Drugs affecting reproductive system Basic & Clinical Pharmacology Drugs affecting reproductive system

Drugs affecting male reproductive system Classification A. Androgens and antiandrogens 　1. testosterone(睾酮 ) 　2. methyltestosterone(甲睾酮) orally effective 3. testosterone propionate (丙酸睾丸素) most commonly used 　4. mesterolone (甲二氢睾酮，美睾酮) 5.fluoxymesterone(氟甲睾酮) 6.testosterone phenyl-acetate(苯乙酸睾丸素) 7.tristeronum compositum testosterone propionate 25mg estradiol benzoate(苯甲酸雌二醇) 1.25mg progesterone 12.5mg，i.m B. Antiandrogens cyproterone(环丙孕酮，环甲氯地孕酮) C. Drugs used to treat erectile dysfunction sidenafil(西地那非)

A. Androgens and antiandrogens Testosterone 睾酮 Testosterone undecanoate 十一酸睾酮 Nandrolone phenylpropionate 苯丙酸诺龙

A. Androgens and antiandrogens Pharmacological effects (1) Development of the male sexual apparatus and secondary sex characteristics (2) Necessary for normal spermatogenesis (精子发生) (3) Increasing protein anabolism (4) Promoting growth of blood cells in bone marrow, especially for red blood cells (EPO ) (5)Other effects: immune regulation, antiinflammation effects,CVS effects

A. Androgens and antiandrogens Clinical uses (1) Replacement therapy in men: hypogonadism (2)Female disorders: dysfunctional uterine bleeding, endometriosis (子宫内膜异位症), advanced breast and ovarian cancers (3) Anemia: aplastic or other anemia (largely replaced by recombinant erythropoietin ) (4) Infirmity (体质虚弱): anabolic steroids (同化激素) (5) Others: male contraception, osteoporosis(either alone or in conjunction with estrogens. Replaced by bisphosphonates) etc.

A. Androgens and antiandrogens Adverse effects - due largely to their masculinizing actions and are most noticeable in women and prepubertal children. (1) Sex dysfunction: virilisation in female(hirsutism, acne, amenorrhea, clitoral enlargement, and deepening of the voice, testosterone> 200–300 mg of per month) increased libido in male (2) Hepatic toxicity occurs early in the course of treatment, the degree is proportionate to the dose. bilirubin levels ↑

A. Androgens and antiandrogens Contraindications pregnant women, infants and young children (somatotropin is more appropriate to produce a growth spurt). male patients with carcinoma of the prostate or breast. renal or cardiac disease predisposed to edema Caution: Several cases of hepatocellular carcinoma have been reported in patients with aplastic anemia treated with androgen anabolic therapy. Erythropoietin and colony-stimulating factors should be used instead.

A. Androgens and antiandrogens Classic anabolic hormones Growth hormone IGF1 and other insulin-like growth factors Insulin Testosterone and analogs Estradiol

Anabolic-androgen steroids (AAS) A. Androgens and antiandrogens Anabolic-androgen steroids (AAS) Drugs which mimic the effects of the male sex hormones testosterone and dihydrotestosterone. They increase protein synthesis within cells, which results in the buildup of cellular tissue (anabolism), especially in muscles. Anabolic steroids also have androgenic and virilizing properties, including the development and maintenance of masculine characteristics such as the growth of the vocal cords, testicles, and body hair (secondary sexual characteristics).

Androgens: Preparations Available and Relative Androgenic:Anabolic Activity in Animals. Drug Androgenic: Anabolic Activity Testosterone 1:1 Testosterone cypionate 1:1 Testosterone enanthate 1:1 Methyltestosterone 1:1 Fluoxymesterone 1:2 Oxymetholone 1:3 Oxandrolone 1:3–1:13 Nandrolone decanoate 1:2.5–1:4

A. Androgens and antiandrogens Agents 1. Nandrolone phenpropionate(durabolin ，苯丙酸诺龙) 　2. Nandrolonedecanoate(癸酸诺龙) 　3. Metandienone (去氢甲睾酮，美雄酮) 　4. Danazol (达那唑) 5. Stanozolol(司坦唑醇)

A. Androgens and antiandrogens Cyproterone 环丙孕酮 Antigonizing androgen receptor; inhibiting hypothalamus-pituitary axis: LH↓, FSH↓, testosterone↓ Used for treatment of prostatic cancer, severe acne and hersulism, and contraception

A. Androgens and antiandrogens Adverse effects 1. Antiandrogenic action gynecomastia (breast growth), galactorrhea (milk outflow), and erectile dysfunction. 2.Liver toxicity high dose (200–300 mg/day). 3. Increased risk of DVT ( in combination with ethinylestradiol ) 4. Other reactions Depressive mood changes Suppression of adrenal function and reduced response to ACTH Osteoporosis- suppresses production of estrogen due to its antigonadotrophic effect

A. Androgens and antiandrogens Other antiandrogens 1.Other receptor Inhibitors Flutamide(氟他米特) Bicalutamide(比卡鲁胺) & nilutamide(尼鲁米特) Spironolactone 2. Steroid synthesis inhibitors- Ketoconazole(酮康唑) 3. Conversion of Steroid Precursors to Androgens Abiraterone(阿比特龙) inhibitor of 17-hydroxylase Finasteride(非那雄胺) inhibitor of 5 -reductase Dutasteride(度他雄胺) similar to but much longer t1/2 than finasteride

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B. Drugs used to treat erectile dysfunction Phosphodiesterase type 5 isoenzyme inhibitors (PDE5I) Sidenafil (西地那非,万艾可） Vardenafil (伐地那非,爱力达） Tadalafil (他达那非,希爱力）

B. Drugs used to treat erectile dysfunction

B. Drugs used to treat erectile dysfunction Sildenafil citrate(Viagra) Acts by inhibiting cGMP-specific PDE5, an enzyme that delay degradation of cGMP, which regulates blood flow in the penis The prime treatment for erectile dysfunction in all settings, including diabetes.

B. Drugs used to treat erectile dysfunction

B. Drugs used to treat erectile dysfunction Clinical uses (1) Sexual dysfunction (2) Pulmonary arterial hypertension (PAH) relaxes the arterial wall, leading to decreased pulmonary arterial resistance and pressure→workload of the right ventricle ↓, symptoms of right-sided heart failure↑ acts selectively in the lungs and penis without inducing vasodilation in other areas of the body →PDE-5 is primarily distributed within the arterial wall smooth muscle of the lungs and penis (3) Altitude sickness prevention and treatment of high-altitude pulmonary edema associated with altitude sickness -such as that suffered by mountain climbers.

B. Drugs used to treat erectile dysfunction Adverse effects 1.Headache, flushing, dyspepsia, nasal congestion and impaired vision, including photophobia and blurred (lead to vision impairment in rare cases) - the most common adverse effects 2. Priapism, severe hypotension, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss -rare but serious

B. Drugs used to treat erectile dysfunction Contraindications Administration of nitric oxide donors Recent stroke or heart attack, or in men for whom sexual intercourse is inadvisable due to cardiovascular risk factors Hypotension (low blood pressure) Severe hepatic/ renal function impairment Hereditary degenerative retinal disorders (including genetic disorders of retinal phosphodiesterases)

Further reading 1.Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor Chapter 40. The Gonadal Hormones & Inhibitors Basic and Clinical Pharmacology, 11e. 2010 The McGraw-Hill Companies. 2. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001046/