1. Drugs affecting reproductive system

2. A. Overview A. Overview

3. Female systemic effects

5. Male sperm sexual and systemic effects

6. A. Overview §Sex hormones and related drugs § Female hormones § Estrogens § Antiestrogens § Progesterone and progestogens § Antiprogestogens § Female contraception drugs § Male hormones § Androgens § Antiandrogens § Anabolic steroids § Male contraception drugs

7. B. Estrogens and antiestrogens

8. 雌二醇

9. Estradiol 雌二醇 Diethylstibestrol 己烯雌酚 Clomiphene 氯底酚胺（氯米酚） 艹

10. B. Estrogens and antiestrogens §Estrogens §1. Pharmacological effects §(1) Development of the female genital tract and of the female secondary sex characteristics. §(2) Maintenance of both proliferative and secretory phases of the uterine endometrium §(3) Ovulation:  (small doses) or  (larger doses) §(4) Development of the breast and lactescence §  (small doses) or  (larger doses)

11. B. Estrogens and antiestrogens §(5) Other actions: § decreasing postmenopausal disturbances in sleep § inhibiting the reabsorption of bone § increasing aldosterone, causing water and Na + retention § decreasing LDL and increasing HDL levels in plasma § increasing factor II, VII, IX, X and coagulation

12. Pharmacological effects of estrogens Estradiol Cytosol estradiol receptor Nuclear estradiol response element Transcription of target genes Responses

13. Intracellular signal transduction of receptors for estrogen and other sex hormones

14. Pharmacological effects of estrogens

15. B. Estrogens and antiestrogens §2. Clinical uses  (1) Postmenopausal syndrome （绝经期综合征） : § Postmenpausal hormone replacement therapy (HRT): § Osteoporosis; vasomotor & CNS symptoms; prevention of cardiovascular disease  (2) Primary hypogonadism ( 卵巢功能不全 ) : replacement  (3) Menstrual disorders （月经紊乱） : § amenorrhea; severe dysfunctional uterine bleeding  (4) Contraception （避孕） §(5) Others: inhibition of lactation § advanced breast cancer (postmenopausal) § prostatic cancer  acne ( 痤疮 ) § neuroprotection ?

16. B. Estrogens and antiestrogens §3. Adverse effects §(1) Oral administration: nausea,vomiting, diarrhea §(2) Cardiovascular effects: § risk of venous thromboembolisis § plasma triglycerides  § hypertension, edema §(3) Others: § gallbladder disease § risk of breast and endometrial carcinoma § potential malformation of the fetuses (X)

17. B. Estrogens and antiestrogens §Antiestrogens  Clomifene (clomiphene) 氯底酚胺 ( 氯米芬，克罗米酚 ) §(1) Effects: Partial agonist/antagonist for estrogen receptor 艹

18. B. Estrogens and antiestrogens §(2) Uses:  anovulatory infertility ( 无排卵性不孕 ) §menstrual disorders §advance breast cancer  functional amenorrhea ( 功能性闭经 )  amenorrhea galactorrhea syndrome ( 闭经溢乳综合征 ) §(3) Adverse effects:  Multiple ovulation with multiple pregnancy ( 多胎 )  ovary tumefaction ( 卵巢肿大 ) §ovarian carcinoma following multiple exposure

20. B. Estrogens and antiestrogens  Tamoxifen 他莫昔芬（三苯氧胺） §(1) A nonsteroid competitive estrogen antagonist §(2) Used for treatment of estrogen dependent breast cancer

21. C. Progestogens and antiprogestogens

22. Progesterone 黄体酮 ( 孕酮 )

23. Progesterone 黄体酮（孕酮） Norethisterone 炔诺酮

24. C. Progestogens and antiprogestogens §Progestogens §1. Pharmacological effects §(1) Converting the uterine epithelium from the proliferative phase to the secretory phase §(2) Inhibiting LH secretion and ovulation  (3) Development of galactophore （ 乳管 ） §(4) Thermoregulation: increasing body temperature §(5) Metabolism: antagonizing aldosterone, inducing hepatic drug-metabolizing enzyme

25. C. Progestogens and antiprogestogens §2. Clinical uses  (1) Menstrual disorders: secondary amenorrhage, exacerbated uterine bleeding, dysmenorrhea ( 痛经 ) and premenstrual syndrome, etc. §(2) Cancers: endometrial cancer, prostatic cancer  (3) Others: endometriosis ( 子宫内膜异位症 ), hormone replacement therapy (HRT), premature pregnancy ( 流 产 ), etc.

26. C. Progestogens and antiprogestogens §3. Adverse effects §GI reactions §Hepatic dysfunction §Potential malformation of the fetuses (D)

27. C. Progestogens and antiprogestogens §Antiprogestogens  Mifepristone 米非司酮 § § A synthetic steroid compound

28. Mifepristone 米非司酮 1. Pharmacological effects1. Pharmacological effects A progesterone receptor antagonist used as an abortifacient in the first two months of pregnancy, and in smaller doses as an emergency contraceptive. C. Progestogens and antiprogestogens

29. 2. Clinical uses (1) Medical termination of intrauterine pregnancies of up to 49 days gestation (up to 63 days gestation in Britain and Sweden) 600 mg + misoprostol 400 µg (2 days later) →terminated 96 to 99% of pregnancies of up to 49 days gestation. If expulsion of fetal tissue does not occur during the observation period, surgical abortion is offered. C. Progestogens and antiprogestogens

30. (3) Termination of pregnancies between 13 and 24 weeks gestation softening and dilatation of the cervix prior to mechanical cervical dilatation for pregnancy termination softening and dilatation of the cervix prior to mechanical cervical dilatation for pregnancy termination in combination with gemeprost ( 前列甲酯 ) in combination with gemeprost ( 前列甲酯 ) (4) Labor induction in fetal death in utero (5) Emergency contraceptive used in smaller doses (10 mg) used in smaller doses (10 mg) C. Progestogens and antiprogestogens

31. (6) Other uses Phase II clinical trials include: Oral contraceptive regular long-term use Oral contraceptive regular long-term use Cancers: uterine fibroids ( 子宫平滑肌瘤 ), endometriosis, major depression with psychotic features, glaucoma, meningiomas ( 脑膜瘤 ), breast cancer, ovarian cancer, and prostate cancer. Cancers: uterine fibroids ( 子宫平滑肌瘤 ), endometriosis, major depression with psychotic features, glaucoma, meningiomas ( 脑膜瘤 ), breast cancer, ovarian cancer, and prostate cancer. Cushing's syndrome: with treatment durations being as long as 10 years without noticeable adverse effect. Cushing's syndrome: with treatment durations being as long as 10 years without noticeable adverse effect. Psychotic major depression: limited by small study group and limited treatment duration Psychotic major depression: limited by small study group and limited treatment duration C. Progestogens and antiprogestogens

32. D. Androgens and antiandrogens

33. §Androgens Testosterone 睾酮 Testosterone undecanoate 十一酸睾酮 Nandrolone phenylpropionate 苯丙酸诺龙

34. D. Androgens and antiandrogens §Androgens §1. 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  )

35. §2. Clinical uses §(1) Replacement therapy: 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  (4) Infirmity ( 体质虚弱 ) : anabolic steroids ( 同化激素 ) §(5) Others: male contraception, etc. D. Androgens and antiandrogens

36. §3. Adverse effects §(1) Sex dysfunction:  virilisation ( 男性化 ) in female  increased libido ( 性欲亢进 ) in male §(2) Hepatic toxicity D. Androgens and antiandrogens

37. Control of androgen secretion and activity and some sites of action of antiandrogens: (1) Competitive inhibition of GnRH receptors (2) Stimulation (+, pulsatilen ) or inhibition via desensitization of GnRH receptors (–, continuous ) (3) Decreased synthesis of testosterone in the testis (4) Decreased synthesis of dihydrotestosterone by inhibition of 5  - reductase; (5) Competition for binding to cytosol androgen receptors.

38. §Antiandrogens  Cyproterone 环丙孕酮 §(1) Antigonizing androgen receptor; inhibiting hypothalamus-pituitary axis: LH↓, FSH↓, testosterone↓ §(2) Used for treatment of prostatic cancer, severe acne and hirsulism, and contraception §(3) Suppression of sex function, hepatic function, etc. D. Androgens and antiandrogens

39. §Other antiandrogens D. Androgens and antiandrogens Finasteride (): inhibiting synthesis of dihydrotestosterone by inhibition of 5  -reductase Finasteride ( 非那雄胺 ): inhibiting synthesis of dihydrotestosterone by inhibition of 5  -reductase Flutamide (): an androgen receptor antagonist Flutamide ( 氟他米特 ): an androgen receptor antagonist

40. E. Contraceptive drugs §Contraceptive drugs §Contraceptive drugs have been identified that inhibit fertility by a number of different mechanisms, for example, preventing ovulation, impairing gametogenesis or gamete maturation, or interfering with gestation.

41. E. Contraceptive drugs §A contraceptive drug should be: §(1) extremely safe as well as highly effective §(2) its action must be quick in onset and quickly and completely reversible, even after years of continuous use  (3) it must not affect libido ( 性欲 )

42. E. Contraceptive drugs §For female: §(1) Inhibition of ovulation §(2) Prevention of fertilization §(3) Inhibition of implantation §(4) Use of spermicides in the vagina §For male: §(1) Direct inhibition of spermatomatogenesis §(2) Indirect inhibition of spermatomatogenesis

43. E. Contraceptive drugs §Steroid contraceptives for femal: § Estrogens + progestogens §1. Pharmacological effects §(1) Inhibition of ovulation §(2) Inhibition of implantation  (3) Increase in viscidity of cervical mucus （宫颈黏液） §(4) Others: interfering uterus or oviducal motility

45. E. Contraceptive drugs §2. Clinical uses §(1) Oral: § short-acting contraceptives § long-acting contraceptives  postcoital ( 事后，探亲 ) contraceptives §(2) long-acting injections §(3) Slow-releasing preparations §(4) Multiphasic preparations

47. 国内常用甾体避孕药成分

48. E. Contraceptive drugs §3. Adverse effects §(1) GI reactions §(2) Menstrual disorders: breakthrough bleeding, amenorrhea §(3) Increased coagulation: venous thromboembolism §(4) Others: edema, depression, weight gain, acne, hirsutism, etc. §Drug interactions: §Hepatic enzyme inducers attenuate the effect of contraceptive drugs

49. E. Contraceptive drugs §For termination of early pregnancy  Mifepristone 米非司酮 §bleeding (treated by prostagladins) §Use of spermicides in the vagina  nonoxinol ( 壬苯聚醇 ), menfenol, alkyl polyethoxy phenoxyethanol ( 聚乙氧烷苯氧乙醇 )

50. E. Contraceptive drugs §For males  Gossypol 棉酚 This compound destroys elements of the seminiferous epithelium ( 生精上皮 ) but does not alter the endocrine function of the testis. GI and hepatic reactions, hypopotassaemia, etc.

51. E. Contraceptive drugs §Other contraceptivesfor males §Other contraceptives for males  Cyproterone acetate ( 环丙氯地孕酮 ) §Androgens §Progestrone-androgen compounds §GnRH analog-androgen compounds

52. F. Drugs acting on uterus smooth muscle §Stimulatants of uterus  Oxytocin 缩宫素（催产素）  Pituitrin 垂体后叶素  Ergot alkaloid 麦角生物碱  Prostaglandins 前列腺素类 §Relaxants of uterus  Ritodrine 利托君  Terbutaline 特布他林  Salbuterol 沙丁胺醇  Magnesiun sulfate 硫酸镁

53. F. Drugs acting on uterus smooth muscle §Stimulatants of uterus  Oxytocin 缩宫素（催产素） §A peptide hormone synthesized in hypothalamus §Small doses (2-5 U): § rhythmic contraction; induction of labor §Large doses (5-10 U): § tonic contraction; postpartum hemorrhage §Cautions in induction of labor: dose, contraindications

54. F. Drugs acting on uterus smooth muscle  Pituitrin 垂体后叶素 §Contracting vasculatures §Used in controlling lung bleeding, and diabetes insipidus §Pale face; BP elevation; palpitation; abdominal pain

55. F. Drugs acting on uterus smooth muscle  Ergot alkaloid 麦角生物碱 胺麦角碱肽麦角碱 Ergometrine 麦角新碱 Methylergometrine 甲基麦角新碱 Selectively contracting uterus smooth muscle Ergotamine 麦角胺 Mainly contracting arteries and veins

56. F. Drugs acting on uterus smooth muscle  Ergot alkaloid 麦角生物碱 §Used in  postpartum hemorrhage （ 产后出血 ）  migration （ 偏头痛 ） §GI disturbances: diarrhea, nausea, and vomiting prolonged vasospasm §Contraindications: obstructive vascular diseases; pregnancy

57. F. Drugs acting on uterus smooth muscle  Prostaglandins 前列腺素类  dinoprostone （地诺前列酮， PGE 2 ）  dinoprost （地诺前列素， PGF 2  ）  sulprostone （硫前列酮）  carboprost （卡前列素）

58. Used in Induction of labor Abortion （流产） : combined with mifepristone Facilitation of labor GI disturbances: nausea, vomiting and abdominal pain Contraindications: bronchial asthma; glaucoma

59. F. Drugs acting on uterus smooth muscle §Relaxants of uterus  Ritodrine (  2 agonist) 利托君  Terbutaline (  2 agonist) 特布他林  Salbuterol (  2 agonist) 沙丁胺醇  Magnesiun sulfate 硫酸镁 (Ca 2+ antagonist) 硝苯地平  Nifedipine (Ca 2+ antagonist) 硝苯地平 (COX inhibitor) 吲哚美辛  Indomethacin (COX inhibitor) 吲哚美辛 §Used in 痛经 ; 早产  dysmenorrhoea 痛经 ; premature birth 早产