Leuprolide
GnRH analog with agonist properties when use in a pulsatile fashion; antagonist properties used when in continuous fashion (downregulates GnRH receptor in pituitary → ↓ FSH and ↓ LH). Clinical use:- Uterine fibroids- Endometriosis- Precocious puberty- Prostate cancer- Infertility Adverse effects: Hypogonadism, ↓ libido, erectile dysfunction, nausea, vomiting
Estrogens
Ethinyl estradiol, DES, mestranol Clinical use:- Hypogonadism or ovarian failure- Menstrual abnormalities (combined OCPs)- Hormone replacement therapy in postmenopausal women Adverse effects:- ↑ risk of endometrial cancer (when given without progesterone)- Bleeding in postmenopausal women- Clear cell adenocarcinoma of vagina in females exposed to DES in utero- ↑ risk of thrombi Contraindications: ER ⊕ breast cancer, history of DVTs, tobacco use in women >35 years old
Clomiphene
Antagonist at estrogen receptors in hypothalamus (SERM).- Prevents negative feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulates ovulation. - Used to treat infertility due to anovulation (eg, PCOS). - SERMs may cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances.
Tamoxifen
Selective estrogen receptor modulator (SERM) - Antagonist at breast- Agonist at bone, uterus Side effects:- ↑ risk of endometrial cancer- ↑ Risk of uterine sarcoma- Hot flashes- ↑ Risk of thromboembolic events- Decreases the risk of osteoporosis and fractures- Cataract - Used to treat and prevent recurrence of ER/PR ⊕ breast cancer
Raloxifene
Selective estrogen receptor modulator (SERM) - Antagonist at breast, uterus- Agonist at bone - ↑ risk of thromboembolic events - No increased risk of endometrial cancer (vs tamoxifen) - Used primarily to treat osteoporosis
Aromatase inhibitors
Anastrozole, letrozole, exemestane - Inhibit peripheral conversion of androgens to estrogen Clinical use:- ER ⊕ breast cancer in postmenopausal women
Progestins
Levonorgestrel, medroxyprogesterone, etonogestrel, norethindrone, megestrol Bind progesterone receptors, ↓ growth and ↑ vascularization of endometrium, thicken cervical mucus. Clinical use:- Contraception (forms include pill, intrauterine device, implant, depot injection)- Endometrial cancer- Abnormal uterine bleeding Progestin challenge: presence of withdrawal bleeding excludes anatomical defects (eg, Asherman syndrome) and chronic anovulation without estrogen.
Antiprogestins
Mifepristone, ulipristal Competitive inhibitors of progestins at progesterone receptors. Clinical use:- Termination of pregnancy (mifepristone with misoprostol)- Emergency contraception (ulipristal)
Terbutaline, ritodrine
β2-agonists that relax the uterus - used to ↓ contraction frequency in women during labor
Danazol
Synthetic androgen that acts as partial agonist at androgen receptors. Clinical use:- Endometriosis- Hereditary angioedema Adverse effects:- Weight gain, edema, acne, hirsutism, masculinization- ↓ HDL levels- Hepatotoxicity- Pseudotumor cerebri
Phosphodiesterase type 5 inhibitors
Sidenafil, vardenafil, tadalafil Inhibit PDE-5 → ↑ cGMP → prolonged smooth muscle relaxation in response to NO → ↑ blood flow in corpus cavernosum of penis, ↓ pulmonary vascular resistance. Clinical use:- Erectile dysfunction- Pulmonary hypertension- BPH (tadalafil only) Adverse effects:- Cardiovascular: Hypotension (especially with nitrates, alpha blockers)- Ocular: Blue discoloration of vision, nonarteritic anterior ischemic optic neuropathy- Genitourinary: Priapism- Headache- Flushing- Dyspepsia
Minoxidil
Direct arteriolar vasodilator Clinical use:- Androgenetic alopecia (pattern baldness)- Severe refractory hypertension
Tamsulosin
α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α1A/D receptors (found on prostate) vs vascular α1B receptors.
Testosterone, methyltestosterone
Agonists at androgen receptors. Clinical use: - Treat hypogonadism and promote development of 2° sex characteristics.- Stimulate anabolism to promote recovery after burn or injury. Adverse effects:- Masculinization in females- ↓ intratesticular testosterone in males by inhibiting release of LH (via negative feedback) → gonadal atrophy- Premature closure of epiphyseal plates- ↑ LDL, ↓ HDL
Copper intrauterine device
Duration of efficacy: 10 years Mechanism:- Cytotoxic endometrial inflammation- Impairs sperm function- Impairs implantation Clinical use: - Long-acting reversible contraception- Most effective emergency contraception Adverse effects: - Heavier or longer menses- Dysmenorrhea- Risk of PID with insertion (contraindicated in active pelvic infection)- Ectopic pregnancy Contraindications:- Wilson disease- Copper allergy- Heavy menstrual bleeding- Acute pelvic infection
Combined contraception
Progestins and ethinyl estradiol; forms include pill, vaginal ring, patch. Estogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge → no LH surge → no ovulation. - Progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus.- Progestins also inhibit endometrial proliferation → endometrium is less suitable to the implantation of an embryo. Contraindications:- Smokers >35 years old (↑ risk of cardiovascular events)- Patients with ↑ risk of cardiovascular disease (including history of venous thromboembolism, coronary artery disease, stroke)- Migrane with aura- Breast cancer- Liver disease
Hormone replacement therapy
Used for relief or prevention of menopausal symptoms (eg, hot flashes, vaginal atrophy), osteoporosis (↑ estrogen, ↓ osteoclast activity). - Unopposed estrogen replacement therapy ↑ risk of endometrial cancer, progesterone/progestin is added. - Possible increased cardiovascular risk.
Tocolytics
Medications that relax the uterus. - Terbutaline, ritodrine (β2-agonist action)- Nifedipine (Ca2+ channel blocker)- Indomethacin (NSAID) - Used to ↓ contraction frequency in preterm labor and allow time for administration of steroids (to promote fetal lung maturity) or transfer to appropriate medical center with obstetrical care.
Finasteride
5α-reductase inhibitor (↓ conversion of testosterone to DHT). Use:- BPH - Male-pattern baldness Adverse effects: Gynecomastia and sexual dysfunction
Flutamide
Nonsteroidal competitive inhibitor at androgen receptors. Use: Prostate carcinoma- Sometimes prescribed concurrently with GnRH agonists to limit the tumor-stimulating effects of initial testosterone rise
Oxytocin
Indications:- Induction or augmentation of labor- Prevention & management of postpartum hemorrhage Adverse effects:- Hyponatremia (similar in structure to ADH)- Hypotension- Tachysystole
Emergency contraception options
Copper IUD:- Copper causes inflammatory reaction that is toxic to sperm & ova & impairs implantation- Time after intercourse: 0-120 h- 99% efficacy Ulipristal pill:- Antiprogestin; delays ovulation- Time after intercourse: 0-120 h- ≥ 85% efficacy Levonorgestrel:- Progestin, delays ovulation- Time after intercourse: 0-72 h- 85% efficacy OCPs: - Progestin, delays ovulation- Time after intercourse: 0-72 h- 75% efficacy
Diaphragm
Description:- Dome-shaped latex, metal, or plastic device that holds spermicide- Placed into the anterior and posterior fornix of the vagina prior to sexual intercourse; must be kept in place for 6 hours after intercourse- Prevents passage of semen into the cervix Contraindications: cervical anomalies or abnormalities (e.g., infection, malignancy), spermicide or latex allergy Complication: toxic shock syndrome
Vasectomy
Description: bilateral tubal ligation and partial destruction/removal of the vas deferens Can be performed under local anaesthesia Complications:- Hematoma- Surgical site infection- Sperm granulomas- Post-vasectomy pain syndrome- Vasectomy failure: Patients should be counseled about potential post-vasectomy pregnancies (approx. 1 in 2000 cases)- Follow-up sperm sample test at three months after surgery to verify azoospermia
Intrauterine device with progestin
Duration of efficacy: 3-5 years Mechanism:- Thickens cervical mucus- Impairs implantation Benefits: Decreases menstrual flow Contraindications:- Active liver disease- Breast cancer- Acute pelvic infection
Absolute contraindications to combined hormonal contraceptives
- Migrane with aura - ≥ 15 cigarettes/day PLUS age ≥ 35 - Hypertension ≥ 160/100 mmHg - Heart disease - Diabetes mellitus with end-organ damage - History of thromboembolic disease, stroke - Antiphospholipid-antibody syndrome - Breast cancer - Cirrhosis & liver cancer - Major surgery with prolonged immobilization - Use < 3 weeks postpartum
