasteride Dutasteride
Act on 1isoform of enzyme 5 alpha
reductase isoenzyme-2. it is ineffective
in female
Act on 2 isoform of enzyme 5 alpha
reductase thus it is effective in female
Very painful injection and gives
burning sensation
Does not give any painful burning
sensation during the injection.
The potency of finasteride is lesser
then dutasteride
More potency than finasteride

31. KETOCONAZOLE
• Used primarily in the treatment of fungal disease, but also an inhibitor of adrenal
and gonadal hormone.
• Displaces estradiol and dihydrotestosterone from sex hormone binding protein
invitro and increase the estradiol: testosterone ratio in plasma.
• USES: Used experimentally to treat prostatic carcinoma.
• Side effect: Reversible gynecomastia

32. SPIRONOLACTONE
• Competitive inhibitor of aldosterone
• Competes with DHT for the androgen receptor in target tissues.
• Reduces 17alpha -hydroxylase activity.
USES: Side effects:
Hirsutism gynecomastia
Dose: 50mg/d