Sex Hormones: Estrogens and Progestins

Sex Hormones: Estrogens and Progestins

Sex Hormones: Estrogens and Progestins

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Estrogens & SERMs - Femme Fatale Hormones

  • Estrogens (e.g., Estradiol, Estrone, Estriol):
    • MOA: Bind nuclear Estrogen Receptors (ER-α, ER-β) → alter gene transcription.
    • Effects: Female development, endometrial proliferation, bone: ↓resorption, lipids: ↑HDL/↓LDL, procoagulant.
    • Uses: Hormone Replacement Therapy (HRT), contraception (with progestins), primary hypogonadism.
    • AEs: Nausea, breast tenderness, thromboembolism (VTE), endometrial hyperplasia/cancer (if unopposed), gallstones. Estrogen receptor genomic and non-genomic signaling
  • SERMs (Selective Estrogen Receptor Modulators): Tissue-specific actions.
    • Tamoxifen:
      • Antagonist: Breast (ER+ breast cancer treatment/prevention).
      • Agonist: Bone (prevents osteoporosis), Endometrium (↑risk of endometrial cancer, hyperplasia), Lipids.
      • 📌 Breast antagonist, Uterus agonist.
    • Raloxifene:
      • Antagonist: Breast, Endometrium (no ↑ endometrial cancer risk).
      • Agonist: Bone (postmenopausal osteoporosis treatment/prevention). ↑VTE risk.
    • Clomiphene Citrate:
      • Antagonist: Hypothalamic ER → ↓negative feedback → ↑GnRH, FSH, LH → ovulation induction (PCOS infertility).
      • AEs: Multiple pregnancies, OHSS.

    ⭐ Tamoxifen, a SERM, is used for ER+ breast cancer but paradoxically increases the risk of endometrial cancer.

Anti-Estrogens - Estrogen Blockade Brigade

  • Selective Estrogen Receptor Modulators (SERMs): Mixed agonist/antagonist activity.
    • Tamoxifen: Breast cancer (ER+), osteoporosis prevention. Risk: Endometrial Ca, thromboembolism.
    • Raloxifene: Osteoporosis (postmenopausal), breast cancer prevention. No endometrial Ca risk.
    • Clomiphene: Ovulation induction (anovulatory infertility). Acts on hypothalamus/pituitary.
  • Aromatase Inhibitors (AIs): Block estrogen synthesis from androgens.
    • Anastrozole, Letrozole (non-steroidal); Exemestane (steroidal, irreversible).
    • Use: ER+ breast cancer (postmenopausal).
  • Pure Estrogen Receptor Antagonist:
    • Fulvestrant: ER+ metastatic breast cancer (after tamoxifen). Degrades ER.

Mechanisms of anti-estrogen drugs

⭐ Tamoxifen is a prodrug, metabolized by CYP2D6; efficacy ↓ with inhibitors (e.g., SSRIs like fluoxetine).

Progestins & Antiprogestins - Pro-Gestation & Foes

  • Progestins (Pro-gestational): 📌 "PROgestins PREpare & PROtect PREgnancy."

    • Natural: Progesterone.
      • Actions: Endometrial support (secretory), thick cervical mucus, ↓ uterine motility.
    • Synthetic (Progestogens):
      • Estranes (19-nortestosterone): Levonorgestrel (androgenic); Desogestrel (less androgenic).
      • Pregnanes (17α-OHP): Medroxyprogesterone acetate (MPA).
      • Others: Drospirenone (antiandrogenic, antimineralocorticoid).
    • Uses: Contraception, HRT (with estrogen to prevent endometrial hyperplasia), DUB, endometriosis.
    • AEs: Weight gain, mood changes, acne, breakthrough bleeding, altered lipids (older agents: ↓HDL, ↑LDL).
  • Antiprogestins:

    • Mifepristone (RU-486): Progesterone receptor antagonist.
      • Uses: Medical abortion (with misoprostol), emergency contraception (EC).
    • Ulipristal Acetate: Selective Progesterone Receptor Modulator (SPRM).
      • Uses: EC (up to 120 hrs post-coitus), uterine fibroids.

      ⭐ Mifepristone, a progesterone receptor antagonist, is combined with misoprostol (a prostaglandin analogue) for effective medical abortion.

Hormonal Contraceptives - Cycle Control Crew

  • MoA:
    • Estrogen: ↓FSH → inhibits follicle dev., stabilizes endometrium.
    • Progestin: ↓LH surge → inhibits ovulation, thickens cervical mucus, endometrial atrophy.
  • Types:
    • COCs: Estrogen + Progestin.
    • POPs: For lactation, smokers >35y, VTE risk.
    • Others: Patch, ring, injectables (DMPA), implants, hormonal IUDs.
  • Benefits: Contraception, cycle control, ↓dysmenorrhea, ↓ovarian/endometrial Ca risk.
  • AEs: Nausea, headache, VTE. 📌 ACHES: Abdominal pain, Chest pain, Headaches, Eye problems, Severe leg pain.
  • CIs: Hx VTE, CAD, CVA, ER+ tumor, active liver disease, smokers >35y.

⭐ Progestin-only contraceptives are preferred in lactating women as estrogens can reduce milk production.

High‑Yield Points - ⚡ Biggest Takeaways

  • Estrogens (e.g., estradiol) are key for female sexual development and endometrial proliferation.
  • Progestins (e.g., progesterone) ensure endometrial secretory changes and maintain pregnancy.
  • SERMs like Tamoxifen (breast cancer, ↑ endometrial risk) and Raloxifene (osteoporosis) have tissue-specific actions.
  • Combined OCPs primarily inhibit ovulation; major risk is thromboembolism.
  • HRT for menopausal symptoms carries risks like VTE and breast cancer.
  • Mifepristone (progesterone antagonist) is used for medical abortion.
  • Clomiphene (estrogen antagonist at hypothalamus) induces ovulation anovulatory infertility cases.

Practice Questions: Sex Hormones: Estrogens and Progestins

Test your understanding with these related questions

Which of the following statements is not true about tamoxifen?

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Flashcards: Sex Hormones: Estrogens and Progestins

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_____ is a selective progesterone receptor modulator (SPRM) that acts as an emergency contraceptive by inhibiting ovulation by inhibiting LH surge

TAP TO REVEAL ANSWER

_____ is a selective progesterone receptor modulator (SPRM) that acts as an emergency contraceptive by inhibiting ovulation by inhibiting LH surge

Ulipristal

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