creation date: 2024-12-29 14:20
tags: Pharmacology


Contraceptives

Short- and Intermediate-Acting Hormonal

Oral Contraceptive Pill

Combined oral contraceptive (COCs)

Mechanism of action

Progesterone inhibits GnRH and LH secretion which suppresses ovulation. This is the main mechanism of contraception. Progesterone also inhibits endometrial proliferation and the cervical mucus remains thickened.

Estrogen also suppresses GnRH which decreases FSH and LH, suppressing ovarian folliculogenesis and ovulation, respectively. Used in conjunction with progesterone, estrogen also stabilizes the endometrium and thus provide a more consistent bleeding pattern.

Failure rates:

  • Perfect use: 0.3%
  • Typical use: 9%
Initiation

Combined OCPs should be taken at the same time each day in order to maximize efficacy. The initiation of the prescription can be:

  • First day of menses (best strategy)
  • On any day (with risk of pregnancy for first 7 days) - some patients prefer to start on Sundays for ease of tracking

If a tablet is missed, the missed dose should be taken as soon as they remember and the next tablet at the regular time (2 dose in 1 day). If a tablet is missed two days in a row, then take the 2 tablets the day the patient remembers and another 2 tablets the day after, before resuming the 1 tablet schedule.

The medication can be prescribed based on the withdrawal bleeding deseried by the patient. Options include:

  • Cyclic (use as packaged with 4-7 days of inert pills): monthly bleeding
  • Extended cyclic (use active pill for 3 months followed by a placebo week)
  • Continuous (only using active pills for a year): may experience breakthrough bleeding, easier to manipulate monophasic pills
Indications
  • Contraception (incl. emergency contraception)
  • Abnormal uterine bleeding
  • Primary dysmenorrhea
  • PCOS/Benign ovarian cysts
  • Endometriosis
  • Menstrual-related migraines (without aura)
  • Acne (some brands)
Adverse effects

Primarily related to estrogen. Common effects include:

  • Headache
  • Breast tenderness
  • GI symptoms (GERD, nausea)
  • Mood swings
  • Irregular bleeding (especially in initial 3-6 months)
  • Worsening acne (in some individuals)

More serious/rare effects include:

  • Venous thromboembolism
  • Cardiovascular conditions
  • Hepatocellular adenoma development
Contraindications
  • Smokers (>15 cigarettes/day) aged >35 - risk of cardiovascular events incl. DVT
  • Uncontrolled hypertension
  • Current or past history of breast cancer
  • Known ischemic heart disease or valvular heart disease
  • Migraine with auras
  • Endometrial cancer
  • Cirrhosis
  • Hepatocellular adenoma
  • Malignant hepatoma
  • History of stroke
  • High cardiovascular risk or thrombogenic mutations
Examples

Options vary in the type of estrogen and progestin used (generic available in parentheses). Packs are available in 21 active + 7 inert tab unless specified.

Monophasic:

  • Marvelon (Apri, Freya, Mirvala, Reclipsen)
  • Yaz, Yaz Plus (Mya) - 24 active/4 inert
  • Yasmin, Yasmin Plus (Zamine, Zarah, Qismette)
  • Demulen 30
  • Alesse (Alysena, Aviane, Esme, Lutera)
  • Min-Ovral (Ovima, Portia)

Multiphasic (dosing changes based on day):

  • Linessa
  • Triquilar
  • Lolo - 24 active/2 estrogen only/2 inert
  • Synphasic
  • Ortho 7/7/7

Extended Cycle:

  • Seasonale (Indayo) - 84 active/7 inert
  • Seaonique - 84 active/7 estrogen only

Progesterone-only pill (POPs)

Mechanism of action

Mechanism is the same as COCs without the stabilizing effect of estrogen.

Failure rates:

  • Perfect use: 0.3%
  • Typical use: 9%
Initiation

The pill should be taken at the same time each day to maximize efficacy. If the POP is not started within the first 5 days of menses, a backup contraceptive should be used for the first 48 hours.

If a dose is missed, the patient should take a dose when they remember and the next tablet at the scheduled time. Additional contraception should be used for 48 hours following a late dose (>3 hours).

Indications
  • Contraception (especially if COCs are contraindicated)
  • Abnormal uterine bleeding
  • Primary dysmenorrhea
  • Endometriosis
Adverse effects
  • Irregular menstrual cycles, amenorrhea, breakthrough bleeding
  • GI symptoms (abdominal pain, nausea)
  • Dizziness
  • Headaches
  • Mood changes
  • Breast tenderness
  • Follicular cysts

Believed to cause weight gain but evidence has not shown association.

Contraindications
  • Suspected or known pregnancy
  • Undiagnosed abnormal uterine bleeding
  • Breast cancer
  • Acute liver disease, liver tumours, or severe cirrhosis
  • History of bariatric surgeries
  • Concurrent use with some antiseizure medications
Examples
  • Micronor (Jencycla, Movisse)

Combined-hormonal Patch

Mechanism of action

Action is functionally the same as combined oral contraceptives.

Failure rate:

  • Perfect use: 0.3%
  • Typical use: 9%
Initiation

The patch is applied once per week for 3 weeks followed by a patch-free week. Can be used continuously without the patch-free week to avoid withdrawal bleeding.

Indications

May be preferred over taking pill daily, especially if patient is not confident in being able to maintain a consistent regime.

Otherwise similar to COCs.

Adverse effects

Similar to COCs.

Contraindications

Similar to COCs.

Examples
  • Evra Transdermal Patch

Combined-hormonal Vaginal Ring

Mechanism of action

Action is functionally the same as combined oral contraceptives. The hormones are absorbed through the vaginal epithelium and enters systemic circulation.

Failure rate:

  • Perfect use: 0.3%
  • Typical use: 9%
Initiation

The flexible ring is worn inside the vagina for 3 weeks followed by a ring-free week for withdrawal bleeding. The ring can be used continuously as well.

Note that the ring does not need to be removed during intercourse.

Indications

May be preferred over taking pill daily, especially if patient is not confident in being able to maintain a consistent regime.

Otherwise similar to COCs.

Adverse effects

Similar to COCs.

Contraindications

Similar to COCs.

Examples
  • Nuvaring Slow Release Vaginal Ring

Progestin-only Injection

Mechanism of action

Functions similarly to progestin-only contraceptive pills except progesterone administered via injection of depot medroxyprogesterone acetate (DMPA).

Failure rate:

  • Perfect use: 0.2%
  • Typical use: 6%
Initiation

DMPA is injected every 3 months either:

  • 150 mg IM
  • 104 mg subq

Subcutaneous self-administration is possible at home with training.

Indications
  • Contraception
  • Intermediate-lasting
Adverse effects

Return to fertility may be delayed - while contraceptive effect may cease 3 months following injection, fertility may take up to 18 months to return.

Other concerns include potential decreased bone mineral density but otherwise similar to POPs.

Contraindications

Similar to POPs.

Examples
  • Depo-Provera-SC (pre-filled syringe) SQ
  • Depo-Provera (Sandoz) IM

Long-Acting Reversible Contraceptives (LARCs)

Intrauterine Device (IUD)

Hormonal IUD

Mechanism of action

T-shaped device inserted into the uterus which releases progestin locally. This prevents fertilization via:

  • Cervical mucous changes (blocks sperm from reaching oocyte)
  • Decreases sperm function and viability via uterine changes

Additionally:

  • Decreases likelihood of implantation via changes to endometrial lining
  • But does not suppress ovulation (due to lack of systemic effect)

Failure rate: 0.1-0.4%

Initiation

Prior to placement, evaluation should be conducted:

  • Ensure there are no contraindication
  • Perform bimanual exam and speculum-assisted visualization of cervix
  • Obtain a pregnancy test (if unable to exclude pregnancy)
  • STI testing (not required but should offer)

Selection of IUD depending on indications (eg. Kyleena for nulliparous patient per smaller size).

Insertion can be performed at any point of the menstrual cycle. Exact procedure is discussed separately.

Indications
  • Long-term, easily reversible contraception
  • Emergency contraception
  • May reduce risk of cervical and endometrial cancers
  • Decreased menstrual pain and bleeding
Adverse effects

Pain/menstrual changes typically resolve within 3-6 months:

  • Temporary cramping and discomfort
  • Abnormal uterine bleeding

40-50% of individuals become amenorrheic after 2 years of use (may not be considered adverse for some patients).

Complications include:

  • Expulsion
  • Uterine perforation
  • Elevated risk of ectopic pregnancy if pregnancy occurs
Contraindications

Universally:

  • Pregnancy or suspected pregnancy
  • Sexually transmitted infection at the time of IUD insertion, including cervicitis, vaginitis, or any other lower genital tract infection
  • Congenital uterine abnormality that distorts the shape of the uterine cavity, making insertion difficult
  • Acute pelvic inflammatory disease
  • History of pelvic inflammatory disease, unless a subsequent successful intrauterine pregnancy has occurred
  • History of septic abortion or history of postpartum endometritis within the last 3 months
  • Confirmed or suspicion of uterine or cervical malignancy or neoplasia
  • Abnormal uterine bleeding of unknown origin
  • Increased risk of pelvic infection
  • Previously inserted IUD that has not been removed
  • Hypersensitivity to device

Specific to hormonal IUDs:

  • Confirmed or suspicion of breast malignancy or other progestin-sensitive cancer
  • Liver tumours
  • Acute liver disease
Examples
  • Jaydess (3 years)
  • Mirena (3 years)
  • Kleenya (5 years)

Copper IUD

Mechanism of action

The copper ions create localized inflammation that decreases sperm viability and function (preventing fertilization). May also decrease likelihood of implantation.

Failure rate: ~0.6%

Initiation

Similar to hormonal IUDs.

Indications
  • Long-acting, easily reversible contraception
  • Emergency contraception
  • Non-hormonal alternative (eg. hormone-sensitive malignancies, risk factor for VTE, migraine with aura)
Adverse effects

Pain/menstrual changes typically resolve within 3-6 months:

  • Temporary cramping and discomfort
  • Heavy menstrual bleeding, dysmenorrhea

Complications include:

  • Expulsion
  • Uterine perforation
  • Elevated risk of ectopic pregnancy if pregnancy occurs
Contraindications

Universally:

  • Pregnancy or suspected pregnancy
  • Sexually transmitted infection at the time of IUD insertion, including cervicitis, vaginitis, or any other lower genital tract infection
  • Congenital uterine abnormality that distorts the shape of the uterine cavity, making insertion difficult
  • Acute pelvic inflammatory disease
  • History of pelvic inflammatory disease, unless a subsequent successful intrauterine pregnancy has occurred
  • History of septic abortion or history of postpartum endometritis within the last 3 months
  • Confirmed or suspicion of uterine or cervical malignancy or neoplasia
  • Abnormal uterine bleeding of unknown origin
  • Any condition that increases the risk of pelvic infection
  • History of previously inserted IUD that has not been removed
  • Hypersensitivity to any component of the device

Specific to copper:

  • Wilson disease
  • Copper sensitivity
Examples
  • Flexi-T
  • Liberte
  • Mona Lisa
  • Nova-T

Progestin Implant

Mechanism of action

The implant in the subdermal upper arm contain extended-release of etonogestrel which functions like other progestin-only hormonal contraceptives.

Failure rate: 0.05-0.1%

Initiation

The implant is inserted at the outpatient clinic using device that shoots the implant into the subdermal region of the upper arm.

The implant is approved for 3 years of use but studies have shown efficacy up to 5 years.

Indications

Generally preferred if progestin-only option is preferred but a long-term contraceptive is desired.

Otherwise similar to POPs.

Adverse effects

Similar to POPs.

Contraindications

Similar to POPs.

Examples
  • Nexplanon

Barrier Contraceptive

Mechanism of Action

Barrier methods prevent fertilization by blocking the sperm from reaching an oocyte. Condoms also provide protection against STIs.

Due to the need to utilize with every sexual encounter, there is a high risk of poor adherence and possible incorrect use.

Options

External condom

  • Thin sheath that covers the penis
  • Failure rates: perfect use 2%, typical use 18%
    Internal condom
  • Thin sheath inserted into the vagina
  • Failure rates: perfect use 5%, typical use 25%
    Diaphragm
  • Large dome-shaped device made of plastic/latex placed in the vagina
  • Used with spermicide or contraceptive gel
  • Can be professionally fitted or single-size non-fitted
  • Failure rates: perfect use 6%, typical use 12%
    Cervical cap
  • Small cap that fits over the cervix
  • Used with spermicide
  • Requires professional fitting
  • Failure rates:
    • Nulliparous: perfect use 9%, typical use 16%
    • Parous: perfect use 26%, typical use 32%
      Contraceptive sponge
  • Foam disc containing spermicide placed into the vagina
  • Over the counter
  • Failure rates:
    • Nulliparous: perfect use 9%, typical use 12%
    • Parous: perfect use 20%, typical use 24%

Behavioural Methods

Mechanism of Action

Change in behaviour in order to avoid fertilization. These are often less effective than other methods.

Options

Fertility awareness-based method

  • Avoid intercourse (or use barrier) during fertile window which consist of the 5 days prior to ovulation and the day of ovulation itself
  • High risk of error and requires regular periods
  • Failure rate: perfect use <5%, typical use 2-23%
    Lactational amenorrhea
  • Breastfeeding induced amenorrhea that suppresses ovulation
  • Nipple stimulation causes increased prolactin which disrupts GnRH
  • Requires the mother to still be amenorrheic, breastfeeding q4-6 hrs, infant <6 months
  • Failure rate: perfect use 1%, typical use <2%
    Coitus interruptus
  • Penis is withdrawn from the vagina prior to ejaculation
  • High risk of error
  • Failure rate: perfect use 4%, typical use 22%

Surgical Sterilization

Mechanism of Action

A surgical procedure permanently ends fertility by either preventing sperm from entering the vas deferens for ejaculation or preventing the oocyte from entering the fallopian tube.

Options
  • Vasectomy (male)
  • Tubal ligation (female)