LONG-ACTING REVERSIBLE CONTRACEPTION (LARC)

M.S. Main Exam Answer | Source: Berek & Novak's Gynecology

DEFINITION

• Require a single intervention (insertion/injection)
• Provide effective contraception for months to years
• Are fully reversible on removal/discontinuation
• Have failure rates < 1% (comparable to sterilization)

CLASSIFICATION FLOWCHART

┌─────────────────────────────────────────────────────────┐
│              LONG-ACTING REVERSIBLE CONTRACEPTION        │
└──────────────────────────┬──────────────────────────────┘
                           │
          ┌────────────────┼─────────────────┐
          ▼                ▼                 ▼
   ┌─────────────┐  ┌───────────────┐  ┌────────────────┐
   │  INTRAUTERINE│  │   HORMONAL    │  │  INJECTABLE    │
   │   DEVICES   │  │   IMPLANTS    │  │  (DMPA)        │
   │   (IUDs)    │  │               │  │                │
   └──────┬──────┘  └───────┬───────┘  └────────┬───────┘
          │                 │                    │
    ┌─────┴──────┐    Nexplanon/           Depo-Provera
    │            │    Implanon             (3 months)
  Copper      LNG-IUD    (3 years)
 (Non-       (Hormonal)
hormonal)

A. INTRAUTERINE DEVICES (IUDs)

Types Available (Per Berek & Novak)

"All IUDs provide safe, long-term contraception with effectiveness equivalent to tubal sterilization." - Berek & Novak

Copper IUD (Cu T380A - ParaGard)

Structure:

• T-shaped polyethylene frame
• Copper wire around stem (total surface area = 380 mm² of copper)
• Copper bands on both cross arms (nearly double copper surface area of earlier devices)
• Monofilament retrieval threads at base

MECHANISM OF ACTION

COPPER IUD                           LNG-IUD
─────────────────────────────        ──────────────────────────────
Releases Cu²⁺ ions continuously      Releases LNG @ 20 μg/day
         │                                      │
         ▼                                      ▼
Enhanced inflammatory response        Thickened, scant cervical mucus
         │                                      │
         ▼                                      ▼
"Biologic foam" in uterine cavity     Endometrial atrophy
(fibrin, phagocytes, enzymes)                  │
         │                                      ▼
         ▼                            Intrauterine inflammatory response
Sperm motility impaired               (85% cycles remain ovulatory!)
         │                                      │
         ▼                                      ▼
Fertilization prevented               Sperm transport blocked

IUD INSERTION TECHNIQUE

FLOWCHART: IUD INSERTION PROCEDURE
────────────────────────────────────────────────────────────
PATIENT SELECTION
    │
    ├── Ensure NOT pregnant
    ├── Screen for STIs (if at risk)
    └── Bimanual exam to assess uterine position/size
         │
         ▼
TIMING OF INSERTION
    ├── Anytime in cycle (if not pregnant)
    ├── Immediately postpartum (within 10 min of placental delivery)
    ├── 4-6 weeks postpartum
    └── Immediately post-abortion (1st or 2nd trimester)
         │
         ▼
INSERTION STEPS
    1. Lithotomy position
    2. Bimanual exam → confirm uterine size, position
    3. Speculum insertion
    4. Cervix cleansed with antiseptic
    5. Tenaculum applied to anterior lip cervix
    6. Uterine sound → measure uterine depth (ideal 6-9 cm)
    7. IUD loaded in inserter tube
    8. Insertion using "withdrawal" technique:
         - Inserter advanced to fundus
         - Arms released
         - Tube withdrawn while IUD stays
    9. Threads trimmed to 3-4 cm from cervical os
   10. Confirm placement (threads visible)
         │
         ▼
POST-INSERTION CHECK
    ├── USG to confirm placement (if doubt)
    ├── Advise patient to check strings monthly
    └── Warn of expulsion signs

CONTRAINDICATIONS

• Pregnancy
• Unexplained vaginal bleeding
• Active PID / STI (current or within 3 months)
• Distorted uterine cavity (fibroids, malformations)
• Cervical/uterine cancer
• Copper allergy / Wilson's disease (for copper IUD)
• Current breast cancer (for LNG-IUD)

• History of ectopic pregnancy (copper IUD)
• Immunocompromised states (use caution)
• Coagulopathy (copper - increases bleeding)

COMPLICATIONS

COMPLICATIONS OF IUD
─────────────────────────────────────────
INSERTION-RELATED        LONG-TERM
─────────────────        ──────────────────────────────
Vasovagal syncope        Menorrhagia (Copper IUD)
Uterine perforation      Dysmenorrhea (Copper IUD)
  (1:1000 insertions)    Amenorrhea (LNG-IUD ~20%)
Expulsion (2-10%         Expulsion (higher in
  in 1st year)             nulliparous/heavy menses)
Fainting                 Strings not visible
                         Ectopic pregnancy (if failure)
                         PID (first 20 days - ↑ risk)

Important exam point: If pregnancy occurs with IUD in situ - ectopic pregnancy must be excluded first. If intrauterine pregnancy: remove IUD (↓ risk of septic abortion, preterm labor) if strings visible.

B. SUBDERMAL HORMONAL IMPLANTS

Nexplanon (Etonogestrel Implant)

• Single, flexible rod: 4 cm long × 2 mm diameter
• Contains 68 mg etonogestrel (active metabolite of desogestrel)
• Releases 60-70 μg/day initially, declining to 25-30 μg/day by year 3
• Barium sulfate impregnated - radio-opaque (visible on X-ray)
• Duration: 3 years

Mechanism of Action

1. Primary: Inhibition of ovulation (LH surge suppressed)
2. Cervical mucus thickening
3. Endometrial atrophy

Insertion Technique - IMPLANT FLOWCHART

NEXPLANON INSERTION
──────────────────────────────────────────────────────
Patient: Non-dominant arm, inner aspect, 8-10 cm
         above medial epicondyle
         │
         ▼
STEPS:
1. Mark insertion site (groove between biceps
   and triceps)
2. Clean and drape
3. Local anesthetic (2 mL lidocaine, subdermal)
4. Pre-loaded applicator with rod
5. Insert needle at 20-30° angle, advance fully
6. Retract obturator while applicator stays
   (rod deposited subdermally)
7. Confirm: PALPATE the rod
8. Apply pressure dressing × 24 hours
         │
         ▼
REMOVAL (after 3 years or on request):
1. Palpate rod → mark distal end
2. Local anesthetic
3. 2 mm incision over distal tip
4. Push proximal end → rod pops out
5. Grasp with mosquito forceps, remove
6. New implant can be inserted immediately
         │
         ▼
BENEFITS:
✓ Most effective LARC (failure rate 0.05%)
✓ Immediate return to fertility after removal
✓ Safe in breastfeeding (progestin only)
✓ Reduces dysmenorrhea
DRAWBACKS:
✗ Irregular bleeding (most common reason for removal)
✗ Requires trained provider for insertion/removal
✗ No STI protection

C. INJECTABLE CONTRACEPTION (DMPA)

COMPARISON TABLE: ALL LARC METHODS

SPECIAL SITUATIONS FLOWCHART

CHOOSING LARC IN SPECIAL SITUATIONS
───────────────────────────────────────────────────────────
POSTPARTUM?
    ├── Within 10 min of placenta → Cu or LNG-IUD
    │   (postplacental insertion - increasing uptake)
    └── 4-6 weeks → Any LARC
         │
BREASTFEEDING?
    ├── Avoid combined hormonal methods
    ├── LNG-IUD, Cu IUD, Implant, DMPA → All safe
    └── Lactational Amenorrhea Method (LAM) also valid
         │  (<6 months, fully breastfeeding, amenorrheic)
POST-ABORTION?
    ├── 1st trimester → Immediate insertion safe
    └── 2nd trimester → Immediate insertion acceptable
         │
NULLIPAROUS/ADOLESCENT?
    ├── Both IUDs and implants: SUITABLE (per Berek)
    └── IUD expulsion slightly higher in nulliparous
         │
EMERGENCY CONTRACEPTION NEEDED?
    ├── Copper IUD: most effective EC (>99% if inserted
    │   within 5 days of unprotected sex)
    └── + Provides ongoing contraception for 10 years

NON-CONTRACEPTIVE BENEFITS

• Treatment of menorrhagia (heavy menstrual bleeding) - FDA approved
• Management of endometriosis pain
• Endometrial protection during estrogen therapy in perimenopausal women
• Management of adenomyosis
• Treatment of endometrial hyperplasia (without atypia)

• Emergency contraception (most effective EC method)
• Preferred in women who cannot use hormones

EFFICACY PYRAMID (Pearl Index)

CONTRACEPTIVE EFFICACY (Failure per 100 woman-years)
─────────────────────────────────────────────────────
MOST EFFECTIVE (TIER 1)
    ▲ Subdermal implant:     0.05%
    ▲ LNG-IUD (52 mg):       0.2%
    ▲ Copper IUD:            0.8%
    ▲ DMPA:                  0.2% (perfect use)

EFFECTIVE (TIER 2)
    ▲ OCP (combined):        0.3% (perfect) / 9% (typical)
    ▲ Patch:                 0.3% (perfect) / 9% (typical)
    ▲ Vaginal ring:          0.3% (perfect) / 9% (typical)

LESS RELIABLE (TIER 3)
    ▲ Condoms, diaphragm, etc.
─────────────────────────────────────────────────────
Note: LARC methods are "forget it and forget it" - no
user compliance required after insertion

RETURN TO FERTILITY

AFTER REMOVAL/DISCONTINUATION
──────────────────────────────────────────────────────
Copper IUD ──────────────────→ Immediate (within days)
LNG-IUD   ──────────────────→ Immediate (within days)
Implant   ──────────────────→ Immediate (next cycle)
DMPA      ──────────────────→ Delayed: 6-18 months
                               (may take up to 22 months)

SUMMARY MNEMONICS FOR EXAM

• LNG-IUD (Mirena, Kyleena, Skyla, Liletta)
• Implant (Nexplanon)
• Copper-IUD (ParaGard)
• Etonogestrel implant (specific type)

• Set and forget
• Affordable long-term
• Fertility returns promptly
• Effective as sterilization

10-MARK ANSWER STRUCTURE GUIDE

1. Definition + Classification (1 mark) - LARC definition, types
2. IUD - Types, Structure, Mechanism (2 marks) - Copper vs LNG
3. Insertion Technique + Timing (2 marks) - steps, postpartum/post-abortion
4. Contraindications + Complications (2 marks) - WHO MEC categories
5. Implant (1 mark) - Nexplanon structure, insertion, MOA
6. Special situations (1 mark) - EC, breastfeeding, nulliparous
7. Non-contraceptive benefits (1 mark) - LNG-IUD therapeutic uses

• All IUDs have efficacy equivalent to sterilization
• LNG-IUD works primarily by local effect; 85% cycles remain ovulatory
• Copper IUD is the best emergency contraception (>99% effective within 5 days)
• Implant has the lowest failure rate of all reversible methods (0.05%)
• DMPA is the only LARC with delayed fertility return (6-18 months)
• Postplacental IUD insertion (within 10 minutes of placenta delivery) is safe and effective
• Nulliparous women and adolescents are eligible candidates for IUDs and implants

HORMONAL CONTRACEPTION & NEWER DEVELOPMENTS IN COC PILLS

M.S. Main Exam - 10 Mark Answer | Source: Berek & Novak's Gynecology

DEFINITION

"ALL hormonal contraceptives, even those containing estrogen, are progestin-dominant - the progestin does the real contraceptive 'work' by either suppressing ovulation or thickening cervical mucus."

CLASSIFICATION FLOWCHART

┌──────────────────────────────────────────────────────────┐
│              HORMONAL CONTRACEPTION                       │
└─────────────────────┬────────────────────────────────────┘
                      │
         ┌────────────┴─────────────┐
         ▼                         ▼
┌─────────────────┐      ┌─────────────────────────┐
│  COMBINATION    │      │   PROGESTIN-ONLY         │
│  (Estrogen +    │      │   (No Estrogen)          │
│   Progestin)    │      └────────────┬────────────┘
└────────┬────────┘                   │
         │                   ┌────────┴──────────┐
    ┌────┴──────────┐        │                   │
    ▼               ▼        ▼                   ▼
  ORAL          PATCH/   Mini-Pill          Injectable
  PILLS         RING     (POP)              (DMPA)
  (COC)        (Evra/    daily              Implant
               NuvaRing)                   (Nexplanon)

A. COMBINED ORAL CONTRACEPTIVE PILLS (COC)

Components

┌──────────────────────────────────────────┐
│         COC PILL COMPOSITION             │
├──────────────────────────────────────────┤
│  ESTROGEN COMPONENT                      │
│  • Ethinyl estradiol (EE) - most common  │
│  • Mestranol (older, requires activation)│
│  • 17β-Estradiol (newer - Zoely)         │
│  • Estradiol Valerate (newer - Qlaira)   │
├──────────────────────────────────────────┤
│  PROGESTIN COMPONENT                     │
│  1st Gen: Norethindrone, Ethynodiol      │
│  2nd Gen: Levonorgestrel, Norgestrel     │
│  3rd Gen: Desogestrel, Gestodene,        │
│           Norgestimate                   │
│  4th Gen: Drospirenone, Dienogest,       │
│           Nomegestrol acetate            │
└──────────────────────────────────────────┘

MECHANISM OF ACTION

HYPOTHALAMUS
     │  COC suppresses GnRH pulsatility
     ▼
PITUITARY
     │  ↓ FSH and LH synthesis
     │  ↓ Ability to respond to GnRH stimulation
     ▼
OVARY
     │  No follicle maturation
     │  No estradiol production
     │  No LH surge
     │  NO OVULATION
     │
     ├──▶ Endometrium: Atrophic (hostile to implantation)
     │
     └──▶ Cervix: Thickened, scant mucus (hostile to sperm)

COC PILL PACKAGING AND REGIMENS

STANDARD REGIMENS
─────────────────────────────────────────────────────────
21/7 Regimen:     21 active pills + 7 placebos
                  → 7-day hormone-free interval
                  → Withdrawal bleed like menstruation
                  → More follicle maturation during 7-day gap

24/4 Regimen:     24 active pills + 4 placebos  (NEWER)
                  → Shorter hormone-free interval
                  → Less follicle maturation = better ovarian
                    suppression
                  → Theoretically more effective

Extended Cycle:   Active pills for 3 months continuously
                  (e.g., Seasonale - 84 active + 7 placebo)
                  → Only 4 bleeds/year

Continuous Cycle: Active pills indefinitely (1 year+)
                  → Amenorrhea develops
                  → Fewer headaches, less dysmenorrhea
                  → More unscheduled spotting initially
                  → PREFERRED for chronic pelvic pain,
                    endometriosis, severe dysmenorrhea

PROGESTINS - GENERATIONS AND PROPERTIES

• Derived from spironolactone
• Anti-mineralocorticoid activity (↓ fluid retention, weight gain)
• Anti-androgenic (improves acne, hirsutism)
• FDA approved for PMDD treatment in women choosing OC contraception
• Studies show better relief of menstrual symptoms, better acne improvement, improved well-being vs LNG/EE OCs

• Combined with estradiol valerate (not EE) - first pill to use natural estrogen
• Effective for abnormal uterine bleeding
• Anti-androgenic properties

NEWER ESTROGENS IN COC

EVOLUTION OF ESTROGEN IN COC PILLS
──────────────────────────────────────────────────────────
1960s-1990s     50-150 μg Mestranol/EE  → High dose, high risk
                         ↓
1990s-2000s     30-35 μg EE             → Lower risk, standard use
                         ↓
2000s           20 μg EE                → Further ↓ thrombosis risk
                   (18% further reduction vs 30-40 μg EE)
                         ↓
2010s-NOW       17β-Estradiol (E2)      → Natural estrogen (Zoely)
                Estradiol Valerate (EV) → Natural estrogen ester
                Estradiol Cypionate     → Injectable form
                         ↓
FUTURE          Estetrol (E4)           → Fetal-origin estrogen
                                          Less liver effect, potentially
                                          safer VTE profile

NEWER DEVELOPMENTS IN COC PILLS

1. Estradiol Valerate / Dienogest (Qlaira) - Quadriphasic Pill

• First pill using natural estradiol (estradiol valerate) instead of EE
• Combined with dienogest (4th gen progestin)
• Quadriphasic dosing: 4 different dose phases over 28 days
• Benefits: More natural hormone profile, FDA-approved for heavy menstrual bleeding

2. 17β-Estradiol / Nomegestrol Acetate (Zoely) - Monophasic

• Uses 17β-estradiol (natural estrogen)
• Combined with nomegestrol acetate (potent, anti-androgenic progestin)
• 24/4 regimen
• Very low androgen activity

3. 20 μg EE / Drospirenone (Yaz, Yasminelle) - 24/4 Regimen

• FDA-approved for PMDD (premenstrual dysphoric disorder)
• 24 active + 4 placebo days (reduces hormone-free gap)
• Anti-mineralocorticoid effect: less bloating/weight gain
• Anti-androgenic: better acne control

4. Extended-Cycle (Seasonale) and Continuous-Cycle (Lybrel) Pills

• Seasonale: 84-day active, 7-day placebo → 4 bleeds/year
• Lybrel: 365-day continuous → no scheduled bleed
• Preferred for women with: endometriosis, severe dysmenorrhea, menstrual migraine, catamenial epilepsy

5. Nestorone + EE Vaginal Ring (1-Year Ring - in development)

• Releases 150 μg Nestorone (non-androgenic progestin, inactive orally) + 15 μg EE daily
• Wear 3 weeks, remove 1 week → up to 13 cycles on one ring
• No refrigeration needed - ideal for low-resource settings
• Population Council developing; FDA NDA pending

NON-CONTRACEPTIVE BENEFITS OF COC

SYSTEM           BENEFIT
──────────────────────────────────────────────────────
MENSTRUAL        ↓ Dysmenorrhea
                 ↓ Heavy periods (oligomenorrhea/amenorrhea)
                 Regulate cycles
                 ↓ PMS/PMDD (drospirenone-containing COC)

REPRODUCTIVE     ↓ Ovarian cysts
                 ↓ Functional cysts
                 ↓ Ectopic pregnancy risk

CANCER           ↓ Ovarian cancer (50% reduction with 5 yrs use)
PROTECTION       ↓ Endometrial cancer (50% reduction)
                 ↓ Colorectal cancer (37-40% reduction)
                 Protection increases with duration of use

SKIN             ↓ Acne (especially drospirenone COC)
                 ↓ Hirsutism

BONE             Maintains bone density (premenopausal)

OTHER            ↓ Risk of benign breast disease
                 ↓ Rheumatoid arthritis risk
                 ↓ PID severity

RISKS AND SIDE EFFECTS

Venous Thromboembolism (VTE) - Most Important Risk

VTE RISK STRATIFICATION WITH COC
─────────────────────────────────────────────────────────
BACKGROUND VTE RISK: 1-5 per 10,000 women/year

COC users (30-35 μg EE): 3-4 per 10,000/year
COC users (20 μg EE):    2-3 per 10,000/year (18% lower)
Pregnancy:               ~12 per 10,000
Puerperium:              ~40-65 per 10,000

Progestin-only OC: NO increased VTE risk
LNG-IUD:           NO increased VTE risk
─────────────────────────────────────────────────────────
PROGESTIN AND VTE RISK:
3rd gen (desogestrel, gestodene) > 2nd gen (levonorgestrel)
Drospirenone → intermediate risk (similar to desogestrel)
2nd gen progestins = LOWEST VTE risk among COCs

Cancer Risks

CONTRAINDICATIONS TO COC (WHO Category 4)

ABSOLUTE CONTRAINDICATIONS (Do NOT use)
────────────────────────────────────────────────────────
CARDIOVASCULAR:
  • History of DVT/PE
  • History of ischemic heart disease
  • Stroke or TIA history
  • Hypertension (SBP ≥ 160 or DBP ≥ 100 mmHg)
  • Complicated valvular heart disease
  • Multiple CVD risk factors (smoking >35 yrs old)

LIVER:
  • Active viral hepatitis
  • Severe cirrhosis
  • Liver tumors (hepatocellular adenoma, HCC)

HORMONAL:
  • Breast cancer (current or recent)
  • Migraines with aura (ANY age)

OBSTETRIC:
  • Pregnancy
  • Breastfeeding < 6 weeks postpartum

OTHER:
  • Smoking + Age > 35 years
  • Prolonged immobilization / major surgery

DRUG INTERACTIONS

DRUGS THAT REDUCE COC EFFICACY (Enzyme Inducers)
───────────────────────────────────────────────────
Antiepileptics: Phenytoin, Phenobarbital, Carbamazepine,
                Oxcarbazepine, Felbamate, Topiramate
Antibiotics:    Rifampin (potent inducer)
Antifungals:    Griseofulvin, Ketoconazole, Itraconazole
Herbal:         St. John's Wort

→ All induce CYP450 → ↓ EE plasma levels → ↑ pregnancy risk

SAFE ANTIEPILEPTICS (NO interaction with COC):
Valproic acid, Lamotrigine, Gabapentin, Levetiracetam,
Vigabatrin, Tiagabine, Zonisamide, Ethosuximide,
Benzodiazepines

COC AFFECTING OTHER DRUG LEVELS:
↑ Half-life of diazepam, alprazolam (reduced oxidation)
↑ Theophylline, caffeine levels
↑ Cyclosporine levels
↓ Salicylate and morphine clearance
↓ Ethanol clearance

ROUTE OF ADMINISTRATION - COMPLETE OVERVIEW

┌────────────────────────────────────────────────────────────────┐
│         ROUTES OF HORMONAL CONTRACEPTIVE ADMINISTRATION        │
├───────────┬──────────────────────────────────────────────────┤
│  ROUTE    │  EXAMPLES + KEY FEATURES                         │
├───────────┼──────────────────────────────────────────────────┤
│  ORAL     │  COC (combined) - daily pill                     │
│           │  POP (progestin-only mini-pill) - daily          │
│           │  Extended-cycle: 84/7 regimen                    │
│           │  Continuous-cycle: 365 days active               │
├───────────┼──────────────────────────────────────────────────┤
│  TRANS-   │  Ortho Evra patch (EE + norelgestromin)         │
│  DERMAL   │  Apply weekly × 3 weeks, off 1 week             │
│           │  Sustained release → constant serum levels       │
│           │  Higher EE exposure vs 35 μg OC (AUC 60% ↑)    │
│           │  Slight ↑ VTE risk vs OC (FDA black box warning) │
├───────────┼──────────────────────────────────────────────────┤
│  VAGINAL  │  NuvaRing (EE + etonogestrel)                   │
│           │  Monthly ring: insert 3 weeks, remove 1 week    │
│           │  NEWER: 1-Year ring (Nestorone + EE)            │
│           │  13 cycles, no refrigeration needed             │
│           │  Steady state levels, avoids first-pass effect  │
├───────────┼──────────────────────────────────────────────────┤
│  INJECT-  │  DMPA 150 mg IM q3 months (Depo-Provera)       │
│  ABLE     │  DMPA 104 mg SC q3 months (Depo-SubQ 104)      │
│           │  Combined monthly injectable (Cyclofem):        │
│           │  DMPA + estradiol cypionate                     │
├───────────┼──────────────────────────────────────────────────┤
│  SUB-     │  Nexplanon (68 mg ENG, single rod)             │
│  DERMAL   │  3 years, most effective reversible method      │
│  IMPLANT  │  Inner non-dominant arm                         │
├───────────┼──────────────────────────────────────────────────┤
│  INTRA-   │  LNG-IUD: Mirena, Kyleena, Skyla, Liletta      │
│  UTERINE  │  Local effect, minimal systemic absorption      │
└───────────┴──────────────────────────────────────────────────┘

STARTING COC - QUICK START PROTOCOLS

WHEN TO START COC?
────────────────────────────────────────────────────────
"Quick Start" (any day):
    • Start same day of visit if not pregnant
    • Use backup contraception for 7 days

"Sunday Start":
    • Start first Sunday after period begins
    • Use backup × 7 days

"Day 1 Start":
    • Start first day of menses
    • No backup needed

POSTPARTUM:
    • Not breastfeeding: Start 3-6 weeks postpartum
      (↑ VTE risk early postpartum, delay COC)
    • Breastfeeding: AVOID combined (estrogen ↓ milk)
      → Use progestin-only alternatives

POST-ABORTION:
    • Immediate start same day (most effective prevention
      of repeat abortion)

MISSED PILL MANAGEMENT

MISSED PILL PROTOCOL
─────────────────────────────────────────────────────────
Missed 1 pill:     Take it as soon as remembered
                   Take next pill at regular time
                   No backup needed

Missed 2 pills     Take 2 pills on day remembered
(Days 1-14):       Take 2 pills next day
                   Backup × 7 days

Missed 2+ pills    Take most recent missed pill ASAP
(Days 15-21):      Discard remaining pills
                   Start new pack immediately
                   Backup × 7 days
                   Consider emergency contraception
                   if unprotected sex in past 5 days

SUMMARY: 10-MARK ANSWER STRUCTURE

1. Definition + Classification (1 mark) - Combined vs progestin-only, routes
2. Components of COC (1 mark) - Estrogen generations + progestin generations
3. Mechanism of Action (2 marks) - HPO axis suppression + local effects
4. COC Regimens + Packaging (1 mark) - 21/7, 24/4, extended, continuous
5. Newer Developments (2 marks) - Natural estrogens, 4th gen progestins, extended cycle, vaginal ring
6. Benefits (non-contraceptive) (1 mark) - Cancer protection, menstrual effects
7. Risks + Contraindications (1 mark) - VTE, cancer, WHO cat 4
8. Drug interactions (1 mark) - Enzyme inducers, safe antiepileptics

Key Exam Facts to Remember:

• Progestin does the real contraceptive work - estrogen mainly assists cycle control
• 24/4 regimen is superior to 21/7 (less follicle maturation in hormone-free gap)
• 20 μg EE has 18% lower VTE risk than 30-40 μg EE
• Drospirenone (4th gen) = anti-mineralocorticoid + anti-androgenic → FDA-approved for PMDD
• Estradiol valerate/dienogest (Qlaira) = first quadriphasic pill with natural estrogen
• Extended/continuous cycling = preferred for endometriosis, dysmenorrhea, catamenial conditions
• COC protects against ovarian cancer (↓50%), endometrial cancer (↓50%), colorectal cancer (↓37%)
• Rifampin is the most important antibiotic that reduces COC efficacy
• Progestin-only pills and LNG-IUD do NOT increase VTE risk

EMERGENCY CONTRACEPTION (EC)

Final Exam Answer | Source: Berek & Novak's Gynecology

DEFINITION

"EC is most effective the sooner it is taken after intercourse." - Berek & Novak

OVERVIEW FLOWCHART

┌─────────────────────────────────────────────────────────┐
│                EMERGENCY CONTRACEPTION                   │
└──────────────────────────┬──────────────────────────────┘
                           │
          ┌────────────────┼──────────────────┐
          ▼                ▼                  ▼
   ┌─────────────┐  ┌────────────┐    ┌─────────────┐
   │  HORMONAL   │  │ANTIPROGEST-│    │  COPPER IUD │
   │    EC       │  │   IN EC    │    │    (IUCD)   │
   └──────┬──────┘  └─────┬──────┘    └──────┬──────┘
          │               │                  │
    ┌─────┴──────┐        │           Best efficacy
    ▼            ▼        ▼           (near 100%)
 Levonorg-  Yuzpe    Ulipristal     Up to 5-7 days
  estrel    Method   Acetate        + ongoing
 (LNG)    (older)   (Ella)          contraception
 ≤120 hrs  ≤72 hrs   ≤120 hrs

HISTORICAL EVOLUTION

TIMELINE OF EMERGENCY CONTRACEPTION
─────────────────────────────────────────────────────────────
1960s   High-dose ESTROGEN (daily × 5 days)
        → Effective but severe nausea, vomiting
             │
             ▼
1970s   YUZPE METHOD (Yuzpe & Smith, 1977)
        EE 100 μg + LNG 0.5 mg × 2 doses (12 hrs apart)
        → More convenient, combined OC used
        → But: 50% nausea, 18-19% vomiting
             │
             ▼
1998    LEVONORGESTREL ALONE (WHO large RCT, 1998 women)
        LNG outperformed Yuzpe:
        • Pregnancy rate: 1.1% vs 3.2%
        • Less nausea: 23% vs 50%
        • Less vomiting: 5.6% vs 18.8%
        → LNG became method of CHOICE
             │
             ▼
2010    ULIPRISTAL ACETATE (Ella) - FDA approved
        → Progesterone receptor modulator
        → Effective up to 120 hours
        → Better efficacy near ovulation
             │
             ▼
NOW     COPPER IUD = Most effective EC
        (near 100% up to 5-7 days)

METHOD 1: LEVONORGESTREL (LNG) ALONE

Preparations and Dosing

• Available without prescription (OTC) since 2013
• Brands: Plan B One-Step, Next Choice, i-pill, Norlevo

Mechanism of Action

LEVONORGESTREL EC - HOW IT WORKS
─────────────────────────────────────────────────────────
PRIMARY MECHANISM:
     Delays or inhibits OVULATION
          │
          ▼
     LNG suppresses the LH surge
     → Delays follicular rupture
     → If given BEFORE ovulation day = effective
          │
     Noe et al. study:
     • 87 women treated 1-5 days BEFORE ovulation → 0 pregnancies
     • 35 women treated ON or AFTER ovulation → 7 pregnancies

THEREFORE:
     LNG works only BEFORE ovulation
     It is NOT an abortifacient
     (Does not disrupt established implantation)

Efficacy

Side Effects (LNG alone - much less than Yuzpe)

• Nausea: 23%
• Vomiting: 5.6%
• Irregular bleeding/spotting
• Headache, breast tenderness (transient)

METHOD 2: YUZPE METHOD (Combined Hormonal EC)

YUZPE REGIMEN (Historical / Still used when LNG unavailable)
────────────────────────────────────────────────────────────
DOSE:   EE 100 μg + LNG 0.5 mg
TIMING: 2 doses, 12 hours apart
        → Must complete within 72 hours of intercourse

Any standard COC pill can be used (multiple pills to reach dose)

EFFICACY: Pregnancy rate ~3.2% (within 72 hrs)
SIDE EFFECTS: Nausea 50.5%, Vomiting 18.8%
         → Anti-emetic (domperidone/metoclopramide)
           recommended 30 min before each dose

DISADVANTAGE vs LNG:
• Higher pregnancy rate (3.2% vs 1.1%)
• Much more nausea/vomiting
• VTE risk (case reports of thrombosis reported)
• LNG alone is SAFER and MORE EFFECTIVE → preferred

METHOD 3: ULIPRISTAL ACETATE (UPA)

Key Details

• Brand: Ella (USA), EllaOne (Europe)
• Class: Selective Progesterone Receptor Modulator (SPRM)
• Dose: Single 30 mg tablet
• Window: Up to 120 hours (5 days)
• Prescription required (unlike LNG)

Mechanism of Action

ULIPRISTAL ACETATE - MOA
──────────────────────────────────────────────────────
Binds progesterone receptor → ANTAGONIST/partial agonist

Primary effect: Delays or inhibits OVULATION
         │
         ▼
When given BEFORE LH peak:
→ Delays rupture of preovulatory follicle by ≥ 5 days
→ This is its PRIMARY mechanism of action

KEY ADVANTAGE OVER LNG:
When ovulation is IMMINENT (LH surge beginning):
→ UPA still delays follicular rupture
→ LNG loses effectiveness at this point

RESULT: UPA is MORE EFFECTIVE than LNG
        when ovulation is imminent or near

UPA vs LNG Comparison

ULIPRISTAL vs LEVONORGESTREL
─────────────────────────────────────────────────────────
Feature            UPA (Ella)           LNG (Plan B)
─────────────────────────────────────────────────────────
Class              SPRM                 Progestin
Dose               30 mg (single)       1.5 mg (single)
Window             ≤120 hours           ≤120 hours
Efficacy overall   Better               Good
Near ovulation     SUPERIOR (65% lower  Less effective
                   pregnancy risk)      at LH surge
Obese women        PREFERRED (OR 2.62   Less effective
                   for pregnancy)       (OR 4.41)
Prescription       Yes                  No (OTC)
Starting HC after  Wait 5 DAYS          Start immediately
Availability       Limited (Rx only)    Wide (OTC)
Drug interaction   CYP3A4 inducers      Few interactions
                   reduce efficacy

UPA and Starting Regular Contraception After Use

• After LNG EC → Start regular hormonal contraception immediately
• After UPA EC → Wait 5 days before starting hormonal contraception
  • Reason: Progestin (desogestrel) given the day after UPA caused ovulation in 45% of cycles vs 3% in placebo group (Berek & Novak, 2015 Ella label update)

METHOD 4: MIFEPRISTONE (Antiprogestin)

MIFEPRISTONE FOR EMERGENCY CONTRACEPTION
────────────────────────────────────────────────────────
Dose for EC:    10 mg (NOT 200 mg used for abortion)

Study: 2,065 women randomized to:
  • Mifepristone 10 mg  → Pregnancy rate 1.3%
  • LNG 2 × 0.75 mg    → Pregnancy rate 2.0%
  Both given up to 120 hours (p = 0.46, not significant)
  Side effects EQUAL between groups

STATUS: Not commercially available at 10 mg dose
        Not being developed specifically for EC use
        (Available only as 200 mg for medical abortion)

METHOD 5: COPPER IUD AS EMERGENCY CONTRACEPTION

This is the MOST EFFECTIVE method of EC

COPPER IUD FOR EMERGENCY CONTRACEPTION
─────────────────────────────────────────────────────────
First described: Lippes et al. (1976)

EFFICACY:
 ┌─────────────────────────────────────────────────────┐
 │  Inserted within 5 days of intercourse = ~100%      │
 │  Inserted within 7 days of intercourse = ~100%      │
 │  (Wu et al. multicenter trial: 1,893 women,         │
 │   0 pregnancies at 1-month follow-up)               │
 └─────────────────────────────────────────────────────┘

MECHANISM (for EC):
  • Toxic effect of Cu²⁺ ions on sperm
  • Prevents fertilization
  • Creates inhospitable endometrial environment
  • Works even AFTER ovulation has occurred
  → Unlike hormonal EC, works post-ovulation

ADVANTAGES:
  ✓ Most effective EC method (near 100%)
  ✓ Works up to 5-7 days (longest window)
  ✓ Works regardless of where woman is in cycle
  ✓ Provides ONGOING contraception (10 years)
  ✓ 94% patients continuing IUD at 12-month follow-up
  ✓ Cost-effective (one intervention, years of protection)
  ✓ Non-hormonal (suitable for women who cannot use hormones)

DISADVANTAGES:
  ✗ Requires provider insertion (trained clinician)
  ✗ Not suitable if STI/PID risk
  ✗ Uterine perforation risk (1:1000)
  ✗ May increase menstrual bleeding/cramping

COMPARISON TABLE: ALL EC METHODS

DECISION FLOWCHART: CHOOSING THE RIGHT EC METHOD

PATIENT PRESENTS FOR EMERGENCY CONTRACEPTION
            │
            ▼
How long since unprotected intercourse?
            │
    ┌───────┴──────────────────────┐
    ▼                              ▼
 ≤ 5 days                      > 5 days
(≤ 120 hours)                 (≤ 7 days)
    │                              │
    ▼                              ▼
Does she want ONGOING         Consider Copper IUD
contraception?                (only option if >5 days)
    │
    ├─── YES ───▶ COPPER IUD (best EC + ongoing)
    │
    └─── NO ────▶ Hormonal EC
                      │
                 Is she OBESE (BMI >30)?
                      │
              ┌───────┴────────┐
              YES              NO
              │                │
              ▼                ▼
         ULIPRISTAL       LEVONORGESTREL
         ACETATE          (Plan B, Plan A)
         (Ella, 30 mg)    (1.5 mg single dose)
              │                │
              ▼                ▼
         Wait 5 days       Start hormonal
         before regular    contraception
         hormonal method   immediately

EC IN SPECIAL SITUATIONS

SITUATION                    RECOMMENDED METHOD
────────────────────────────────────────────────────────────
Obese women (BMI >30)       UPA preferred over LNG
                             (LNG plasma levels ↓ in obese)
                             Copper IUD equally effective

Cannot use hormones          Copper IUD (best option)
(VTE history, breast Ca)

On enzyme inducers           Copper IUD preferred
(rifampin, AEDs)             (UPA levels reduced by CYP3A4
                              inducers; LNG also less safe)

Wants ongoing contraception  Copper IUD (most cost-effective
                              long-term option)

Risk of STI/PID              LNG or UPA (avoid IUD)

Breastfeeding                LNG safe; UPA - avoid
                              (insufficient data in
                              breastfeeding)

After failed barrier         Any EC within time window

Rape/sexual assault          LNG or UPA immediately;
                              STI prophylaxis also given;
                              Copper IUD if >72 hours or
                              ongoing protection desired

MECHANISM SUMMARY DIAGRAM

HOW DIFFERENT EC METHODS WORK
─────────────────────────────────────────────────────────────

Timeline:
    Intercourse → Sperm transport → Fertilization → Implantation
         │              │                │               │
         │         LNG/UPA/Yuzpe         │          (Pregnancy
         │         act HERE by      Copper IUD          established)
         │         delaying         acts here too
         │         ovulation        → Prevents
         │                            fertilization
         ▼                            AND alters
    (sperm in                         endometrium
    female tract
    remain viable
    3-5 days)

KEY POINT:
• All EC methods work BEFORE implantation
• No EC method disrupts an ESTABLISHED pregnancy
• EC is NOT an abortifacient
• Mifepristone at 200 mg = abortifacient (different drug, different dose)

NON-CONTRACEPTIVE POINTS FOR EXAM

1. Reassure about mechanism (not abortifacient)
2. Expect next period within 1 week of expected date
3. If next period >1 week late → pregnancy test
4. Start regular contraception as soon as possible
5. EC does NOT protect against STIs
6. EC can be used more than once (but not as regular method)
7. Counsel about regular contraception options going forward

EXAM-READY SUMMARY TABLE

High-Yield Exam Points:

• LNG EC = delays ovulation (primary MOA) - NOT abortifacient; works only before ovulation
• WHO large RCT (1,998 women): LNG pregnancy rate 1.1% vs Yuzpe 3.2%
• UPA is superior to LNG when ovulation is imminent; preferred in obese women
• Copper IUD = most effective EC (near 100%); works up to 5-7 days; also provides 10 years ongoing contraception
• After LNG: start hormonal contraception immediately; after UPA: wait 5 days
• UPA efficacy reduced by CYP3A4 inducers (rifampin, barbiturates, anticonvulsants)
• 94% of women who received copper IUD as EC were still using it at 12 months (cost-effective)
• LNG plasma levels are significantly lower in obese women → reduced efficacy; UPA levels are unaffected by obesity

CENTCHROMAN (ORMELOXIFENE / SAHELI / CHHAYA)

Short Notes | Final Exam

IMPORTANT NOTE ON SOURCE

• Park's Textbook of Preventive & Social Medicine (which confirms it as "Chhaya" in India's national family planning basket)
• Shaw's Textbook of Gynaecology and DC Dutta's Textbook of Gynecology (Indian gynecology references)
• The pharmacological literature on ormeloxifene

DEFINITION

BASIC CLASSIFICATION FLOWCHART

┌────────────────────────────────────────────────────────┐
│                   CENTCHROMAN                          │
│               (ORMELOXIFENE)                           │
└───────────────────────┬────────────────────────────────┘
                        │
        ┌───────────────┼───────────────┐
        ▼               ▼               ▼
   CHEMICAL CLASS    RECEPTOR       ORIGIN
   Non-steroidal     SERM           Developed in India
   Benzopyran        (Selective     CDRI, Lucknow, 1991
   derivative        Estrogen       First indigenous
                     Receptor       oral contraceptive
                     Modulator)

CHEMICAL STRUCTURE

• Belongs to benzopyran group (chromene derivative)
• Non-steroidal
• NOT a progestin, NOT an estrogen
• Mechanism differs completely from conventional hormonal pills

MECHANISM OF ACTION

HOW CENTCHROMAN WORKS
────────────────────────────────────────────────────────────

CENTCHROMAN
    │
    ▼
Acts as SERM on uterine estrogen receptors
    │
    ├─────────────────────────────────────────────┐
    ▼                                             ▼
ESTROGEN ANTAGONIST               ESTROGEN AGONIST
at UTERUS                         at BONE / LIVER
    │
    ▼
↓ Estrogen effect on endometrium
    │
    ▼
ASYNCHRONY between ovulation and implantation
(ovulation may occur, but endometrium is not
receptive at the right time)
    │
    ▼
Blastocyst passes through uterus
without implanting
    │
    ▼
CONTRACEPTIVE EFFECT
────────────────────────────────────────────────────────────
SECONDARY EFFECTS:
• Accelerates transport of fertilized ovum through fallopian tube
  (anti-estrogenic effect on tubal motility)
• Creates hostile endometrial environment
• Thickens cervical mucus (some contribution)

KEY POINT: Does NOT suppress ovulation
           (unlike conventional OCP)

DOSING SCHEDULE

DOSING REGIMEN
────────────────────────────────────────────────────────
DOSE:        30 mg per tablet (standard dose)

SCHEDULE:
  FIRST 3 MONTHS:
  ┌──────────────────────────────────────────┐
  │  Take TWICE A WEEK × 12 weeks (loading)  │
  │  e.g., Monday and Friday every week      │
  │  (Any 2 days, 3-4 days apart)            │
  └──────────────────────────────────────────┘
              ↓
  FROM 4th MONTH ONWARDS:
  ┌──────────────────────────────────────────┐
  │  Take ONCE A WEEK (maintenance)          │
  │  Same day every week                     │
  └──────────────────────────────────────────┘

Start:  On Day 1 or Day 2 of menstrual cycle

Pearl Index: ~1.5 to 2.5 per 100 woman-years
             (Acceptable efficacy, not as high as COC)

ADVANTAGES

ADVANTAGES OF CENTCHROMAN
────────────────────────────────────────────────────────
NON-HORMONAL:
  ✓ No estrogen → No VTE risk
  ✓ No progestin effects
  ✓ Safe in women with contraindications to hormones

OVULATION PRESERVED:
  ✓ Normal ovarian function maintained
  ✓ Normal hormonal milieu continues
  ✓ Rapid return of fertility on stopping

METABOLIC SAFETY:
  ✓ No effect on weight
  ✓ No effect on blood pressure
  ✓ No glucose metabolism change
  ✓ No lipid profile change
  ✓ No nausea or vomiting (major advantage over OCP)

CONVENIENCE:
  ✓ Once-a-week dosing (after initial phase)
  ✓ Better compliance than daily pills
  ✓ Simple regimen

AVAILABILITY:
  ✓ Available free under Government of India's
    national family planning programme (Chhaya)
  ✓ 14.1 lakh users in India (2018-19 data, Park's)

ADDITIONAL USES:
  ✓ Treatment of dysfunctional uterine bleeding (DUB)
  ✓ Treatment of mastalgia (fibrocystic breast disease)
  ✓ Being studied for endometriosis, PCOD management

DISADVANTAGES AND SIDE EFFECTS

DISADVANTAGES
────────────────────────────────────────────────────────
MENSTRUAL EFFECTS:
  • Oligomenorrhea (delayed periods) - most common
    side effect; can cause concern/anxiety
  • Cycle lengthening in some women

EFFICACY:
  • Pearl Index ~1.5-2.5 (less effective than COC)
  • Requires strict weekly schedule after loading phase

CLINICAL:
  • Delayed return to fertility in occasional users
    (though generally rapid)
  • Limited data on long-term use beyond 5 years
  • Not effective as emergency contraception

AVAILABILITY:
  • Not widely available outside India
  • Not part of WHO essential medicines list

CONTRAINDICATIONS

CONTRAINDICATIONS TO CENTCHROMAN
────────────────────────────────────────────────────────
• Pregnancy (teratogenic potential)
• Lactation (limited safety data; avoid)
• Hormone-receptor positive breast cancer
  (SERM effect - use with caution)
• Anovulatory states (mechanism depends on
  asynchrony, less effective if no ovulation)
• Severe hepatic disease
• Desire for pregnancy in near future

COMPARISON WITH CONVENTIONAL OCP

INDIA-SPECIFIC CONTEXT (Park's)

CENTCHROMAN IN INDIA'S NATIONAL PROGRAMME
────────────────────────────────────────────────────────
Brand name:    CHHAYA (Govt. supply) / SAHELI (market)
Programme:     Part of India's National Family Planning
               Basket of contraceptive choices
Developed by:  CDRI (Central Drug Research Institute),
               Lucknow - FIRST indigenously developed
               oral contraceptive in India (1991)
Users (2018-19): 14.1 lakh (Park's data)
Delivery:      Available at Sub-centres and above
               Can be provided by ASHAs, ANMs, LHVs
Classification: Spacing method (reversible)

SUMMARY FLOWCHART

PATIENT WANTS ORAL CONTRACEPTION
            │
            ▼
Can she take hormones?
            │
    ┌───────┴──────────┐
    NO                 YES
    │                  │
    ▼                  ▼
CENTCHROMAN        Consider COC/POP
(non-hormonal)
    │
    ▼
30 mg tablet
Twice weekly × 3 months
→ Then once weekly
            │
    ┌───────┴────────────────────┐
    ▼                            ▼
MECHANISM:                 ADVANTAGES:
Asynchrony between         No hormones
ovulation + implantation   No VTE risk
                           Once-a-week
                           No nausea

EXAM HIGH-YIELD POINTS

1. Class: SERM (Selective Estrogen Receptor Modulator) - non-steroidal, non-hormonal
2. MOA: Creates asynchrony between ovulation and uterine receptivity; does NOT suppress ovulation
3. Dose: 30 mg; twice weekly × 3 months, then once weekly
4. Developed by: CDRI Lucknow, India; first indigenous oral contraceptive (1991)
5. Brand names: Saheli (original), Chhaya (Govt. supply)
6. Pearl Index: ~1.5-2.5 per 100 woman-years
7. Key advantage: No estrogen side effects; no VTE risk; no nausea; no weight gain
8. Key side effect: Oligomenorrhea / cycle lengthening (most common)
9. Additional use: Dysfunctional uterine bleeding, mastalgia
10. India programme: Part of national family planning basket under Chhaya programme