Notes on Pharmacology of Reproduction and Hormonal Contraceptives

Learning Objectives

  • Understand the effects of various reproductive hormones and their clinical uses:
    • Estrogens
    • Antiestrogens
    • Selective Estrogen Receptor Modulators (SERMs)
    • Progestogens
    • Antiprogestogens
  • Examine the pros and cons of postmenopausal Hormone Replacement Therapy (HRT).
  • Learn the effects of Oral Contraceptive Pills (OCPs) including combined pills and progestogen-only pills, their mode of action, benefits, and drawbacks.

Overview of the Neurohormonal Control of the Female Reproductive System

  • Menstrual Cycle:
    • Starts with menstruation; governed by hormones including FSH, LH, estrogen, and progesterone.
  • Key Hormones:
    • Gonadotropin-Releasing Hormone (GnRH) - Regulates release of FSH and LH from the anterior pituitary.
    • FSH: Stimulates ovarian follicle development and estrogen release.
    • LH: Triggers ovulation and progesterone release from the corpus luteum.
    • Estrogen: Promotes endometrial proliferation; exerts negative feedback on anterior pituitary and hypothalamus.
    • Progesterone: Regulates the secretory phase of the menstrual cycle; also exerts negative feedback, supporting pregnancy.

Drugs Affecting Female Reproductive Functions

Estrogens

  • Natural: Estradiol (E2), Estrone (E1), and Estriol (E3).
  • Synthetic: Ethinylestradiol and others.
    • Mechanism of Action:
    • Bind to nuclear receptors (ERα, ERβ) for gene transcription, and membrane receptors for rapid action.
  • Effects:
    • Promote development of secondary sexual characteristics.
    • Used in contraception with progesterone, and estrogen replacement therapy (ERT) for menopause.
    • Risks: Increase thromboembolism risk, especially at higher doses.

Selective Estrogen Receptor Modulators (SERMs)

  • Mechanisms: Mixed agonist/antagonist effects depending on tissue specificity.
  • Examples:
    • Tamoxifen: Antiestrogen in breast tissue, used in breast cancer treatment.
    • Raloxifene: Antiestrogenic effects in the breast and uterus, estrogenic in bone, for osteoporosis prevention.

Antiestrogens

  • Clomiphene:
    • An ER antagonist preventing estrogen feedback inhibition, used to stimulate ovulation in PCOS.

Progestogens

  • Examples: Natural progesterone, synthetic forms like medroxyprogesterone.
  • Clinical Uses:
    • Contraceptive methods (combined or progestogen-only OCPs).
    • ERT to prevent endometrial hyperplasia.

Antiprogestogens

  • Mifepristone (RU-486):
    • Progesterone receptor antagonist, used for medical termination of early pregnancy and as a glucocorticoid receptor blocker.

Postmenopausal Hormone Replacement Therapy (HRT)

  • Purpose: Counteract decreased estrogen levels post-menopause.
  • Benefits:
    • Relieves menopausal symptoms, protects against osteoporosis, improves sleep and cardiovascular health.
  • Drawbacks:
    • Risks of endometrial and breast cancer, thromboembolism, and withdrawal bleeding.

Contraception and Contraceptives

Non-Hormonal Methods

  • Methods: Condoms, diaphragms, spermicides, sponges.
  • Drawbacks: Higher failure rates and potential for TSS.

Hormonal Contraceptives

  • Types: Combine estrogen and progestogen (OCP) or progestogen-only.
  • Combined Pill: Suppresses ovulation, alters endometrial lining, and thickens cervical mucus.
  • Progestogen-only Pill: Reduces sperm passage and alters endometrial conditions for potential implantation.

Emergency Contraception

  • Methods: Levonorgestrel or IUD insertion within 72 hours post-intercourse.

Drug Interactions with OCP

  • Antibiotics: Can decrease effectiveness of OCP by altering E2 recirculation due to changes in gut bacteria.
  • CYP Inducers: Medications like phenytoin and rifampin may reduce OCP efficacy.

Other Hormonal Contraceptive Routes

  • Transdermal Patch: Higher EE2 exposure, better adherence but may not be as effective in obese women.
  • Vaginal Rings: Risk of expulsion can lower efficacy.