Drugs affecting reproductive system Basic & Clinical Pharmacology

Drugs affecting reproductive system

Basic & Clinical Pharmacology

ClassificationClassification

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.mB. Antiandrogens

• cyproterone( 环丙孕酮，环甲氯地孕酮 )

C. Drugs used to treat erectile dysfunction • sidenafil( 西地那非 )

Drugs affecting male reproductive systemDrugs affecting male reproductive system

A. Androgens and antiandrogensA. Androgens and antiandrogens

AndrogensAndrogens

Testosterone Testosterone 睾酮睾酮 Testosterone undecanoate Testosterone undecanoate 十一酸睾酮十一酸睾酮

O

O

HCH2CH2

O

C

Nandrolone phenylpropionate Nandrolone phenylpropionate 苯丙酸诺龙苯丙酸诺龙

http://upload.wikimedia.org/wikipedia/commons/1/13/Steroidogenesis.svg

Pharmacological effectsPharmacological effects

(1) Development of the male sexual apparatus and secondary (1) Development of the male sexual apparatus and secondary sex characteristicssex characteristics

(2) Necessary for normal spermatogenesis ((2) Necessary for normal spermatogenesis ( 精子发生精子发生 ))

(3) Increasing protein anabolism(3) Increasing protein anabolism

(4) Promoting growth of blood cells in bone marrow, especially (4) Promoting growth of blood cells in bone marrow, especially for red blood cells (EPO for red blood cells (EPO ) )

(5)Other effects: immune regulation, antiinflammation (5)Other effects: immune regulation, antiinflammation effects,CVS effectseffects,CVS effects


Clinical usesClinical uses

(1) Replacement therapy(1) Replacement therapy in men: hypogonadism in men: hypogonadism

(2)Female disorders:(2)Female disorders: dysfunctional uterine bleeding, dysfunctional uterine bleeding, endometriosis (endometriosis ( 子宫内膜异位症子宫内膜异位症 ), advanced breast and ), advanced breast and ovarian cancersovarian cancers

(3) Anemia:(3) Anemia: aplastic or other anemia (largely replaced by aplastic or other anemia (largely replaced by recombinant erythropoietin )recombinant erythropoietin )

(4) Infirmity(4) Infirmity ( ( 体质虚弱体质虚弱 ): anabolic steroids (): anabolic steroids ( 同化激素同化激素 ) )

(5) Others:(5) Others: male contraception, osteoporosis(either alone or male contraception, osteoporosis(either alone or in conjunction with estrogens. Replaced by in conjunction with estrogens. Replaced by bisphosphonates) etc. bisphosphonates) etc.


Adverse effectsAdverse effects - due largely to their masculinizing actions and are most - due largely to their masculinizing actions and are most

noticeable in women and prepubertal children.noticeable in women and prepubertal children.

(1) Sex dysfunction:(1) Sex dysfunction: • virilisation in female(virilisation in female(hirsutism, acne, amenorrhea, clitoral

enlargement, and deepening of the voice, testosterone> 200–300 mg of per month) )

• increased libido in maleincreased libido in male

(2) Hepatic toxicity (2) Hepatic toxicity • occurs early in the course of treatment, the degree is proportionate

to the dose. bilirubin levels ↑



Contraindications

1. pregnant women, infants and young children (somatotropin is more appropriate to produce a growth spurt).

2. male patients with carcinoma of the prostate or breast. 3. 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.


Classic anabolic hormonesClassic anabolic hormones

1.1. Growth hormone Growth hormone

2.2. IGF1 and other insulin-like growth factors IGF1 and other insulin-like growth factors

3.3. Insulin Insulin

4.4. Testosterone and analogsTestosterone and analogs

5.5. Estradiol Estradiol

Anabolic-androgen steroids (AAS)Anabolic-androgen steroids (AAS)

• Drugs which mimic the effects of the male sex hormones Drugs which mimic the effects of the male sex hormones testosterone and dihydrotestosterone. testosterone and dihydrotestosterone.

• They increase protein synthesis within cells, which results They increase protein synthesis within cells, which results in the buildup of cellular tissue (anabolism), especially in in the buildup of cellular tissue (anabolism), especially in muscles. muscles.

• Anabolic steroids also have androgenic and virilizing Anabolic steroids also have androgenic and virilizing properties, including the development and maintenance of properties, including the development and maintenance of masculine characteristics such as the growth of the vocal masculine characteristics such as the growth of the vocal cords, testicles, and body hair (secondary sexual cords, testicles, and body hair (secondary sexual characteristics). characteristics).


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


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 )

• Antigonizing androgen receptor; inhibiting hypothalamus-Antigonizing androgen receptor; inhibiting hypothalamus-pituitary axis: LH↓, FSH↓, testosterone↓pituitary axis: LH↓, FSH↓, testosterone↓

• Used for treatment of prostatic cancer, severe acne and Used for treatment of prostatic cancer, severe acne and hersulism, and contraceptionhersulism, and contraception


AntiandrogensAntiandrogens

Cyproterone Cyproterone

环丙孕酮环丙孕酮


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


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

Other antiandrogensOther antiandrogens

×

×

http://upload.wikimedia.org/wikipedia/commons/1/13/Steroidogenesis.svg

B. Drugs used to treat erectile dysfunctionB. Drugs used to treat erectile dysfunction

Phosphodiesterase type 5 isoenzyme inhibitorsPhosphodiesterase type 5 isoenzyme inhibitors (PDE5I)PDE5I)

• Sidenafil (Sidenafil ( 西地那非西地那非 ,, 万艾可）万艾可）• Vardenafil (Vardenafil ( 伐地那非伐地那非 ,, 爱力达）爱力达）• Tadalafil (Tadalafil ( 他达那非他达那非 ,, 希爱力）希爱力）


Sildenafil citrate(Viagra)Sildenafil citrate(Viagra)


• Acts by inhibiting cGMP-specific PDE5, an enzyme that delay Acts by inhibiting cGMP-specific PDE5, an enzyme that delay degradation of cGMP, which regulates blood flow in the penisdegradation of cGMP, which regulates blood flow in the penis

• The prime treatment for erectile dysfunction in all settings, The prime treatment for erectile dysfunction in all settings, including diabetes.including diabetes.

http://upload.wikimedia.org/wikipedia/commons/4/48/Sildenafil.svg


Clinical usesClinical uses

(1) Sexual dysfunction(1) Sexual dysfunction(2) Pulmonary arterial hypertension (PAH)(2) Pulmonary arterial hypertension (PAH)• relaxes the arterial wall, leading to decreased pulmonary relaxes the arterial wall, leading to decreased pulmonary

arterial resistance and pressurearterial resistance and pressure→→workload of the right workload of the right ventricle ventricle ↓↓, symptoms of right-sided heart failure, symptoms of right-sided heart failure↑↑

• acts selectively in the lungs and penis without inducing acts selectively in the lungs and penis without inducing vasodilation in other areas of the body →PDE-5 is primarily vasodilation in other areas of the body →PDE-5 is primarily distributed within the arterial wall smooth muscle of the distributed within the arterial wall smooth muscle of the lungs and penislungs and penis

(3) Altitude sickness(3) Altitude sickness• prevention and treatment of high-altitude pulmonary prevention and treatment of high-altitude pulmonary

edema associated with altitude sickness -such as that edema associated with altitude sickness -such as that suffered by mountain climbers.suffered by mountain climbers.



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

ContraindicationsContraindications

1.1. Administration of nitric oxide donorsAdministration of nitric oxide donors2.2. Recent stroke or heart attack, or in men for whom sexual Recent stroke or heart attack, or in men for whom sexual

intercourse is inadvisable due to cardiovascular risk factorsintercourse is inadvisable due to cardiovascular risk factors3.3. Hypotension (low blood pressure) Hypotension (low blood pressure) 4.4. Severe hepatic/ renal function impairment Severe hepatic/ renal function impairment 5.5. Hereditary degenerative retinal disorders (including genetic Hereditary degenerative retinal disorders (including genetic

disorders of retinal phosphodiesterases)disorders of retinal phosphodiesterases)


Further readingFurther reading

1.Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor1.Bertram G. Katzung, Susan B. Masters, Anthony J. TrevorChapter 40. The Gonadal Hormones & InhibitorsChapter 40. The Gonadal Hormones & InhibitorsBasic and Clinical Pharmacology, 11e. 2010 The McGraw-Hill Basic and Clinical Pharmacology, 11e. 2010 The McGraw-Hill Companies.Companies.2. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001046/2. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001046/

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Drugs affecting reproductive system Basic & Clinical Pharmacology