Harvey's Garden

Reproductive system drugs

4 min read

Gonadotropin-Releasing Hormone (GnRH) Analogs & Antagonists

  • GnRH Agonists
    • Drugs: Leuprolide, Goserelin
    • Mechanism:
      • Pulsatile administration: Agonist effect → ↑ FSH, LH release (used for infertility).
      • Continuous administration: Downregulates GnRH receptors on the anterior pituitary → ↓ FSH, LH release → ↓ testosterone (in men) and estrogen (in women).
    • Clinical Use (Continuous):
      • Prostate cancer
      • Endometriosis & leiomyomas (fibroids)
      • Precocious puberty
    • Adverse Effects:
      • Initial flare-up of symptoms (e.g., bone pain in prostate cancer).
      • Hypogonadism symptoms: hot flashes, ↓ libido, gynecomastia.
  • GnRH Antagonists
    • Drugs: Degarelix, Ganirelix
    • Mechanism: Directly block GnRH receptors → immediate suppression of FSH, LH.
    • Clinical Use: Prostate cancer (Degarelix), prevent premature LH surge in IVF (Ganirelix).
    • Adverse Effects: Hypogonadism symptoms, injection site reactions. No initial flare-up.

Drugs Affecting Sex Hormones

  • Selective Estrogen Receptor Modulators (SERMs)
    • Tissue-specific agonist/antagonist activity.
    • Tamoxifen:
      • Antagonist at breast.
      • Agonist at uterus, bone.
      • Use: ER+ breast cancer.
      • Adverse Effects: ↑ risk of endometrial cancer, thromboembolic events (DVT/PE), hot flashes.
    • Raloxifene:
      • Antagonist at breast, uterus.
      • Agonist at bone.
      • Use: Osteoporosis in postmenopausal women, prophylaxis for breast cancer.
      • Adverse Effects: Thromboembolic events, hot flashes. (No increased risk of endometrial cancer).
    • Clomiphene:
      • Antagonist at estrogen receptors in the hypothalamus.
      • Mechanism: Prevents normal negative feedback → ↑ release of GnRH → ↑ FSH/LH → stimulates ovulation.
      • Use: Infertility (e.g., PCOS).
      • Adverse Effects: Hot flashes, ovarian enlargement, multiple gestation pregnancy.
  • Aromatase Inhibitors
    • Drugs: Anastrozole, Letrozole, Exemestane
    • Mechanism: Inhibit peripheral conversion of androgens to estrogens.
    • Use: ER+ breast cancer in postmenopausal women.
    • Adverse Effects: Osteoporosis, arthralgias.
  • Antiandrogens
    • Finasteride:
      • Mechanism: 5α-reductase inhibitor (blocks conversion of testosterone → DHT).
      • Use: Benign Prostatic Hyperplasia (BPH), male-pattern baldness.
    • Flutamide, Bicalutamide:
      • Mechanism: Competitive inhibitors at androgen receptors.
      • Use: Prostate cancer (often with GnRH agonists to block initial flare).
    • Spironolactone:
      • Mechanism: Inhibits steroid binding, acts as an androgen receptor antagonist.
      • Use: Hirsutism in PCOS.
      • Adverse Effects: Hyperkalemia, gynecomastia.

Contraception & Uterine Drugs

  • Combined Hormonal Contraceptives (Estrogen + Progestin)
    • Mechanism: Estrogen suppresses FSH release (inhibiting follicle development); Progestin suppresses LH surge (preventing ovulation), thickens cervical mucus, and thins the endometrium.
    • Contraindications (High-Yield):
      • Hx of thromboembolism (DVT/PE)
      • Smoker >35 years old
      • Migraine with aura
      • Severe hypertension
      • History of estrogen-dependent tumor (e.g., breast cancer).
  • Abortifacients
    • Mifepristone: Progesterone receptor antagonist → necrosis of decidua.
    • Misoprostol: Prostaglandin E1 (PGE1) analog → induces uterine contractions.
    • Typically used together for medical abortion.
  • Uterine Stimulants (Oxytocics)
    • Oxytocin: Used to induce/augment labor; control postpartum hemorrhage.
    • Methylergonovine: Ergot alkaloid used for postpartum hemorrhage. Contraindicated in HTN due to vasoconstrictive effects.
  • Tocolytics (Relax Uterus)
    • Use: Delay preterm labor.
    • Terbutaline: Beta-2 agonist.
    • Nifedipine: Calcium channel blocker.
    • Indomethacin: NSAID (prostaglandin inhibitor).

Drugs for Erectile Dysfunction

  • PDE-5 Inhibitors
    • Drugs: Sildenafil, Tadalafil, Vardenafil
    • Mechanism: Inhibit phosphodiesterase-5 → ↑ cGMP → prolonged smooth muscle relaxation in the corpus cavernosum → ↑ blood flow.
    • Adverse Effects: Headache, flushing, dyspepsia, cyanopsia (blue-tinted vision).
    • Contraindication: DO NOT USE WITH NITRATES (e.g., nitroglycerin) → can cause severe, life-threatening hypotension.

Tamoxifen

Mechanism of action

  • Competitive antagonist on the estrogen receptors of the breast → ↓ breast cancer cell growth
  • Agonist on estrogen receptors in the following tissues:
    • Bone tissue → inhibition of osteoclasts → ↓ risk of osteoporosis and fractures
    • Endometrium → ↑ proliferation
    • Myometrium → ↑ proliferation

Indications

Side effects

Raloxifene

Mechanism of action

  • Competitive antagonist on estrogen receptors in the following tissues:
    • Breast → ↓ breast cancer cell growth
    • Endometrium and myometrium → ↓ proliferation (in contrast to tamoxifen)
  • Agonist on estrogen receptor in bone tissue → inhibition of osteoclasts

Indications

Side effects

Clomiphene

Mechanism of action

  • Blocks hypothalamic estrogen receptors, thereby inhibiting negative feedback and increasing release of FSH and LH to trigger ovulation

Indications

  • Infertility (for ovulation induction)

Side effects

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