STEPTRACKERPHARMACOLOGY + REPRODUCTIVE | ENDOCRINE | HIGH-YIELD REVIEW

Reproductive Hormones

Estrogens, progestins and androgens — and drugs that mimic, block or switch them selectively — treat contraception, menopause, infertility, cancer and prostate disease.

FOCUS ON
Combined OCPs: estrogen + progestin → ↓ LH/FSH → no ovulation; progestin thickens cervical mucus. ↓ Ovarian and endometrial cancer. Risks: VTE (↑ clotting factors), hypertension, hepatic adenoma, stroke; contraindicated in smokers > 35, migraine with aura, prior VTE, estrogen-dependent cancer. SERMs: tamoxifen (antagonist breast, agonist uterus/bone → endometrial cancer, VTE); raloxifene (antagonist breast/uterus, agonist bone → osteoporosis; VTE); clomiphene (hypothalamic antagonist → ↑ GnRH → ovulation; multiple births, visual changes). Aromatase inhibitors (anastrozole, letrozole): postmenopausal ER⁺ breast cancer, ovulation induction; osteoporosis. Androgen: testosterone (hypogonadism; erythrocytosis, ↓ sperm). 5α-reductase inhibitors (finasteride, dutasteride): BPH, alopecia; ↓ PSA. Antiandrogens: flutamide, bicalutamide, enzalutamide; abiraterone (CYP17); spironolactone. PDE5 inhibitors. Mifepristone + misoprostol: abortion. Tocolytics: nifedipine, indomethacin, terbutaline; MgSO₄ for neuroprotection.
DRUG
MECHANISM
USE
ADVERSE · NOTES
Combined OCP
Estrogen + progestin → ↓ GnRH, LH surge
Contraception, PCOS, dysmenorrhea, acne
VTE, HTN, hepatic adenoma; avoid smokers > 35, migraine with aura
Progestin-only methods
Thick mucus, endometrial thinning (± anovulation)
Contraception when estrogen contraindicated; LNG-IUD for heavy bleeding
Irregular bleeding; depot medroxyprogesterone → bone loss
Emergency contraception
Levonorgestrel or ulipristal → delay ovulation · copper IUD
Within 3–5 days
Copper IUD most effective
Menopausal hormone therapy
Estrogen (+ progestin if uterus present)
Vasomotor symptoms, vaginal atrophy
Unopposed estrogen → endometrial cancer; VTE, stroke, breast cancer (combined)
Tamoxifen
SERM: breast antagonist, endometrium and bone agonist
ER⁺ breast cancer (premenopausal), prevention
Endometrial hyperplasia/cancer, VTE, hot flashes · CYP2D6 activation
Raloxifene
SERM: bone agonist, breast and uterus antagonist
Osteoporosis, breast cancer risk reduction
VTE, hot flashes; no endometrial cancer
Clomiphene
Blocks hypothalamic estrogen feedback → ↑ FSH, LH
Anovulatory infertility (PCOS)
Multiple gestation, ovarian enlargement, visual disturbance, hot flashes
Anastrozole · letrozole · exemestane
Aromatase inhibitors → ↓ peripheral estrogen
Postmenopausal ER⁺ breast cancer; letrozole for PCOS ovulation
Osteoporosis, arthralgias
Testosterone · oxandrolone
Androgen receptor agonists
Hypogonadism, delayed puberty
Polycythemia, testicular atrophy, infertility, acne, ↑ LDL
Finasteride · dutasteride
5α-reductase inhibitors → ↓ DHT
BPH, male-pattern baldness
Sexual dysfunction, gynecomastia; PSA halves; teratogenic to male fetus
Flutamide · bicalutamide · enzalutamide
Androgen receptor antagonists
Prostate cancer (with GnRH agonist)
Gynecomastia, hepatotoxicity (flutamide)
Abiraterone
CYP17 (17α-hydroxylase) inhibitor
Castration-resistant prostate cancer
Mineralocorticoid excess → give with prednisone
Ketoconazole · spironolactone
↓ Androgen synthesis · androgen receptor block
Hirsutism (PCOS)
Gynecomastia (in men)
Tocolytics
Nifedipine, indomethacin (< 32 wk), terbutaline
Delay preterm labor 48 h for steroids
Indomethacin → ductus closure, oligohydramnios

Mechanism — SERMs act differently by tissue

BreastTamoxifen and raloxifene block
→
BoneBoth stimulate (protect)
→
EndometriumTamoxifen stimulates; raloxifene doesn't

Both raise VTE risk — estrogen-like effect on liver clotting factors.

Breast cancer endocrine therapy

STATUS
DRUG
MAIN RISK
Premenopausal ER⁺
Tamoxifen
Endometrial cancer, VTE
Postmenopausal ER⁺
Aromatase inhibitor
Bone loss
HER2⁺
Trastuzumab
Cardiotoxicity

How it's tested

COMMON CONFUSIONAromatase inhibitors don't work alone in premenopausal women — the ovaries keep producing estrogen (and ↓ feedback ↑ ovarian drive).
THE TRAPPostmenopausal bleeding in a woman on tamoxifen → evaluate the endometrium; don't blame the drug and wait.
YOUR APPROACHTissue targeted → agonist or antagonist → receptor or enzyme → expected tissue-specific adverse effect.

If you see… think…

Postmenopausal bleeding on breast cancer therapy → tamoxifen endometrial effect
Osteoporosis drug that lowers breast cancer risk → raloxifene
Twins after infertility pill → clomiphene
Joint pain, bone loss on breast cancer drug → aromatase inhibitor
DVT in a 38-year-old smoker on the pill → estrogen-induced hypercoagulability
Polycythemia in a man on gel therapy → testosterone
PSA halved after starting BPH drug → finasteride
Hypokalemia and HTN on prostate cancer drug → abiraterone (give prednisone)
Pregnant women shouldn't handle crushed tablets → finasteride
Tocolytic causing ductus closure → indomethacin