Pharmacology/Part 9/9.5 Sex Hormones

9.5 Sex Hormones & Contraceptives

Sex hormone pharmacology includes estrogens, progestins, and androgens for hormone replacement, contraception, and treatment of hormone-sensitive conditions.

Estrogens

Forms:

  • Ethinyl estradiol: Oral contraceptives (synthetic, potent)
  • Conjugated estrogens: Hormone replacement (Premarin)
  • Estradiol: Transdermal patches, vaginal creams

Uses:

  • • Oral contraception (with progestin)
  • • Hormone replacement therapy (HRT) in menopause
  • • Hypogonadism, Turner syndrome

⚠️ Adverse Effects:

  • Thromboembolism: DVT, PE, stroke (↑ coagulation factors)
  • • Endometrial cancer (unopposed estrogen)
  • • Breast cancer risk (long-term HRT)
  • • Nausea, breast tenderness, headache
  • • Cholestasis, gallstones
  • Contraindicated: History of VTE, breast cancer, pregnancy

Progestins

Forms:

  • Medroxyprogesterone: HRT, contraception (Depo-Provera)
  • Norethindrone, levonorgestrel: Oral contraceptives
  • Etonogestrel: Implant (Nexplanon)

Uses:

  • • Oral contraception (combined or progestin-only)
  • • HRT (protect endometrium from estrogen)
  • • Abnormal uterine bleeding
  • • Endometriosis

Adverse Effects:

  • • Weight gain, bloating
  • • Irregular bleeding
  • • Mood changes, depression
  • • Bone loss (high-dose medroxyprogesterone)

Oral Contraceptives

Combined (Estrogen + Progestin)

Suppress ovulation (↓ LH/FSH), thicken cervical mucus, thin endometrium. >99% effective with perfect use.

  • • Monophasic, biphasic, triphasic formulations
  • • Benefits: Regulate menses, ↓ ovarian/endometrial cancer, ↓ acne
  • ⚠️ Avoid in: Smoking + age >35, VTE history, migraine with aura

Progestin-Only ("Mini-Pill")

Thicken cervical mucus (primary), suppress ovulation (inconsistent). Safe in breastfeeding, smokers, VTE risk.

  • • Norethindrone, desogestrel
  • • Must take at same time daily (strict timing)
  • • Irregular bleeding common

Androgens & Antiandrogens

Testosterone

Forms:

  • • IM injections (testosterone cypionate, enanthate)
  • • Transdermal gels, patches
  • • Buccal, nasal formulations

Uses:

  • • Male hypogonadism
  • • Delayed puberty
  • • Gender-affirming therapy (FTM)

Adverse Effects:

  • • Polycythemia (↑ erythropoiesis; monitor Hct)
  • • Acne, oily skin
  • • Gynecomastia (aromatization to estrogen)
  • • Testicular atrophy, ↓ sperm count
  • • Hepatotoxicity (oral 17α-alkylated forms)
  • • Sleep apnea exacerbation
  • ⚠️ Contraindicated: Prostate cancer, male breast cancer

Antiandrogens

Finasteride & Dutasteride

  • • 5α-reductase inhibitors (block DHT formation)
  • • Benign prostatic hyperplasia (BPH)
  • • Male pattern baldness (finasteride 1 mg)
  • ⚠️ Sexual dysfunction, ↓ libido, gynecomastia

Flutamide, Bicalutamide

  • • Nonsteroidal androgen receptor antagonists
  • • Prostate cancer (with GnRH agonist)
  • • Hepatotoxicity (monitor LFTs)

Spironolactone

  • • Aldosterone antagonist with antiandrogen effects
  • • Hirsutism, acne (PCOS)
  • • Gender-affirming therapy (MTF)

Selective Estrogen Receptor Modulators (SERMs)

Tamoxifen

  • Breast: Antagonist (treats ER+ breast cancer)
  • Uterus: Agonist (↑ endometrial cancer risk)
  • Bone: Partial agonist (maintains density)
  • ⚠️ Hot flashes, VTE, endometrial cancer

Raloxifene

  • Breast: Antagonist (prevents breast cancer)
  • Uterus: Antagonist (no endometrial cancer risk)
  • Bone: Agonist (treats osteoporosis)
  • • Lower VTE risk than tamoxifen