Oral Contraceptives & HRT

Introduction

• Hormonal contraceptives — Estrogen ± progestin (or progestin alone) preparations giving reversible suppression of fertility — they separate fertility control from coitus, are ~100% effective on perfect use, and allow complete return of fertility on stopping. Enovid (norethynodrel + mestranol) was the first FDA-approved Pill (1961).
• Menopausal hormone therapy (MHT / "HRT") — Estrogen ± progestin given to relieve the perimenopausal syndrome (vasomotor instability, urogenital atrophy) and prevent bone loss; doses are substantially lower than contraceptive doses.
• Potency anchor — 0.625 mg conjugated equine estrogen (CEE) ≈ 5–10 µg ethinylestradiol. MHT uses ~0.625 mg CEE/day whereas combined OCs use 20–35 µg ethinylestradiol/day — so the potency-adjusted estrogen dose in MHT is lower than in OCs.
• Estrogen pharmacology essentials — Most potent natural estrogen is 17β-estradiol (> estrone > estriol); ethinyl substitution at C17 (ethinylestradiol, mestranol) blocks first-pass metabolism and confers oral activity. Two receptor subtypes — ERα (uterus, breast, bone, vessels) and ERβ — act via estrogen response elements; oral estrogen also drives hepatic synthesis of clotting factors, SHBG, angiotensinogen (the basis of VTE and hypertension risk).
• Progestin pharmacology essentials — Natural progestin is progesterone; synthetics are graded by androgenicity — 1st gen norethindrone, 2nd gen levonorgestrel/norgestrel, 3rd gen desogestrel/norgestimate/gestodene (less androgenic). Drospirenone is spironolactone-derived (antimineralocorticoid + antiandrogenic). Progesterone thickens cervical mucus, transforms endometrium and reduces GnRH-pulse frequency — the substrate for contraceptive action.