Oestrogens and Progestins Pharmacology
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Direct answer
Ethinylestradiol 30 micrograms combined with levonorgestrel 150 micrograms — the archetypal combined pill — suppresses FSH and LH to block ovulation, thickens cervical mucus and renders the endometrium hostile: a triple mechanism asked in every viva. Natural oestradiol suffers heavy first-pass metabolism, so oral therapy uses ethinylestradiol or conjugated equine oestrogens, while patches and gels avoid the hepatic first pass. Progestins span norethisterone and levonorgestrel, medroxyprogesterone acetate (DMPA 150 mg every three months) and the levonorgestrel intrauterine system (52 mg, five years). Emergency contraception is levonorgestrel 1.5 mg within 72 hours, sold over the counter in India. Oestrogen contraindications anchor the topic: migraine with aura, prior VTE, breast cancer, active liver disease and smoking over 35.
What you must remember
- Combined pill mechanism: ovulation inhibition (LH surge abolished) + cervical mucus thickening + endometrial atrophy; failure below 1 per 100 woman-years with perfect use.
- Non-contraceptive benefits: cycle regularity, dysmenorrhoea relief, ovarian and endometrial cancer risk reduction, acne improvement (with anti-androgenic progestins like drospirenone).
- DMPA 150 mg IM every 12 weeks: amenorrhoea and bone mineral density concerns with prolonged use, plus delayed return of fertility up to a year — part of India's national family planning basket.
- LNG-IUS 52 mg: five years of contraception plus first-line treatment for heavy menstrual bleeding; systemic progestin exposure is minimal, so it suits lactation.
- Progestin-only pill (desogestrel 75 micrograms daily): the contraceptive of lactation and of oestrogen-contraindicated women; a missed dose beyond 3 hours demands backup for 48 hours.
- Emergency contraception: levonorgestrel 1.5 mg single dose within 72 hours of unprotected intercourse (works before the LH peak, not after); ulipristal 30 mg to 120 hours; mifepristone 10 mg is used in some settings.
- Oestrogen harms: venous thromboembolism (about 2-4-fold relative risk, highest in the first year), cholestatic jaundice, gallstones, migraine worsening, blood pressure rise — hence the WHO medical eligibility categories examiners quote.
- HRT framing: lowest effective dose, oestrogen alone after hysterectomy, oestrogen plus progestin with an intact uterus (unopposed oestrogen causes endometrial hyperplasia and cancer).
Choosing between formulations in practice
A 24-year-old wants contraception; she is healthy, has regular cycles and no migraine. A combined pill with levonorgestrel — the cheapest, best-evidenced progestin — is a rational Indian default (available free through government channels as Chhaya in several states for the centchroman alternative). Two years later, breastfeeding her first child, she is switched to the progestin-only pill or an LNG-IUS because oestrogen reduces milk volume. Her 36-year-old sister, a smoker with migraine aura, must avoid oestrogen entirely: the progestin-only pill, DMPA, LNG-IUS or a copper IUD are the options; this is precisely the sorting step exams test through WHO eligibility category III and IV labels. Their mother at 51, flushes disrupting sleep, may use transdermal oestradiol 50 micrograms with cyclical micronised progesterone — the transdermal route avoiding first-pass effects on clotting factors — planning review annually and stopping after the lowest effective duration.
Where students slip
The recurring viva error is attributing combined-pill thrombosis risk to "the progesterone part"; the oestrogen dose and type drive it, with third-generation progestins (desogestrel, gestodene) adding a smaller independent increment — a distinction examiners reward. The second slip is mechanism language for emergency contraception: levonorgestrel delays or abolishes the LH surge before follicular rupture and is ineffective once ovulation has occurred; it is not an abortifacient, a point worth stating precisely in the Indian context. Third, candidates forget why the progestin-only pill's missed-pill window is 3 hours, not 12: progestins clear fast, and cervical mucus protection wanes quickly without an ovarian-suppression cushion to fall back on.
Frequently asked questions
What are the three mechanisms of the combined oral contraceptive pill?
Pituitary FSH/LH suppression blocking ovulation, cervical mucus thickening that bars sperm, and endometrial changes that prevent implantation — ovulation inhibition is primary.
Which contraceptives are preferred during lactation?
Progestin-only methods — the desogestrel mini-pill, DMPA and the levonorgestrel IUS — since oestrogen suppresses prolactin-driven milk production.
How is levonorgestrel emergency contraception used, and what is its window?
1.5 mg as a single oral dose within 72 hours of unprotected intercourse, ideally as early as possible; it postpones the LH surge and fails once ovulation has happened.
Why must oestrogen be combined with progestin in HRT when the uterus is intact?
Unopposed oestrogen drives endometrial hyperplasia and carcinoma; progestin counteracts this and is unnecessary after hysterectomy.
What limits long-term use of DMPA?
Reversible reduction in bone mineral density (boxed warning territory), plus unpredictable delayed return of ovulation — usually one to two years after stopping.