RH/SH/GU 02: Hormonal Contraceptives

🩸 Days 1–5: Menses (Period)

• Estrogen (E) = low

• Progesterone (P) = low

• The uterus sheds last month’s lining → period

💡 Low hormones = brain says:

🌱 Days 1–14: Follicular Phase

• Brain releases GnRH → FSH

• FSH stimulates follicles in ovaries

• One follicle starts maturing an egg

• That follicle makes estrogen

👉 Estrogen slowly rises

• Thickens uterine lining

• Prepares body for possible pregnancy

🔴 ~Day 14: Ovulation

• Estrogen peaks → triggers LH surge

• LH surge = egg released

🚨 THIS is the key fertility event

🌙 Days 14–28: Luteal Phase

• Empty follicle becomes corpus luteum

• Makes progesterone

• Progesterone:

  • Stabilizes uterine lining

  • Makes uterus “pregnancy-ready”

If no pregnancy:

• Progesterone & estrogen drop

• Lining sheds → next period

🧠 Now the BIG CONCEPT:

Hormonal contraceptives abolish this entire cycle

🤰 “Mimicking Pregnancy” (this line is VERY important)

During pregnancy:

• Estrogen & progesterone are consistently high

• No ovulation happens

Hormonal contraceptives do the same thing:

• 🚫 No hormone peaks

• 🚫 No LH surge

• 🚫 No ovulation

📌 That’s why the slide says:

That “period” on birth control?
➡ Withdrawal bleed, not a real menstrual cycle.

💊 Combined Hormonal Contraceptives (CHC): HOW they work

🧠 Step 1: Shut down the brain

Estrogen + progestin suppress:

• Hypothalamus → ↓ GnRH

• Pituitary → ↓ FSH & ↓ LH

Estrogen:

• Suppresses FSH

• No follicle development
  👉 no egg to ovulate

Progestin:

• Suppresses LH

• No LH surge
  👉 no ovulation

💡 No egg + no LH = no pregnancy

🏠 Step 2: Change the uterus (backup protection)

Progestin effects:

• Endometrium becomes:

  • Thin

  • Underdeveloped

  • Less vascular

👉 Implantation is very unlikely

🚪 Step 3: Block sperm at the cervix

Progestin thickens cervical mucus

• Sticky

• Viscous

• Hard for sperm to swim through

🧩 Summary of CHC Mechanisms (exam GOLD)

1. 🚫 Prevent ovulation (main mechanism)

2. 🧱 Thin uterine lining

3. 🚪 Thicken cervical mucus

💊 Estrogen dose: why ≤35 mcg ethinyl estradiol?

Older pills = higher estrogen → more risk

Lower estrogen = safer

✔ Less:

• Nausea

• Bloating

• Breast tenderness

🚨 High estrogen is linked to:

• Thromboembolic events (VTE)

• Stroke

• MI

• ↑ breast cancer risk (small but relevant)

➡ That’s why modern pills use ≤35 mcg EE

🧪 Types of estrogen

• Ethinyl estradiol (most common)

• Estradiol

• Estetrol (newer)

  • Naturally produced in pregnancy

  • Thought to have less clot risk (still emerging data)

🚨 MI & Stroke Risk (important nuance)

• CHCs slightly ↑ risk of MI & stroke

• Risk increases with:

  • Higher estrogen dose

  • Smoking

  • Age ≥35

  • HTN, migraines with aura, etc.

👉 This is why patient selection matters

🧩 PART 1: Progestins in CHCs – the BIG IDEA

🔑 Core concept

• Androgenic effects (acne, hair, oily skin)

• VTE risk

• Extra “bonus” properties (anti-androgenic, anti-mineralocorticoid)

💡 Exams LOVE asking:
“Which progestin would you choose for THIS patient?”

👶 1st Generation Progestins

Norethindrone, Ethynodiol diacetate

• Derived from testosterone

• Mildly androgenic

• Older agents

🧠 Think:

💪 2nd Generation Progestins

Levonorgestrel, Norgestrel

• More androgenic than 1st gen

• Longer half-life

• Slightly ↑ VTE risk (≈ 6 / 10,000 women)

📌 Why they still matter:

• Very effective

• Common in IUDs

• Reliable cycle control

🧠 Think:

🌸 3rd Generation Progestins

Desogestrel, Norgestimate, Etonogestrel

• Less androgenic

• Better for acne than 2nd gen

• Slightly ↑ VTE risk (esp desogestrel)

🧠 Think:

💖 4th Generation Progestins

Drospirenone

✨ SPECIAL SNOWFLAKE ✨

• Derived from spironolactone

• Anti-androgenic

• Anti-mineralocorticoid

• Progestogenic activity ✔

Pros:

• ↓ acne

• ↓ hirsutism

• ↓ bloating / water retention

Cons:

• Highest VTE risk in CHCs

  • 10–15 / 10,000 women

• Risk of hyperkalemia

🧠 Think:

🚨 Context matters!

VTE perspective:

• CHC VTE risk (worst-case): 10–15 / 10,000

• Pregnancy VTE risk: 17 / 10,000

📌 EXAM PEARL:

🧠 PART 2: Relative Hormone Activity (how to read that table)

You do NOT memorize the plus signs.
You memorize the trend:

📌 If patient has:

• Acne

• Hirsutism

• PCOS vibes

👉 Avoid 2nd gen, consider 3rd or drospirenone

🎗 PART 3: Cancer Risks – HIGH YIELD but very logical

🎀 Breast Cancer

• Slight ↑ risk while currently using or recently stopped

• Risk disappears after 10 years off

• Absolute risk is small

🧠 Exam phrasing:

🧫 Cervical Cancer

• ↑ risk with longer duration

• Risk declines after stopping

🧡 Endometrial Cancer

• ↓ risk ≥30%

• Protection ↑ with longer use

🥚 Ovarian Cancer

• 30–50% lower risk

• Protection lasts up to 30 years after stopping

🔥 THIS IS HUGE.

🧠 Colorectal Cancer

• 15–20% lower risk

🎯 One-line summary:

⚖ PART 4: Side Effects = Hormone Too LOW vs Too HIGH

This is PURE EXAM GOLD.

💧 Estrogen LOW

• Breakthrough bleeding (early/mid-cycle)

• Hot flashes

• Night sweats

👉 Think: menopause vibes

🌊 Estrogen HIGH

• Nausea

• Bloating

• Breast tenderness

• Headache

• Hypertension

• Melasma

• Clotting risk

🌙 Progestin LOW

• Late-cycle spotting

• Delayed bleed

🧱 Progestin HIGH

• Weight gain

• Acne

• Fatigue

• Mood changes

• ↑ LDL, ↓ HDL

• Hirsutism

🧔 Androgen Excess

• Oily skin

• Acne

• Hirsutism

• Edema

• ↑ libido

🧠 Pattern:

🚫 PART 5: Contraindications to CHCs (VERY HIGH YIELD)

🚨 Absolute “NO ESTROGEN” situations:

Memorize this list. No negotiation.

• ❌ Migraine with aura (ANY age)

• ❌ History of VTE / PE

• ❌ Known thrombophilia

• ❌ Smoker >35 years (>15 cigarettes/day)

• ❌ Uncontrolled HTN

• ❌ Ischemic heart disease / MI

• ❌ Stroke history

• ❌ Breast cancer

• ❌ <6 weeks postpartum (breastfeeding)

• ❌ Complicated diabetes (vascular disease)

📌 If estrogen is contraindicated:
👉 Think progestin-only or non-hormonal

⚠ “Pause and investigate”

• Undiagnosed vaginal bleeding → rule out cancer first

• ---

  🚨 Serious Side Effects of CHCs — A C H E S

  This is 100% memorization but also clinically meaningful.

  🅰 Abdominal pain

  → Think liver / gallbladder / clot

  🅲 Chest pain or shortness of breath

  → Pulmonary embolism / MI

  🅷 Headache (severe, sudden)

  → Stroke

  🅴 Eye problems

  → Retinal thrombosis / stroke

  🅢 Severe leg pain

  → DVT

  📌 Counseling line:

  “If you ever have ACHES symptoms, stop the pill and seek urgent care.”

  ---

  🧠 Patient Factors to Consider (how pharmacists THINK)

  You’re not memorizing this list — you’re screening for risk.

  🔍 Always ask yourself:

  1. Is estrogen safe?

  2. Will they actually take it correctly?

  3. What does the patient want?

  ---

  🧩 Key Factors (grouped logically)

  🫀 VTE / cardiovascular risk

  • Smoking

  • Age

  • Obesity

  • Hypertension

  • Migraine with aura

  🤱 Hormonal sensitivity

  • Breastfeeding

  • Postpartum

  • Estrogen intolerance

  ⏰ Adherence

  • Daily pill vs long-acting

  • Non-adherence history

  💊 Practicality

  • Drug–drug interactions

  • Cost

  • Frequency

  • Formulation

  💕 Reproductive goals

  • Short-term vs long-term

  • Reversibility

  • Desire for pregnancy

  ---

  👩‍⚕ Patient Populations — WHAT TO DO & WHY

  ---

  🚬 Smoking + Age >35

  🚨 Absolute contraindication to CHCs

  Why?

  • Estrogen + smoking = ↑ MI + mortality

  • Older high-dose OCs were especially dangerous

  👉 What to use instead:

  • Progestin-only pill

  • Injection

  • IUD

  🧠 Exam shortcut:

  Smoker + ≥35 = NO estrogen

  ---

  🩸 Hypertension

  • CHCs can raise BP 6–8 mmHg

  • Effect is independent of estrogen dose

  Acceptable:

  • Age <35

  • BP well controlled

  • Frequent monitoring

  Special note on drospirenone

  • Anti-aldosterone → ↑ potassium

  • Watch patients on:

    • ACE inhibitors

    • ARBs

    • K⁺-sparing diuretics

    • Aldosterone antagonists

  📌 Think:

  “Good for bloating, bad for potassium”

  ---

  🧠 Migraines

  ❌ Migraine WITH aura

  • ↑ ischemic stroke risk

  • CHCs contraindicated

  ✅ Migraine WITHOUT aura

  • CHCs can be considered if:

    • Healthy

    • Non-smoker

    • No other risk factors

  👉 When unsure: progestin-only

  ---

  🧪 Dyslipidemia

  • Estrogen ↑ triglycerides

  • Uncontrolled TGs → pancreatitis risk

  🚨 Avoid CHCs if:

  • Dyslipidemia + CAD/DM/HTN/smoking

  ---

  ⚖ Obesity

  • Obesity itself ↑ VTE risk

  • Estrogen adds more risk

  Preferred:

  • Progestin-only injection

  • Progestin-only IUD

  🚫 Transdermal patch

  • Avoid if >90 kg

  • Reduced efficacy + ↑ estrogen exposure

  🧠 Exam pearl:

  Patch + obesity = 🚩

  ---

  🤱 Postpartum Contraception — VERY HIGH YIELD

  🚨 Postpartum = hypercoagulable state

  • VTE risk already elevated

  • Estrogen makes it worse

  ---

  🍼 Breastfeeding considerations

  • Estrogen ↓ milk production

  • Infant exposure concerns

  ---

  ✅ Guideline recommendations

  Canadian Contraception Consensus:

  • Progestin-only for ALL postpartum patients, regardless of breastfeeding

  WHO:

  • CHCs not recommended before 6 months postpartum if breastfeeding

  📌 Real-world practice:

  Most patients stay on progestin-only for ~1 year postpartum

  ---

  🧠 FINAL PATTERN TO REMEMBER

  When in doubt:

  • Postpartum?

  • Smoker >35?

  • Migraine with aura?

  • High VTE risk?

  👉 Avoid estrogen → choose progestin-only

🌙 Progestin-Only Pills (POPs) — WHEN & WHY

🔑 Big idea

✅ Who can/should use POPs:

• Past VTE

• High risk of MI or stroke

• Smokers ≥35

• Migraine with aura

• Estrogen side effects

• Breastfeeding

• Postpartum

📌 Evidence reassurance
Tepper et al. 2016:
➡ No increased odds of venous or arterial events with most progestin-only contraceptives

🧠 Exam phrase:

💊 Drospirenone vs Norethindrone POPs

(this comparison is VERY testable)

🟣 Drospirenone POP (e.g. Slynd)

MOA:

• Primarily suppresses ovulation

• Strong antigonadotropic effect (↓ LH)

Dosing:

• 24 active + 4 inert pills

• More forgiving

Missed dose rules:

• <48 hours → take ASAP, no backup

✨ Pros:

• Better ovulation suppression

• Better bleeding control

• Less strict timing

⚠ Cons:

• Anti-mineralocorticoid → hyperkalemia risk

• Watch ACEI / ARB / K⁺-sparing diuretics

🔵 Norethindrone POP (e.g. Movisse, Jencycla)

MOA:

• Prevents ovulation in ~40–50% of cycles

• Main action = thickens cervical mucus

• Alters endometrium

Dosing:

• Continuous, no breaks

Missed dose rules:

🚨 VERY strict

• Must be taken within 3 hours

⚠ Cons:

• Higher failure if non-adherent

• More breakthrough bleeding

🧠 Exam shortcut:

🔬 Drug–Drug Interactions (VERY HIGH YIELD)

🔑 Rule to memorize:

(That blank on your slide = DECREASE)

⚙ Phase I Metabolism

Most hormones → CYP3A4

➡ Anything that induces CYP3A4 ↓ hormone levels

⬇ Drugs that DECREASE efficacy

(enzyme inducers)

🚨 This list is exam gold

Antiepileptics:

• Carbamazepine

• Phenytoin / fosphenytoin

• Phenobarbital

• Oxcarbazepine

• Topiramate

• Eslicarbazepine

• Lamotrigine* (↓ lamotrigine levels too!)

Antibiotics:

• Rifampin

• Rifabutin
  (beta-lactams usually NOT clinically significant)

Antivirals:

• Efavirenz

• Nevirapine

OTC / NHP:

• St. John’s Wort

Misc:

• Modafinil

• Mycophenolate

• Chronic dexamethasone

📌 Counseling pearl:

⬆ Drugs that INCREASE hormone levels

(CYP inhibitors)

• Grapefruit juice

• Ritonavir, cobicistat

• Diltiazem, verapamil

• Macrolides

• High-dose azoles (ketoconazole, itraconazole, fluconazole)

⚠ Risk:

• ↑ estrogen → ↑ VTE risk

▶ Starting Oral Contraceptives (Quick Start)

This is OSCE-friendly.

✅ You can start:

• Any day of the cycle

• Same day as visit

• No need to wait for next period

• PAP smear not required first

Requirements:

• Rule out pregnancy

• Check BP, BMI

• STI testing if indicated

Counseling:

• Use condoms x 7 days initially

• Condoms for STI prevention

• Explain missed doses

• Review ACHES warning signs

💊 Types of CHC Pills (don’t overthink)

🟦 Monophasic

• Same estrogen + progestin dose

• Simplest

• Best adherence

• Most commonly used

🟨 Biphasic

• Estrogen constant

• Progestin increases once

• Rarely used

🟧 Triphasic

• Progestin changes 3 times

• No clinical advantage

• Harder adherence

🧠 Exam tip:

🧠 Choosing the RIGHT Pill

👶 Youth:

• ≥ 30 mcg EE

• Lower doses → ↓ bone mineralization

👩 Initial choice (most patients):

• Monophasic

• 20–25 mcg EE

• Low-androgen progestin

🚫 Estrogen contraindicated:

• POP

• Drospirenone POP preferred if adherence issues

🚨 DIANE-35 (VERY IMPORTANT SLIDE)

What it IS:

• Cyproterone acetate + ethinyl estradiol

• Potent anti-androgen

Approved indication:

• Severe acne

• Failed other therapies

• Short-term use only

What it is NOT:

❌ NOT a contraceptive
❌ NOT for long-term use

🚨 Issue in Canada:

• 35–40% prescribed off-label for birth control

• ↑ unnecessary thrombosis risk

🧠 Exam wording:

🧠 ULTRA-HIGH-YIELD SUMMARY

If estrogen is unsafe → POPs
If adherence is poor → Drospirenone POP
If on enzyme inducers → Expect ↓ efficacy
If postpartum or breastfeeding → Progestin-only
If acne/hirsutism → Anti-androgenic progestins
DIANE-35 ≠ birth control 🚫

🩹 Transdermal Contraceptive Patch (Evra)

💊 What it is

• Norelgestromin + Ethinyl Estradiol

• Releases 200 µg progestin + 35 µg EE daily

• Combined hormonal method (so estrogen rules apply)

🗓 How to use

• Apply once weekly for 3 weeks

• Then 1 patch-free week

• Application sites:

  • Buttock

  • Abdomen

  • Outer arm

📌 If NOT started on day 1 of menses → backup x 7 days

🚨 BIG EXAM RED FLAGS

⚖ Weight

• Avoid if >90 kg

• ↑ failure rate

🩸 Estrogen exposure

• ~60% MORE estrogen exposure than a 35 µg EE pill

• → ↑ thromboembolic risk

• FDA warning exists

🤢 Side effects

• More nausea & vomiting

• More breast tenderness

🧠 Exam pearl:

💍 Vaginal Ring

💊 What it is

• Etonogestrel + Ethinyl Estradiol

• Releases:

  • 120 µg etonogestrel

  • 15 µg EE daily

🗓 How to use

• Self-insert

• In for 3 weeks

• Out for 1 week

🚨 Expulsion rules (VERY testable)

• If ring is out >3 hours:

  • Reinsert ASAP

  • Backup x 7 days

  • Finish cycle

  • Start next ring without a break

📌 Avoid concurrent tampon use (may dislodge)

🩸 VTE risk

• ~8 / 10,000 per year

• Slightly higher than most CHCs (~6 / 10,000)

🧠 Pattern:

💉 Injectable Contraceptive (DMPA – Depo-Provera)

💊 What it is

• Depot-medroxyprogesterone acetate

• Progestin-only

✅ Who benefits most

• Breastfeeding

• Estrogen intolerance or contraindication

• Poor adherence

• On enzyme-inducing seizure meds

• Wants long gaps between dosing

🗓 How to use

• Injection every 12 weeks (3 months)

• IM or SC

• Given within 5 days of menses onset

• Bypasses first-pass metabolism

⚠ DISADVANTAGES (HIGH YIELD)

⏳ Return to fertility

• Delayed

• Avg ~10–12 months

• Can be up to 18 months after last injection

🦴 Bone mineral density

• Associated with bone loss

• May not fully reverse

• Especially important in:

  • Adolescents

  • Long-term users

⚖ Weight gain

• ~1 kg/year

• ~5 kg after 5 years

🧠 Exam wording:

🔑 QUICK COMPARISON (EXAM MODE)

🧠 ONE-LINE TAKEAWAYS

• Patch = higher estrogen exposure → higher VTE risk

• Ring = similar to CHCs, watch expulsion timing

• DMPA = great for adherence, bad for bones & fertility delay

🩸 Breakthrough Bleeding (BTB)

📌 Definition

🔍 Why BTB happens (PATTERNS, not memorization)

⬇ Estrogen → ↑ BTB

• Low estrogen pills

• Early months of therapy

⏰ Poor adherence → ↑ BTB

• Missed pills

• Late pills

• Patch off too long

• Ring out too long

🚬 Smoking

• Increases spotting & BTB

🦠 Infection

• Chlamydia = classic cause

💊 How to reduce BTB

• ↑ estrogen dose

• ↑ progestin potency

• Improve adherence

• Counsel patience

📌 Key reassurance:

⏰ Missed Combined Hormonal Contraceptives

(this is VERY exam-y but there’s a logic to it)

🔑 Core rules to remember

1. Week 1 matters the most

2. >24 hours = missed

3. Backup = 7 days

4. Consider emergency contraception if Week 1 + missed

📅 Week 1 (highest pregnancy risk)

Missed pill >24 hours

Patch >24 hours
Ring >3 hours

👉 Do ALL of this:

• Take pill / reapply patch / reinsert ring ASAP

• Backup contraception x 7 days

• Consider emergency contraception

📅 Week 2 or 3

Missed <3 pills / patch <3 days / ring <3 days

• Take/reapply/reinsert ASAP

• Continue pack as usual

• No hormone-free interval

  • Skip placebo

  • Start next pack immediately

Missed ≥3 pills / patch ≥3 days / ring ≥3 days

• Same as above

• Backup contraception x 7 days

• Consider EC

🧠 Exam shortcut:

🛠 Managing Adverse Effects (VERY testable)

🧴 Acne

• ↑ estrogen

• Switch to less androgenic progestin

• Drospirenone is a fave

💕 Breast tenderness

• ↓ estrogen dose

🩸 Breakthrough bleeding

• Early/mid-cycle → ↑ estrogen

• Late-cycle → ↑ progestin dose or potency

🤕 Headache

• ↓ estrogen

• Less progestin activity

• Consider progestin-only

🧠 Migraines on CHC

🚨 STOP estrogen

• Switch to progestin-only

🤢 Nausea

• ↓ estrogen

• Progestin-only option

⚖ Weight gain

• ↓ estrogen

• Less androgenic progestin

• Progestin-only

🧠 FINAL SUMMARY (THIS IS EXAM GOLD)

• ↑ Estrogen (>50 mcg) = ↑ VTE & MI risk

• All contraceptives are >99% effective with perfect use

• Typical use failure:

  • Pill / Patch / Ring ≈ 9%

• Patch = higher estrogen exposure

• Depo = bone loss + weight gain + delayed fertility

• Missed CHC = >24 hours

• Week 1 is the highest risk

• Postpartum → progestin-only

• Progestin-only methods are best when estrogen is contraindicated