Reproductive Pharm

Anti-androgens

• Types:
  • Finasteride: 5-alpha reductase inhibitors (BPH and male-pattern alopecia)
    
  • Flutamide: Non-steroidal competitive inhibitor at androgen receptors (prostate carcinoma)
    
  • Ketoconazole: inhibits 17,20 desmolase required in T synthesis
    
  • Spironolactone: inhibits 17,20 desmolase and 17-alpha hydroxylase as well as steroid binding

Ketoconazole and spironolactone

• Clinical Use:
  • Treatment of androgenic effects in PCOS
• Side Effects:
  • Amenorrhea and Gynecomastia

Tamsulosin

• MOA:
  • Alpha-1 receptor antagonist used to treat BPH: relaxes smooth muscle
    
  • Selective for Alpha-1-A,D subtypes found on prostate rather than vascular alpha-1-B receptors

Aromatase Inhibitors

• Types:
  • Anastrozole
    
  • Letrozole
    
  • Exemestane
• MOA:
  • Inhibition of peripheral conversion of androgens to estrogen
• Clinical Use:
  • ER-positive BC in postmenopausal women

Clomiphine

• Clinical Use:
  • Infertility due to anovulation (PCOS)
• Side Effects:
  • Hot flashes
    
  • Ovarian enlargement
    
  • Multiple simultaneous pregnancies
    
  • Visual disturbances

Danazol

• MOA:
  • Synthetic androgen that acts as partial agonist at androgen receptors
• Clinical Use:
  • Endometriosis
    
  • Hereditary angioedema
• Side Effects:
  • Weight gain
    
  • Edema
    
  • Acne
    
  • Hirsutism
    
  • Masculinization
    
  • Decreased HDL
    
  • Hepatotoxicity

Estrogen

• Types: 
  • Ethinyl estradiol
    
  • DES
    
  • MEstranol
• Clinical Use:
  • Hypogonadism or ovarian failure
    
  • Menstrual abnormalities
    
  • Hormone replacement therapy in postmenopausal women
    
  • Men with androgen-dependent prostate cancer
• Side Effects:
  • Increased risk for endometrial cancer
    
  • Bleeding in postmenopausal women
  • Clear cell adenocarcinoma of the vagina (DES exposure to the fetus)
    
  • Hypercoagulability
    
  • Contraindicated in patients with ER-positive breast cancer or a history of DVT

Hormone replacement therapy

• Treats: Menopausal symptoms (hot flashes vaginal atrophy) and Osteoporosis
  
• Estrogen alone increases risk for endometrial and breast cancer
  
• Progesterone is added
  
• Possibly increased CV risk

Progestins

• Types:
  • Levonorgestrel
    
  • Medroxyprogesterone
    
  • Etonogestrel
    
  • Norethindrone
    
  • Megestrol
•  MOA:
  • Bind Progesterone receptors which decreases growth and increases vascularization of the endometrium and thickens cervical mucus
• Clinical Use:
  • Contraception (pill IUD implant or depot injection)
    
  • Endometrial cancer
    
  • Progestin challenge: withdrawal bleeding excludes anatomic defects that could cause infertility

Antiprogestins

• Types:
  • Mifepristone
    
  • Ulipristal
• MOA:
  • Competitive inhibitors of progestins at progesterone receptors
• Clinical Use:
  • Termination of pregnancy: mifepristone plus misoprostol ( prostaglandin analogue)
    
  • Emergency contraception (Ulipristal)

Combined contraception

• Type:
  • Progestins and Ethinyl Estradiol
•  Contraindications:
  • Smokers > 35 year olds (risk of CV events)
    
  • History of venous thromboembolism, CAD or CVA
    
  • Migraines (especially with aura)
    
  • Breast cancer

Copper IUD

•  MOA:
  • Produces local inflammatory reaction toxic to sperm and ova: prevents fertilization and implantation
    
  • Hormone-free
• Clinical Use:
  • Long-acting reversible contraception
    
  • Most effective emergency contraception
• Side Effects:
  • Heavier longer menses and dysmenorrhea
    
  • Risk of PID with insertion
    
  • Contraindicated with active pelvic infection

Leuprolide 

• MOA:
  • GnRH analog with agonist properties when used in a pulsatile fashion and antagonist properties when used in a continuous fashion (downregulates GnRH receptors in pituitary resulting in decreased FSH and LH)
• Clinical Use:
  • Uterine fibroids (continuous)
    
  • Endometriosis (continuous)
    
  • Precocious puberty (continuous)
    
  • Prostate cancer (continuous)
    
  • Infertility (pulsatile)

PDE-5 Inhibitors

• Types:
  • Sildenafil
    
  • Vardenafil
  • Tadalafil
• MOA:
  • Inhibition of PDE-5 – increased cGMP – prolonged smooth muscle relaxation in response to NO – increased blood flow in corpus cavernosum of the penis and decreased pulmonary vascular resistance
• Clinical Use:
  • Erectile dysfunction
    
  • Pulmonary HTN
    
  • BPH (Tadalafil only)
• Side Effects:
  • Headache
    
  • Flushing
    
  • Dyspepsia
    
  • Cyanopia (blue-tinted vision)
    
  • Life-threatening hypotension in patients taking nitrates

Minoxidil

• MOA:
  
  • Direct arteriolar vasodilator used for androgenic alopecia and severe refractory HTN

Raloxifene

• MOA:
  • ER Antagonist at breast and uterus but agonist in bone
• Clinical Use:
  • Osteoporosis
• Side Effects:
  • Increased risk for thromboembolic events

Ritodrine and Terbutaline

• MOA:
  • Beta-2 agonists that relax the uterus: used to decrease contraction frequency in women during labor

Tamoxifen

• MOA:
  • ER antagonist at the breast
    
  • Agonist at bone and uterus
• Clinical Use:
  • Treatment and prevention of recurrence of ER/PR positive BC
• Side Effects:
  • Increased risk for endometrial cancer and thromboembolic events

Testosterone or methyltestosterone

• Clinical Use:
  • Hypogonadism
    
  • Promote secondary sex characteristics
    
  • Stimulate anabolism to promote recovery after burn or injury
• Side Effects:
  • Masculinization in females
    
  • Decreases intra-testicular testosterone in males by inhibiting release of LH (via negative FB): gonadal atrophy
    
  • Premature closure of epiphyseal plates (children)
    
  • Increased LDL and decreased HDL