Pharmacology of Contraception Study Notes

Pharmacology of Contraception

Introductory Case

  • Patient Overview: 22-year-old nulliparous woman seeks contraception advice.
    • Current Status: Sexually active, not using any birth control.
    • Patient Weight: 61.4 kg; Height: 163 cm; Blood Pressure: 108/70 mm Hg.
    • No smoking history.
    • Medical History: Migraines without aura, treated with propranolol.
    • Family History: Positive for breast cancer (mother and maternal aunt); no personal history.

Case Discussion Questions

  • a) What additional information do you need to know before recommending a contraceptive for this patient?
  • b) What oral contraceptive agent would you recommend for the patient and why?
  • c) What education would you provide regarding risks associated with oral contraceptive use?

Learning Objectives

  1. Discuss the physiology of the female reproductive system.
  2. State the mechanism of action of hormonal contraceptives.
  3. Discuss risks associated with contraceptive use.
  4. Compare efficacy and safety of oral contraceptives (OCs) with other methods of contraception.
  5. Describe advantages and disadvantages of various contraceptives.
  6. Provide patient education regarding barrier methods of contraception.

Introduction to Contraception

  • Definition: Contraception depicts the strategies aimed at preventing pregnancy post sexual intercourse.
    • Mechanisms:
    • Barrier Methods: Prevent viable sperm from contacting a mature ovum.
    • Implantation Preventive Methods: Create an unfriendly uterine environment preventing fertilized ovum implantation.
  • Variability: Effectiveness, safety, and patient acceptance vary among contraceptive methods.

Epidemiology of Unintended Pregnancy

  • Public Health Issue: 37% of pregnancies are unintended; highest rates in women aged 20-34.
  • Teen Pregnancy Rates: Account for 11% of total births in the U.S.; slow decline observed.
  • Abortion Statistics: Half of unintended pregnancies end in abortion, while 40% occur in sexually active couples using contraception.
  • Effectiveness Measurement Challenge: Determining contraceptive method efficacy is complex due to various failure factors.
    • Failure Types:
    • Method Failure: Arises from incorrect usage despite perfect compliance.
    • User Failure: Regular mistakes in method use.

Physiology of the Menstrual Cycle

  • Phases:
    1. Follicular Phase (Preovulatory)
    2. Ovulatory Phase
    3. Luteal Phase (Postovulatory)
  • Cycle Duration: Median cycle is 28 days; ranges from 21 to 40 days influenced by hormonal regulation.

Detailed Cycle Phases

  • Follicular Phase:
    • Days 1-4: Rise in FSH levels; recruitment of follicles.
    • Days 5-7: Dominant follicle's enlargement and estradiol, androgen, progesterone synthesis.
    • Estradiol Functions: Stops the menstrual flow from the previous cycle; thickens endometrial lining and increases cervical mucus production.
  • Ovulatory Phase:
    • LH Surge: Occurs from sustained estradiol levels leading to ovulation. Typically occurs 24-36 hours post-estradiol peak.
    • Fertilization: Optimal time for fertilization is 2 days before ovulation to the day of ovulation.
  • Luteal Phase:
    • Post-ovulation, the corpus luteum synthesizes androgens, estrogen, and progesterone, maintaining endometrium.
    • If pregnancy occurs, hCG maintains corpus luteum; if not, degeneration occurs leading to menstruation.

Prevention of Pregnancy Using Contraceptives

  • Goals: Prevent pregnancy while offering health benefits:
    • STDs prevention (condoms),
    • Menstrual cycle regularity improvement (hormonal contraceptives),
    • Management of perimenopause symptoms.
  • Methods of Contraceptives:
    1. Non-pharmacologic Methods:
    • Periodic abstinence, coitus interruptus, barrier techniques (condoms, diaphragms).
    1. Pharmacologic Methods:
    • Spermicides (creams, jells), hormonal contraception.

Characteristics of Ideal Contraceptive Methods

  • Desired Traits:
    • Ease of use, safety, efficacy, minimal side effects, natural method preference (naturalness), non-hormonal options, reversibility.
  • Challenge: No single method meets all criteria simultaneously.

Summary of Spermicides

  • Functionality: Blocks sperm before ejaculation.
  • Vasectomy: A male birth control method.

Hormonal Contraception Overview

  • Components of Hormonal Contraceptives:
    • Combination of estrogen and progestin or progestin alone.
  • Evolution: Hormonal contraceptive options have expanded from oral preparations to include patches, rings, injections, and implants.

Estrogens

  • Mechanism: Suppress FSH release, block LH surge, stabilize endometrial lining, manage cycle control.
  • Common Synthetic Estrogens: Ethinyl estradiol (EE) and mestranol.
  • Dosage Range: Most combined OCs, patches, rings contain 20 to 50 mcg of EE.

Progestins

  • Functionality:
    • Thickens cervical mucus, impacts tubal motility, induces endometrial atrophy, blocks the LH surge.
  • Variability: Different progestins exhibit varying levels of progestational activity and effects on estrogenic, antiestrogenic, and androgenic activity.

Efficacy of OCs

  • Perfect-use Efficacy Rate: 99%.
  • Adjustment Over Time: Current OCs have lower doses of estrogen and progestin compared to past formulations; previously high-dose formulations had significant risks.

Types of Oral Contraceptives

  • Monophasic OCs: 21-day regimen followed by a 7-day placebo phase.
  • Biphasic and Triphasic Regimens: Mimics natural hormonal changes, recommended for women over 35 or those with risk factors for excessive menstrual bleeding.
  • Extended-cycle OCs: Increase hormone pill usage to 84 days for reduced menstrual cycles (4 cycles a year).
  • Minipills: Progestin-only tablets; less effective but suitable for smokers, breastfeeding, and women with health issues.
    • Ectopic pregnancy risks are higher (3-5%).

Emergency Contraceptives

  • Options: Progestin-only, combined OCs (EE + progestin).
  • Timing: Should be taken within 72 hours post unprotected sex; multiple dosing may be required.
  • Preferred Regimen: Two tablets of 0.75 mg levonorgestrel.

Combined Hormonal Contraceptives (CHCs)

  • Prescribing Considerations: Medical history and BP assessment vital before prescribing; both benefits and risks must be discussed with patients.

Non-contraceptive Benefits of OCs

  • Advantages: Relief from menstrual problems, decreased anemia risk, reduced ovarian and endometrial cancer risks, lowered risks of ovarian cysts, and ectopic pregnancies.

Initiation of Oral Contraceptives

  • Methods of Initiation:
    1. On day 1 of the menstrual cycle.
    2. The first Sunday after the cycle begins.
    3. On the fifth day of the menstrual cycle.
  • Popular Method: Sunday start for potential period-free weekends.

Choosing an Oral Contraceptive

  • Initial choice depends on hormonal content, preferred formulation, and concurrent health conditions. Recommended OC contains ≤35 mcg of EE and ≤0.5 mg of norethindrone if no health issues.

Drug Interactions with COCs

  • Precautions with Other Medications: Anticonvulsants, antibiotics, antacids, and other medications can reduce the efficacy of COCs.
  • Potential Risks: COCs may hinder the effects of various medications including anticonvulsants, anticoagulants, and steroids.

Adverse Effects and Management Strategies

Types of Adverse Effects

  1. Estrogen Excess:
    • Symptoms: Nausea, breast tenderness, menstrual weight gain, dysmenorrhea.
    • Management: Decrease estrogen content, consider extended or continuous regimens, NSAIDs for dysmenorrhea.
  2. Estrogen Deficiency:
    • Symptoms: Vasomotor symptoms, nervousness, low libido.
    • Management: Assess for pregnancy; increase estrogen content if menses needed.
  3. Progestin Excess:
    • Symptoms: Increased appetite, weight gain, bloating, acne.
    • Management: Decrease progestin levels or change to less androgenic options.
  4. Progestin Deficiency:
    • Symptoms: Dysmenorrhea, late-cycle bleeding.
    • Management: Increase progestin or consider alternative contraceptives.

Specific Considerations in CHC Use

  • Age > 35 Years: Low-dose CHCs are acceptable for nonsmoking women. No increase in MI or stroke risk for nonsmokers in this group.
  • Hypertension: Small BP increases associated; OCs suitable for well-controlled hypertension cases.
  • Diabetes: New progestins minimally affect carbohydrate metabolism; CHCs permitted in younger women without complications.
  • Dyslipidemia: Most low-dose CHCs have negligible effects. Uncontrolled dyslipidemia necessitates alternative contraceptive methods.
  • Thromboembolism: Estrogen increases VTE and PE risks; contraindicated in women with a history of thromboembolic events.

Special Concerns

  • Migraine: Women with migraines may need to discontinue CHCs due to stroke risk, especially those with aura.
  • Breast Cancer History: Recent personal history of breast cancer is a contraindication for usage.
  • Smoking Risks: Caution required if prescribing CHC to smokers over 35 years.

Specific Contraceptive Methods

Transdermal Patch

  • Method: Ortho Evra patch (0.75 mg EE, 6 mg norelgestromin); effective like combined OCs below 90 kg. It is changed weekly for 3 weeks.

Injectable Progestins

  • DMPA (Depo-Provera): Administered every 3 months; effective >99% with perfect use, but delayed fertility postdiscontinuation often occurs.
  • Common Side Effects: Irregular menstrual cycles, breast tenderness, slight weight gain.

Intrauterine Devices (IUD)

  • Description: T-shaped, medicated devices; effective >99%. Mechanisms include disrupting sperm function and preventing implantation.

Subdermal Progestin Implants

  • Implanon: 4-cm implant releasing etonogestrel; effective for up to 5 years with a high efficacy rate. Possible effects: irregular bleeding, headaches, and weight gain.

Evaluation of Therapeutic Outcomes

  • Follow-up appointments essential for adherence and monitoring health issues. Contraceptive effectiveness can be assessed using pregnancy tests. Annual BP checks recommended for CHC users along with screenings for diabetes, STDs, and other health concerns.

Further Reading

  1. Oxford Handbook of Obstetrics and Gynecology: 3rd ed, Chapter 20.
  2. Pharmacotherapy Principles and Practice: 5th ed, Chapter 48 on gynecology and obstetrics disorders (contraception).

Thank you!