Drugs affecting reproductive system
Drugs related to female hormones
Estrogens
Antiestrogens
Progesterone and progestogens
Antiprogestogens
Female contraception drugs
Drug related to male hormones
Androgens
Antiandrogens
Anabolic steroids
Male contraception drugs
Estrogens
1. Pharmacological effects
(1) Development of the female genital tract and of the female secondary sex characeteristics.
(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)
(5) Other actions:
decreasing postmenopausal disturbances in sleep
inhibiting the reabsorption of bone
increasing aldosterone and causing water and Na+ retention
decreasing LDL and increasing HDL levels in plasma
increasing factor II, VII, IX, X and coagulation
2. Clinical uses
(1) Postmenopausal syndrome（绝经期综合征）:
Postmenpausal hormone replacement therapy (HRT):
prevention of osteoporosis;
- Fractures of the spine, wrist, and hips decrease by 50-70% and spinal bone density increases by ~5% in women treated with estrogen within 3 years of the onset of menopause and for 5–10 years thereafter.
treat vasomotor & CNS symptoms
- hot flushes, vaginal dryness, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating.
prevention of cardiovascular disease
-lowers LDL ,TG; raises HDL levels
-endothelial vasodilatation properties , anti-inflammatory
(2) Primary hypogonadism (卵巢功能不全): replacement
vaginal atrophy, hypoestrogenism
(3) Menstrual disorders
amenorrhea , dysmenorrhea, and oligomenorrhea;
severe dysfunctional uterine bleeding
(4) Contraception
(5) Others:
suppress lactation after child birth
advanced breast cancer (postmenopausal) and prostatic cancer
-hormone-sensitive or hormone-receptor-positive cancers
-hormone therapy, or anti-estrogen therapy (not to be confused with hormone replacement therapy)
acne
neuroprotection
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
Clomifene
氯米芬 (克罗米酚)
(1) Effects: Partial agonist/antagonist for estrogen receptor
(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.
Progestogens
1. Pharmacological effects
(1) Converting the uterine epithelium from the proliferative 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
2. Clinical uses
(1)Menstrual disorders
secondary amenorrhage, exacerbated uterine bleeding, dysmenorrhea (痛经) and premenstrual syndrome, etc.
artificially induce progestogen withdrawal bleeding.
- Norethindrone acetate
-medroxyprogesterone acetate
(2) Cancers megestrol acetate
solid malignancy, especially gastric and pancreatic cancer,
improve appetite and reduce wasting.
used in combination with dexamethasone.
effects take several weeks to become apparent, but are relatively long-lived compared to those of corticosteroids.
the only drugs to increase lean body mass.
(3) Others
endometriosis (子宫内膜异位症), hormone replacement therapy (HRT), premature pregnancy (流产), etc.
3. Adverse effects
GI reactions
edema
virilization (男性化)
acne
hirsulism (多毛)
weight gain etc.
Mifepristone 米非司酮
Clinical uses
1.Medical termination of intrauterine pregnancies of up to 49 days gestation
3. termination of pregnancies between 13 and 24 weeks gestation
softening and dilatation of the cervix prior to mechanical cervical dilatation for pregnancy termination
in combination with gemeprost
4.Labor induction in fetal death in utero.
5. emergency contraceptive
used in smaller doses (10 mg)
taken after sex but before ovulation→prevent ovulation and so prevent pregnancy.
C. 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
Steroid contraceptives for female
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
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
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.
4. Drug interactions:
Hepatic enzyme inducers attenuate the effect of contraceptive drugs
Contraceptives for male
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.
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
Oxytocin 缩宫素（催产素）
Pharmacological effects
Uterine contraction
important for cervical dilation before birth and causes contractions during the second and third stages of labor.
assist the uterus in clotting the placental attachment point postpartum- during the first few weeks of lactation.
However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition are normal.
Clinical uses
Small doses (2-5 U): rhythmic contraction; induction of labor
Large doses (5-10 U): tonic contraction; postpartum hemorrhage
relatively safe when used at recommended doses, and side effects are uncommon
Cautions in induction of labor
Ergot alkaloid 麦角生物碱
Pharmacological effects
1.Uterine smooth muscle stimulation
Selectively and determined by the functional state of the uterus
2.Vessel-contracting effect
Directly contract artery and venous vessels
Damage vascular endothelial cells at high dose
Lead to dry gangrene of the extremities after long term use
3.α-receptor blocking effect
Reverse the BP-elevating effect of NA
Used in
uterus bleeding
postpartum hemorrhage（产后出血）
migraine（偏头痛）
Adverse effects
GI disturbances: diarrhea, nausea, and vomiting prolonged vasospasm
Contraindications
obstructive vascular; pregnancy
Prostaglandins 前列腺素类
dinoprostone（地诺前列酮，PGE2）
dinoprost（地诺前列素，PGF2）
sulprostone（硫前列酮）
carboprost （卡前列素）
Used in
Abortion（流产）: combined with mifepristone
Facilitation of labor
Adverse effects
GI disturbances: nausea, vomiting and abdominal pain
Contraindications bronchial asthma; glaucoma