Pharmacology of drugs affecting the Reproductive System, Uterus, and Contraception

Sexual Differentiation

  • Bipotential Structures:
    • Genital tubercle
      • Male: Glans penis
      • Female: Clitoris
    • Urethral folds & groove
      • Male: Shaft of penis
      • Female: Labia minora, opening of vagina & urethra
    • Labioscrotal swellings
      • Male: Shaft of penis & scrotum
      • Female: Labia majora
    • Gonad (cortex)
      • Male: Regresses
      • Female: Forms ovary
    • Gonad (medulla)
      • Male: Forms testis
      • Female: Regresses
    • Wolffian duct
      • Male: Becomes epididymis, vas deferens & seminal vesicle (testosterone present)
      • Female: Regresses (testosterone absent)
    • Müllerian duct
      • Male: Regresses (Mullerian inhibiting substance present)
      • Female: Becomes Fallopian tube, uterus, cervix & upper 1/3 of vagina. (MIS absent)

Hormones

  • Male Hormones: MIS, Testosterone, Ins13
  • Female Hormones: Absence of male hormones
  • Adrenal Steroids: Cortisol hormones, Sex hormones.
  • Steroid Action:
    • Steroid diffuses into the cell and binds to the receptor in cytosol or nucleus.
    • The steroid-receptor complex binds to DNA, affecting transcription and translation.

Hypothalamic Hormonal Pathways

  • Hypothalamus secretes trophic hormones (GnRH).
  • Anterior pituitary releases gonadotropins (FSH, LH).
  • Gonads produce androgens, estrogens, and progesterone.
  • These hormones act on target tissues.

Female Hormonal System

  • Hypothalamic Releasing Hormone: GONADOTROPIN RELEASING HORMONE (GnRH)
  • Anterior Pituitary Hormones: GONADOTROPINS (FSH & LH)
  • Ovarian Hormones: ESTROGEN & PROGESTERONE

Follicle Development and Ovulation

  • Follicle Development:
    • Primordial follicle → Primary follicle → Preantral follicle → Early antral follicle → Mature follicle
    • Granulosa cells and theca cells are key components.
  • Ovulation:
    • LH surge induces collagenase production, weakening the follicle wall.
    • Prostaglandin increases, causing vasodilation.
    • Follicle swells and ruptures, releasing the ovum.

Effects of Estrogen

  • Maturation: Stimulates development of vagina, uterus, fallopian tubes, mammary glands, and secondary sexual characteristics.
  • Endometrium: Promotes growth of the uterine lining.
  • Metabolic: Maintains skin structure and vascularity, decreases bone resorption, decreases intestinal motility, and stimulates enzyme synthesis.

Effects of Progesterone

  • Metabolism:
    • Stimulates lipoprotein lipase activity.
    • Increases basal insulin levels and insulin response.
  • Other Effects:
    • Inhibits ovulation by suppressing LH.
    • Thickens cervical mucus.
    • Decreases fallopian tube motility.
    • Thickens the endometrium.

Oral Contraceptives

  • Contain estrogen and progestin to prevent pregnancy.
  • Mechanisms:
    • Suppresses GnRH, inhibiting ovulation.
    • Alters cervical mucus, hindering sperm entry.
    • Thins the endometrium.
  • Types:
    • Monophasic: Fixed dose of estrogen & progestin.
    • Biphasic: Fixed estrogen, progestin increased in the second half of the cycle.
    • Triphasic: Estrogen fixed or varied, progestin in 3 phases.

Oral Contraceptives - Progestin Types

  • 19-Nortestosterone Derivatives:
    *Estranes (Norethindrone family): Norethindrone, Norethindrone acetate.
    *Gonanes (Levonorgestrel family): Levonorgestrel, Norgestrel.
    *Spironolactone derivative: Drospirenone

Oral Contraceptives - Side Effects

  • Bleeding/spotting, dizziness, nausea, weight changes, chloasma, pigmentation, and fungal infections.

Normal Menstrual Cycle

  • Cycle Length: 24 – 35 days
  • Duration: 3 – 7 days
  • Flow (Volume): 30 – 80 ml

Post-Coital Contraception (Emergency)

  • Conjugated estrogens, ethinyl estradiol, diethylstilbestrol, mifepristone, L-Norgestrel, or Norgestrel with ethinyl estradiol can be used.

Hormone Injections

  • Depo Provera (progesterone): IM injection every 3 months.
  • Cyclofen (estrogen): IM injection monthly.
  • Mechanisms of Action: Prevent ovulation, increase cervical mucus viscosity, and thin the endometrium.

Implants (Progesterone)

  • Inserted subdermally; long-term use (3-5 years).
  • Suitable for those who cannot tolerate estrogen.
  • Mechanisms: Inhibits ovulation, thins the endometrium, and thickens cervical mucus.

Tubal Ligation (Tubectomy) & Vasectomy

  • Effective for preventing pregnancy.
  • Tubectomy: Fallopian tubes are tied and cut.
  • Vasectomy: Vasa deferentia are cut.

Condoms

  • Effectiveness 80-90%.
  • Applied during erection before intercourse and removed after ejaculation.

Intrauterine Devices (IUDs/Spiral)

  • Inserted into the uterus.
  • Made of silicone, silicone + copper, or copper + silver.
  • Long-term use (~10 years); high effectiveness (~99%).
  • Mechanism: Antifertility effect by mechanically hindering sperm transport in the fallopian tubes.